Drew Endy, Stanford professor and synthetic biology evangelist, gave an interesting overview of the subject in general and "The iGEM Revolution" in particular at a Long Now seminar on September 16 in San Francisco. A summary will be posted soon, as well as complete video.
Endy is convinced that this is the century of biology, and in particular of making things with biology. He even invoked "Steve & Steve" (Jobs & Wozniak) — a common trope among synthetic biology types — claiming that the technology he started with was even cruder than the first Apple (which didn't even have a screen). The implication is, of course, that these new tools will lead to an equivalent technical, economic and social revolution.
Some DiY biotech initiatives do struggle along on a shoestring, but the analogy is misleading. iGEM has 20,000 alumni, Endy said, scattered among labs worldwide. Stanford's department of bioengineering alone has two dozen core faculty, plus associates and consultants; this is not a small operation, nor are those in Cambridge and elsewhere. Allied Market Research is hawking a report claiming that the global synthetic biology market will reach $38.7 billion by 2020.
Yet Endy admitted, in the Q&A, that "we need to figure out what we wish for." Which might help to explain why (as he complained) movies always seem to show biologists as villains, although he and others in the field seem to view themselves, sincerely though not always humbly, as white knights and revolutionary heroes bringing salvation and transcendence to the planet. Sadly for them, Hollywood has not yet come up with the "realistic heroic narratives" that Endy thinks are needed to promote biotech to the general public.
The beleaguered direct-to-consumer (DTC) gene testing company 23andMe just cannot catch a break. And its problems seem to be largely of its own making.
Last year, the company stopped responding to the FDA’s letters. In response, the FDA finally sent a cease-and-desist letter that basically restricted the company to providing raw data and doing ancestry tests. Sales fell by 50%. CEO Anne Wojcicki has been putting a brave face on this, calling it "a really good experience for 23andMe because it's taking us up a level,” and hired four executives with healthcare backgrounds.
Then Vox, which launched in April as a fact-based website covering both news and background, started looking into some of the possible issues that DTC testing can raise, and published two articles on September 9th. The general overview was:
The author explained that through his 23andMe gene test, he had discovered a previously unknown half brother — his father's previously unacknowledged or unknown son. Then the rest of his family found out.
Years of repressed memories and emotions uncorked and resulted in tumultuous times that have torn my nuclear family apart. My parents divorced. No one is talking to my dad. We're not anywhere close to being healed yet and I don't know how long it will take to put the pieces back together.
Vox also revealed that 23andMe was about to move from an opt-in to an opt-out model of revealing close relationships. Up till now, customers have had to answer “Yes” to a question asking if they wanted to find their closest relatives in the company database; the change would have meant that anyone could accidentally be put in touch with family members they didn’t know existed.
The thinking behind the change seems to have been that privacy is no longer possible, a concept that is fashionable in some circles. Apparently Wojcicki did not know about this move, since she soon stated that this was "a decision that should have come to my attention but it did not.” She reversed it. And announced that:
Science writer David Dobbs has definitively described the voracious appetite of the “selfish gene” meme, pointing out that the notion of individual genes exercising power on the outcome of events has been so good at mass producing itself, that “the selfish gene has become a selfish meme.”
All “genes of the week” have something in common: they never actually live up to their billing. For starters, it is never true that a single gene just does something. Genes work together, and genomes work with their environments. But this inconvenient reality has done amazingly little to stem genetic determinism, or the funding of research that relies upon its framework.
How could this be true? Is it really the case, as Dobbs posits, that “the gene-centric model survives because simplicity is a hugely advantageous trait for an idea to possess?”
The adventures of “smart genes” provide an illuminating case study.
There are some people who really want to find the genetic basis of intelligence. The sole effort of BGI’s Cognitive Genomics Lab, for example, is to investigate the genetics of human cognition. The fascinating documentary film DNA Dreams sheds light on the hopes of those involved with this project. They harbor no doubt that there is a genetic basis for intelligence; the only question is when they’ll uncover it and how limitless the possibilities will be once they do. Embryo selection and modification to ensure smarter babies are among the future scenarios they envision.
But the future doesn’t seem to be cooperating. Project leader Bowen Zhao confidently promised data in three months time in February, 2013; it has now been nineteen months and we are still waiting.
In the meantime, two of the Cognitive Genomics Lab’s illustrious “collaborators and advisors,” Robert Plomin and Steven Pinker, are among the 59 co-authors of a brand new PNAS study, which Nature has called “one of the largest, most rigorous genetic studies of human cognition.”
The paper, published on September 5, is called “Common genetic variants associated with cognitive performance identified using the proxy-phenotype method.” It claims that three gene variants are associated with both educational attainment and higher IQ scores. The study is a follow-up of the 2013 Science study, “GWAS of 126,559 Individuals Identifies Genetic Variants Associated with Educational Attainment.”
What is remarkable about these studies is how little what they “identify” actually matters. Over 100,000 genomes were studied in each, but the results are so limited that they could easily fail to be replicated and become one of the many of a decade’s worth of publications on gene associations that the editors of Behavior Genetics disparage as “wrong or misleading and have not contributed to real advances in knowledge.”
In the Science study, three gene variants were found that each correlated with roughly one month’s difference in a person’s total amount of schooling. In the PNAS study, three gene variants were found that each correlated with about 0.3 points on an IQ test. Results this inconsequential could easily be no more than false positives.
Study co-leader Daniel Benjamin was upfront about this fact. He told Nature, “We haven’t found nothing.”
Whatever mechanisms are working on the partial heritability of intelligence, it doesn’t seem to be a defined group of “smart genes.” The authors of the PNAS study have suggested that looking into more than one million people’s genomes could help explain the genetic basis of cognitive ability a little bit better.
But the problem isn’t in the numbers, it’s in the framework. Genes are not selfish; they don’t act on their own for virtuous or nefarious ends. Heritability is much more complex than genes.
So, can we finally put the notion of “smart genes” behind us?
Posted by Carmel Shalev, Biopolitical Times guest contributor on September 15th, 2014
Pattaramon Chanbua, Thai surrogate mother to Baby Gammy.
This summer two separate incidents highlighted the deeply troubling problems that can arise in inter-country surrogacy arrangements. In the most extensively covered situation, the “Baby Gammy” case, an Australian couple left their infant son who has Down syndrome with his Thai surrogate mother and returned home with his twin sister. The husband was then discovered to have been convicted of multiple child sex offenses that took place between the early 1980s and early 1990s against girls as young as 5.
What should we make of these disturbing stories? Should we see them as revealing the ingenuity of consumers (commissioning parents and particularly fathers) in devising ways to exploit women as breeders in the unregulated global market of medically assisted reproduction? Is Baby Gammy’s story best understood as a tale of eugenics by a man convicted of abusing children (his words: "I don't think any parent wants a son with a disability")? What does the story of the Japanese man who fathered (perhaps “sired” is the better term) all those infants share with Theresa Erickson's international baby-selling fraud, which also involved the abuse of unknowing women?
Both stories raise policy questions about inter-country medically assisted reproduction, including the screening of intended parents, the parentage and citizenship status of children born of international commercial surrogacy, and these children’s welfare and interests in knowing their bio-social origins as a matter of identity.
Intermediaries in surrogacy agreements have certainly been ingenuous in navigating the economic opportunities and legal loopholes of the global market for their own profit. It appears from The New York Timesreport that Chinese women have been traveling to Thailand for impregnation, presumably to return home to carry a pregnancy and give birth to a child within a commercial surrogacy arrangement. In the wake of recent restrictions on international commercial surrogacy in India and Thailand, intermediaries operating out of other designation countries have devised schemes to transport surrogate mothers from those countries across borders to Nepal, where they are to give birth. These practices are conducive if not tantamount to trafficking in human beings. So is the cross-border movement of women who are paid to provide ("donate") eggs in response to the needs of infertile and post-fertile women and of single and gay men.
It is well-known that women who provide their bodily resources in transnational reproductive collaborations are subject to physical, emotional and social risks. Some egg providers and surrogate mothers have suffered irreversible damage to their own fertility. In India, where international commercial surrogacy has been most thoroughly studied and documented, some surrogate mothers are confined ("housed") in hostels following conception and for the duration of pregnancy, and subjected to 24/7 surveillance and control. In general, most surrogate mothers undergo Cesarean section in birthing, often without any clinical indication, for the convenience of intended parents or medical personnel. Double standards of medical care and ethics are pervasive, while emotional and social harms are neglected.
As The New York Timescoverage notes, the surrogacy industries of Thailand and India are outgrowths of both countries' economic policies that promote a private market of medical tourism. Medical tourism is problematic in any event: private healthcare markets exacerbate disparities in the distribution of resources at both local and global levels. Travelling abroad for medical care is wrought with additional risks of fraud and exploitation (e.g., unproven stem cell therapies) or downright criminality (e.g., organ trafficking). These issues are compounded in the case of reproductive tourism, because at stake is the birth of a child.
Who should be held responsible for the harms to women and children involved in inter-country surrogacy arrangements? Women who work as surrogates or egg providers are certainly not to blame. Unfettered consumer desire, in the guise of a neoliberal “right to reproduce,” may be a major driver of the market. But medical entrepreneurs are at the heart of the matter.
Professional medical associations should take responsibility to prevent medical practitioners from dehumanizing women and children as commodities. Nations too should act to quell abuses perpetrated by their own nationals, both inside and outside their borders. And the international community must intervene in the unregulated global market to protect, promote and sanction the human dignity and human rights of women and children.
Carmel Shalev, JSD, is chair of the Department for Reproduction and Society at the International Center for Health, Law and Ethics, Haifa University.
A newly released ComRes study conducted by the charity CARE has found that only 18% of British adults support “the creation of 3-parent children via genetic modification.”
The poll concerns the currently illegal technique, variously known as “3-person IVF” or more euphemistically as “mitochondrial donation,” which could move into UK fertility clinics shortly following an upcoming Parliamentary vote.
The technique involves the combination of one woman’s nuclear DNA with another woman’s mitochondrial DNA in the creation of a new child, with the hope of avoiding the transmission of mitochondrial disorders from an intending mother. It is currently illegal in the UK and several dozen other countries because it results in the modification of the genetic code passed down through the generations, something also explicitly prohibited in The Council of Europe’s Convention on Human Rights and Biomedicine.
Contrary to the protestations of advocates of the procedure — including the HFEA — total support for changing the law to allow use of the technique is even less than the number who “strongly oppose” the move (23%), let alone the total opposition (46%). Only 5% “strongly support” the move, while just over a third of respondents answered “don’t know.”
A US FDA committee considered the safety and efficacy of the technique in February and concluded that significantly more animal and embryonic research is needed before human clinical trials should be considered. When the participants in the latest poll learned that scientists around the world “have expressed concerns about the safety of the procedures for the children conceived” 42% were even less likely to support the change in UK law.
Furthermore, a full 65% agreed that the UK Government “should delay the introduction of 3-parent children until the surrounding medical, safety, and ethical issues can be better dealt with.”
The degree of public support on this issue has long been controversial. Indeed, a similar poll conducted by ComRes in February showed a much closer split (women opposed the procedure 36–31 but men supported it 40–31). That one, however, included slightly different wording, and did ask for reactions to the suggestion that “the procedure might help reduce the conception of children with some hereditary diseases,” which on balance made it significantly more likely that respondents would support a change in the law. It is clear that when dealing with powerful new biotechnologies, “wording effect” is a very significant factor.
It is also certain that there is a substantial reluctance among the British public to rush into such a major change. By 44–11 percent, the public thinks the government is “in a hurry” and not “making patient safety its first priority.” It’s also a vote-loser: Pushing on would make 44% of respondents less likely to vote for the government, and only 6% more likely. That’s the least of the reasons to suspend this process, but it just might be the most crucial.
George Church, professor at Harvard and MIT, multi-faceted researcher, entrepreneur, author and advocate of open-access genomics, gives good quote. He means what he says, and expresses it succinctly and vividly. The latest publication to exploit this is The Economist, which just ran a feature about him called "Welcome to my genome" that includes some of Church's predictions for human genetic modification:
In the future Dr Church sees a world in which individuals tinker with their DNA to eliminate diseases, give their offspring extra abilities or simply to look more attractive. … To travel beyond the Earth, astronauts could also have their bodies altered to give them a better chance of surviving the journey. They could be genetically engineered to resist radiation and osteoporosis, a weakening of the bones which would result from prolonged weightlessness. Those that remain on Earth could be altered to reduce their carbon footprint [by making] people smaller.
Church also endorses the concept of "backing up my brain into another that I have in my back-pack" and (smiling) suggests that things people "think are a million years away or never, are actually four years away."
This might be a shock to Neal Jordan, a young science-fiction author, who set his recently-published mind-uploading book Transgod 500 years in the future. Such uploading is also discussed in another new book, The Proactionary Imperative: A foundation for transhumanism, by Steve Fuller and Veronika Lipinska. Carl Elliott reviewed it in this week's New Scientist under the descriptive online headline, "a manifesto for playing god with human evolution." In print, the title was the catchier "More, or less, than human?" — presumably because the piece closes with the important observation that:
It is precisely because the powerless and disadvantaged have always made such tempting research subjects that strict controls on medical research are essential.
Newly published in the UK, though not due out in the United States till next February, is yet another book that considers such issues, Sapiens: A Brief History of Humankind by the Israeli historian Yuval Noah Harari. His take is darker than that of the techno-optimists. Not only does he question whether modern people are happier than our stone-age ancestors, he is deeply concerned that coming human enhancements will lead to a more unequal society than any we have seen:
"In the 20th century, the main task of medicine was to bring everybody to a certain level of health and capability. It was by definition an egalitarian aim," Harari told the Guardian. "In the 21st century medicine is moving onwards and trying to surpass the norm, to help people live longer, to have stronger memories, to have better control of their emotions. But upgrading like that is not an egalitarian project, it's an elitist project. No matter what norm you reach, there is always another upgrade which is possible."
As a consequence of the efforts of Church (who is mentioned specifically) and others:
"In the 21st century, there is a real possibility of creating biological castes, with real biological differences between rich and poor," said Harari. "The end result could be speciation. We're used to being the only human species around, but there is no law of nature that says there can only be one species of human. With this kind of upgrading treatment we could have, in the not too distant future, more than one human species on Earth again."
Harari is by no means the first to suggest this. Lee Silver notoriously made that prediction — which he seemed to relish — in Remaking Eden, which was first published in 1997. At that time, such expansive views of human possibilities were fueled by the approaching end of the Human Genome Project. Gene interactions turned out to be more complicated than was once hoped, and the wilder speculations died down for a bit. But now, with the advent of more precise gene-altering tools such as Crispr, ambition seems to be rising again, and the repeated warning is regrettably relevant.
The Economist is a business-focused newsmagazine, and notes that since 2007, "Dr Church has co-founded 12 biotech companies and advised many more." His enterprises are mostly focused on genomics, diagnostics, therapeutics and synthetic biology, with a possible sideline coming in DNA-based data storage — all related to his research. They are not apparently driving his choice of projects so much as derived from what he finds and publishes. But he does have a very capitalist orientation, leading him to tell the magazine:
We're well beyond Darwinian limitations to evolution. Evolution right now is in the marketplace.
Church is expressing here an odd combination of hubris and passivity. His ambition takes him "beyond Darwinian limitations" — he can casually discard a few billion years of evolution — and yet he is irresistibly bound to the current economic system. He has that the wrong way round.
A lively and informative three-day forum convened in The Hague from August 11-13. The International Forum on Intercountry Adoption and Global Surrogacy brought together nearly a hundred scholars, women’s health and human rights advocates, and policymakers from 27 countries at the International Institute of Social Studies of Erasmus University, the Forum’s host organization.
The Forum aimed to provide a venue “to discuss ways to improve international standards around the evolving practices of cross-border adoption and surrogacy, in which children typically move from poorer to wealthier countries.” The Center for Genetics and Society chaired the “Global Surrogacy Practices” thematic area of the conference.
Serendipitously, the Forum occurred in the wake of headlines about two disturbing surrogacy incidents in Thailand. In one case, an Australian couple was accused of abandoning their baby son, who has Down syndrome, with his Thai surrogate mother and returning home with his twin sister (1, 2); the husband was then revealed to have been convicted of multiple child sex offenses that took place between the early 1980s and early 1990s against girls as young as five. In the other news story, a young Japanese businessman fathered sixteen children since June 2013 with Thai surrogate mothers, claiming that he wanted a large family (1, 2).
These incidents took surrogacy out of its usual celebrity-driven spotlight and highlighted the risks of unregulated international surrogacy arrangements for a broader public. For Forum participants, they also underlined concerns about children born as a result of contract pregnancies, and set the stage for discussions of the “best interests of the child,” which is a foundational concept of the 1993 Hague Convention on Intercountry Adoption (HCIA).
By design, the Forum took place in advance of the Hague Conference on Private International Law’s upcoming considerations of its work on intercountry adoption and surrogacy. Implementation of the HCIA, and ongoing concerns about patterns of fraud and “failed” adoption, will be discussed by its Special Commission in spring 2015. In roughly the same time frame, the Hague Conference staff (known as its “Permanent Bureau”) expects to receive guidance from its member countries about whether and how to move ahead toward a possible convention on international surrogacy. Members of the Hague Conference Permanent Bureau participated in the Forum, and indicated their active interest in the discussions and evidence presented there.
Forum participants who have focused on surrogacy and those who have worked on intercountry adoption learned a great deal from each other over the course of the three-day event. Adoption experts presented data regarding the past and present challenges of international adoption faced in countries such as Ethiopia and Guatemala, while surrogacy experts shared findings from India, Mexico, Israel, and elsewhere. Several anthropologists and advocates presented accounts of their fieldwork with surrogate mothers in India, a major destination for international surrogacy, and the country in which it has been most intensively studied.
Meeting jointly and in smaller groups, participants identified and discussed several similarities between intercountry adoption and surrogacy, surrogacy and explored how lessons learned from decades of work by the international adoption community might inform surrogacy practices. One issue that is now more or less settled in the adoption context is that adopted children are entitled to “legal openness” about their biological origins; this raises the question of whether children born in surrogacy arrangements should also be granted access to information about their genetic and gestational origins. Adoptees repeatedly stressed the preservation of records as a primary concern for surrogacy practice. Another question turns on the similarities between the situations of birth mothers of adoptees and surrogate mothers, and on how their health, interests and rights can be protected. A third concerns the role of intermediaries in the two practices, and whether, and under what conditions, agencies are part of the solution or part of the problem.
Differences between intercountry adoption and international surrogacy are also instructive, and were the focus of many discussions at the Forum. In the case of adoption, the assumed starting point is a child in need of a home; with surrogacy, it’s adults who wish to create a child in order to become parents. Also, most countries see intercountry adoption as a practice that at least in some circumstances should be supported; in contrast, most countries currently prohibit commercial surrogacy altogether and face the quandary of what to do when their citizens flout these laws and go abroad to the handful of jurisdictions that allow it.
Participants whose work has focused on issues of parentage and citizenship of children born in international surrogacy arrangements, and those focused on the conditions of women working as surrogates, were able to easily agree that any international convention – as well as other policy or advocacy efforts – should protect the rights and well-being of all parties: children, women working as surrogate mothers, and intended parents. There was also agreement that any international convention should be structured so that it does not pressure jurisdictions that prohibit commercial surrogacy to loosen their laws.
In its Preliminary Report on the Issues Arising from International Surrogacy Arrangements (March 2012), the Hague Conference Permanent Bureau focused primarily on the “best interests of the child” in intercountry surrogacy arrangements, especially these children’s citizenship and parentage status. But the Report also covers concerns about psychological and health issues they may face, and includes strong language about the urgency of addressing the documented patterns of abuse and human rights violations against surrogate mothers.
While Forum participants shared strong concerns about the problems that intercountry surrogacy arrangements raise, and about minimum standards for any projected international convention, many were fundamentally unsettled about commercial surrogacy itself and about the best policy option for addressing it. Some consider commercial surrogacy unacceptable, on the grounds that it commodifies and commercializes both babies and women’s reproductive capacities. From this view, commercial surrogacy should be prohibited because it exploits women, especially those who have few other economic options, and constitutes a form of baby selling.
Others believe that harms to surrogate mothers can be addressed by defining contract pregnancy as a form of work, and establishing regulation and oversight to improve labor conditions. Their views are based either on a pragmatic sense that international surrogacy is already an established fact and that policies to protect those involved are urgently needed, or on the belief that surrogacy can benefit women who have few other options for earning the kind of money this work can bring them. Some participants reported that they changed their mind on these questions during the Forum, in one direction or another; most agreed that the animated and thoughtful exchanges had opened their minds to aspects of the issues they had not previously considered or taken seriously.
The Forum’s discussions and deliberations made clear that the issues raised by international commercial surrogacy are complex and that opinions about it are varied, even among women’s health advocates and feminist scholars. The wide range of concerns expressed, and the evidence on which they are based, will help inform the Hague Conference as it continues to consider the feasibility of a convention on international surrogacy.
Recordings of the Forum’s three plenary sessions will soon be posted on its public website, and a report on the discussions and deliberations will be published later this fall.
The British government continues to move toward legalizing a form of inheritable genetic modification that would combine eggs or embryos from two women in an effort to prevent the transmission of mitochondrial disease. But the controversy over the technique, variously known as "3-person IVF," "mitochondrial replacement," and "nuclear genome transfer," is far from over, and the issues received a public airing in the House of Commons on September 1st.
This was not the official government-initiated debate — that remains some way off — but one brought by a group of MPs who urged the government "to delay bringing forward regulations on mitochondrial replacement" until more research had been completed. (The British system combines the executive and legislative powers but also allows some time for debates requested by members of parliament who do not hold party or government office.) The complete transcript is available, as is archived video.
Opinion in the House of Commons was clearly divided. About half of those who spoke favored moving forward with the technology, some for rather crass reasons ("this is a great piece of British scientific advance"), some out of understandable concern for individual constituents who suffer from mitochondrial diseases. The debate also stirred some local newspapers to feature patients criticizing MPs for "standing in the way of a pioneering new treatment" or wanting to "help future generations."
Perhaps the most striking speech, however, was delivered by Conservative former minister Sir Edward Leigh, who stressed the ethical issues around inheritable genetic modification:
Bioethicists have up until this point expressed almost universal consensus on germ-line genetic modification of our fellow humans, rejecting it as grievously immoral and completely unethical. The consensus is worth pointing out as we must know what the proponents of mitochondrial transfer are asking us to dissent from. They are asking us to dissent from opinion in every other country in the world. In this age of globalisation, we will be divorcing ourselves from the entire community of nations in terms of bioethics. Do we really want to become a rogue state in terms of bioethics?
Leigh was featured in the report by the conservative Daily Telegraph, but this was not a party-political issue. Labour MP Jim Dobbin — a scientist by training — was concerned about the lack of evidence, and cited David King of Human Genetics Alert, who "fears that science is racing ahead of ethics [and] that we are in danger of creating designer eugenic babies." (Stuart Newman and Paul Knoepfler were quoted by the conservative MP Fiona Bruce, who introduced the motion.) Another Labour MP, Robert Flello, endorsed the ethical concerns and stressed the public safety issues:
To put it crudely, there is every possibility that we could be legislating to allow techniques that could cause damaged embryos, resulting in further damaged children. That is not spin; it is a reasonable assumption based on the available data. Newcastle University's own paper concluded that, compared with control experiments, 50% fewer eggs fertilised through pronuclear transfer reached the blastocyst stage-in other words, pronuclear transfer is twice as likely to cause the embryos to fail. … We might not know the result for many generations. We might not know whether some damage has been caused until three, four or five generations later. We simply cannot know that.
The Parliamentary Under-Secretary of State for Health, Jane Ellison, called it a "thought-provoking debate" and did acknowledge that some Members had concerns. She stressed that the draft regulations "would also bring into place important safeguards" but remained committed to moving forward. To what extent the concerns expressed will affect the final proposals remains unclear.
The summer's "ice bucket challenge" has brought an extraordinary amount of attention to amyotrophic lateral sclerosis (ALS), a neurodegenerative disease impacting nerve cells in the brain and spinal cord. What you may not know about ALS is that it is only very rarely inherited, at least through any determined genetic mechanism. It is currently thought that "only about 5% of all patients with ALS will have a genetic change" causing the disease. Genetic testing is available for patients who have both symptoms and a family history, but it is rarely recommended.
This does not mean that genetic testing for ALS will not be marketed to people concerned for their health, or for that of their children, especially given the peak in interest at this time. Genetic screening for the "breast cancer genes" BRCA1 and BRCA2 has become widespread, and prenatal genetic tests to detect them are also on the rise. But as with ALS, the vast majority of breast cancer cases have nothing to do with inherited genes.
Of course, there are plenty of traits that are more clearly and commonly linked to genetic variations. Prenatal genetic testing for such conditions significantly raises the stakes of what can be done with that knowledge.
All parents-to-be must be able to make their own choices about their ability to raise any child, but unfortunately too many are presented with a prenatal diagnosis without accompanying information about what it actually means for their child or their family. The slick marketing of prenatal genetic testing has sparked concern about its propensity to dehumanize conditions while normalizing specific responses. This is certainly true for the most frequent chromosomal disorder, Down syndrome, which has also been a prevalent media subject this summer thanks to a couple of strange and sad happenings.
The most sensational story has been that of Baby Gammy, the boy with Down syndrome who was left with his Thai surrogate mother when his Australian parents returned home with only his twin sister, who did not have that extra chromosome. People around the world were outraged as the (still contentious) details emerged: that the parents had asked the birth mother to have an illegal abortion, that they then left Gammy in Thailand when they believed he had mere days to live, that the father had previously been convicted for 22 child sex offenses. The more recent coverage of a California couple who had a similar experience further highlights the prevalence of people unwilling to care for a child with Down syndrome, not to mention the problems that can arise when competing values clash in cases of third-party reproduction.
In a separate incident, Richard Dawkins made a tone-deaf comment on Twitter last week in response to a woman's musings about the ethical dilemma she would personally face if she was pregnant with a child with Down syndrome. His advice: "Abort it and try again. It would be immoral to bring it into the world if you have the choice."
Dawkins has since gone on the defensive and insists that his words have been taken out of context. But these remarks swell a trove of other examples of his intolerance. And his choice of words in this comment cut to the heart of the problem with prenatal genetic testing: What happens when the technology no longer enables a woman's freedom to choose, but turns into a societal pressure to have the most "normal" child possible? What happens when only certain lives are considered morally acceptable?
In response to Dawkins' statement, the UK Down's Syndrome Association put out a statement that highlights the risks of intolerance for differing ways of being, and points to a more thoughtful way forward:
People with Down's syndrome can and do live full and rewarding lives, they also make a valuable contribution to our society. At the Down's Syndrome Association, we do not believe Down's syndrome in itself should be a reason for termination, however, we realise that families must make their own choice. The DSA strives to ensure that all prospective parents are given accurate and up to date information about the condition and what life might be like today for someone with Down's syndrome.
Dawkins is not the only prominent figure to have publicly displayed prejudice about Down syndrome. In a recent piece in The Guardian, Ian Birrell recalled bioethics professor John Harris telling him on TV that it is "morally wrong" for parents to choose a child with a disability if science offers an alternative. Birrell countered:
Those preaching this new eugenics conflate health and disability, harm and difference. They dismiss how diversity enriches the world, reject complex issues of choice, ignore implications of inferiority…. This is not to quibble with any woman's sacred right to choose, merely to highlight the casual acceptance that disabled lives are second-rate and can be discarded as too burdensome.
Structural discrimination toward people with disabilities is still common. But the outrage over Baby Gammy's abandonment and Dawkins' comment provides a spark of hope. Apparently many people cherish human diversity, and reject the view that Down syndrome is something to be weeded out just because we now have a technology that could enable us to do so.
The policing and criminalization of pregnant women’s bodies has a long history that is soaked in discrimination. Methods used have ranged from coercive sterilizations, to forcing women to give birth in shackles, to imprisoning women for taking drugs while pregnant, to increasing restrictions on women’s access to safe abortions.
The recent focus in the scientific community on epigenetics – the way in which environmental stimuli impact gene expression – must contend with the deep scars and ongoing struggles of this contentious reality.
Mounting research that suggests the importance of a healthy environment for a growing fetus, as well as throughout a person’s life, may be used in incredibly positive ways to enable much needed societal changes: For example, it can support efforts to increase access to fresh food in dismally dry “food deserts,” and to help provide non-criminalized treatment for addiction. The responsible dissemination of information can also help empower people to make better choices for themselves and their family.
But there is also the chance that this information will be brandished as shiny new scientific data to be used once again to justify only more ardent vilification of mothers and pregnant women.
A letter submitted to Nature last week titled “Society: Don’t blame the mothers,” addresses exactly this concern. The co-authors – seven academics working on the developmental origins of health and disease and the cultural studies of science – point to recent press headlines, noting how epigenetic research is already being simplistically depicted to prioritize maternal fault and under-represent compounding paternal, familial, and societal factors.
Given that it is now known that stress and diet can cause epigenetic harm to sperm, leading to increased problems in offspring, there is certainly no scientific basis for the near-exclusive focus on women and their habits.
A Science Special Issue on parenting published last week also addresses the impact of epigenetics on offspring, but thankfully includes many different reports that portray a much more complex picture of the different ways that both parents and society can profoundly impact children’s development.
The articles cover a wide range of topics. “Parenting from before conception” takes an in-depth look at the impact of epigenomics due to the age and environmental exposures of both parents. It further discusses transgenerational impacts, as well as epigenomic variation beyond the DNA, including noncoding RNA and the mitochondria.
An article titled “An experiment in zero parenting” reports that serious neglect and lack of stimulation – as evidenced in Romania's Abandoned Children – can lead to severe cognitive and emotional distress, causing long-term changes to the development of the brain and “profound intellectual delay,” though eventual care can lead to some improvement.
“Neural control of maternal and paternal behaviors” discusses the fact that there is “a large range of intrinsic and environmentally driven neural modulation and plasticity,” pointing to how different factors impacting the neural system can lead to drastic changes in parental behavior, and again stressing the importance of parental interaction for children’s healthy development. Additionally, “The biology of mammalian parenting and its effect on offspring social development” investigates “the hormonal and neural regulation of mammalian parenting and its consequences for infant social development,” pointing to such phenomena as the activation of certain neural pathways after a child is born that encourages parents to nurture and protect their child, which in turn impacts the neural systems of that child.
“Nature's first functional food” highlights how mothers’ breast milk had been a chronically under-studied super-food full of unique complex carbohydrates providing all kinds of protections for infants. “Maternal mental illness” poses hard questions about our societal priorities, pointing to the hardships that women can face in “the only developed country in the world without paid maternity leave.”
Many of the new findings reported in this special Science issue have disturbing implications for the impact of IVF and other assisted reproductive techniques on the health of resulting offspring. Here are some words of caution (extracted from three different articles) about the kinds of detrimental changes caused by manipulations involved in IVF:
1. “At least in mice, conception by IVF alters later placental and fetal development, growth trajectory after birth, and metabolic parameters and behavior in adult life.”
2. “In vitro procedures expose the early embryo to highly unusual conditions, with possible long-term health consequences as the child ages.”
3. “ART-conceived animals do appear more likely to have problems metabolizing glucose, and this effect may be transmitted to subsequent generations, probably through epigenetic changes.”
It seems clear that assisted reproductive technologies, as well as the environmental and social structures we find ourselves in, carry under-studied risks not only for our children, but for future generations. Parents-to-be deserve to know about all of these factors so they can make informed decisions about how to live their lives and raise their families. And policy makers now have the important opportunity to use this data to help create powerful changes to the structure of our society.
The fact that biology is much more mutable than we have previously believed is not only of relevance to pregnant women, but to all of us and to the society we live in. Focusing on “the dangerous womb” is far too simplistic, and a problematic omission of other compounding factors.
Posted by Victoria Massie, Biopolitical Times guest contributor on August 21st, 2014
On Friday, August 15th, I was one among a multitude of people finding a seat in Booth Auditorium at UC Berkeley Law School for Celebrating Troy Duster. But the event turned out to be as much a family reunion as a celebration, a testament to the work done by organizers Osagie Obasogie and Duana Fullwiley.
For the sake of formalities, there was an agenda, and panels throughout the day pointed to themes that have been central to Troy’s work: the “slippery slopes” of political inclusion and racial science around understanding health disparities; the technique of engaging scientists on race in genetic research; the work of the sociologist in policing, forensics, and behavioral science; and lastly “connecting the dots” between Troy’s work in the academy and his commitment to the public and community engagement. But with each panelist’s approach to the podium, it became increasingly undeniable that every reference to the “Dusterian”—after all, Ruha Benjamin pointed out, we have “Bourdieuian”—analytical method of recontextualizing in context, of noting the pre-frame, was inextricably tied to the love and care infused and cultivated in each of their relationships with the man of the day.
I first met Troy Duster in Rochester, NY in the summer of 2009. I had just finished my sophomore year of college, and was beginning to research the various social ties entangled within the genetic ancestry testing results my dad had sent me eight months earlier. Make no mistake, I found my father’s test results to be a godsend. Although I came to the University of Rochester with the sole purpose of pursuing a molecular genetics major, I quickly found my passion for the double helix in jeopardy during my first semester when I was introduced to anthropology, and specifically the lecture on how race is socially constructed. It was an idea that was new and yet so familiar as I found myself finally able to put my lived experiences into words. I came to learn that all the times I found myself being denied the full potential of my identity as a black woman had less to do with my inadequacies of being able to fit into a box and more to do with the conditions that make such a box possible. Intoxicated by the first taste of this form of self-aware liberation, I yelled to my friends as we met for lunch “Race doesn’t exist!” Full with hunger and anxious to beat the noon rush at our favorite dining hall, they began to resist my statement, only to find the refusal to surrender to my adamant assertion futile in reaching our ultimate goal: eating.
Over time, I would learn that neither my friends nor I had managed to get race right. When my father surprised me with an email containing the results of an ancestry test he had taken for himself, I found myself confronted with the context I had left out at lunch. Specifically, I began recognizing that saying race does not exist does not change the way race comes to matter. In the attempt to piece together the silences inherited by those whose ancestors’ personhood was considered property, my father extended to me information of a home we weren’t supposed to know. But even this new form of knowing was one I met with skepticism. It bridged together my love for DNA and my interests in race, but in ways that provided more questions than answers, so much so that I could spend a summer researching them in 2009. And having been lucky enough to have had an advisor who did her Ph.D. at NYU, I was immediately pointed to Troy’s work.
Five years later, having just finished my qualifying exam in the anthropology department at Berkeley, and preparing for my upcoming year and a half of fieldwork for the same project, I am still indebted to my first meeting with Troy’s work in Rochester. And as I sat in Booth Auditorium, listening to the countless scholars who Troy influenced and who have also influenced me, I couldn’t help but be in awe and at home at the same time. People from across the country came together to celebrate the many ways Troy seemed to simultaneously embody and exceed the title of scholar, activist, teacher and friend, but with a swagger-infused humility not easily mirrored but always inspiring us with the everyday challenge to try.
The sad saga of Nicholas Wade, former international reporter turned laughing stock, seems to be staggering toward its inevitable end. However, the issues that he — unintentionally — highlighted remain, and badly need to be addressed.
Wade's fatuous book, A Troublesome Inheritance: Genes, Race and Human History (see 1, 2), has drawn what surely must be the definitive response from, at last count, 143 population geneticists. Essentially (to quote Marshall McLuhan, as scripted by Woody Allen) they each say:
You know nothing of my work.
The scientists published a short letter in The New York Times Book Review on August 8, commending the July 10th review of Wade's book by David Dobbs and thanking Dobbs "for his description of Wade's misappropriation of research from our field to support arguments about differences among human societies." The letter notes that:
Wade juxtaposes an incomplete and inaccurate account of our research on human genetic differences with speculation that recent natural selection has led to worldwide differences in I.Q. test results, political institutions and economic development. We reject Wade's implication that our findings substantiate his guesswork. They do not.
We are in full agreement that there is no support from the field of population genetics for Wade's conjectures.
The letter was noticed in various corners of the press, including the Los Angeles Times and the [London] Independent, as well as the news pages of Nature and Science. Some of the readers' comments in Science are a source of grim humor if you are so inclined.
Wade is not backing down. In a response [pdf, here or here], he accuses his critics of being "driven by politics, not science" and claims to have "seen no basis" for the "repeated assertions that the book is scientifically inaccurate."
This is rubbish. Wade did seem to have a poor connection when discussing the book with Agustin Fuentes on May 5; perhaps he failed to hear everything that was said. Perhaps he did not read the reviews by credentialed scientists from several disciplines with the care and attention they deserve (for instance, 1, 2, 3, 4, 5); perhaps, like a child afraid of the wicked witch, he closed his eyes and skipped over the ugly parts. Or perhaps he is so convinced of his own unique insight that mere facts bounce off the carapace that protects his prejudices.
Whatever the reason, Wade (who still insists that he opposes racism on principle) seems desperate to engage with his critics. But they are right to refuse: He claims to correct them in their own field, and he is wrong. There is no further debate to be had with one who will not learn.
There is, however, a continuing and even growing need to have a series of related discussions, which should involve both academics of many specialities and the public in general, at all levels of formal and informal education. Population geneticists and anthropologists may be quite clear about the fallacies that surrounded the subjects of race and genetics, but it is equally obvious that some psychologists and physicists are not. Some Americans may blithely insist that we live in a post-racial society; most of us know better.
Sticking strictly to fields directly connected with genetics, racial fallacies and simplistic interpretations of inadequate data have been — are being — used in attempts to sell race-based medicine, for instance, as well as relatively trivial ancestry scams. Race-based forensic applications of technology, biased databases, even advocacy of predictive sentencing, need to be addressed, critiqued, corrected and discarded. The social construction of race needs to be addressed at social, cultural and political levels.
Cherry-picking from scientific papers to misrepresent their conclusions in order to bolster prejudice must not be allowed to continue.
That is the big lesson to be drawn from Wade's experience.
Personalized medicine may, eventually, have an important role to play in society. If and when it does, the differential distribution of alleles between populations is not really going to be vital: what will matter is that a given patient has a given allele, and whether it is rare or common in a particular geographic or cultural milieu will largely be irrelevant (except for effects of the external environment).
But it's going to take both a lot of research and a lot of discussion to reach that point. If Wade's hasty grab for the spotlight helped to make that clear, then something useful came of it. Perhaps it can yet be the start of an important discussion.
The notoriety of the Tuskegee syphilis study is unparalleled in the field of bioethics. Last week marked the 42nd anniversary of the horrific experiment’s termination, and many people took the opportunity to recall Tuskegee and examine its relevance to the treatment of human research subjects today.
Half a century ago, what the US Public Health Service did in Tuskegee was considered acceptable medical practice. Its researchers willingly endangered the lives of hundreds of African American men in rural Alabama, leading them to believe that they were being treated for “bad blood.” They could have been treated for the syphilis they actually had, since penicillin had become an available treatment by then.
But in the name of improving scientific understanding of the disease, all relevant information and treatment were purposefully kept from them. They were unknowing participants in a 40-year-long medical study to test the natural progression of syphilis and the full extent of its toll on black bodies.
Wives and children of the men contracted the disease, and numerous people died, but it was not until there was a leak to the press in 1972 that the study finally came to an end.
According to Alexander Cockburn in Whiteout: The CIA, Drugs, and the Press, “the lead researchers remained unapologetic.” Dr. John Heller, the Director of the Public Health Service's Division of Venereal Diseases, said, “For the most part, doctors and civil servants simply did their job. Some merely followed orders, others worked for the glory of science.”
Anyone familiar with the twentieth century’s record of other medical experimentation horrors will recognize this sentiment. In many ways, Tuskegee is just one among many examples of how easy it is for good people to believe they are doing good science. It also demonstrates that it can take decades before those in power will see, or say, otherwise.
That day finally did come for the Tuskegee experiment, and one of its legacies is the Belmont Report, which lays out fundamental principles for safeguarding human research subjects. These include protecting the autonomy of all people and treating them with honesty and respect; following the philosophy of “do no harm” in order to minimize potential risks; and ensuring that procedures are non-exploitative.
Despite the history of grave abuses in medical research, the notion of objective science never quite seems to go away. Twitter users talked about the danger of this in a great discussion thread on the day of the Tuskegee anniversary:
“myths of objectivity and value-free science are not only false but also harmful”
“We inadvertently reinforce the erroneous idea that policies tht arent explicitly detrimental must not b harmful at all”
“Science in and of itself is not an inherently noble value or cause. Applying #bioethics allows what we do to be noble”
A common thread throughout the discussion was the need for more work to ensure that people of color and other vulnerable communities are not exploited in medical experiments. In other words, we need to hone our historical perspective, but we also need to open our eyes and see what is happening all around us, right now, even though we tend to think that “now we know better.”
But do we? A report by Carl Elliott published late last month details the extent to which the pharmaceutical industry routinely tests new drugs on people who are homeless or mentally ill. Companies are well aware that many people in these situations will comply with a lot, for very little in compensation. Elliott uncovered accounts of people starting to take addictive drugs just to qualify for a particular study; of drug study recruiters approaching residents right outside a homeless shelter; of negligent care in what became a fatal incident.
Elliott points out a troublesome trend that has taken place since Tuskegee [bold added for emphasis],
Not long ago, such offers would have been considered unethical. Paying any volunteer was seen as problematic, even more so if the subjects were poor, uninsured, and compromised by illness. Payment, it was argued, might tempt vulnerable subjects to risk their health. As trials have moved into the private sector, this ethical calculus has changed.
In the 1970s, after a series of notorious research abuses, legislators pushed for a central federal agency with the power to protect human research subjects. The medical research establishment fought this idea, however, and when the National Research Act was passed in 1974 a very different alternative followed:a patchwork system of small ethics committees known asInstitutional Review Boards. The boards were originally located in hospitals and medical schools, but clinical research has since moved into the private sector. Many are now for-profit companies that review studies in exchange for a fee.
With ethics now being determined on a case by case basis, often in a setting ripe with conflicts of interest, and utterly opaque due to companies’ view that clinical trials are commercial secrets, is it any wonder that lack of trust is widespread, especially among vulnerable communities?
This is not a problem of ignorance.
On the contrary, how could anyone who is paying attention trust our current for-profit patchwork system to ensure that medical experiments are undertaken in an ethical and just way?
Posted by Victoria Massie, Biopolitical Times guest contributor on August 7th, 2014
Elaine Riddick is one of North Carolina's sterilization survivors
Willis Lynch says the nurse asked him to sing her a song as she slipped the mask over his face. It was the serenade of lifetime, but it would be years before Lynch learned that this song slipped him into cutting the ties that could bind him to a future generation of his making.
In 1947, at the age of 14, Lynch was one of an estimated 76,000 people who were forcibly sterilized through the state of North Carolina’s selective sterilization program, which ran from 1929 to 1974. It was a program that, according to pamphlets, aimed to protect the broader state’s citizenry from the burdens imposed by those it identified as “moron,” “feebleminded,” “(mental) defectives,” and/or “a person of little intelligence.”
These categories allowed the state to codify and target the sterilization of those who did not fit its profile of an ideal citizen: the poor, people of color, people with disabilities, and even victims of rape who became pregnant. The assumption was that all citizens had a duty to protect the parenting of “a healthy, normal baby,” and that those targeted for sterilization should voluntarily give up their reproductive rights.
In reality, people often found themselves forced to choose between being released from state institutions and receiving welfare benefits, or losing their right and their ability to have children. Under the sterilization program, voluntary surrender was a cover for an insidious ultimatum. In other words, North Carolina – like more than 30 other states with laws allowing eugenic sterilization – found it more efficient to deny the possibility of future generations to certain people, rather than attend to the structural, socioeconomic and political issues that make poverty, racism and rape not only possible but normal.
North Carolina’s history of sterilization has come to the surface this summer as the state began accepting claims from those who were involuntarily sterilized. This step toward offering compensation to victims and their families made North Carolina the first state in the country to do so.
And yet in spite of this major symbolic victory, Lynch’s all-too familiar song lingers, harmonized now to the tune of Kannapolis citizenry turned into human research subjects in the name of bio-banking.
“Sequenced in the U.S.A.”
Located on the outskirts of Charlotte, Kannapolis was a town once known as the largest towel manufacturer in the world. Most of those who lived in Kannapolis depended on Cannon Mill as the linchpin of the local economy. But a little over a decade ago, the town experienced the largest single layoff in the state’s history as the mill’s doors were permanently closed.
Since then, Kannapolis has become a hub for biotech research and innovation, in part due to a billion-dollar investment by Los Angeles real estate magnate and businessman David H. Murdock. According to a revealing article in The Pacific Standardcalled “Sequenced in the U.S.A.: A Desperate Town Hands Over Its DNA,” Murcock “stepped in to transform Kannapolis into a $1 billion mecca for biotechnology and life sciences research,” building a 350-acre research complex on the site of the demolished Cannon Mills.
The town’s former blue-collar laborers aren’t the kind of people who will find jobs at Murdoch’s high-tech institute. But they now find themselves bombarded with “opportunities” to provide urine and blood samples for its research efforts, including one called the MURDOCK Study. At schools, churches, and health care facilities, there is a very high likelihood that recruiters will be waiting under a tent to collect local biological material so that researchers can connect family histories to genetic sequences in the pursuit of personalized medicine.
But despite the fact that the local raw material may help biotech ventures make billions of dollars, guess how participants are compensated: a $10 gift card to WalMart.
The argument can be made that participants are at least getting some form of compensation for their contributions to the study, and some told the Pacific Standard that they are taking part in the study “for the good of their grandchildren and future generations.” But questions remain.
Can one consider consent to be informed when Kannapolites are being invited to relinquish their biological material for use in a future that has yet to come and may never come to pass, that cannot be predicted, and that is only as speculative as the venture capital supporting the biotech industry? Shouldn’t we be given pause by the legacy of Henrietta Lacks, an African American woman whose cells were taken without her consent to produce the first known human immortal cell line for medical research?
According to international consensus, research subjects are to be expected to know the “nature, duration, and purpose” of experiments in which they take part. The MURDOCK study has no temporal end in sight, and the nature of the projected research has yet to be made clear. The assumed public good may turn out to be one that much of the public cannot share.
Despite assurances by researchers that participants can withdraw from the study at any time, once blood and urine is taken, the material and information is out of their control. Participants are informed that they can make no claims to the benefits of the commercial products that may be made possible by the biological materials and information they provide.
The state of North Carolina once promoted eugenic sterilization as a technique to protect the public. Today, it hosts private-public a biotech industry effort to build lucrative biobank-based ventures. Are there similarities to which we should be paying attention?
Victoria Massie is currently a graduate student at UC Berkeley, pursuing a Ph.D. in Sociocultural Anthropology with a designated emphasis in Science & Technology Studies. Her research examines the transnational circulation of genetic ancestry testing information by African-Americans, particularly between (but not exclusive to) the United States, Cameroon, and Sierra Leone. She is also a poet, and a summer intern at the Center for Genetics and Society.
Headlines around the world have broadcast the heart-wrenching story of the Australian couple who took home their healthy baby daughter and left her twin brother with his Thai surrogate mother after learning that he had Down syndrome. Thousands of news articles have been written since the news was first reported last week, and conflicting versions of what happened have not yet been fully resolved. By all accounts, the story of baby Gammy has gotten more shocking every day.
After several days of media attention, the Australian commissioning parents were identified. Shortly thereafter, court documents were discovered revealing that the babies’ father has been convicted of 22 child sex offences in Australia, including offenses against a girl who was seven years old and two more under thirteen.
And now, the couple seems to have vanished. Child protection services tried to find them without luck, and their dog was taken away from their empty house by animal protection officers.
Apparently no formal contract was ever signed between the commissioning parents, the surrogacy agency, and Pattaramon Chanbua, the woman they paid to carry and deliver their babies. The head of the unidentified Bangkok fertility clinic could now face jail time. More shockingly, 21–year-old Chanbua, who has been caring for Gammy since he was born, could also face jail time for her involvement with commercial surrogacy, despite claiming that she never knew commercial surrogacy is illegal in Thailand because she saw so many websites offering it online.
Thankfully, Gammy is in good hands for now. More than $230,000 has been raised via GoFundMe by the organization Hands Across the Water for the life-saving health care Chanbua would not have been able to afford on her own.
If there is any silver lining in this heart-wrenching debacle, it is that it is now clearer than ever that regulation and oversight of cross-border surrogacy is sorely needed to prevent more cases of neglect and harm to women and children.
Several initiatives have surfaced recently that hope to move genomics more effectively toward medical applications. They are trying to link genomic and phenotypic data, establish baselines for health, and use computational techniques to move the science forward. Some seem more promising than others; even discounting for self-promotion, Craig Venter may be leading the pack.
The highest-profile and clearly most political announcement was made in the UK by Prime Minister David Cameron on August 1. It firms up the proposals for Genomics England, which plans to sequence 100,000 genomes — 40,000 from patients suffering from cancer and other rare diseases; 35,000 from their relatives; and 25,000 from the cancer cells themselves.
The broad outlines of this are not new, and were cogently critiqued by Helen Wallace of GeneWatch UK a couple of months ago, on grounds of effectiveness (dubious) and privacy (very worrying, and addressed even by The Observer). Commercial exploitation is also a concern. The project is a partnership between the government, the Wellcome Trust, and Illumina, which will perform the sequencing. Cameron is pushing it hard:
This agreement will see the UK lead the world in genetic research within years. As our plan becomes a reality, I believe we will be able to transform how devastating diseases are diagnosed and treated in the NHS and across the world.
In the US, there has been a more surprising, though much smaller-scale, development: The embattled direct-to-consumer testing company 23andMe has scored a $1.4 million grant from the National Institutes of Health. It’s pin money to the Googleplex, of course, but some kind of validation. This will help them refine web-based surveys, collect phenotypic data, dip the company’s toes into whole-genome screening, and accomplish the:
Enablement of external non-23andMe researchers to access aggregate de-identified data from the 23andMe database to further accelerate the pace of human genetic research.
Back at the mothership, Google X (the “semi-secret" research arm that works on everything from self-driving cars to Glass) has had another bright idea: They will work out what is normal for humans. The Baseline Study is in its early days but involves "70-to-100 experts from fields including physiology, biochemistry, optics, imaging and molecular biology.” They’ll study 175 (and, later, more) people in great detail (partly using wearable devices, including glucose-monitoring contact lenses), and of course they are being, that is, will be, careful:
Baseline will be monitored by institutional review boards, which oversee all medical research involving humans. Once the full study gets going, boards run by the medical schools at Duke University and Stanford University will control how the information is used.
The genomics research establishment is somewhat skeptical, it seems. Yaniv Erlich of the Whitehead Lab at MIT tweeted:
Breaking: Google moonshot study (that does exactly what has been done in genomics for years)
Daniel MacArthur, who has been working in the field for a long time, and is currently based at Harvard, the Broad Institute and Massachusetts General Hospital, took an even less charitable view in several tweets, including:
Late to this, but calling this Google study a moonshot just absurdly devalues that term …
I confidently expect Google to be AT LEAST as successful in life sciences as they have been in social media
But Craig Venter is ahead of them all, at least in his own analysis. And he has hired one of Google’s hot shots, Frank Ochs, who basically made Google Translate work. According to MIT Technology Review:
Venter says that he’s sequenced 500 people’s genomes so far, and that volunteers are starting to also undergo a battery of tests measuring their strength, brain size, how much blood their hearts pump, and, says Venter, “just about everything that can be measured about a person, without cutting them open.” This information will be fed into a database that can be used to discover links between genes and these traits, as well as disease.
That’s only the start. The goal is a million human genomes sequenced by the end of the decade. Venter remains absolutely committed to the DNA-programming view of humanity, but appropriately humble about the lack of advances over the last decade or so:
I’ve had my genome for 15 years, and there’s not much I can learn because there are not that many others to compare it to.
The story of baby Gammy and his "surrogate" mother, Pattaramon Chanbua, hit headlines around the world last week. Six-month-old Gammy, born with Down syndrome and a congenital heart condition, was conceived as a result of a commercial surrogacy arrangement between Chanbua, a Thai national, and an unknown Australian couple who abandoned him at birth.
Chanbua, a 21-year-old mother of two other children, was offered 350,000 baht (approximately US $11,000) to be a surrogate. She told an Australian ABC reporter that her family was struggling to pay off debts when she and her husband agreed to the arrangement:
The money that was offered was a lot for me. In my mind, with that money, one, we can educate my children, we can repay our debt.
When she became pregnant with twins, Chanbua was promised an additional 70,000 baht (approximately US $2000). Then, at four months into the pregnancy, doctors discovered that one of the babies had Down syndrome.
According to reports, the Australian commissioning couple (the genetic parents of the children) said they did not want a baby with Down syndrome. “They told me to have an abortion but I didn’t agree because I am afraid of sin,” Chanbua reports.
An abortion would have been illegal under Thai law unless the mother’s health was at risk.
On the birth of the children, Chanbua was paid the original amount, but not the extra money. The Australian couple took Gammy’s twin sister home with them, and left Chanbua and her family to care for Gammy. This put her in a desperate situation, unable to pay for his medical needs.
The Thai newspaper Thairath published Gammy's story last week, and an online campaign to raise money for his treatment was launched shortly afterwards. The story has been met with outrage and compassion from hundreds of people who have now donated close to $200,000.
A spokesman for Australia's foreign affairs department has expressed "concern" about the reports and said it is in consultation with Thai authorities over surrogacy issues.
The Thai government quickly announced that it will now be illegal to pay for surrogacy in Thailand, and that the practice can be undertaken only in circumstances in which the surrogate is related to the intended parents, and the intended parents are medically infertile. People who remove children from Thailand without the approval of the government would also be subject to Thai anti-trafficking laws.
Some agencies and lawyers who facilitate surrogacy arrangements have responded primarily with concern that hundreds of would-be-parents may be left unable to satisfy their longing for a family. They suggest that it would be better to permit commercial surrogacy in Australia.
These responses stand in stark contrast to the many people who see Baby Gammy’s plight as highlighting the extent to which commercial surrogacy arrangements can exploit and commodify women and children. Chanbua entered into the arrangement because her family was desperate and in debt. This was no "win-win" situation, whatever the outcome: rather, it was one in which surrogacy brokers and a relatively wealthy Australian couple took advantage of another family’s dire circumstances. Baby Gammy’s situation only serves to emphasize the extent to which money influenced and drove the transaction.
In my country, Australia, all states and territories prohibit commercial surrogacy arrangements. New South Wales, Queensland and the Australian Capital Territory also prohibit travelling to other countries to engage in such practices. The Australian government lists such prohibitions in its reports to the United Nations as forming part of our laws against the sale and trafficking of children and of meeting our obligations under international law. Some people who are travelling abroad and engaging in commercial surrogacy are breaking laws.
Should Australia as a consequence of such incidents now change its laws to permit commercial surrogacy? I would respond to this question with a resounding “no.” While careful regulation of altruistic surrogacy arrangements allows an alternative avenue to having a family, introducing profit into such arrangements places women and children at risk. Baby Gammy is but one example of this. His twin sister—who may never know that he exists or the circumstances of her birth—is another. Pattaramon Chanbua is a third.
The majority of nations that have established laws on surrogacy prohibit commercial arrangements. However, because a few permit surrogacy (for example, India, Guatemala, Russia, the Ukraine, and some U.S. states), brokers, lawyers, and clinics continue to encourage people wishing to have children to "forum shop" to "realise their dreams.” The result has too often been complex situations for children, commissioning person(s), and women working as surrogates. In some cases, problems have arisen about legal parentage and citizenship for children; this has been the primary focus of many recent news stories.
But we should not lose sight of the significant international human rights issues reflecting social, economic and racial disparities between surrogate mothers and commissioning person(s), involving the exploitation and commodification of women and children. These are clearly illustrated by the baby Gammy case.
One Australian surrogacy facilitator referred to the “market” in remarks about baby Gammy that were reported in a major newspaper. The use of this term is telling in itself. While this case has raised the need for further discussion, let me suggest that the discussion should not address how to support such a market, or to introduce or broaden the market to Australia. Rather, it should focus on how to protect the rights and welfare of children and women in line with established global human rights standards. In my view, this includes taking a strong stance against commercial surrogacy.
Sonia Allan is Senior Lecturer in Law at Macquarie University. Her research focuses on wide-ranging health-related ethical, legal, human rights and regulatory issues. She has worked extensively in advocating for women and children in situations in which assisted reproduction has been used and researching the regulation of new biotechnologies. Her latest major work is The Patient and the Practitioner: Health Law and Ethics in Australia, co-authored with Meredith Blake (2014).
Last month, the California Senate unanimously approved bill 1135, which bans the sterilization of inmates as a form of birth control. The bill will soon be put before the Assembly and could become state law this year. If it passes and is signed by the Governor, the sterilization of prison inmates will be permitted only in cases of life threatening emergencies or when medically necessary.
Evidence of unauthorized sterilizations in California prisons emerged through the persistent efforts of Justice Now and an extensive investigation by Corey Johnson of the Center for Investigative Reporting. State Senator Hannah-Beth Jackson, vice-chair of the California Legislative Women’s Caucus, spearheaded the request for a state audit and authored SB 1135.
According to the California State Auditor, more than 39 out of the 144 bilateral tubal ligations performed on inmates from fiscal years 2005-06 to 2012-13 were done without lawful consent. Even more alarming, there is no evidence that the inmates’ physician signed the required consent form for 27 of the sterilization procedures.
The audit additionally says that “the true number of cases in which Corrections or the Receiver’s Office did not ensure that consent was lawfully obtained prior to sterilization may be higher.” In other words, there could be even more victims of sterilizations who are unaccounted for because they are still unaware that the procedure was performed.
With the SB 1135 approved unanimously and on its way to the Assembly, it’s easy to forget about California's murky history with sterilizations. During the twentieth century, dozens of U.S. states had laws permitting explicitly eugenic sterilization. Some 20,000 procedures were performed between 1909 and 1963 in California, the highest number in any state.
This history was raised in the legislature in 2003. Governor Gray Davis issued an apology, and a state resolution was passed that
urges every citizen of the state to become familiar with the history of the eugenics movement, in the hope that a more educated and tolerant populace will reject any similar abhorrent pseudoscientific movement should it arise in the future.
Yet the resolution presents no outline for making this idealistic “urging” a reality.
When I learned of the continuing sterilizations in California, it seemed to me that the 2003 apology and resolution were empty. As an effort to truly help prevent “any similar abhorrent pseudoscientific movement to arise,” I worked on a petition to incorporate the history of the eugenics movement into California schools’ curricula. The approval of Senate Bill 1135 would also help challenge the re-emergence of eugenic ideologies, as well as prevent abuses in California’s prisons.
Sixty French personalities, including prominent politicians of the left and center-left, senior scholars and mainstream feminists, have signed an open letter urging President François Hollande to affirm his opposition to surrogacy contracts and to reinforce the country’s legal prohibition against them. The letter, published on July 14 in Libération and posted as a petition on Avaaz.org, was a response to last month’s European Court of Human Rights (ECHR) ruling that France must grant children born abroad via contract pregnancy arrangements official recognition of their parentage.
The European Court ruled in late June on cases brought by two French families whose children were conceived with their fathers’ sperm and third-party eggs, and carried and delivered by surrogates in California and in Minnesota. The children have been living with the parents in France, but without legal recognition of their parental status.
Signers of the petition include the former President of the European Commission Jacques Delors, former Socialist Prime Minister Lionel Jospin, former Minister of Women's Rights Yvette Roudy, and former head of the French Communist Party Marie-George Buffet.
The letter reminds President Hollande of his commitment against surrogacy contracts, known in French as GPA (gestation pour autrui), and asks him to "fight against the soliciting of French clients by surrogacy agencies.” It characterizes surrogacy contracts as “contrary to the principle of respect for the person, both the woman who carries the child [and] the child who is commissioned.” And it highlights the difficult situation created for France by the ECHR ruling, which in effect offers affluent French citizens a way around their own country’s laws. If the ECHR decision is accepted, the letter says, there will “effectively be a market in babies” in France, though only some will be able to afford it:
Mr. President, how will you explain to French women and French men
that if they have money, they can go buy a baby abroad and register him
or her as their son or daughter with French civil status, while if they
are not wealthy enough, they will be subject to the ban that would
remain applicable to surrogacy contracts made in France?
The letter does recognize that the legal status of children born as a result surrogacy arrangements abroad should be addressed:
It is conceivable to find technical solutions to improve the legal
situation of children living on French soil without succumbing to what
is a triumph of the child-making industry, and without costing them the
status of human being by recognizing the surrogacy contracts that
designated the child as a thing.
More than a decade after the historic completion of the Human Genome Project, the ethical, legal and social issues (ELSI) are far from being sorted out. The role of genetic information in the courtroom, in research projects, in for-profit companies, at all stages of pregnancies, and in insurance companies is being negotiated across multiple planes on a daily basis. With so many competing interests, reaching consensus on responsible usage can feel like a pipe dream. Nonetheless, important strides have been made in several of these areas through recommendations, regulations, and tireless advocacy.
Are there lessons to be learned from these struggles that might help ease the growing pains of the upcoming projects to understand the brain?
The brain projects are certainly shaping up to be no less momentous or controversial. According to the 1.2 billion pound, ten-year undertaking in Europe known as the Human Brain Project,
Understanding the human brain is one of the greatest challenges facing 21st century science. If we can rise to the challenge, we can gain profound insights into what makes us human, develop new treatments for brain disease and build revolutionary new computing technologies.
The BRAIN Initiative in the United States (called the cousin of Europe’s Human Brain Project) is no less ambitious. It is set to receive $4.5 billion in federal funding over the next 12 years.
These projects will help make sense of what is probably the least understood part of the human body. The origins of our thoughts, memories, desires, actions, and emotions could become less elusive and provide important keys for helping people deal with neurological disorders.
But already at this early stage, extensive criticisms have been voiced. Most strikingly, the conceptual starting place of even being able to successfully map the brain in an intelligible way has been questioned. New York University research psychologist Gary Marcus recently pointed out in a New York Times op-ed that we don’t even know what a good theory of the brain would look like because “[b]iology isn’t elegant the way physics appears to be.” He continued,
We know that there must be some lawful relation between assemblies of neurons and the elements of thought, but we are currently at a loss to describe those laws... The problem with both of the big brain projects is that too few of the hundreds of millions of dollars being spent are devoted to spanning this conceptual chasm.
Additionally, the methodology and reach of the projects have been criticized. There are now over 700 signatories to an open letter to the European Commission from the European neuroscience community. The letter states that the signing parties will boycott the Human Brain Project unless it is amended to be more open, inclusive and flexible.
There are also huge ethical concerns that need to be addressed more comprehensively in both projects. Nature called them “a laundry list of ethical issues,” including “the responsible use of cognitive-enhancement devices, the protection of personal neural data, the prediction of untreatable neurodegenerative diseases and the assessment of criminal responsibility through brain scanning.”
Another risk worth noting is how the influx of resources and excitement for a single element of human biology can overshadow other important factors and encourage biological determinism, even when such a focus is inappropriate or even harmful. Chipping away at the genetic determinism caused by the HGP has been a challenge. In these brain projects, we have an opportunity to learn from such experiences and not start completely from scratch. Otherwise, in five years time, the “gene of the week” phenomenon could simply become the “neuron of the week.”
Opening up our brains for examination is going to stir up not only these issues, but also completely novel ones. We need to learn from past mistakes and be ready to deal with new issues as they arise. For now, it is heartening to see the amount of discussion taking place around the world about these complexities. Hopefully those at the forefront will not merely be defensive about their “grand vision,” but also realize that incorporating both scientific and social complexity in at the early stages is the best route forward for everyone.
The Centers for Disease Control and Prevention (CDC) suffered real embarrassment the other week, and we are all very fortunate that the consequences were not worse. Dozens of employees "were potentially exposed to deadly anthrax spores" (though no one got sick) and a lethal strain of flu virus accidentally contaminated a much milder sample that was distributed to a Department of Agriculture lab. Meanwhile, six 60-year-old vials of smallpox virus were found in an old refrigerator at NIH, two of which contained live specimens.
As Laurie Garrett eloquently put it: Oops. Her must-read piece in Foreign Policy was titled:
It’s 10 o'Clock — Do You Know Where Your Bubonic Plague Is? Spilled smallpox, missing SARS, and rogue scientists with mutant H1N1. If you’re not scared, you should be.
The "missing SARS" refers to an incident in France last year; not CDC, but certainly fitting the pattern. The agency’s head, Thomas R. Frieden, was appropriately “stunned and appalled” by the recent incidents (especially since no one had even told him immediately about the flu error). We can assume that, even if heads don’t roll, procedures will be tightened and many presumably sensible changes will be made. As The New York Times noted solemnly in an editorial:
A small careless error in these experiments could be devastating.
These revelations provide the context for an unusual proposal of caution and public consultation made by a number of very prominent scientists last week. A group of researchers has proposed that policymakers and the public carefully consider the consequences before the introduction of a new practice known as "gene drives," which could lead to "addressing ecological problems by altering entire populations of wild organisms."
The way this might happen is by making very specific changes (using Crispr technology) to the genome of a sexually reproducing organism. These will create truly “selfish” genes — their frequency in a population will increase, even though they are less likely to reproduce. The engineered genes “drive” themselves through the population, possibly even driving the population to extinction. This sounds strange, but it was proposed in theory by Austin Burt in 2003, and technology is now catching up.
There is a peer-reviewed article in eLife by Kevin Esvelt, Andrea Smidler, Flaminia Catteruccia & George Church that gives a 39-page overview of the rapidly developing science. It is accompanied in Science Express by a three-page "discussion of risk governance and regulation intended specifically for policymakers.” The principal contributors to that are Kenneth Oye and Kevin Esvelt, who are joined by eight others (including all the eLife co-authors). Useful summaries can be found in the Boston Globe, MIT Technology Review, Science Insider and MIT News.
They are of course quite right. These potentially huge environmental interventions deserve broad and careful consideration. And we do not have an adequate regulatory structure, nor a robust political or cultural tradition, nationally or internationally, to handle the novel questions involved.
The first application of this kind of approach seems likely to be on mosquitoes. But that is already well under way, albeit with older technology, making this more than a little misleading:
A Call to Fight Malaria One Mosquito at a Time by Altering DNA
That’s the headline The New York Times gave Carl Zimmer’s story. But in fact Oxitec, a British company that is not mentioned in either of last week’s scientific papers, has been working on modifying mosquitoes for years; The New Yorker had a feature on them in 2012. Oxitec focuses on dengue fever, which the US scientists mentioned, but perhaps that's less dramatic for whipping up public support than malaria. (Genewatch UK has much more on Oxitec and GM insects here.)
What the emphasis on mosquitoes does indirectly show is the scarcity of obviously appealing goals for using such an intrusive and potentially overwhelming technology. Sure, everyone can get behind eliminating malaria and dengue fever. And some people might like to rid the Great Lakes of invasive carp. No one likes rats, which as an invasive species are said to cause $19 billion in damage every year. And there is talk about reversing the evolution of plants that have become resistant to herbicides.
All this suggests is that gene drives are part of a potentially very powerful technology whose application is as yet not entirely clear. The scientists involved deserve to be commended for raising the issue of appropriate regulation, and we should note that one of the safety proposals is a plan to reverse such interventions should there develop a problem. But the principal lesson of the recent CDC failures is surely that human error will always find a way through.
Sitting down to watch the science fiction film The Perfect 46, I had the strange sensation of walking through a hall of mirrors. Intriguingly meta-conscious, and perceptibly close to reality, this film highlights the world of direct-to-consumer (DTC) genetics and makes it clear that this technology, now at our real-world doorsteps, could drastically shape our very near future.
The story centers on the aptly named company ThePerfect46, which starts off with a seemingly innocuous mission. Taking advantage of the fact that most Californians have had their genomes sequenced by this undefined point in time, it simply offers to analyze a couple’s genomes alongside each other to determine their ability to have a disease-free child.
But founder and CEO Jesse Darden isn’t content to stop there. In a move that sparks internal controversy and leads to one staff person abandoning the project, he rolls out version 2.0, which allows the company to search through giant databases and match random people together based solely on their ability to create genetically “ideal” children. The film cuts back and forth between a tense situation unfolding for Darden, flashbacks of his life, and a documentary film made about his rise and fall.
While The Perfect 46 is a fictional film, it is being promoted by a real-life website purporting to actually sell ThePerfect46 product (kudos for the smart marketing ploy!).
Darden, played quite well by Whit Hertford, is the star of The Perfect 46. He is a Steve Jobs-esque anti-hero: the disliked techie genius, the man behind the company that aims to improve humanity but ends up causing great harm. Darden comes across as “a tortured genius… a character that can be lauded and loathed in equal measure.” He is romanticized as smart and entrepreneurial, but his considerable personal and inter-personal flaws are never out of view.
Perhaps by now both Darden and ThePerfect46 sound strangely familiar. If so, it’s probably because the similarities to companies and products that actually exist right now are jarring. This is a kind of science fiction that is only just barely fictional.
In fact, writer and director Brett Ryan Bonowicz calls The Perfect 46 “science factual.” He invited a number of researchers to be consultants on the film and strove to show “a respect for science.” The scientific community has applauded his use of “authentic science” and raved about how the film is “a refreshing change of pace” because it doesn’t dissolve into a dystopian nightmare. Here Bonowicz elaborates on why he pursued this approach,
By making the film as factually accurate as possible, the conversation that the film creates should, I think, spark something that a more futuristic, fantastic treatment perhaps cannot. The topics we cover in the film – genetics, eugenics, the moral and ethical implications of a consumer genetics service, and the role of government vs. a DTC model – are discussions that deserve to be out in the public. This is a film of the moment.
In fact, you may find reality to be even more bizarre than this particular fiction. Just last year, the infamous DTC genetics company 23andMereceived a patent for "gamete donor selection based on genetic calculations." The premise of the technology was that it could allow people to choose a sperm or egg provider based on probabilities of having a child with the kinds of characteristics they desired including “height, eye color, gender, personality characteristics and risk of developing certain types of cancer.” In response to backlash from the media about its “designer baby patent” with drop-down menus of characteristics, 23andMe assured everyone that it no longer had any plans to pursue the full range of possibilities described.
Another company, GenePeeks, has remained undaunted. GenePeeks launched just months ago, founded by molecular biologist Lee Silver, who writes broadly about how positive eugenics is both laudable and inevitable, and Anne Morriss, the mother of a sperm donor-conceived son who inherited the rare recessive disease MCADD.
GenePeeks’ “Matchright” is remarkably similar to the product offered by ThePerfect46. For $1995, “GenePeeks digitally combines your DNA and the DNA of potential donor matches to create a preview of thousands of personal genomes that your child could inherit, focusing on a panel of genes involved in childhood health and disease.” Based on this information, you can then preview your personal “catalog” of donors and further weed them out based on your preference for such characteristics as height, eye color, hair color, education level, and ethnicity.
What GenePeeks hasn’t marketed yet is its ability to test for much more than “health and disease.” But the patent it was awarded in January explicitly lists many non-medical traits: aggression, weight, breast size/shape, drinking behavior, drug abuse, eating behavior, ejaculation function, emotional affect, eye color/shape, hair color, height, learning/memory, mating patterns, sex, skin color/texture, and social intelligence, among others. It is thought to be possible to screen for just some of these traits, but all are covered by the patent.
Furthermore, GenePeeks doesn’t intend to limit its availability to sperm banks. It plans to expand soon and become available for “anyone planning a pregnancy in advance.” Of course, there is at least one fundamental flaw in the methodology of all these schemes: two people can have an infinite number of children with a full range of characteristics. Choosing a “preferred” donor can’t possibly absolve all risk.
In fact [spoiler alert], in The Perfect 46, a bug in the company’s algorithm results in the birth of 24 children with a severe genetic disorder. The horrific mistake causes the company to close its doors and forces Darden into solitude, where he continues to develop his work and reflect on what went wrong. What is perhaps most remarkable about the scenario is that no one is ever found to be at fault, even when some of the children die, and at least one suicide results. While Darden is depicted as a broken man, devastated by the fault in a system he designed, he is relatively unmoved by personal stories, including one about a loving couple that divorced after hearing they were “incompatible.” In his mind, “Just because I created something doesn’t mean I’m responsible for how people use it.”
Is this the kind of language that will be used around technologies governing life and death in our market-driven culture? The film probes many such important questions. How quickly does the right to know become the responsibility, or even the requirement, to know? What will people do with this information? And what happens, and who is accountable, when it is wrong?
Furthermore, can changing the kinds of people who are born really be considered “preventative medicine?” When recommendations about who is “fit” to be born are made by a commercial entity, does the absence of state involvement make the actions less eugenic? Is “perfection” what we ought to strive for? If so, what do we make of the founder – who is anxious, anti-social, awkward, not good-looking, and in the end, in “an irony that was lost on no one,” infertile?
The desire to know and control more, even when the meaning of the knowledge and our ability to control it is imperfect, can be powerful. But while it makes marketing sense for drug and genetic testing companies to pathologize more and more conditions, it probably doesn’t make sense for us. As these technologies become increasingly present in our lives, that point risks getting lost.
You can find upcoming screenings of this thought-provoking film here, and check out CGS’s personal genomics news page here. Can you make it through the hall of mirrors, discerning the difference between fiction and reality?
As The New York Times pointed out in a front-page article this past Sunday, “hiring a woman to carry a child” is not allowed in “most of the world.” But cross-border surrogacy, which took off in India more than a decade ago, continues to spread and grow. Now, a range of challenges connected to the practice is being addressed by a high-profile media account, a ruling of the European Court of Human Rights, and an upcoming international conference.
The U.S. as a destination for contract pregnancy
The New York Times story’s focus is on people from outside the U.S. who arrange a contract pregnancy here because it is illegal in their home countries. The featured commissioning parents in “Coming to U.S. for Baby, and Womb to Carry It” by Tamar Lewin are a gay Portuguese couple. Their story – and the baby they are now happily raising – frames the lengthy piece, but Lewin also details the obstacles and tribulations they faced, including a close brush with a sketchy surrogacy agency, a miscarriage, costs in the hundreds of thousands of dollars, and challenges getting citizenship in Portugal for their son.
Lewin also includes critical comments from two feminist scholars, McGill University emeritus professor Abby Lippman and Ingrid Schneider of the University of Hamburg’s Research Center on Biotechnology, Society and the Environment. And she tells the story of Arizona surrogate Heather Rice, who came into conflict with the couple that hired her when, 21 weeks into her pregnancy, an ultrasound showed a problem with the fetus she was carrying.
The article attracted more than 500 comments; an analysis by CGS summer intern Victoria Nichols (available by request) found those expressing opposition or concern about commercial cross-border surrogacy outnumbering those expressing support for it by about 4 to 1.
(As a side note on media coverage, the shortened version of the article that appeared in the San Francisco Chronicle on July 9 omitted nearly all the material that would raise concerns about cross-border surrogacy – including the problems encountered by the Portuguese couple; the comments by Lippman and Schneider; Rice’s story; the cases of US surrogacy agencies, which are entirely unregulated, that have ripped off both intending parents and surrogates; and more.)
European Court of Human Rights rules on children of surrogacy
The legal status of children born as a result of cross-border surrogacy arrangements – that is, their officially recognized parentage and citizenship – has become an increasingly pressing issue. Difficult situations can arise when commissioning parents from countries that prohibit commercial surrogacy flout these laws by hiring surrogates in one of the few jurisdictions that allow it.
Most of the time, the parent’s countries have permitted these children to return home with their social parents. But sometimes they live in legal limbo for years. In late June, the European Court of Human Rights (ECHR) ruled on cases brought by two French families whose children were conceived with their fathers’ sperm and third-party eggs, and carried and delivered by surrogates in California and in Minnesota. The children have U.S. citizenship because of their birth place, and their parentage had been legally established in the United States. They have been living with their families in France, but without legal recognition of their parental status.
The ECHR did not question France’s right to prohibit commercial surrogacy, but ruled that refusing to grant legal status to the parent-child relationships of children born to surrogate mothers abroad “undermined the children’s identity within French society.”
An international conference on cross-border surrogacy
These questions and many others will be considered at the upcoming International Forum on Intercountry Adoption & Global Surrogacy, to be held this August in The Hague, Netherlands. The forum will bring together women’s health advocates, scholars, and policy and legal experts from around the world; its objective is
to produce a body of knowledge that will inform the work of the Hague
Convention as it moves ahead with implementation of the Hague Convention
on Inter-Country Adoption, and with plans to create a convention on
The Center for Genetics and Society is chairing the forum’s thematic area on “Global Surrogacy Practices.” We’ll be reporting in this blog on the forum’s deliberations and recommendations.
Posted by George Estreich, Biopolitical Times guest contributor on July 10th, 2014
A microscopic image that shows a genome being removed from a donor egg. 1. Manipulation pipette. 2. Donor egg. 3. Holding pipette. 4. Zona pellucida (encircling the egg). 5. Location of the oocyte genome (or nuclear DNA) before removal. Photograph from the New York Stem Cell Foundation.
On June 27, the New York Times Magazine’s cover story was “The Brave New World of Three-Parent IVF” by Kim Tingley, a feature article on the new technique it calls “mitochondrial replacement therapy.”1 That technique would combine the nuclear DNA of two people with the mitochondrial DNA of a third, creating an embryo with three immediate genetic parents, in an attempt to avoid one kind of inherited mitochondrial disease. Human trials are currently proposed.
Because this procedure would cross the line into inheritable genetic modification—a bright line that forty-four countries have agreed, as a matter of policy, not to cross—I was curious to see how the Times would report on the procedure. Human biotechnologies are rocketing ahead under the radar; for many readers, the article will be an influential introduction to the issues. Since the article was presented as a feature, and not an opinion piece, the writer had an obligation to present the issues in a balanced way.
Unfortunately, Tingley’s reporting is strongly tilted in favor of the procedure: for her, it’s clear that fears of a brave new world are overblown, and potential benefits underrated.
Structurally, this bias is evident throughout. The article is anchored by a profile of the likable and apparently idealistic scientist Dieter Egli, an advocate of the procedure; we see him reflecting humanely, practicing science competently, listening carefully to opponents. In a truly balanced article, someone who disagreed with Egli would also be profiled, but no one opposing the technique is given remotely equal narrative weight.
Also profiled are families who benefited from cytoplasmic transfer, a precursor to the technique; the families are shown in color photographs, their heartfelt gratitude is recorded, and the health (and intelligence) of their children is emphasized. No such treatment is given to those who question the procedure. Their views are often represented by fearful anonymous comments; when people are quoted on the record, they are represented in brief snippets. Often, their objections are subsequently answered, giving those in favor of the procedure the last word. Significantly, strong arguments against the procedure are omitted.
Tingley’s rhetoric is broadly familiar from writing that advocates the adoption of new technologies. Therefore, “The Brave New World of Three-Person IVF” offers a case study of the way pro-technology assumptions have been absorbed into mainstream media. To show the pervasiveness of these ideas, I’ll dissect a single, pivotal paragraph, examining it point by point: in slow motion, as it were.
What often gets lost in the loaded language of the debate over three-parent babies is the fact that ordinary human reproduction is, by definition, genetic modification. The risks involved are unpredictable and potentially tragic; the subject of the experiment is a future person who cannot consent. We constantly try to control this process, to “design” our children, starting with our choice of sexual partner. During pregnancy, we try to “enhance” them by taking folic acid, not smoking, avoiding stress; once they’re born, we continue the process with vaccines and nutritious food, education, clean air and drinking water. Some of these pre- and postnatal environmental factors, we now know, change their biology in heritable ways. Is mitochondrial replacement, because it takes place in a petri dish, any more unnatural or morally repugnant than this? Would the answer change if the technique turns out to cure age-related infertility in addition to preventing disease?
Now, in slow motion:
What often gets lost in the loaded language of the debate over three-parent babies…
The paragraph’s opening move is familiar: to decry the quality of debate (“loaded language”), and to position the writer as rational. By implication, Tingley will offer language that is non-loaded and clear.
…is the fact that ordinary human reproduction is, by definition, genetic modification.
Words that conjure the rational—fact, definition—are opposed to “loaded language.” But to say “reproduction” is identical to “genetic modification” is neither factual nor definitive. It is an analogy: an argumentative chimera, engineered by the writer.
(1) The technique has many names: three-parent IVF, three-person IVF, mitochondrial transfer, maternal spindle transfer. The differences are not insignificant. Strictly speaking, it is the nucleus, not the mitochondria, which is transferred. I use the phrase “three-person IVF,” which avoids the multiple meaning of “parents.”
Alan Trounson, until very recently president of the California Institute for Regenerative Medicine (CIRM), has accepted a position on the board of StemCells, Inc., a company that has had $19,399,504 in grants from CIRM. If the clinical trials that CIRM is partly funding pay off, he could make a bundle on stock options (details of his compensation are not available). David Jensen, of the California Stem Cell Report, brought this to light, and much more.
That looks bad, but there is much more. Jensen's dogged reporting over the last two years established that the $19m "forgivable loan" was only approved after controversial lobbying by former CIRM chair Robert Klein that resulted in the main board overruling the recommendation of their scientific advisers.
Financially, the $19m is the least of it. Irving Weissmann, the cofounder (and still an active board member) of StemCells, Inc., has had four grants from CIRM totaling $35,420,939.
Weissman was an active pitchman for Proposition 71, which set up CIRM, appearing in TV ads that mentioned his work at Stanford (he directs the Institute of Stem Cell Biology and Regenerative Medicine) but not his entrepreneurial efforts.
But $55m is far from the end of the money involved. Stanford University has had more awards for more money than any other institution: 80 grants totaling $280,768,314. UCLA is second, at $215m, and no other institution has received close to that amount.
One anonymous researcher emailed Jensen:
Are they really more than twice as good as UCSF ($132,650,363), and three times better than USC ($104,858,348) and UC Irvine ($98,591,836)?
Let's be blunt: This looks like a pay-off. Technically, what Trounson and Weissman and StemCells, Inc., just did may not be illegal. But it's shameless.
Trounson is well aware of conflicts of interest, which have swirled around CIRM before. Indeed, he has in the past recused himself from discussions of grant applications from StemCells, Inc., and Jensen has documented other scandals. All of which were thoroughly predictable. They were baked into the structure of the agency. The potential for conflicts of interest was one of the main critiques of Proposition 71, as shown in this September 2004 Nature report:
Critics slate ethical leeway in California stem-cell proposal
Which quoted one of the proposition's authors saying that any such charges were baseless:
"We want to avoid even the appearance of a conflict," says Weissman.
Yup, same guy. Just a month later he was refusing to comment on reports that his stock options in — yup — StemCells, Inc. could benefit from passage of the proposition. Richard Hayes, then Executive Director of CGS, put the problem tactfully to Science:
We're concerned that Prop 71 gives interested parties enormous power over a huge sum of public funds and restricts public accountability.
We were right. (The full 2004 CGS analysis is here.)
Trounson, who made $490,008 a year as President of CIRM, quit his job to return to Australia and spend more time with his family; the StemCells, Inc., press release confirms that he is returning to Melbourne. Nevertheless, his "unique combination of leadership experiences make him a very valuable addition to our board at this transformational time for our Company." Doing what?
Of course, Trounson was also aware that CIRM has been approaching a critical turning point, as articles in both Nature and the San Francisco Chronicle (which featured StemCells, Inc.) pointed out last week. This kind of revolving-door appointment can only hurt the agency, not to mention Trounson's personal reputation.
The Chronicle ran another story when this news broke, confirming that Trounson will receive cash and stock. It also quoted John Simpson, of Consumer Watchdog, who wrote in an email:
"A reasonable 'cooling-off period' — say two years — would have been appropriate before Trounson joined the board of a private company enjoying CIRM's largess. I can only hope Trounson sees his error and steps down from StemCells Inc.'s board."
CIRM should take a long look at its practices and procedures, which have never served the agency well — and especially should consider its obligations to the public, who fund it. There can be practical difficulties in balancing expertise and objectivity; the best scientists in any field do tend to know each other well. All the more reason to be especially careful. This kind of obviously problematic conflict of interest can and should easily be avoided.
On July 2nd, Nature announced the retraction of the two high-profile papers (1, 2) published in January that described what came to be known as STAP cells, as well as a related commentary. The Editorial announcing the retractions describes the underlying process:
Between them, the two papers seemed to demonstrate that a physical perturbation could do what had previously been achieved only by genetic manipulation: transform adult cells into pluripotent stem cells able to differentiate into almost any other cell type. The acronym STAP (stimulus-triggered acquisition of pluripotency) became instantly famous.
The errors, some of them identified during the institutional misconduct investigation (pdfs, 1 & 2), others by the authors of the papers (the retractions are combined), include several misrepresentations of Figures, sloppy handling of data that may have been deliberate, reuse of material from an earlier thesis that used a different process, switched samples and plagiarism (which might have been due to a simple omission of citation). In the court of public opinion, however, the crucial fact is that no one has been able to duplicate the results.
The official retractions are linked from the papers (it is Nature's policy to annotate rather than delete retracted material). Three articles by David Cyranoski (1, 2, 3) in Nature's News section, which is editorially independent, provide more details, and Paul Knoepfler has compiled a linked timeline covering the five-month controversy. (See also Science, The New York Times, Time, etc.) Knoepfler also obtained answers to half a dozen questions he posed to the journal, which provide some more detail about the process that, clearly, failed.
The two principal scientists, however, are maintaining that their work is fundamentally sound. From the retractions (signed by the eight and eleven co-authors):
We apologize for the mistakes included in the Article and Letter. These multiple errors impair the credibility of the study as a whole and we are unable to say without doubt whether the STAP-SC phenomenon is real. Ongoing studies are investigating this phenomenon afresh, but given the extensive nature of the errors currently found, we consider it appropriate to retract both papers.
Charles Vacanti, who first had the idea, issued a statement saying "that he still believed the concept would be proven right." Haruko Obokata, who developed it, "will attempt to recreate the widely-trumpeted findings" under video surveillance over the next five months.
Other scientists don't give them much of a chance, according to the Boston Globe. Rudolf Jaenisch considers the question "finally settled" and criticizes Harvard for its "deafening" official silence. Yoshiki Sasai, one of the co-authors of both papers, says that "it has become increasingly difficult to call the STAP phenomenon even a promising hypothesis." Harvard's Leonard Zon is even blunter:
"I don't think there's any shred of hope for these cells."
This is a rapid about-face for Nature, which is the butt of deserved criticism for missing some of the issues that post-publication review revealed. Most such retractions used to take much longer; the Science retraction of Hwang Woo-suk's two human-stem-cell papers took almost two years from the publication of the first, though the second was only eight months old. Social media made a difference, as Knoepfler has noted, and we can expect similar speedy scrutiny in future.
For it's almost certain that something like this will happen again. Nature and Science and presumably other journals, are tightening their review processes, but it remains true that, as a Washington Postsurvey of mishaps and worse said:
Science is open to error, misinterpretation and even fraud
Now, he hopes to do something about that. In April, Ioannidis and Steven Goodman launched a new center at Stanford:
Scholars at the Meta-Research Innovation Center, or METRICS, will focus on conducting research about research.
The effort is timely, and Ioannidis seems to be both smart and appropriately cynical, according to The Economist:
Dr Ioannidis plans to run tests on the methods of meta-research itself, to make sure he and his colleagues do not fall foul of the very criticisms they make of others. "I don't want", he says, "to take for granted any type of meta-research is ideal and efficient and nice. I don't want to promise that we can change the world, although this is probably what everybody has to promise to get funded nowadays."
The first-ever Disability Rights Leadership Institute on Bioethics (DRLIB for short) brought together about 65 U.S. disability rights advocates to discuss a wide range of issues. The Institute, held in April in Arlington, VA, included presentations – and vibrant discussions – on:
Withholding Medical Treatment, Diane Coleman (Not Dead Yet)
Assisted Suicide Laws, Marilyn Golden (Disability Rights Education & Defense Fund)
Keynote speaker, Liz Carr (comedian and BBC drama series actor; UK Not Dead Yet activist)
International Perspectives in Europe and Canada on Assisted Suicide and Euthanasia, Nic Steenhout (Vivre dans la Dignité) and Amy Hasbrouck (Toujours Vivant / Not Dead Yet Canada)
Key Issues in Reproductive Technologies, Marcy Darnovsky (Center for Genetics and Society) and Silvia Yee (Disability Rights Education & Defense Fund)
Wrongful Birth/Wrongful Life Torts, Samantha Crane (Autistic Self Advocacy Network)
The speakers’ presentations, powerpoints, and recommended readings are now available online at the DRLIB website, and lead organizers Diane Coleman and Marilyn Golden have each written a description of and reflection on the event.
Razib Khan, a PhD student at UC Davis studying the evolutionary genetics of cats, admits that he has “an obsession with genetics.” Two years ago, he sent 23andMe a genetic sample of his 2-month-old daughter so that she could be “easily slotted into the bigger genomic family photo album.”
At the time he predicted that “in the very near future, parents will be able to avail themselves of precise and accurate genomes of their future child in utero.” And just last month he declared, “The future is here, deal with it.”
So it is.
When Khan’s wife became pregnant with a boy, they didn’t waste any time. She had a biopsy of tissue taken from her placenta sent for testing of chromosomal abnormalities. The test showed that the boy was healthy, but Khan wanted to know everything.
After some difficulty, he obtained the original sample from the lab that had tested it and, using his own lab’s high-speed sequencing machine (usually reserved for plants and animals), sequenced the fetus’ entire genome. Using free online software, he was then able to determine 7,000 “genetic variants of interest.” Apparently there was nothing to worry too much about because Khan reported, “It’s mostly pretty boring. So that is good.”
And so his son was born in California earlier this month, becoming the first known healthy baby in the US to have had his entire genome sequenced before birth.
What will it be like to grow up with 7,000 “genetic variations of interest”? At what age will he be told about which? Will he be treated differently because of any of them? Or encouraged to develop specific skills or behaviors? The limited guidelines available for dealing with the genetic testing of children have already been flouted.
Although Khan told MIT Technology Review that sequencing his son “was more cool than practical,” he also “did it to show where technology is headed.” Is this really what most parents will want?
Khan is blunt about the rationale for extensive sequencing in utero – parents will still have a choice about whether to carry out the pregnancy. And he freely acknowledges that this technology throws us headlong into “the second age of eugenics.” But he believes that “the ability to select for quantitative traits” is “a major goal.” And though he regrets that perfection may still be far off, he notes that whole genome sequencing allows one to “select for mutational load” and exclaims,
The marketing pitch for this writes itself: imagine you, but bright of mind, and beautiful of face!
When a technology is so directly imbued with the values that motivated recent human atrocities, what are the avenues for responsible integration? The question of which lives are worthy of existence is one that, in my mind, should never be uncontroversial.
Kevin Mitchell, an Associate Professor in Developmental Neurobiology in Ireland, discussed some of these issues in a blog post last year and concluded,
In the meantime, before we go proposing scientifically impractical and morally questionable extreme measures, we have a proven and powerful tool to make people smarter: education.
The category Latino is a valid cultural artifact, and often self-identified. But it's not really a race in any modern sense of the term, and the genetic evidence surely shows that it is far too broad a grouping to be scientifically appropriate without serious qualification. Yet it is used, even in some current peer-reviewed papers.
One that does not use the term is an article published in Science this month on the genetics of Mexico. The country's population is large and ethnically, linguistically, geographically, economically and culturally diverse. It is also genetically complex, and this article by a large and distinguished team of scientists provides new details. It also suggests some important implications for genomic research and likely for personalized medicine in general:
The genetics of Mexico recapitulates Native American substructure and affects biomedical traits
The study included 511 Native Mexican individuals from 20 indigenous groups, and 500 mestizo (mixed-race) individuals from ten states; nearly a million SNPs were analyzed for each. The variation was striking. From the abstract:
Some groups were as differentiated as Europeans are from East Asians. Pre-Columbian genetic substructure is recapitulated in the indigenous ancestry of admixed mestizo individuals across the country. Furthermore, two independently phenotyped cohorts of Mexicans and Mexican Americans showed a significant association between subcontinental ancestry and lung function.
The first implication for research is clearly that a lot more samples are needed. If this much variation was hidden in Mexico, how much may there be in pockets of Europe and Asia, let alone Africa? Somehow "the" human genome seems more elusive than ever.
That, in turn, carries implications for personalized medicine, as well as for the apparently hard-to-kill concept of genetic race. Consider another paper published this month (there is a bit of overlap among the authors) in JAMA:
Association of a Low-Frequency Variant in HNF1AWith Type 2 Diabetes in a Latino Population
This is another substantial study, and it did tease out a rare allele that is associated with an increased risk for diabetes. However, it "was observed in 0.36% of participants without type 2 diabetes and 2.1% of participants with it." In other words, the five-fold increase in risk leaves 98% of patients unaccounted for. Indeed, this may be an example of "geneticizing disease" as Michael Montoya discussed in his 2011 book Making the Mexican Diabetic.
It's worth noting, as co-author Karol Estrada points out at the Genomes Unzipped blog, that
The variant … was not found in publicly available genetic databases, including 1000 Genomes, Exome Sequencing Project, and dbSNP. Therefore, we would have missed this variant even if we had used the latest genotyping array technology and imputed (i.e., inferred the presence of) variants that were not directly genotyped.
That's yet another argument for more extensive genomic research, in particular (as Estrada stresses) among non-European populations. But the ellipses hide this apparently positive statement:
The variant was found only in people who live in Mexico or the southern U.S. and identify as Latino.
Culturally, they probably do so identify. But is it really appropriate to turn that sociopolitical category into what seems to be used as a genetic category? Even culturally, the variant may be associated with a sub-population (in which it may perhaps be significantly more common); the article suggests that all 52 carriers have "at least 1 segment of inferred Native American ancestry." It seems that the use of Latino is sloppy, at best.
Still, there may be thousands of people who have that allele, and they may have particular treatment needs. That would certainly be an appropriate use of genetic analysis in personalized medicine. But the practical difficulties remain substantial. Just for a start, and setting aside privacy and related issues: who do you test, how do you test them, who pays? Will insurance companies cover a 1-in-50 shot? And what about those with the allele but no symptoms?
Eventually, genomic analysis is likely to make an important contribution to routine medical treatment. But clearly there is quite some distance to go.
And we would all be wise to avoid the tendentious use of imprecise terms.
Scientists around the world are campaigning in favor of sensible regulation of stem-cell therapies. We have two reactions: (1) kudos for this important work; and (2) it's about time.
The highest-profile selling-stem-cells scandal at present is in Italy, where the Stamina Foundation has been described as a "criminal organization that has defrauded about a thousand patients since 2006 by administering a dangerous and unapproved [stem cell] treatment in exchange for money." A profile in The Verge describes its founder, Davide Vannoni, as a "con man," and a long article in Nature by scientists Elena Cattaneo and Gilberto Corbellini details their exhaustive (and exhausting) efforts to stop him:
We recommend that all scientists stand up for the scientific method. Science depends on public institutions and is done in the public interest — we have a duty to defend both.
The recent conference of the International Society for Stem Cell Research (ISSCR) opened with a panel discussion about how to sort the real from the bogus treatments. (Note: none of this is in any way related to the STAP cells controversy.) ISSCR's website includes a useful fact sheet, a backgrounder on "How Science Becomes Medicine," and even, on the front page, a link to the 2010 60 Minutes investigative report on "21st Century Snake Oil."
It's time to take a strong stance against unregistered cellular therapies, which can undermine legitimate research efforts.
Trounson still calls for increased funding of stem cell research. And CIRM is still promoting the development of cures, certainly, but is putting some effort into explaining why they may yet take a while.
This is a welcome change. A little perspective is called for, however: CIRM was sold to the public in 2004 with the strong implication that cures were imminent. The Proposition 71 Voters Guide argument in favor was presented by Cures for California, and the initiative was presented as "Proposition 71, the California Stem Cell Research and Cures Initiative." (It was also going to be an economic miracle.)
Scientists led the way in talking about "life-saving cures" and advocates campaigned under the slogan "Countdown to Cures." Professor and entrepreneur Irv Weissman donned a white coat for commercials, presented himself as a doctor, and assured the TV audience:
The chances for diseases to be cured from stem-cell research are high…. If the promise of stem-cell research comes true, we can hope for a single treatment with the right stem cells to cure diseases every family has.
The hype wasn't limited to California, as Marcy Darnovsky explained in Democracy:
On the national scene, vice presidential candidate John Edwards told a crowd in October 2004 that embryonic stem-cell research would allow people like Christopher Reeve to "get up out of that wheelchair and walk again." In a speech at the Democratic convention, Ron Reagan Jr. predicted that cloning-based stem-cell research could produce for each of us a "personal biological repair kit." The rhetoric grew so heated that Princeton University President and geneticist Shirley Tilghman, a supporter of such research, warned that "some of the public pronouncements in the field of stem-cell research come close to over-promising at best and delusional fantasizing at worst."
Of course, the claims of cures around the corner carefully avoided including a timetable. But in a report published two days after the election, Weissman told the San Francisco Chronicle:
If somebody comes up with a saleable product in five years, I'll be shocked. If we don't have lots of therapies in 20 years, I'll be even more shocked.
Right. There has been a decade of hype about the potential of stem cells. CIRM is approaching the end of its mandate — and money — and looking for more. All of a sudden, they are taking a more … realistic … line. But is it really any surprise than some patients are, well, impatient?
Some scientists have been taking a more balanced view all along. UC Davis Professor Paul Knoepfler's Stem Cell Blog, in particular, has been doing great work for several years critiquing while also supporting the field. Knoepfler designated Elena Cattaneo 2013's Stem Cell Person of the Year; the ISSCR awarded Cattaneo along with Paolo Bianco and Michele De Luca the 2014 Public Service Award.
It's excellent that more scientists are now publicly calling for oversight. Perhaps they will learn a broader lesson: Do not over-promise "cures" in an effort to raise money. Or, as Bianco and Douglas Sipp, another long-time monitor of the field, argued in Nature last week:
However, the industry’s narratives of choice, empowerment, and healthy babies are well-rehearsed and powerful. And they can already be seen in the promotion of a still-illegal technique known as "three-person IVF," which would combine genetic material from two women and one man in an attempt to create a child without the intended mother’s mitochondrial disease. UK researchers, and their funders, have been lobbying the UK government for years to change the law against human inheritable genetic modification in order to allow this into fertility clinics as soon as possible.
There has been little commentary to date about the economics of "3-person IVF." However, a recent report from the UK Department of Health notes that one of the hopes of legalization is that it would “encourage inflows of foreign direct investment into the industry in the UK.”
According to the report, a woman considering this procedure should expect to undergo at least four cycles of egg extractions, at an estimated total cost to her of 80,000 pounds (about US$136,000.) Although very few women would be candidates for the techniques, the revenue stream to private companies would be on the order of 533,000 pounds (about US$905,000) even if only ten women a year decide to go ahead.
The women who will be encouraged to spend such sums on these experimental and invasive techniques deserve the full story. Although the official line from those promoting the techniques has long been that there is no evidence that they are unsafe, there is in fact a lot of reason to doubt their safety.
The risks to any resulting children include all of the following – notably, the first is new evidence just published this month:
According to Jörg Burgstaller and Joanna Poulton, mitochondrial genetics scientists at the Vetmeduni Vienna and the John Radcliffe Hospital in Oxford, even a tiny amount of carryover mutated mitochondria can lead to disease in a resulting child if they are preferentially replicated (a phenomenon that the authors show is more widespread and dangerous than previously believed.) Burgstaller states,
So far it was believed that this minimal ‘contamination’ is of no consequence for the baby. However, our data show that the effect may have dramatic consequences on the health of the offspring.
Klaus Reinhardt, Damian K. Dowling, and Edward H. Morrow, three evolutionary biologists working in the UK and Australia, note that there are continuous complex interactions that take place between the nucleus and mitochondria, which could be disrupted by this procedure and lead to adverse outcomes, including potential infertility in males. They have concluded,
There are reasons to believe that it is premature to move this technology into the clinic at this stage.
This person would develop from a fertilized egg in which all but a few genes (those of the mitochondria), not just those of the male parent, come from a source other than the egg itself. This clearly makes any such person a product of wholesale genetic engineering. We do not know nearly enough about the process of embryonic development for the FDA to even contemplate approving this procedure.
Enucleation of eggs is traumatic, and has been compared to major transplant surgery; damage to the developmental potential of eggs from these procedures was observed in both recent papers on MST. There is no body of data that would validate use of these techniques in a clinical setting.
Paul Knoepfler, Associate Professor in the Department of Cell Biology and Human Anatomy at UC Davis School of Medicine, states
Moving one oocyte nucleus into the enucleated oocyte of another person could trigger all kinds of devastating problems (most likely through epigenetic changes) that might not manifest until you try to make a human being out of it. Then it’s too late.
Even Shoukhrat Mitalipov and other researchers at Oregon Health and Science University working to develop these techniques acknowledge that the majority of human zygotes they have produced showed abnormal fertilization, something that was not seen in their animal models and which they cannot explain.
Both the women who may be offered "3-person IVF" as a viable way to have a healthy child, and the women who would provide their eggs and serve as “mitochondrial donors,” have a right to know that no one can actually say whether these crude manipulations will work. And even if the daunting risks are fully disclosed, it would be wise for anyone considering "3-person IVF" to keep in mind how the fertility industry markets standard IVF: by selling exaggerated hope to desperate patients.
Posted by George Estreich, Biopolitical Times guest contributor on June 6th, 2014
A recent Biopolitical Times post highlighted a landmark discovery: the expansion of life’s alphabet. To the puny assortment of A, T, G, and C—the nucleotides that are the “rungs” on DNA’s ladder, and whose varying sequences are the basis for life as we know it—scientists in California have now created two new synthetic nucleotides: X and Y. This is great news for synbio Scrabble fans, who, in addition to tag, cat, and Gattaca, can now spell tax and gay.
As a writer, and also as a fan of Darwin’s endless forms most beautiful—the phrase, the theory, the forms themselves—I was curious about the addition of the new letters. The four existing nucleotides were good enough to spell out plane trees, Dimetrodons, coral reefs, Tasmanian tigers, rainbow trout, and us—the endless forms evolved over aeons, some vanished, some vanishing at human speed—so why add more? What new forms will we evolve on purpose, to accompany those evolved by the wisdom of time and accident? Why complicate so simple a beginning?
As Pete Shanks notes, Dr. Floyd Romesburg, the Scripps Institute scientist who led the work, explained his project with a metaphor:
If you have a language that has a certain number of letters, you want to add letters so you can write more words and tell more stories.
Among writers, the second person is not without controversy. It is the plaid-jacketed salesman of narrative, throwing its arm around the reader to tell her what she knows and what she wants, and it often produces recoil where it aims at intimacy. So it is for me: it may be that new nucleotides = new amino acids = new organisms, but it does not follow that new letters = new words = new stories. I know lots of writers, but none of us have been thinking, “If only there were thirty letters in the alphabet, then I could finish my novel, The Story of Jimβθ!” Newness depends on thinking and imagination, operating on and in the language we have received, an evolved and evolving thing, created by everyone but by no one in particular, and comprehensible because shared. From so simple a beginning, we get endless forms, some more beautiful than others; but the stories are legible and meaningful because they spring from a common alphabet.
Scientists are more media-savvy than they used to be, and metaphor, one of the traditional tools of literature and persuasion, is part of the game. The right metaphor can soothe fears, explain the recondite, familiarize the unfamiliar. It is scary to say, “we want to create, not only new life, but a new kind of life, one fundamentally different from every single organism that has ever lived.” But who could be against telling more stories? Everyone loves stories! We associate stories with entertainment, meaning, and self-expression. Stories are good. You can never have too many of them.
But to have a story, and to be one, are not the same. George W. Bush can have a story, and so can Lassie, or a tapeworm. But none of these creatures is a story, something designed deliberately and in molecular detail by a single creator, written into existence, letter by letter, word by word. So when Romesburg writes “you can write more words and tell more stories,” that assumes that it is okay to design new creatures in the first place. Turning Romesburg’s rhetorical you to a literal one, I would ask, If a new story is a new creature, then what stories do you want to tell? We have no cultural limit on stories, on their complexity or intricacy: will there be any limits on the stories told with the new letters, or on their ability to replicate, or on the ability of the designed creatures to interact with the evolved?
We live in an ecosystem of persuasion. Our words permeate the world and change the world. Until not that long ago, “life writing” was a genre, and “rewriting nature” a metaphor. It is not that humans haven’t directed the evolution of organisms through agriculture and domestication, or tried, at least, to direct our own; it’s that only recently have we been able to literally rewrite the code of life. We live among metaphors, even as the old metaphors collapse, and under the flag of one patented, invented word after another (Synthorx, Editas), our story is being revised.
George Estreich received his M.F.A. in poetry from Cornell University. His first book, a collection of poems entitled Textbook Illustrations of the Human Body, won the Gorsline Prize from Cloudbank Books. His memoir about raising a daughter with Down syndrome, The Shape of the Eye, was published in SMU Press’ Medical Humanities Series. Praised by Abraham Verghese as “a poignant, beautifully written, and intensely moving memoir,” The Shape of the Eye was awarded the 2012 Oregon Book Award in Creative Nonfiction. Estreich lives in Oregon with his family.
Over the past couple of months, there has been a cascade of
proposals for — or at least discussions about — regulating synthetic
biology, and they are beginning to be noticed. It’s about time!
The technology is edging into the marketplace, at least as proof
of concept, and various stakeholders are establishing positions. Some
kind of regulation will eventually happen, but we can expect some major
struggles first. For instance, if our present institutions are less
than adequate to oversee the new processes — and all but the most
starry-eyed boosters agree that they are — should they be replaced or
expanded? In the U.S. context, what legislation will be required, and
how will it get through Congress?
Perhaps most critically, from the point of view of those of us who
are skeptical about utopian promises, how can we ensure that social,
economic, ethical and other factors are considered? For too long safety
has been very narrowly interpreted, and substantial equivalence far too
broadly assumed. Will those definitions really be retained when it
comes to governing completely novel organisms whose biological and
social disruptions are potentially vast, difficult to predict, and
perhaps impossible to reverse?
The two most significant of the five reports listed immediately
below are those arising from a process undertaken by the international
Convention on Biological Diversity, which is soon to resume, and from
the federally funded overview produced by a small team led by members
of Craig Venter’s organization; both are likely to be sources of
discussion for some time to come.
Nicholas Wade’s book A Troublesome Inheritance: Genes, Race and Human History has been out for a month, and the fuss, such as it was, seems to be dying down. As of June 6, its Amazon rank has dropped to 1300 (it did briefly hit 21), while Barnes and Noble has it at 34,695, and in The New York Times it’s only at 7 in Science Times, below the long-running hit about Henrietta Lacks.
A roundup of reviews by a supporter essentially confirms that those scientists who bothered to review the book panned it. The Genetic Literacy Project is listed as a positive review, but in fact that’s just a report on Charles Murray's piece in the Wall Street Journal. The minority who were predisposed to agree with his thesis — self-described "race realists" and the like, including some anti-semites at David Duke's site — by and large came away wondering why Wade didn’t go further.
So, is "scientific racism" dead? Unfortunately, it's too soon for that particular funeral. This was just a bad book.
The biologists and anthropologists have taken mighty whacks at A Troublesome Inheritance, though the historians seem to have wisely ignored it. As one raised British, however, I cannot resist quoting Wade’s summary (derived from the work of Gregory Clark) of the changes in England that led to the Industrial Revolution:
Most children of the rich had to sink in the social scale, given that there were too many of them to remain in the upper class. Their social descent had the far-reaching genetic consequence that they carried with them inheritance for the same behaviors that had made their parents rich. The values of the upper middle class — nonviolence, literacy, thrift and patience — were thus infused into lower economic classes and throughout society. Generation after generation, they gradually became the values of the society as a whole.
This is nuts. On many levels, even without the posited evolution of the English gene pool. Did the aristocracy really get rich by being patient, thrifty, well-read pacifists? Uh, no. What Wade is caricaturing here is the petit-bourgeois social armament against exploitation by their employers. It’s bad history, bad economics, bad sociology, bad psychology … to go along with the crackpot science.
But the topic is important, not because this book is a menace to society — though it would be if taken seriously — but because the category error that confuses human genetic variation with socially constructed race remains all too common.
Racial diversity crucial to trials of drugs, treatments
Diversity is certainly important. A trial that included only or mostly men for a condition that also affects women would obviously be lacking, though sadly unsurprising. (A recent paper showed that evolutionary biologists studying genitalia still tend to study penises.) Social communities may indeed be worth studying, for their shared environmental and attitudinal responses. And that does tend to map, to an extent, with self-identified race.
But to think that the problem of genetic diversity in a population sample has been adequately addressed by applying socially constructed race is to make a crucial mistake. And one that may have serious consequences, as social disadvantages are redefined as genetic, with all the baggage that can entail.
Wade repeatedly insists that he actively opposes racism:
The issue is how best to sustain the fight against racism in light of new information from the human genome that bears on race.
That was from his attempt to answer his critics. Anthropologist Agustín Fuentes (whose early conversation with Wade about the book set the prevailing tone of well-warranted critical dismissal) responded, again, that Wade knows not whereof he speaks:
Humans vary biologically, and we are not all the same. But there is only one biological race at present in our species. Understanding that, and the science behind it, is critical.
The UK Human Fertilisation and Embryology Authority (HFEA) has just released an update on the safety and efficacy of three-person IVF. (In response to the agency’s call for comments, the Center for Genetics and Society had submitted a letter that was signed by 53 prominent scholars, scientists and advocates from around the world.) The HFEA report will help inform the upcoming Parliamentary vote on whether to make an exception to the UK law that currently prohibits inheritable genetic modification of humans.
The techniques under consideration are being proposed for women with a rare form of mitochondrial disease who wish to have an unaffected and mostly genetically related child. They require the extraction of the nucleus from her egg or embryo followed by its reinsertion into another woman’s egg or embryo. Any resulting child would inherit nuclear DNA from the intended mother and mitochondrial DNA from an anonymous egg provider.
The HFEA panel’s strongest statement of endorsement is that “the evidence it has seen does not suggest that these techniques are unsafe.” The HFEA has been saying this for three years now, and it should not be interpreted to mean that the techniques are safe.
In fact, the report acknowledges that “there are still experiments that need to be completed before clinical treatment should be offered.”
One set of experiments that is considered “essential” is the study of cells of early embryos created via these techniques to determine the levels of heteroplasmic mosaicism, which could include an amplified proportion of carryover mutated mitochondria. If this is found, it could severely compromise the health of a future child and lead to him or her developing mitochondrial disease down the road.
Other embryonic experiments that are recommended prior to use in humans include an analysis of the number and appearance of chromosomes found in cells, a detailed analysis of epigenetic modifications and gene expression, and the use of induced pluripotent stem cells derived from patients carrying different mitochondrial mutations. This final study would be of particular value since, barring one study in mice in 2005, there have been no experiments done on eggs or embryos that actually have mutated mitochondria.
In addition to these important proof-of-concept studies that have not been completed, the report also mentions that there have been some worrying outcomes from past studies. For example, in 2011, the HFEA considered proven success of pronuclear transfer (PNT) in a non-human primate model to be “critical.” Then in 2012 the agency found that “[f]rom unpublished data it appears that Macaque zygotes do not survive the PNT process well.” Instead of heeding this huge red flag, the HFEA simply rescinded the requirement of any primate model at all. This reversal was explained as a concession to the argument that continuing experiments on macaques would be “unethical.” Does that imply that the decision makers are exercising less caution with humans?
Here is the HFEA’s response to the inherently high degree of uncertainty and risk that this technique would pose:
The panel strongly recommends that permission is sought from the parents of the children born from MST or PNT to be followed up for an extensive period... any female born following MST or PNT should be advised, when old enough, that she may herself be at risk of having a child with a significant level of mutant mtDNA, putting her child, and if female, subsequent generations at risk of mitochondrial disease.
Elsewhere in the report, the panel makes a small concession to the huge ethical, social, and political implications of these procedures.
Furthermore, although not within the scope of this review, it is important to note that issues other than purely scientific need also to be considered.
We urge the UK government, the public, and Members of Parliament not to let enthusiasm for novel technologies trump the need for clear evidence and for serious consideration about the policy implications of a decision on these controversial techniques.
Rudy Rupak, CEO and founder of Planet Hospital, in the “Happy Room” at Cancun Fertility Centre, one of the company’s Mexican partner clinics
Another high-profile surrogacy agency, Los Angeles-based medical tourism company Planet Hospital, stands accused of deceiving its clients and stealing their money. According to a report earlier this month by Al Jazeera America, one of these clients has compiled information from 40 couples who say they were victimized by Planet Hospital founder Rudy Rupak Acharya, and turned it over to the FBI’s Consumer Fraud division in San Diego.
Both news stories report that Planet Hospital has removed surrogacy from the list of medical tourism procedures it offers.
Planet Hospital founder Rudy Rupak Acharya comes in for a whopping dose of criticism, which by all accounts is well deserved. Former CGS staffer Doug Pet encountered Rupak when he wrote about the company’s so-called "India bundle," an arrangement meant to “streamline” the arrival of a baby by implanting clients’ embryos in two surrogates at the same time. Initially, Planet Hospital advertised that commissioning parents could order an abortion if both surrogates became pregnant.
Detailed accounts by clients who say they were swindled can be found online (for example, here, here and here), but Al Jazeera and Bay Area Reporter have so far offered the only media coverage.
Perhaps this is because surrogacy industry scandals have become a bit like old news. In 2011, two prominent attorneys pled guilty and were sent to prison on criminal charges connected with an elaborate international surrogacy fraud. The same FBI office that has been contacted by Planet Hospital’s former client investigated that case; its press release bore the pull-no-punches title “Baby-Selling Ring Busted.”
Al Jazeera’s investigative report is part of a series that includes “a guide to some of the international surrogacy hotspots” and an article about wealthy Chinese couples who come to the US for surrogacy. Both its coverage and the lengthy article about Planet Hospital in the Bay Area Reporter focus entirely on the financial and emotional damages done to those who commissioned pregnancies. Neither outlet asks whether any surrogates may have been left mid-pregnancy with no prospect of getting paid, which has occurred in previous surrogacy scandals. And neither mentions the many reports from India of disturbing practices that harm women who work as surrogates there.
Human cloning made a media comeback in the last year, with news of three different research groups making embryonic stem cells out of embryos cloned from adult cells, only 17 years after the technique worked to create Dolly the sheep. The scientists have stated clearly that these cloned embryos are meant for research and therapeutic purposes, and that they oppose any efforts to create human clones.
The breakthrough also means that it is now just a matter of time before reproductive cloning is achieved. Probably within the next decade, as one scientist has told me.
As CGS has repeatedly asserted, it really is the time for that federal ban.
What might our unregulated Brave New World look like? BBC America’s television series, Orphan Black by Canadian director John Fawcett, nails it. Now into its second season, this show is seriously good, and starting to get some real recognition.
[SPOILER ALERT] It all begins when Sarah Manning, an English punk who has stolen her boyfriend’s cocaine stash so she can get money to take care of her young daughter, falls asleep on the train and wakes up to find herself at Huxley station. (The cultural references are copious so keep your eyes out.) She moves toward the only other person around, and is shocked to see a woman who looks exactly like herself, if only she were showered and wore a dress suit. Things get interesting fast, as the look-alike jumps in front of the next train, committing suicide before the two can share a word. Quick on her feet, Sarah grabs the purse her double left behind and runs, composing a plan to steal the cash and get her life back on track before anyone can know the difference.
It doesn’t quite work out as she hopes. Sarah soon finds herself deep in a world of secrets and murders that make her former life as an orphan on the run seem easy in comparison. After meeting three more women who look exactly like her, Sarah is finally let into the secret: the women are not long lost twins, but the result of an illegal medical experiment; they are clones. They look the same, but life has dealt them each very different cards. There’s a Ukrainian assassin raised by an ultra-religious group called the Proletheans who have taught her that clones are an abomination of nature, a lesbian grad student with dreads researching the clones’ genetic makeup, and an uptight suburban soccer mom who wears lululemon and funds the “clone club’s” efforts. It turns out that the one who killed herself was a pill-popping investigative cop.
Sarah’s original plan to take the money and run - with daughter (the only known offspring of a clone) and adopted brother (Felix Dawkins) in tow - slowly fades as she starts to unravel the mystery of her existence, and become entwined with the lives of her genetic identicals. The clones slowly realize that their origin story lies with a pro-eugenic scientific movement called Neolutionism, a group that boasts of its ability to self direct the evolution of humanity. The movement’s front man, the charismatic but not-quite-right Dr. Aldous Leekie, is a figure reminiscent of futurist Ray Kurzweil, and he’s got a following to match. In response to a reporter’s question about what his ideal human would look like, Leekie jokingly suggests “people with white hair and one white eye.” Not long after, a whole slew of “Freeky Leekies” pops up, “enhanced” to have those very characteristics.
Not wanting his precious clone creations to be far from reach, Leekie has assigned each clone her own “monitor,” people the women believe are their loved ones, but who actually track their every step. In the season one finale, it is revealed that his control goes further when Cosima (the grad student with dreads) cracks the code she found encrypted in each of their genomes. It turns out to be a patent held by Leekie and his obviously prosperous Dyad Institute.
In the real-world United States, “claims directed to or encompassing a human organism are ineligible” for patents. However, Orphan Black is deliberately ambiguous about where it takes place. Complicating the issue, the show examines the question, what does it mean to be human? The United States Court of Appeals for the Federal Circuit just ruled that cloned animals cannot be patented based on the notion that they are the genetic replica of naturally occurring organisms, but could even a tiny portion of synthetic DNA render one distinct?
Orphan Black certainly doesn’t shy away from drama or controversy, but it manages to pose the big questions without ever coming off as contrived. This is a memorable, unique series, and it seems likely that it will inform public opinion on human cloning for some time. Given the current technological media storm, we all ought to join the conversation. Orphan Black provides the perfect, fun excuse to do so.
Scientists Add Letters to DNA’s Alphabet, Raising Hope and Fear
The article described a significant step forward in the use of "novel DNA." Two artificial nucleotides (X and Y) were added to E. coli, along with the usual A, C, G and T. The bacteria reproduced more or less normally, propagating the unnatural X-Y base pair until the supply of X and Y ran out. (That is touted as a safety feature.)
The publication in Nature by Floyd Romesberg, Denis Malyshev et al, from The Scripps Research Institute in La Jolla, California, and New England Biolabs, is titled:
A semi-synthetic organism with an expanded genetic alphabet
In the long run, some scientists hope for completely self-replicating artificial DNA, without the need for feedstock, and perhaps even “fully alien” with a completely different genetic system. (Romesberg calls that impossible, but he may be exemplifying Clarke’s First Law.) Fully functional artificial DNA remains at least a long way away; the same team first announced the replication of unnatural DNA in 2005, and formal discussion of "adding to the genetic alphabet” (Nature, 1990) goes back much further.
One result of developing this approach could be to produce far more amino acids (perhaps up to 172), and thus perhaps novel proteins. Romesberg told The New York Times:
If you have a language that has a certain number of letters, you want to add letters so you can write more words and tell more stories.
That’s a strained metaphor, and the Times story also notes that four could be the most efficient number of nucleotides anyway. However, the inevitable subhead, in this case to a good story at the well-connected U-T San Diego, becomes:
Scripps scientists widen genetic code within organism, unlocking the door to new treatments, other advancements
“New treatments” is a stretch at this point, but just in case they pan out, the Scripps team has partnered with Avalon Ventures to launch a company called Synthorx “to synthesize solutions for the discovery and development of novel therapeutics, diagnostics and vaccines.”
Other recent developments in synthetic biology include:
International consortium building synthetic yeast — Teams from the U.S., China, U.K., Singapore, India and Australia are cooperating in an effort to make the first synthetic version of a complex living organism; “better beer,” they say, which may be a mistake.
CC Sabathia, a starting pitcher for the New York Yankees, is making $23 million this year, and the same or more for at least the next two, maybe three years. But his knee hurts, which probably explains why he's been having a lousy season. It turns out that he has degenerative problems in his right knee, "which required a cortisone shot and stem cell injections."
Some stem cell treatments are controversial, and illegal in the U.S. (Why else would Texas-based Celltex now be treating U.S. patients in Mexico?) But the reinjection of adult stem cells extracted from your own bone marrow, and not altered, is in fact legitimate. How much that helps, and for what conditions, is another question. The evidence that it speeds up healing is "largely anecdotal in human patients."
The stem-cell approach to sports medicine is relatively new. ESPN reported, in December 2012:
For the past three years, however, Andrews has been experimenting with a new strategy. "Stem cells," he says. "What we call biologics. They're on their way, and that will be a transformational event." Very quietly - "We don't advertise it," Andrews says, "and we don't want to sensationalize it" - he and his colleagues at clinics in Birmingham, Ala., and Gulf Breeze, Fla., have been performing stem cell injections on professional athletes. He won't name names, but Andrews has mostly employed stem cells in the deteriorated knees of football players, and virtually all of them have reported significant decreases in pain and inflammation. "It's early," he says, "but the results have been remarkable."
I keep predicting the next thing is biologics - stem cell therapy, gene therapy, robotic surgery. That's what we're really working on right now. We haven't gotten to the research basis that we need to prove how to handle stem cell therapy and gene therapy, but it's coming. In those cases, we're hoping to biologically enhance the healing process. For example, make ACL surgery heal better, longer and quicker. That's not a performance-enhancing situation. It's a healing-enhancement situation. It's perfectly legal and hopeful.
Yankee outfielder Carlos Beltran headed for Andrews this month, too. The doctor "confirmed the diagnosis of a bone spur in the right elbow" but there are no reports of stem cell treatment, which would likely follow rather than replace the surgery that may be needed. Reports also suggest that Sabathia may need surgery "at the latest, in the offseason." The best case seems to be that he is out till July. And he may have to settle for the $5 million buy-out for 2017.
Why I won’t give a sample of my DNA to DeCODE Genetics
My first reaction was that the searching spiders had turned up another ancient tale as if it were new. DeCODE genetics was founded in 1996, with the controversial goal of turning the entire population of Iceland into a massive genetic database, which would be linked to everyone’s medical records, and genealogical information. From this, the company would identify genes for medical conditions and turn an enormous profit. (The 2008 book Promising Genomics covers the story; it “investigates how deCODE Genetics…became one of the wealthiest companies of its kind, as well as one of the most scandalous.”)
It was a grand and ambitious scheme. Iceland’s population (about 280,000 in 2000) is assumed to be generally homogeneous, which seemed likely to help isolate the alleles related to disease, according to the theory of the time. And Iceland has a national health service, administered by the Department of Welfare, with no competing private hospitals. It also has extensive genealogical records, and DeCODE supplied the funds to turn them into a database.
There was quite the boom. The government passed legislation in 1998 setting up the Health Sector Database, and everyone was going to get rich! Except it never actually happened as originally planned. (See “Genome and Nation” [pdf] by UC Berkeley Professor in Bioethics and Society and CGS Advisory Board member David Winickoff.) The national and international controversy became intense; many people saw this as private exploitation of a public good, and there was increasing awareness about the issues of privacy and consent. In 2003, the Icelandic Supreme Court ruled that the company needed to get consent from individuals — not just the government — in order to access their health records.
The collapse of the dot-com boom in 2000–2002 didn’t help; the whole biotech sector suffered, not to mention that a lot of small investors lost their shirts. On top of all this, the science was not working quite as expected. The company did in fact identify a lot of genes as at least partially connected with various conditions. But it never managed to find genomic data specific enough to develop blockbuster treatments. Not surprisingly, therefore, the profit part turned out to be rather hard to achieve. In fact, the company burned through more than half a billion dollars before finally going bust in 2009.
But now DeCODE is baaaack.
For driven entrepreneurs such as DeCODE's Kári Stefánsson, bankruptcy is apparently only a step in the direction of success. Some rather slick machinations resulted in Amgen owning DeCODE, while a spin-off called — cleverly — NextCode aimed to "market diagnoses based on Decode research to doctors and hospitals in the USA.”
And now the next act: This year, DeCODE began going door to door in Iceland collecting DNA samples and consent forms. And they’ll give you a T-shirt in exchange.
Evidently, the company had less than a third of the population in its database when it went bust, and they want the rest. So they have hired the nation’s official search and rescue team (ICE-SAR), for less than $20 a sample, to go door to door. Sigmundsdóttir does not wish them luck:
Predictably there has been a major furore over all this here in Iceland. A group of academics and experts, including the head of the Centre for Ethics at the University of Iceland, have harshly criticized the collection and the way it is being executed. For me personally, the ICE-SAR involvement is the most distasteful element of the whole thing. I resent being manipulated like that, and resent that a wonderful organization like ICE-SAR is being abused in such a manner. Like many others I plan to bin the package from Kári and personally donate ISK 2,000 [about $18] to ICE-SAR, in lieu of the funds that Kári, Hannes and co. would have donated on my behalf.
The United States Court of Appeals for the Federal Circuit has ruled that cloned animals cannot be patented because they are the genetic replica of naturally occurring organisms. The methods for cloning the animals can be patented, but not the animals themselves. The patent under consideration was filed by the creators of Dolly the Sheep, Keith Campbell and Ian Wilmut of The Roslin Institute.
A potential caveat of the ruling is that if a clone were shown to be different enough from the original, perhaps it would be eligible for patent protection. But then the scientists would have to admit that clones do not actually produce identical copies, and where’s the fun in that?
The ruling for In re Roslin Institute relied on some of the reasoning from last year’s critical Supreme Court ruling in Association for Molecular Pathology v. Myriad Genetics, Inc. in which it was unanimously decided that human genes, even when isolated by human ingenuity, are naturally occurring phenomena and thus not patentable. That ruling was an important victory in reclaiming the common heritage of humanity and limiting corporate control of our bodies and health.
This latest ruling has been hailed as a victory for those who morally oppose animal cloning for its horrible success rates that lead to unnecessary animal suffering. There are plenty of reasons why cloned animals should not be the future of the world’s livestock.
But some people are worried about the impact of this limitation for the burgeoning field of regenerative medicine.Carl Gulbrandsen, managing director of the Wisconsin Alumni Research Foundation, said, “The whole area of personalized medicine is going to get impacted by this sort of rationale.” IP Watchdog's President and Founder Glenn Quinn exclaimed more bluntly, "Sadly, until further notice, personalized medicine is dead!”
Their concern is that this ruling will derail a potential future in which cells, tissues, and organs (specifically designed to resemble their natural counterparts) are made-to-order in labs for people with degenerative diseases, since these bio-products are now likely to be ineligible for patent protection.
However, it’s unlikely that scientists will entirely abandon research on these endeavors since they can still patent their methods. And frankly, it’s probably for the best that biotech companies will be less likely to own our very breath.
The United Kingdom may be on the verge of becoming the first country in the world to allow fertility specialists to create embryos with permanently altered genetic makeup. Parliament is expected to decide later this year whether to allow an exception to the UK law that prohibits inheritable genetic modification. If the proposal is approved, it would be limited to a very specific procedure for a very specific reason – nuclear genome transfer between two different women’s eggs for the purpose of allowing a woman to have a mostly genetically related child who does not inherit her mitochondrial dysfunction. However, it could disrupt the existing de facto international policy agreement that human germline modifications should not be permitted.
Approval of this technique – known by several terms including “mitochondrial manipulation” and “three-person embryos” – would not constitute approval for other kinds of inheritable genetic manipulations. But nowhere else in the world has a policy or technical line been drawn at this curious point. All other countries that have considered human germline modification have prohibited it, as has the UK. If a country that is a respected biomedical hub chips away at this prohibition, it could create reverberations in policy around the world.
A new report in Reproductive BioMedicine Online by Tetsuya Ishii addresses this concern. It is called “Potential impact of human mitochondrial replacement on global policy regarding germline gene modification” and in it, Ishii argues that the UK must be aware that it is making this decision within a global society.
The article addresses a number of points: ethical issues surrounding egg procurement as well as the potential slippery slope to other kinds of germline modification; safety concerns that could be much more serious than those associated with already accepted forms of assisted reproduction; and both short-term and long-term consequences to biomedical policy around the world.
In the short term, Ishii notes that a change in UK law could encourage the US, Japan, China, and Israel in particular to consider this technique as well. In the longer-term, he considers the advancing state of other genome-editing technologies (which he address more thoroughly in another recent paper in Trends in Biotechnology) and points out that when considered on a global scale,
Legalization in the UK might cause another slide down the slippery slope to full-blown germline gene modification because the slope to further genetic modification will seem less steep than is the case with the current total ban.
The importance of Ishii’s report is its examination of the full policy context of approving the proposed technique, and its insistence that responsibility in this sector now requires a global perspective. Additionally, Ishii offers conclusions in line with many recent statements (see the previous Biopolitical Times blogs below) that there is not enough data on any front to move forward in good conscience with so-called “mitochondrial replacement.” He states,
It is concluded that international harmonization is needed, as well as further ethical and practical consideration, prior to the legalization of human mitochondrial replacement…
As a member of a global society, the UK Government and Parliament should sufficiently discuss scientific, ethical and legal justifications for human mitochondrial replacement.
Adult stem cells have been moving into clinical trials for several conditions but especially as treatments for heart disease. Dozens of studies have been published, and the results have been generally, if modestly, encouraging. Now a very disquieting meta-analysis, published in the BMJ (British Medical Journal), is casting cold water on some of these findings.
Alexandra Nowbar and colleagues at Imperial College London analyzed 133 reports from 49 trials using bone marrow stem cells in patients with heart disease. The effect evaluated was "mean left ventricular ejection fraction." They found 604 “discrepancies” in design, methods or results, based only on careful reading of the published reports. That is unfortunate, to say the least, but here’s the really disturbing finding:
The more discrepancies, the better the reported outcome.
The high-discrepancy group (5 trials with over 30 discrepancies each) showed a mean effect size of 7.7%. The next group (3 trials with 21–30) showed 5.7%. Those with 11–20, 3.0%. Those with 1–20, 2.1%. And:
[I]n the five trials without discrepancies the effect of bone marrow stem cell therapy on ejection fraction is zero.
Nature, in an editorial, calls this “a shocking reality check.”
There is more. Two papers by Harvard’s Piero Anversa and colleagues that described regeneration as a result of stem-cell treatment have been withdrawn or questioned. Another new study, published in Nature, suggests that regeneration may be at a “functionally insignificant level.” A survey published by The Cochrane Library did find some "moderate quality evidence” that bone marrow stem cells were beneficial, but then that’s what almost all the studies Nowbar et al. addressed found, too.
The analysis of stem cell studies clearly suggests confirmation bias — the tendency to search for or interpret information in a way that confirms one's preconceptions. That does not completely invalidate the research, but it certainly raises questions, both about methodology and about the peer review process.
Analyzing 25 years of research in the evolution of genitals, the authors found a strong bias towards studying male animals — a disparity that has got worse over time.
That clearly points to (presumably unconscious) bias.
Scientists are people, and these things will happen, so peer reviewers and other gatekeepers clearly need to be more aware of what can go wrong and catch such errors early. The stem cell field was terribly damaged by fraud a decade ago. It would be truly tragic if patients have had their hopes raised again only to be dashed.
Untitled DocumentUpdate 5/12/14: A review of the book by Jonathan Marks has now been posted at In These Times.
Nicholas Wade has just published a new book, titled A Troublesome Inheritance: Genes, Race and Human History. A veteran science journalist, with The New York Times and before that both Science and Nature, Wade might be thought to be in a great position to report on this contentious topic.
Over the past 15 years or so, since the announcement that the human genome had been “mapped,” geneticists have certainly not been reticent about searching for hypothesized racial differences in DNA. Indeed, this has been part of Wade’s beat since at least 2001 (e.g., 1, 2, 3, 4, 5, 6). Race also featured in a chapter of his 2006 book, Before the Dawn.
But he is presenting his new book as a brave exercise in truth-telling:
Scientists are afraid to talk about race. They know that they risk being denounced as racists and having their careers destroyed if they even mention the subject, so they refer to it instead in code words. So I decided that I would write a book that explained what we know about race and what the consequences might be, and I think [Ashley] Montagu made a terrible mistake, though I share his motives.
Montagu was the anthropologist who, in the 1940s and 1950s, did perhaps more than any other social scientist to establish the idea that race is primarily a social construct rather than a biological reality.
Today the genomics community may be somewhat uncomfortable addressing the issue of race and genetics head-on, but anthropologists are not. The first serious public examination of Wade’s current project came on May 5 in a webinar (still available online) organized by the American Anthropological Association, which was set up as a “discussion” featuring Wade and Notre Dame Professor Agustín Fuentes, moderated by AAA Executive Director, Dr. Edward Liebow.
It was not so much a discussion as a debate, and in my view Fuentes defeated Wade thoroughly, though it was all very polite (too polite). Fuentes was well prepared, and able to identify, cite and comment on every study that Wade brought up to support his thesis. More important, he kept hammering away at the definition of “race” — as in, Mr. Wade, can you tell us, what is it? If you are going to claim that certain kinds of genetic variation between populations constitute a racial grouping, how do you define it?
Mostly Wade ignored the question. To the extent that he addressed it, he dismissed it as unimportant. Whether there are three or five races, or more, and where the boundaries are drawn: these are mere details until we admit the possibility of discussing race. (I’m being a little kind to him here myself; he burbled.)
Wade is full of factoids; the impressive thing about Fuentes’ performance was that he was familiar with all of them. That inevitably led to some points of agreement. For instance, at one point, Wade started to speculate about what percentage of genetic divergence would constitute a sub-species, and zoologically, they were in broad theoretical agreement. However, Wade seemed to be edging towards very dangerous waters when it came to the concept of human sub-species. Unfortunately, Fuentes and moderator Liebow were too polite to shove him in.
Which is a shame. The first reviews, and the most enthusiastic early reception, have been on blatantly racist websites. Jared Taylor reviewed it at American Renaissance (which promotes “race realism”) on March 2; John Derbyshire at VDare (an anti-immigration site) on March 14. The marketing department at Penguin, which published Troublesome Inheritance, offered pre-release copies (CGS got one too) with the pitch that the book will produce "a heated debate," presumably on the theory that controversy boosts sales. On the day of publication, May 6, Bryce Laliberte at Social Matter (“not your grandfather’s conservatism”) called it “certain to be this year’s most important book,” and opined emphatically that
The KKK were right.
Laliberte does call the KKK “bad guys,” but he blames the ills of society on “the academic and activist leftists” who promote “the notion that individuals and groups are essentially interchangeable.” He is sure that Wade will be vindicated, and offers a notably full-throated endorsement. Other writers of this ilk had their doubts, expressed for example by Taylor:
However, there is much waffling in this book, which was no doubt meant to ward off beatings but that, at least to undeceived readers, rings of timidity.
Derbyshire refers to “squid ink” that he assumes is intended to deflect critics. Some of the commenters at these sites, and even Stormfront (white pride world wide) are more charitable, suggesting that Wade had guts, hit “a solid double” and implying that perhaps he had to hold back in order to keep his job.
Wade’s arguments aren’t necessarily wrong, just because they look like various erroneous arguments from decades past involving drunken Irishmen, crafty Jews, hot-blooded Spaniards, lazy Africans, and the like.
Wade insists that his intent is absolutely not racist:
I think it’s best to say that racism is wrong as a matter of principle, as a matter of absolute principle, and that way you don’t care what the science says, because you’re not going to change your mind about your principles.
That was at the webinar (around 17 minutes in), where neither Fuentes nor Liebow pushed Wade on the subject of his supporters. Anthropologist Jonathan Marks might have been a stricter interviewer, based on this from his March blog post “Genetics as political ideology”:
By implication, then, the only way to understand claims about human genetics is to understand that they are never value-neutral, and are invariably politically valent. This means that scientists ought to be just as accountable to justify the deducible political implications of their work as they are to justify the data collection and statistics.
Wade clearly takes the opposite view. He’s wrong all round.
Jason Silva, whose website identifies him as FILMMAKER • FUTURIST • EPIPHANY ADDICT, riffs on transhumanism at the Daily Beast, which is not notorious for the stringency of its editors. Silva claims (citing Peter Diamandis, whom he is misquoting) that
more change has occurred in the last 100 years than in the last billion.
Let’s see … formation and dissolution of pangaea; increase in oxygen from about 10% of present-day levels; origin of multi-cellular eukaryotes; all of the previous big five mass extinctions...but what is all that compared with the development of the smartphone, eh?
Or did he mean million? (But what’s an order of magnitude or three among scientists?)
Well, there have been some noticeable changes in that time frame too, notably in the genus homo.
The new film Transcendence has gotten pretty terrible reviews. I mean, this is the kind of sci-fi film that gets 18% on Rotten Tomatoes. I went to see it prepared to leave with nothing. But honestly, although it didn’t spend much time on elegant dialogue, subtle plot lines, or convincing love scenes, Transcendence gave me plenty to think about.
Maybe it’s the Brit in me; they’ve been kinder to it over there. As leading UK film critic Mark Kermode put it in his largely positive video review, the film falls into the category of “ideas-movies first and plot-movies second.” So I won’t waste much time with the plot, but I can assert that the ideas that propel Transcendence are fascinating.
The movie tackles classic sci-fi archetypes with new possibilities: uploading a human consciousness into a computer, nanotechnology, synthetic biology, and regenerative medicine. All of the technologies described are based on things that scientists are working on right now. And the film provides a pretty good jumping-off point for thinking about what these quickly approaching technologies will actually mean for society.
Johnny Depp, who plays the central character, explains in an interview that this is what makes Transcendence unique.
This film is foretelling of what is to come. It’s not like ooh, this might happen, ooh we might be able to do this one day in 100 years, 200 years. No, this is technology that will be in use, and is in use to some degree today, but will be in full use in 30-40 years. I mean this is our future.
One could easily mistake the film’s plotline with prominent futurist Ray Kurzweil’s description of “The Singularity,” which he is certain humanity is “on the verge” of achieving.
In this new world, there will be no clear distinction between human and machine, real reality and virtual reality. We will be able to assume different bodies and take on a range of personae at will. In practical terms, human aging and illness will be reversed; pollution will be stopped; world hunger and poverty will be solved. Nanotechnology will make it possible to create virtually any physical product using inexpensive information processes and will ultimately turn even death into a soluble problem.
But, ambiguity is what makes this subject matter compelling. I think this is what the movie gets absolutely right.
The tension created by radical biotechnologies is fascinating. We want to improve the world around us, but what are we willing to sacrifice along the way? Of course it’s more complicated than right and wrong. The uploaded version of Dr. Will Caster (Depp) plays the villain when he puts his own consciousness into other people. But he plays the hero when he tells his wife that he merely built the world she always wanted. In the end, if we’re uncomfortable it’s because we must wonder if the lovely Dr. Evelyne Caster (Rebecca Hall), the character we are encouraged to like the best, was the monster all along. While Will was satisfied with understanding the natural world, it was Evelyne who wanted to change it.
There is another reason that I suspect caused many people to dislike the movie: It paints a pretty grim picture. Unlike the much-celebrated Her, which made the case that one really could fall in love with an A.I., Transcendence is more interesting for the ways in which it critiques this kind of connection. Uploaded Will seems to be able to respond lovingly to Evelyne, but she feels betrayed and invaded when she learns that he has been doing this through continuous evaluation of her heart rate, chemical imbalances, and brain activity. In one scene, she gets so sick of his omnipresence that she asks him to make all his screens go black, though it’s understood he is still there.
In other words, this is the technology that is supposed to save us, but it only takes one conscious machine and a few years for things to get so out of hand that we are forced to abandon it all, the good with the bad. I understood the ending to be a sinister warning that if synthetic organisms ever do run amok they can never fully be retracted. But others understood the final scene to be a sappy ending to the scientists’ love story, so you’ll have to ponder that one for yourself.
One thing is for sure. We are in an era in which some are completely infatuated with technology and its promise to enhance us as individuals and as a society. One reviewer of that ilk calledTranscendence “fear-mongering,” “anti-science crap.” According to another Kurzweil enthusiast, “Technology is how we impregnate the world with mind, it is how we extend the reach of our consciousness, how we extend our agency.” How could anyone stand in the way of that kind of Manifest Destiny?
My guess is that Transcendence is paying the price for showing that hot new biotech, doing exactly what it promises to do, could lead to disaster. As far as our story goes, we’re still in the hero phase. But hey, we’re only human.
For the third time in less than a year, human embryonic stem cells (hESCs) have been derived by cloning (that is, somatic cell nuclear transfer or SCNT) and reported in a major peer-reviewed journal. As a result, there is a renewed campaign for so-called “therapeutic cloning,” in which stem cells for medical treatments would be tailored to match a particular patient’s genome. And there is definitely a new push to extract and exploit women’s eggs.
The first published report, in Cell (online last May), was by Shoukhrat Mitalipov and his Oregon Health and Science University team. Their work was confirmed earlier this month in Cell Stem Cell by a consortium mostly from the Korean CHA conglomerate, with Robert Lanza of Advanced Cell Technology and other American contributors. A second confirmation by another research group, headed by Dieter Egli and colleagues at the New York Stem Cell Foundation, was published on April 28th as a Letter to Nature.
In all cases, the success rate was very low, and surprisingly variable. In the latest paper:
Although nuclear transfer blastocysts could be obtained with an efficiency of approximately 10%, developmental efficiency varied between different oocyte donors, even when other aspects of the nuclear transfer protocol were kept constant.
Overall, the latest experiments used 512 eggs from 35 women and developed four cell lines.
Nevertheless, these papers clearly represent a technical step forward for SCNT in humans. Other researchers are likely to adopt the new techniques, putting cloned human embryos into labs around the country. This underlines the urgent need to establish, at a federal level, legal prohibitions against human reproductive cloning. Though none of the scientists involved in these SCNT investigations supports such abuse of their work, there is clear reason for concern: A number of fertility doctors and others have made headlines with claims to be engaged in efforts to produce cloned human beings, the latest involving John Lennon’s tooth.
We also need much firmer federal regulation of the use of women’s eggs for research. Egli actually moved his work from Massachusetts to New York to take advantage of looser rules. The CHA organization has been vague about where and how the eggs they used were obtained; they may even have broken California’s law, which forbids paying for eggs (beyond reimbursement for expenses).
The sheer volume of women’s eggs required for SCNT is one of the reasons that personally tailored stem cells lines are unlikely to become a staple of medicine. (The women in the latest experiment were apparently paid about $8000 each — which comes to over a quarter of a million dollars for the four lines — and that would of course only be start of the costs involved, even for a limited application.) But that is exactly the goal that Egli has in mind, according to the Associated Press:
The new work is a step toward providing genetically matched replacement cells for transplant, said Dieter Egli of the New York Stem Cell Foundation Research Institute in New York.
“When you think about wider application of this technology for patients with diabetes, cardiovascular disease, [and others], you are talking about hundreds of millions of people. When you start talking about numbers like that, it’s just not going to be practical to use these cells in that patient-specific way.”
Indeed. Lanza’s proposed solution is to develop banks of therapeutic cells, so "you try to match tissue types, like with organ transplant now.” This is quite puzzling: It is unclear why it would require SCNT at all, rather than relying on embryonic stem cell lines derived from embryos that would otherwise be destroyed after IVF treatments. In any case, Lanza does remain committed to developing SCNT. After all, he just co-authored a paper on the subject, whose summary says:
Our study therefore demonstrates the applicability of SCNT for adult human cells and supports further investigation of SCNT as a strategy for regenerative medicine.
Despite its many dangers and drawbacks, there may be a role for SCNT in research, even if induced pluripotent cells (iPSCs) turn out to be an easier and more reliable source of therapeutic cells. Doug Melton of the Harvard Stem Cell Institute, who called the latest paper an impressive technical achievement, believes that
the cells would be useful as a research tool rather than a source of transplants. They could help scientists uncover what triggers Type 1 diabetes, he said, which could in turn lead to better therapies.
If research cloning is to be pursued, the United States must join the dozens of countries that have already established strict prohibitions against human reproductive cloning. And we must put in place firm, national and international, standards about the provision of eggs by women.
Evolutionary biologist and social commentator Richard Lewontin has written an article about synthetic biology for the New York Review of Books. (Originally behind a paywall, it now seems to be generally available.) Given the publication and the author, this ought to be good news. But it's not.
The piece is presented as a review of two documents: Laurie Garrett's article "Biology's Brave New World: The Promise and Perils of the Synbio Revolution," Foreign Affairs (Nov./Dec. 2013); and The Principles for the Oversight of Synthetic Biology, by Friends of the Earth US, the International Center for Technology Assessment and the ETC Group, endorsed by well over 100 organizations including the Center for Genetics and Society. By convention, the New York Review of Books offers a wide license to roam around a general subject, and this author seems particularly well qualified to do that.
Lewontin has for years been a prominent critic of genetic determinism, and also notable for his leftist politics. He is not only an extraordinarily distinguished biologist, but also a highly rated author of elegant little books for the general public about biology and its social implications. But this article not only fails to illuminate, it actively muddles the discussion it might have illuminated.
The start is promising, though the tone is archly magisterial, with its references ranging from Galatea to Galvanists. As his focus switches to Garrett's survey, Lewontin responds to a quote cited early in that piece:
Venter declared, "There's not a single aspect of human life that doesn't have the potential to be totally transformed by these technologies in the future." Not a single aspect! Does that mean he is promising me that I might literally live forever?
Presumably that is sarcasm, but it's hard to tell, because the subject is immediately dropped in favor of a portentous paragraph of rather hackneyed questions about resolving conflicts between "public and private good" in which "those who control and profit from material production" are unlikely to be reliable counselors.
A brief discussion of the 2011 controversy about engineering a particularly nasty flu virus pivots from a mention of bioweapons, which are Garrett's main focus, to "a broader and seemingly more constructive motivation," namely making money and new things. And this is where Lewontin brings in The Principles. And where his common sense, not to mention generosity of spirit, flies right out the window.
He starts by citing this quote from philosopher and environmental activist Vandana Shiva:
Synthetic biology, the next wave of genetic engineering, allows seed, pesticide and oil companies to redesign life so that they can make more money from it.
While it is undoubtedly true that the entrepreneurial desire to make more money motivates much of the innovation in agriculture, as in all other fields of production in a capitalist economy, there are other goals listed by the authors of The Principles for the Oversight of Synthetic Biology and any reasonable person must be in sympathy with most of them.
That's just bad writing. Is he agreeing with or trying to qualify the assertion by Shiva that he quotes? Also, the goals he finds sympathetic are not those of the entrepreneurs, they are part of what the document calls the "principles necessary for the effective assessment and oversight of the emerging field of synthetic biology."
The goals Lewontin approves are indeed the easy ones: protecting public health, worker safety and the environment; and holding corporations and manufacturers accountable. But even here, he seems skeptical to the point of cynicism about whether pursuing these objectives is worth doing. Returning to this point a bit later in his article he asserts that a "single complainant would be unlikely to procure relief." (He may be unfamiliar with the lawsuit that molecular biologist Becky McClain filed against Pfizer after she was exposed to genetically modified agents while working for the company; it took her about a decade but she won.)
Lewontin's flip interpretation of The Principles is that it "gives the impression of being primarily intended as an opportunity to challenge present societies by making generalized demands that are in direct contradiction with existing economic and social structures." For example, he highlights the goal that government bodies with the full participation of the public [his added emphasis] should develop a research agenda guided by the public interest. In response, he comments:
But the research agenda of the United States Department of Agriculture is,
and always has been, largely guided by the interest of the producers of
agricultural products and inputs to agriculture. The voters around
Manhattan, Kansas, matter more to the USDA than do the shoppers on the
Upper West Side.
The first sentence is regrettably true; the second is cute, but dumb. And why should this unfortunate and undemocratic state of affairs be left uncriticized and untouched?
Beyond that, Lewontin ridicules the idea of public engagement in these issues on the grounds that "the public" — which he puts in quotes, as if the term were strange and in itself ridiculous — "lacks the necessary technical knowledge to decide between conflicting assertions of technical experts." How true that is. And how irrelevant to ethical discussion. Not to mention that improving public engagement is now a task getting significant attention. Interesting innovations such as "deliberative democracy" are now being applied to such tricky technical and ethical issues as privacy in relation to genetic data banks.
But when Lewontin moves on to the issue of inheritable genetic modification, his disdain becomes even more apparent.
The manifesto states that "the use of synthetic biology to change the human genetic makeup…must be prohibited." This is preposterous but is stated as if it were self-evident.
He tries to justify his own preposterous assertion (which is stated as if it were self-evident) by insisting that we have "insufficient evidence of any side effects because they have not been systematically investigated" and that there is "no reason in principle" to ban single-gene alterations that are passed down to future generations. This from the man who wrote (in the same publication, in 1997):
The fallacy of genetic determinism is to suppose that the genes "make" the organism. It is a basic principle of developmental biology that organisms undergo a continuous development from conception to death, a development that is the unique consequence of the interaction of the genes in their cells, the temporal sequence of environments through which the organisms pass, and random cellular processes that determine the life, death, and transformation of cells.
The unpredictability of outcome when genetic changes are made to the human germline is a technical cause for concern — children and their mothers may suffer. It is, however, by no means the only reason for concern. The CGS web page on "Inheritable Genetic Modification Arguments Pro and Con" (see also here) provides a very brief introduction to a debate that has occupied important minds for generations, though it is only now approaching its commercial realization. This is how Lewontin returns to the topic, near the conclusion of his piece:
At the end of the discussion of public health and worker safety a passing reference is made, without any developed discussion, to the possibility of altering the human species as a whole, reminding us of Victor Frankenstein's construction gone wrong:
Any alterations to the human genome through synthetic biology—particularly inheritable genetic changes—are too risky and fraught with ethical concerns. [My italics.]
That's his argument? Italicizing a phrase and adding "[My italics.]"? I take it that he is dismissing these concerns, but he does not even deign to say so! The piece closes, immediately after that, with this magnificent insight:
The question of the relative risks and advantages of various programs in synthetic biology, like all such cost-benefit analyses, cannot be considered without asking, "The costs and benefits to whom?"
Indeed. If only he had tried to unpack that statement and elaborate it, instead of wasting his energy and our time on a glibly dismissive attack. Lewontin could have offered a constructive critique. This article is more like a ferocious assault by a comfortable cynic with a motive to target idealists who actually hope to make a difference. I had hoped for better.
Happy DNA Day! Eleven years ago today the Human Genome Project came to a close. The years since have seen countless refinements of that initial understanding of the human genome and the roles that genes do and do not play in determining who we are. These years have also served to remind us of the complexity of the universe and our imperfect knowledge of its mechanisms – how is it possible that amoebas have 200 times more DNA than we do?! Genetic determinism may finally (slowly) be starting to be acknowledged as an archaic notion, an unscientific concept that’s been impossibly muddied by all the strange ways in which the world actually works.
But perhaps this DNA Day will be remembered not for our increased understanding of the human genome, but for our increased attempts to change it.
On April 15, the US Patent and Trade Office awarded its first patent for the components and methodology of CRISPR – the “powerful new way to edit DNA,” that allows “customizing the genome of any cell or any species at will.” There are still serious technical problems to work out, but there’s no denying that this is currently one of the hottest areas in biotech research. Feng Zhang of the Massachusetts Institute of Technology, one of the recognized leaders of the field and the listed inventor on the patent, was one of Nature’s 2013 “Ten people who mattered this year,” an MIT Technology ReviewInnovator Under 35 in 2013, and recently received The National Science Foundation’s Alan T. Waterman Award.
The patent was given to the Broad Institute of MIT and Harvard, but they may well choose not to enforce it too strictly. Many other organizations are currently using the patented methodology, including the startup Editas, which was co-founded by Zhang and hopes to utilize CRISPR to treat a broad range of genetic diseases. Another founder of Editas is Jennifer Doudna, who was actually the first to uncover the multiplicity of uses possible for the CRISPR system. She and the University of California have their own patent application pending, and it’s unclear if that can be granted now.
According to MIT Technology Review, “the Broad is keeping a tight lid on their plans for the patent,” but it would be surprising if they were to opt to retain the technology for their exclusive use. Broad Institute director Eric Lander has actively criticized the idea of using patents to restrict research, in an amicus brief in the Myriad case. Also, as a member of the Global Alliance, it would be strange if Broad opted for onerous restrictions; they may see the point of holding the patent as primarily avoiding abuse of the technology (though definitions of abuse may vary).
Genetic modification got another boost recently, as the FDA just granted its first approval of a gene therapy treatment. The company Celladon received breakthrough status for its treatment MYDICAR, which showed substantial promise in its Phase 1 trial for reducing heart failure in people lacking a sufficient amount of a particular enzyme. The death of Jesse Gelsinger in 1999 caused many to take a step back from gene therapies. But a stringof recent articles have concluded that the technology is making a comeback and Celladon’s success seems to suggest that is the case.
Genome editing opens up many possibilities, but attempting to perfect what we imperfectly understand will surely lead to some unintended consequences. A new report from Tetsuya Ishii et al. in Cell titled “Caution required for handling genome editing technology” makes the case that new genome editing technologies show promise, but raise technical issues such as unforeseen toxicity, off-target mutagenesis, and mosaic modifications. The authors point out that some of the new technologies blur the boundaries of current regulations and they argue that this moment “may provide an important opportunity to form a new global consensus for future regulations in the field of genetic engineering.” Additionally, they note that “in order to achieve a better relationship between biotechnology and society, researchers must act with caution and establish a scientifically valid assessment method for evaluating organisms that have been modified with genome editing.”
As efforts to manipulate DNA ramp up, and creep into our bodies and the bodies of those we love, safeguards will be critical. The implementation of guidelines by next DNA Day would be an achievement worth celebrating.
Last week's Global Summit on Childhood in Vancouver, a gathering of some 500 advocates for children and childhood, included a session titled "Genetically Modified Babies? An Immediate Threat to Children and What Advocates Can Do Right Now"
Mothers for a Human Future's Enola Aird and I spoke about the proposal pending in the UK for clinical trials of the "three-person embryo"
technique that would constitute inheritable genetic modification. Draft regulations are being finalized now, and will be delivered to Parliament as soon as next month.
Information for delegates to the Summit - and anyone else - who would like to communicate about this proposal to MPs and other authorities in the UK can be found here. Also online are the flyer for our session and our PowerPoint presentation.
Concern about the safety, efficacy, familial and societal implications of such socially and biologically radical procedures has been growing among advocates for children and childhood. Recent commentaries include several by Enola Aird at MomsRising.org:
Synthetic biology is a fascinating area of research, but its practitioners really seem to be flailing when it comes to commercial justification. The most highly publicized product has been synthetic artemisinin, a malaria treatment, which reached the market last year but seems to be of little commercial value and is probably socially harmful — all in all, a mistake, for various reasons described below. Right behind that has been the on-again, off-again, now on-again, attention given to biofuels, which have long been "the fuel of the future, and always will be."
Now it seems that the artificial food industry is taking up the tattered banner. New Scientist recently published a useful overview of the commercial market for synthetic biology products. Colin Barras, who wrote it, identifies a variety of synthetic food additives and flavorings that are on or close to market. Unsurprisingly, none of them seems likely to feed the starving.
Valencene, a citrus flavor, is already quietly on sale, from Allylix (a California company with investment from the German chemical giant BASF) and Isobionics, which is based in the Netherlands. The same two companies also make nootkatone, a flavor (and insect repellent) originally derived from grapefruit. Other food-type products that are in the pipeline for synthetic production include:
saffron, the most expensive spice in the world, thus ripe for replacement
stevia, a zero-calorie sweetener
resveratrol, a grape-based health supplement of unproven value
But the big struggle may be about vanilla. Evolva, a Swiss company, has found a biological way to make synthetic vanillin that it claims tastes better and costs less than the chemical version that has been on sale since the 19th century. Friends of the Earth is doing sterling work alerting the public, and encouraging a consumer backlash, focused in particular on ice cream. (Their efforts include a petition to Haagen Dazs, Dreyer's, Edy's, Baskin Robbins and other ice cream makers; more information with links to a social-media campaign is here.)
Despite some obligatory greenwashing, these food-type products are being made for purely commercial reasons; the hope is that they will be cheaper than the currently sold alternatives. (Synthetic resveratrol flopped once, but Evolva hopes to improve manufacturing efficiency.)
That puts them in a different category than artemisinin, whose development was financed by a $42 million grant from the Gates Foundation; no pharmaceutical company would put up the cash. It was touted quite deliberately as a flagship product, as these three quotes from the Barras article, taken together, demonstrate:
"We thought, gosh — this is something we could make." — Jay Keasling, founder of Amryis, the company that developed artemisinin, when assessing possible molecules to synthesize
"What's more inspiring than trying to benefit that many people on the planet? It's almost like the Apollo project — it's going to get kids into science and technology." — Rob Carlson, Biodesic
"The artemisinin project is most useful because it reminded people that biology is not just a science but also a technology for making stuff." — Drew Endy, Stanford
Note that none of these even suggest that artemisinin is a good product. It's not. This article (likeothersbefore) lays out clearly that synthetic artemisinin is not needed and is hurting small farmers. Moreover, even if it were justifiable, chemical rather than biological synthesis would have been an easier and quicker approach. But making the product was never really the point; the point was to prove that the science could be commercialized — and heal the sick too. As Michael Pollan wrote in 2001 about "golden rice" (which is still not ready), it is a "purely rhetorical technology."
Amyris, the company, keeps stumbling on (check the stock price over the last five years), though there has been talk of bankruptcy. Keasling left years ago, having made some $17 million when the company went public, and the French pharmaceutical company Sanofi took over the artemisinin project. Sanofi almost tripled the efficiency of the final process with better chemistry, and is committed to "a no-profit, no-loss production model." Amyris is now working on cosmetics, fragrances, polymers, solvents and lubricants as well as fuels, with a variety of partners. Something may hit!
Artemisinin did succeed in putting synthetic biology into the public consciousness, albeit under a false flag. These food additives may be sneakier. They too may devastate the economy of large numbers of small landholders; they may or may not have negative environmental or even health effects; but, unless a sustained campaign highlights them, they are likely to fly under the radar.
And then, someone will point to them and say, "What's the problem with <my product>, nootkatone's been on the market for years?"
Richard Koo at the Bioethics blog of the Icahn School of Medicine at Mount Sinai reminds us that we were remiss last year in chronicling the ambitions of Dmitry Itskov. If the name rings a bell, it's probably because Itskov made a big splash in the U.S. in June 2013, with the "second annual 2045 Global Future Congress" held at Manhattan's Lincoln Center. (The first was held in Moscow, in February 2012.) The theme was:
Towards a New Strategy for Human Evolution
Itskov was then a 32-year-old Russian internet millionaire (not, he insisted, a billionaire) who felt unfulfilled by the prospect of mere material success. His slightly spacey shtick combined technological optimism with an emphasis on spirituality. He envisaged creating — by the year 2045 — "avatars" into which we can upload our personalities and loosen the shackles of mere corporeal reality. Spiritual self-improvement would then become the proper work of humanity. "The strategy is based on carrying out two revolutions: spiritual and sci-tech." There is still a promotional video on YouTube, detailing the path to the the era of neo-humanity.
With that, and a willingness to lay out an estimated $3 million, he gathered an endorsement from the Dalai Lama, a feature in The New York Times, and interesting speakers for his $800-a-head extravaganza, which "nearly 800" attended. The event attracted a number of the usual suspects in transhumanist circles (Peter Diamandis, Ray Kurzweil, Martine Rothblatt, Natasha Vita-More), some academics (Marvin Minsky, George Church, Roger Penrose), religious people of various persuasions, and others including James Martin, who gave the Oxford Future of Humanity Institute its start.
The man behind all this explained, in a video interview, that he himself was more of a catalyst and a visionary than a scientist:
I'm creating the concept which can further cause the public demand which can further significantly increase the speed of development of the science.
So: big splash, lots of press (in addition to The New York Times, Forbes, Motherboard, HuffPost, GEN, CNN, MIT Technology Review and more). And since then? Well, pretty much bupkis, far as I can tell. There is a website, 2045.com, which claims to have 33,816 members enrolled (via Twitter or Facebook, or any of three Russian sites). It's been updated with a few relevant news articles (none of the latest ones mention the project), but I see no hint there of a Third Congress. Maybe Itskov fell out with Putin or is off in a retreat in Dharamsala or something.
Koo's Bioethics post also mentions the recent life-extension efforts by Google and Craig Venter, and asks some sensible questions:
Should we humans be going down this road at all to seek immortality or longer life?
Do these three projects, announced within the span of a year, portend the privatization of the quest for immortality or longer life?
Can privatizing the quest for immortality and long life become problematic?
How about regulating it?
There are serious questions about relying upon the capricious whims of rich individuals to perform actual research. If Itskov has indeed dropped out of sight, that should remind us just how short an attention span can be. But … why did so many take him so seriously?
The documentary film DNA Dreams is now available in full on YouTube. You can also watch an interesting interview with the Dutch filmmaker Bregtje van der Haak here.
The film provides an unparalleled view into the inner workings of BGI Shenzhen, “the world’s largest genomics organization” that is, among other things, engaged in a controversial project to “uncover” the genetic basis of intelligence. The film is full of candid conversations with the researchers involved about their visions for the technologies under development.
For more information on this fascinating documentary, see this review.
States in blue currently allow DNA to be taken upon arrest
California's Proposition 69, which was passed in 2004, expanded the police right to collect and store DNA data. Perhaps most controversially, Prop 69 required the collection of samples from anyone arrested for a felony, which can then be kept in the database even if the arrestee is never convicted of a crime. The ACLU has been challenging this all along, as unconstitutional, and will continue to press its lawsuit despite a setback on March 20.
The California case was put on hold when the U.S. Supreme Court agreed to consider a similar but not identical Maryland law, which it eventually upheld. That ruling was narrow, and referred to "serious crimes." On that basis, the Ninth Circuit Court of Appeals in San Francisco unanimously declined to declare the collection of DNA upon arrest to be absolutely unconstitutional [pdf]. However, the ruling also suggested that there could be a distinction between "serious crimes" and "all felonies" which a lower court might consider. Judge Milan D. Smith vehemently disagreed on this point with the other ten justices, and filed a separate concurrence asserting, "This case is over."
There's an analysis of the March decision by Jennifer Wagner at Genomics Law Report and by Hank Greely at the Stanford Law and Biosciences Blog (with links to more background). Wagner suggests that legislative remedies are more likely to constrain the collection of DNA than judicial ones, and notes that efforts to provide them are underway in Sacramento. Greely thinks there may be a viable distinction between "serious crimes" and "all felonies" but is understandably reluctant to predict how future courts might rule.
Similar controversies are brewing in other states, with several recent developments. Oklahoma now seems to be reluctant to take DNA upon arrest, but Georgia will probably decide to do so. Wisconsin is fine-tuning its legislation. Overall, according to Forensic Magazine, 27 states were collecting DNA samples upon arrest in February, at least in some circumstances.
The National Conference of State Legislatures' (NCSL) DNA Laws Database shows a slightly lower number, but seems to be a little out of date, as is this September 2012 article from the Department of Justice. The NCSL's remains the most convenient searchable database. It allows searches by state and various categories, including "collection of DNA samples from arrestees," that return summaries of the relevant state law as well as the statute number.
The implementation of forensic DNA databases continues to raise concerns about civil liberties, privacy and racial justice in countries around the world. Ireland is set to establish a system shortly, and South Africa is expanding DNA collection. The patchwork of laws in the United States seems likely to remain in flux for some years to come. There may still be a possibility of establishing safeguards, but we are running out of time.
The Scientiston April 1st (but seriously) addressed the burning question, Is there a genetic component to entrepreneurial success? Biopolitical Times discussed this four years ago, when we noted that Case Western professor Scott Shane was touting a book called Born Entrepreneurs, Born Leaders: How Your Genes Affect Your Work Life.
At the time, we were gentle on the researchers but critical of the media reports about their work. This time, it’s the other way round.
The Scientist’s rundown focused again on Shane. He and others keep looking, using registries of twins and genome-wide association studies (GWAS), but the results are distinctly meager. One study, for instance, found that women inherited the propensity to become entrepreneurs, but men did not. We leave some speculation to the reader, but the researcher suggested that women face extra hurdles, so:
only those people who are really determined, who have that genetic makeup [to their advantage], emerge as entrepreneurs because of the hardship in the environment.
Men, however, make up for any genetic disadvantage by relying on social support. Lean in, guys.
Shane is now speculating that the impulse to start a business may be connected to thrill seeking. He and his colleagues found a so-called “candidate gene” that could explain — wait for it — an estimated — really — "0.5 percent of the likelihood of becoming an entrepreneur."
Perhaps they are on the wrong track. Roy Thurik, another entrepreneurship researcher, sadly concludes that "his own GWAS study also measured the wrong outcome” and he should have focused on psychology. However:
That being said, “with the wrong measure and the wrong phenotype, we came so close” to identifying candidate genes.
How close? Well, so close.
Shane’s book is still available but The Scientist didn’t give it a plug.
A “DNA sweep” or “DNA dragnet” refers to the practice of police officers asking large numbers of people to voluntarily give DNA samples in order to help solve a crime. It is a controversial practice that is infrequently used because it can easily impose on what the New York Times has called “constitutional protections against compelled self-incrimination and unreasonable search and seizure.”
The principle that participation is voluntary is fragile, since refusing is interpreted by at least some police officials as itself constituting probable cause for the search. When DNA collections occur at a workplace, particularly when workers’ employment is insecure, people can face particular pressure to comply.
This was the case in a recent DNA sweep in Ontario, Canada, in which police officers went from farm to farm asking migrant workers, many of whom varied significantly from the description of the suspect, to submit their DNA for an investigation into a violent sexual assault. A complaint has now been filed with the Office of Independent Police Review Director, alleging misconduct and racial profiling.
“Despite the fact that the police had specific details about the suspect that should have narrowed the scope of the investigation (i.e. height, age and physical appearance), all black and brown migrant workers were approached during the DNA sweep,” the complaint states…
“If the police are permitted to conduct an investigation without respect of our rights and engage in deplorable practices such as arbitrary detention and racial profiling, then our legal rights to be presumed innocent until proven guilty will be reduced to nothing more than an empty slogan.”
Justicia for Migrant Workers, a group that found and interviewed 44 of the 100 people who voluntarily gave samples, learned that roughly half of those they spoke to were shorter than the specified height of the suspect, and about half were older than 41, when the suspect was said to be in his twenties.
A review of the Ontario Provincial Police department is now underway. The results will be made public in about six months.
Although DNA can be an important tool for solving crimes and exonerating the innocent, the very nature of a large-scale DNA sweep is imprecise and legally questionable. The ease with which a DNA sweep can cause harm to innocent people and increase discrimination against minority communities and impoverished neighborhoods ought to seriously limit its use by a reputable police force.
On March 20, I participated in Saint Mary’s Hall high school’s annual Issues Day in San Antonio, Texas. The topic this year, chosen by a committee of the junior class, was Genetic Engineering: Conscious Evolution or Immoral Technology? (See the program here.)
The other speakers were Daniel Eichner, Executive Director of the Sports Medicine Research & Testing Laboratory; Ron Epstein, Professor Emeritus of Dharma Realm Buddhist University; Doug Frantz, Associate Professor of Chemistry at The University of Texas at San Antonio; Linda MacDonald Glenn, Assistant Professor at the Center for Biomedical Ethics Education and Research, Albany Medical College; and Jeffrey Steinberg, Director at The Fertility Institutes.
Each of the speakers came to the question from a different perspective, which provided for fascinating presentations and a rich, passionate debate during the “crossfire” that followed. Students tweeted their questions to a shared Twitter wall and David Henderson, Chief of the DWI Task Force at the Bexar County District Attorney’s Office, moderated the lively discussion.
The students who chose the topic of human genetic engineering for the event recognized the importance of grappling with this question now, as new technologies and potential changes in policies around the world could make a procedure that constitutes human germline modification a reality this year.
I was happy to participate in the event and have the opportunity to discuss these important issues with so many bright young people. Photos of the event will be available soon; join CGS on Facebook to view them when they do.
Posted by Diane Beeson, Biopolitical Times guest contributor on March 26th, 2014
For millions today, the concept of family is being redefined. Modern assisted reproduction techniques have enabled infertile couples (straight or gay) and people without partners to have children, and to be genetically related to their children, but in a non-traditional way.
These children have a genetic link to only one parent, while also being genetically related to a person not involved in their upbringing – the “donor” of sperm or eggs, who often remains anonymous. Such arrangements, which have become increasingly common over the past couple decades, raise an important question for those conceived via “donor” egg or sperm: Is secrecy about their origins in the children’s interest?
A new “donor community” is emerging to challenge the secrecy that the authors argue has too long surrounded sperm, egg and embryo donation. Donor-conceived offspring are using communication and genetic technologies to search for, and find, their sperm or egg donors, half-siblings and other genetic relatives.
No one has been more influential in this movement to end donor anonymity than author Wendy Kramer, who with her son Ryan founded the Donor Sibling Registry. In this stunningly honest book, she and her coauthor, family and adoption law expert Naomi Cahn, make a compelling case that secrets have a corrupting influence on family life.
Opponents of openness justify their position with the argument that what matters is the social relationship of the intended parents to the offspring, not the genetic tie to the donor. Yet, as the authors make clear, this is a highly hypocritical stance given that many families choose donor conception over adoption precisely because they want at least one parent to have a genetic connection to their child.
The authors draw on the experience of many donor-conceived offspring and their family members to convincingly argue that openness about donor conception is the best path to strengthening bonds with social parents and other family members, as well as providing more complete medical information. Openness, in their view, is essential to the self-esteem and healthy identity formation of the donor-conceived child and adult.
Chapters in the book are specifically addressed to parents, offspring, and prospective parents. Personal experiences of many members of the “donor community” are interlaced with research findings and sensitive advice for negotiating the social and emotional challenges of each stage of the process of disclosing donor conception, searching for, and connecting with genetic relatives. Moving accounts of Wendy and her son’s often frustrating, but ultimately successful, search for his anonymous donor and the discovery of half-siblings keep the reader turning pages.
The authors stop short of questioning the unbridled commercialization of human gametes in the US. They accept the euphemistic use of the term “donation” for what are, in fact, sales of eggs and sperm — usage that reveals our cultural ambivalence about these practices. Yet they acknowledge the discomfort among some donor offspring that one’s biological parent “so easily sold their genetic heritage.”
The concluding chapter makes six excellent recommendations for reforms related to the fertility industry, the most significant being a call to end donor anonymity. If implemented, these would go a long way toward humanizing reproductive medicine in the US and bring us more in line with practices in other developed nations.
The letter points to the risks and cautions that emerged in discussions by members of a US Food and Drug Administration Advisory Committee at last month’s meeting about the safety and efficacy of “mitochondrial manipulation” techniques that would constitute a form of human germline engineering. In particular, the letter notes that after some eleven and a half hours of discussion, the FDA concluded that more animal and in vitro data is needed prior to any human trials.
Based on a review of the HFEA’s published documents, it appears that a number of the concerns raised by the FDA advisory committee may not yet have been fully considered in the HFEA’s past reviews.
The HFEA’s “Call for evidence” was apparently posted quietly on March 7, with responses due just two weeks later on March 21.
The HFEA now has an opportunity to carefully examine this information. Its review of the current scientific evidence about the safety and efficacy of so-called “mitochondrial manipulation” techniques will be sent to the Department of Health in May, and then presented to the Parliament when it votes on the issue later this year.
Please see the letter to the HFEA review panel here. For much more information on this issue, see CGS's "3-Person Embryo" resource page.
If you agree with its concerns, or have other safety and efficacy issues that you would like to bring to the attention of the HFEA panel, we encourage you to email them to the Mitochondria Review Policy Team at firstname.lastname@example.org.
Notwithstanding the March 21 deadline, we hope the review panel will consider all the communications it receives.
New DNA-editing technology spawns bold UC initiative The University of California, Berkeley, and UC San Francisco are launching the Innovative Genomics Initiative (IGI) to lead a revolution in genetic engineering based on a new technology already generating novel strategies for gene therapy and the genetic study of disease.
UC Berkeley, UCSF Use $10M Gift to Launch CRISPR Initiative, Center
The project is the latest of several initiatives to explore the potential of the Crispr gene-editing technology. Executive Director Jennifer Doudna was one of the founders, late last year, of Editas, a commercial venture based on the same research. Also announced by UC Berkeley was an Entrepreneurial Fellows program, which "will coordinate with the QB3 Startup-in-a-Box program to help launch new companies that address important societal challenges and create new jobs in California."
The UC campuses are putting up $2 million total; the $10 million is coming from the Li Ka Shing Foundation, which was set up by Asia's richest man. The foundation was reported in 2012 to have assets of $8.3 billion (it made a bundle on Facebook and other high-tech investments), while Li Ka-shing personally is said to have assets of $31 billion.
The Foundation has been involved with UC Berkeley for several years, having put $40 million into the Li Ka Shing Center for Biomedical and Health Sciences, which opened in 2012. It has also been active at Stanford University ($37 million) and in January announced a $3 million grant for a joint venture between Stanford and Oxford University. Altogether it has dispersed at least $1.6 billion.
In 2013, the usually publicity-shy billionaire attended the launch of the £20m (about $33 million) Li Ka Shing Centre for Health Information and Discovery at Oxford with Prime Minister David Cameron. (His British connections go back to the days when Hong Kong was a colony; he was knighted in 2000 [pdf] for "services to British industry and to medical research.") The link with Stanford is a natural outgrowth of this enterprise.
The Oxford project is a controversial "big data" center, which has been criticized by, among others, Helen Wallace of GeneWatch UK for showing "a shocking disregard for democratic processes and for people's right to choose where their personal and genetic information can end up, and how it can be used."
By coincidence, the New York Times published a long article on March 15 titled:
Billionaires With Big Ideas Are Privatizing American Science
We may be sure it's a coincidence because the article mentioned two dozen major philanthropists by name – but not Li Ka-shing. Several other prominent donors were passed over too, including stem-cell activist Jim Stowers (who died on March 17); John Templeton, whose foundation focuses on connecting science and religion; John Sperling, who provided the original money behind pet cloning; and Peter Thiel, whose largesse has favored the Methuselah Foundation, Humanity Plus, the Seasteading Institute and the Singularity Institute among others.
Which rather underscores the message that science funding is, at the least, at risk of being seriously distorted by the charitable efforts of a few very wealthy people. The Times piece estimated the combined fortunes of 18 of those mentioned as $390 billion. That is more than ten times the annual budget of the National Institutes of Health.
Together, they could practically replace the NIH, and they are already "terrifically important," as NIH director Francis Collins admits.
Bill Gates has been signing up lesser billionaires to pledge to give away most of their fortunes; he has about 100, says the Times, pledging to give away over $125 billion. Among the goals: eradicating diabetes; vanquishing cancer; maintaining the competitive edge of American science.
Without wishing to look gift horses in their mouths, it's nonetheless easy to criticize these mostly elderly men for trying to stave off aging (Larry Ellison, the Google guys) or even seeking immortality (Thiel). And it may be understandable that they seek cures for their own prostate cancer (David Koch, Michael Melkin) or their children's diseases (Eli Broad, among others) or the Parkinson's that Sergey Brin may fear is looming. But there is a bigger distortion, and a harder one to counteract: the focus on technology and on tangible structures in general – buildings, computers – rather than on social processes and values, and the way we implement them through government.
Another article in the same newspaper, on the same day, described the "longevity gap" between Fairfax County, Virginia, and McDowell County, West Virginia. Fairfax is rich, with a median household income of $107,000; McDowell has a median income about one-fifth as much ($21,574). Men live 18 years longer, on average, in Fairfax; women, 12 years longer.
As a society, do we want to do something about that?
Genomics is important science, and Crispr technology may eventually be useful. But high-tech personalized medicine, if and when it appears, is almost certainly not going to benefit the residents of McDowell County, or any area of generalized poverty, in the short or even medium term. Well-directed interventions based on current medical knowledge, however, might.
Funding issues are bubbling to the surface, in part because of continuing pressure to cut government spending. Corporate funding of research is increasing; a March 19 article in Nature argues that this is a good thing (though many are wary). In the UK, some scientists are expressing concern that too-specific grants may hinder innovative science. And Craig Klugman, at Bioethics.net, warns about the effect of "the new patrons of science" who demand practical results:
The challenge for scientists is that funding is in many ways less assured than with the federal grant system. If a patron does not like what comes out of the lab, becomes disenchanted with a person, becomes interested in different issues, experiences a decrease in wealth, or is tired of waiting for results, the money can dry up over night.
A just-completed poll has found that the UK public is deeply conflicted about the UK government's move to legalize the creation of "3-person embryos."
The techniques under consideration – now called "mitochondrial donation" by the U.K Government – could allow a woman with a rare form of mitochondrial disease to have a healthy child that looks like her, but would mix-and-match the genetic material of three different people and result in risky inheritable changes to every one of the resulting child's cells.
The Human Fertilisation and Embryology Authority (HFEA) held a public consultation on the social and ethical concerns of what they called "mitochondria replacement" last year that also revealed deep uncertainty about allowing this experimental technology. The majority of people who responded to the largest (and only open) part of the HFEA's consultation said they opposed the legalization of the techniques. Unfortunately, for some reason the HFEA nonetheless represented the final results of that consultation as showing "broad support."
The just-completed poll was commissioned by the Christian charity CARE, and conducted by the market research agency ComRes, whose other clients include BBC, British Red Cross, Oxfam, and Lloyd's Banking Group.
The Government has suggested that the public is broadly supportive of the creation of three-parent children. This is certainly not the finding of our professionally conducted, representative polling.
The new poll found that
More women oppose the introduction of highly controversial techniques to help reduce the chances of women with human mitochondrial disease passing it on to their children than support it.
The poll asked 2,031 people three sets of questions. Overall, 35% supported changing the UK law to permit "3-parent embryos," 34% opposed it, and 31% said they didn't know. But out of the women who responded, who made up 52% of the total, only 31% supported the change while 36% opposed it.
Additionally, when people were told that "a number of scientists in the UK and abroad have expressed concerns about the safety of the procedures for the children conceived and any children they might go on to have," 41% of participants said they were less likely to support the legalization.
Participants were then asked whether they agreed or disagreed with a series of statements, which included the following:
Introducing regulations to permit 3-parent embryos is a welcome development at the current time.
Only 22% agreed. 38% disagreed and 41% said they didn't know.
Taking into account all the other pressures on Government, it is right for the Coalition Government to introduce regulations to permit 3-parent embryos at the present time.
Only 18% agreed. 41% disagreed and 41% said they didn't know.
Given that it's currently illegal to grow most GM crops for commercial purposes on the grounds of safety, it ought to be illegal to create genetically modified children.
Only 20% disagreed. 44% agreed and 36% said they didn't know.
These polling results were announced at a parliamentary meeting held at Westminster Hall on March 12 by Conservative MP Jacob Rees-Mogg. He spoke passionately against the techniques, calling them "a multi-generational experiment with the lives of people" and pointing out that tests the HFEA had previously said should be conducted before any clinical trials have not yet been done.
CARE Chief Executive Nola Leach pointed out that
No mother wants to give a child human mitochondrial disease but neither do they want to give them potentially debilitating chromosomal abnormalities.
These new data and resources are a welcome addition to the ongoing discussion about these techniques. According to Health Minister Jane Ellison, MPs will be allowed to come to their own conclusion and vote with their conscience at the parliamentary vote that will follow the conclusion of the now open consultation in a few months time.
For more than a decade scientists have been saying that a genomic revolution will transform medicine, making it possible to scan all of a person's DNA to predict risk and customize medical care.
Well, we've got the machines. Where's the revolution?
Researchers at Stanford University have helped explain the hold-up in their just-published report in the Journal of the American Medical Association (JAMA).
The report describes a study that sought to identify the strengths and weaknesses of the clinical application of whole genome sequencing. Twelve healthy adults were sequenced and each was found to have between two and six genetic mutations that are linked to disease. Arguably, that knowledge is a strength, but there were some clear weaknesses.
Nine of the 12 participants had their initial Illumina Inc results confirmed by a second company, Complete Genomics Inc, in order to evaluate the reproducibility of the results. It was found that
fewer than one-third of insertion/deletion variants in inherited disease genes were confirmed by the second sequencing platform.
Additionally, it was found that
Depending on sequencing platform, between 10% and 19% of inherited disease genes were not consistently covered at a read depth that was sufficient for a comprehensive survey of genetic variants.
Due to the inconsistency of the data, the study clinicians were unsure what to report to the participants, and often disagreed among themselves about what further action to recommend.
One participant discovered she had a mutation in the BRCA1 gene, and chose to have her ovaries removed as a preemptive measure against the greater risk of ovarian cancer that mutation confers. No other actionable results were mentioned.
The study concluded that there are major challenges to be overcome before whole genome sequencing (WGS) can be utilized in a clinical setting. It states that WGS is
associated with incomplete coverage of inherited disease genes, low reproducibility of genetic variation with the highest potential clinical effects, and uncertainty about clinically reportable WGS findings.
The PHG Foundation also recently put out a report about the clinical use of whole genome sequencing that highlighted a number of “challenges to delivering reliable and useful results and the potential risks to patients and the health service if these challenges are not overcome.”
However, when we note the challenges of WGS becoming useful in a clinical setting, we shouldn’t automatically assume that overcoming them will lead to the most desirable outcome. While genetic testing companies and drug companies have a powerful economic incentive to market this product to new customers, it’s certainly possible that what makes sense for patients is to keep WGS for specific purposes.
The shift that WGS promises is to a focus on personalized health care based on a complete understanding of one’s genes. But it is also a shift to preventative care for diseases that may or may not ever show up. While some people will appreciate this knowledge, others may feel burdened by it. Not everyone wants to know they have a heightened risk of dying from a disease they can do nothing to prevent.
Anne Wojcicki, CEO of 23andMe, likes to make the argument that personal genomics will drive healthcare costs down, but there’s no evidence of that. The cost of the sequencing and the interpretation for the JAMA study (not including the downstream costs of clinical tests and referrals) came out to about $15,000 per participant. While this is significantly less than the costs of WGS used to be, it’s still a lot of money for very little useful information.
Donna Dickenson makes the argument in her book Me Medicine vs. We Medicine that while personalized healthcare shows potential in some cases, it can come at the cost of our commitment to public health initiatives. A comment from Geraldine Merola on the NPR article highlights the point,
$15K each and they tested 12 subjects to find 1 mutation that may or may not lead to breast cancer... $180,000 is an awful lot of mammograms!
Posted by Miriam Zoll, Biopolitical Times guest contributor on March 12th, 2014
Data about the risks involved in high-tech assisted reproduction have
until recently been scarce. The industry naturally touts success rates
and downplays failures, and the Centers for Disease Control and
Prevention (CDC) has largely been restricted to sharing only
self-reported data from clinics with the public. But this is
changing—and families intending to use these technologies should be
aware of the full implications of the statistics that are available.
month, for instance, the Society for Assisted Reproductive Technologies
announced that a record number of babies were born – 61,740 – as a
result of the 165,172 in vitro fertilization (IVF) cycles performed at
379 of its member clinics in 2012.1
On the surface,
this announcement may be perceived as an endorsement for the success of
reproductive medical services that have, undoubtedly, helped many
couples over the last 35 years to bear the children they might otherwise
not have been able to. As we celebrate the births of these babies,
however, it is also important to recognize that the vast majority of IVF
cycles continue to fail, and that not all infants born from these
procedures are healthy – or even survive.
In the U.S., the CDC
collects the most comprehensive (though self-reported) data. The CDC’s
preliminary 2012 data, from 456 infertility clinics, shows an overall 71
percent failure rate per cycle nationally.2 Of the 176,275 women who underwent ART cycles that year, only 51,294 experienced a live birth, which is defined by the CDC as:
a delivery in which at least one fetus was live born … regardless
of gestational age at birth … These signs of life include breathing,
beating of the heart, pulsation of the umbilical cord, or definite
movement of the voluntary muscles.3
The UK Department of Health has released draft regulations and begun a three-month public consultation for what it terms “mitochondrial donation.” After the consultation concludes, final regulations will be written and then put before Parliament for a vote. According to media reports, it is possible that licensed fertility clinics in the UK could offer the techniques before the end of this year.
These controversial oocyte and embryo manipulation techniques, which would result in trans-generational changes to the human genome, have also been widely covered in the US media recently. Last week’s FDA public meeting to discuss them coincidentally took place two days prior to the UK’s announcement, which had been expected for months.
Certainly, each country is watching the other. Perhaps neither is quite sure it wants to be the first to violate the widespread international agreement against modifying the human germline, and incur the controversies that will inevitably ensue. But there also are those in both countries who are eager to stay at the forefront of a new biomedical field.
If the FDA pays any attention to what came out of its advisory committee meeting, it will require much more substantial research to be carried out prior to human clinical trials. For now, the UK is further along in its policy process. Unless members of Parliament are made aware of the many social and safety concerns raised by these techniques, a “rubber stamp” vote could be in the works. Based on the 47-page document the Department of Health has released, there are many reasons for concern.
MISREPRESENTATIONS IN THE SUMMARY
What should we call it? One of the document’s misrepresentations is its title. “Mitochondrial Donation” is the most euphemistic terminology for these techniques I’ve seen. As the document acknowledges, it’s not mitochondria that are being moved around; the techniques actually involve “the transfer of nuclear material between eggs and embryos.” And, of course the term “donation” is a well known euphemism for what really occurs in the market for women’s eggs.
How many people are affected? The “Executive summary” gets off to a bad start. The second and third sentences say,
“It is estimated that 1 in 200 children are born every year in the United Kingdom with some kind of mitochondrial DNA disorder. Serious mitochondrial disease can have a devastating effect on families including the premature death of children, painful debilitating and disabling suffering, long-term ill-health and low quality of life.”
This framing will certainly encourage readers’ sympathy for anything that can lessen this level of devastation. But it is extremely misleading. While it is true that about 1 in 200 people have some kind of mitochondrial mutation, the vast majority are completely healthy. Most accounts clearly acknowledge this. But you have to make it to page 41 of the Department of Health’s document to come across the explanation that
“Mitochondrial disease currently affects around 12,000 people in the UK, with one in every 6,500 babies born with a form of the disease. The technique being legalized here will apply to the most severe cases in the first instance. An estimate provided by the Wellcome Trust Centre for Mitochondrial Research at the University of Newcastle suggests mitochondria donation treatment could apply to up to 10 cases per year initially.”
That paints quite a different picture.
GM humans? The document’s sole mention of the highly problematic fact that, if approved, these techniques will result in genetically modified babies, is in one paragraph that states that they would “only substitute, rather than alter” DNA. Though this is an important distinction to make in writing regulations, the child’s DNA will be altered. In fact, the paragraph concludes that “it would though be a form of germ line modification.”
Is there really public support? In its discussion of last year’s public consultation conducted by the Human Fertilization and Embryology Authority (HFEA), the document does note that the majority of people who responded to the open questionnaire (which – with over 1,800 responses – had by far the largest numbers) were opposed to the technique. But it downplays the importance of this fact, saying that these views were from “a self-selected sample,” as if that should discredit them. On the contrary, the fact that this was the only section of the public consultation in which participants were not hand-selected by those in charge of the process says a lot.
What will it cost? A truly fascinating part of the document is the section that projects what these procedures would actually cost for the women who are interested in them. The estimated cost of a successful “mitochondria donation treatment” is £80,000 (about $133,000). This cost accounts for two rounds of standard IVF to extract eggs from two women, one round of PGD to test for the presence of mitochondrial disease in the extracted embryos, and an assumption that it will take four cycles to generate a successful conception.
This price tag puts the proposed treatment out of reach for most people. Further, the document notes that “it is possible that this is an under-estimate of the actual cost.” That does seem likely, since there are important differences from traditional IVF that would likely drive up the costs. Finding egg donors would be more time consuming and expensive because each would have to undergo additional examination to make sure they have no mitochondrial mutations of their own; only a handful of embryologists have the skills to carry out this procedure; and it seems highly unlikely that success rates using these techniques would mirror those of traditional IVF. CONCERNS WITH THE REGULATIONS
As the Department of Health document explains, when the UK in 2009 decided that the country’s law prohibiting human germline modification could be amended to allow mitochondrial manipulation techniques down the road, “the Government of the day gave an assurance that such regulations would not be made until any proposed techniques were considered to be effective and safe for use in treatment.”
“The techniques have not passed the necessary safety tests so it is unnecessary and premature to rush ahead with legalization.”
I agree. Nonetheless, here are some comments on the draft regulations as they currently stand.
Less risky alternatives. The Department of Health’s draft regulations set two preconditions for eggs and embryos that can be used in this procedure: they must have a particular risk of mitochondrial abnormality, and there must be significant risk that a person with this abnormality will develop a serious disability or illness. I think a further condition ought to be set: that there are no safer alternatives available. Given the UK clinics that already offer embryo screening (pre-implantation genetic diagnosis, or PGD) for the prevention of the transmission of mitochondrial disease, and the growingevidence of its efficacy in most cases, candidates for oocyte or embryo modification should consider it first.
Mandating no disclosure to children. The draft regulations state that at the age of 16, a person who thinks they were born following this technique could ask the HFEA for confirmation and view information on their donor’s medical history, but would not be given access to the donor’s identity. The regulations also say that women who provide their egg cytoplasm and mitochondria are determined to be “not related to any children who were, or might have been, born following treatment services using their donation,” so
“therefore no provision is made to allow access to information in connection with entering into a marriage, civil partnership or intimate physical relationship, nor to access information about other children who share the same donor.”
This seems short-sighted. Even though the HFEA thinks that mitochondrial donors should be treated more like organ donors than gamete donors, we don’t know whether any kids that are born will feel the same way. WHAT’S NEXT?
Though the chances might be low, I do think it’s possible that the UK will decide not to move forward with these experimental techniques. The document notes that
“The Government has decided to proceed with regulations. However, before taking the decision to submit regulations for the scrutiny and approval of Parliament, we will ask the HFEA to reconvene the Expert Panel a further time to provide an updated assessment of the safety and efficacy of these techniques.”
It adds that “When the amendment was made no commitment was given on a timescale for making regulations,” and in response to opposition at that time, it was determined that they would only be used “once the techniques involved were considered to be effective and safe for use in treatment.”
Could this be a hint that some of those involved want a potential out? The safety and efficacy of mitochondrial manipulations were just considered in detail at the FDA meeting, and a long litany of problems emerged. Hopefully, the UK Department of Health and the members of Parliament will take note. For that reason, taking part in this public consultation may turn out to be very important.
An FDA committee held a historic public meeting last week to discuss the scientific, technologic, and clinical issues related to experimental procedures that would alter the human germline. The February 25-26 meeting of the Cellular, Tissue, and Gene Therapies Advisory Committee was webcast live, and will be available in archived form in a couple of weeks.
What was most striking about the meeting was that the committee members, many of whom are scientists themselves, are so wary of the techniques at this time. Questions about efficacy and safety – in fact a litany of concerns about every aspect of these techniques – largely dominated the discussions. And although the FDA’s pre-meeting briefing document explicitly put social and ethical issues outside the scope of the discussion, a myriad of these problems also edged their way in.
I highly recommend watching the webcasts – particularly the afternoon session of the first day, which included public comments, discussion by committee members, and a summary of the deliberations by chair Evan Snyder. But if you don’t have time for that, please read on for an overview of what transpired.
The beginning of the first day was devoted to scientific presentations, most by researchers who are developing mitochondrial manipulation techniques: Gerald Shadel of Yale University, Salvatore DiMauro of Columbia University, Marc-André Sirard of Université Laval, Keith Latham of Michigan State University, Shoukhrat Mitalipov of Oregon Health and Science University (OHSU), Dieter Egli of Columbia University and the New York Stem Cell Foundation Research Institute, and Mary Herbert of Newcastle University.
The work described by Mitalipov at OHSU and by Herbert at Newcastle University has enjoyed the lion’s share of media attention. Their labs have been conducting animal and in vitro research on spindle transfer and pronuclear transfer, two of the mitochondrial manipulation techniques proposed as ways to enable women affected by mitochondrial disease to have unaffected and genetically related children. Both research teams are eager to move to human clinical trials in their respective countries.
After the research presentations, time was scheduled for public comments from people who had contacted the FDA in advance. Seven people were each given four minutes to speak; among them were Marcy Darnovsky, Executive Director of the Center for Genetics and Society; Jaydee Hanson, Director of the International Center for Technology Assessment; Stuart Newman, Professor of Cell Biology and Anatomy at New York Medical College; Enola Aird, Founder and Director of Mothers for a Human Future; and Sheldon Krimsky, Professor of Urban & Environmental Policy & Planning and Public Health and Family Medicine at the Tufts School of Medicine. (Links on their names go to samples of their writings on this issue.)
Not one member of the public spoke in favor of the techniques. The points raised by the speakers included these:
If the FDA were to approve these techniques, it could be the first time any jurisdiction in the world had authorized intentional genetic modification of children and their descendants, and the agency would be making this decision with little or no input from the public or elected officials.
The FDA is the wrong agency to have jurisdiction over such techniques.
These techniques could be a gateway technology for human cloning and germline engineering.
Any child resulting from this procedure would develop from a fertilized egg in which the non-mitochondrial maternal genes derive from a second woman, the intended mother, a situation with potentially harmful biological incompatibilities and deleterious trans-generational impacts.
Approval of clinical trials would represent an unprecedented level of human experimentation for which there can never be truly informed consent.
These techniques would pose risks to young women recruited to donate their eggs.
Preferable alternatives for having healthy children are available to the small number of women who would be candidates for these techniques.
These techniques may not be specific enough to prevent further attempts at inheritable genetic engineering.
There has already been “mission creep” in proposals for applications of these techniques: the discussion has moved from considering them solely for the prevention of serious disease to also considering them for some cases of infertility.
The committee’s discussion followed. While different members seemed to lean in different directions about whether the techniques should move to clinical trials – some seemed in favor, some against, some undecided – the discussion was notable and informative because of the range and seriousness of the safety concerns raised by a large majority of them. (A roster of committee members gives their titles and affiliations.) Linda Dahlgren pointed out that data for clinical trials are not sufficient, and that the studies carried out so far have limited relevance as a proof of concept. Douglas Diekema said that, as head of an IRB, he would need to see larger sample sizes and long-term follow-up in the animal studies before he would be able to give approval. Sharon Reeder spoke as a woman who has mitochondrial disease about the huge physical toll giving birth took on her body, landing her in a wheelchair. She noted that it’s extremely challenging for children to live with chronically ill parents, and that she hopes more research will be done on treatments for people who already have mitochondrial diseases.
Larry Couture pointed out that we can’t predict the impact of these kinds of modifications down the line and that grading blastocysts is a not a good enough measure of health. He also refuted the argument that babies born to mixed-race couples could tell us anything about the health of babies resulting from these experiments, since they have inherited genes from two, and not three, people. Steven Goldman noted that in vitro trials will need to be very specific about which mutations in which tissues they are supposed to be treating, adding that the variability of mitochondrial diseases may make rigorous interpretation of clinical trials impossible. Tabassum Ahsan pointed out that better metrics would be needed for quality control of donor oocytes, and that it will be very difficult to define success in any trial. Timothy Cripe asserted that the bar for any pre-clinical trials will have to be high, given that this isn’t a treatment for sick people.
David Keefe’s remarks were particularly compelling. Apologizing for quoting Donald Rumsfeld’s notorious comments about “weapons of mass destruction” in Iraq, Keefe said, “There are things we know. There are things we don’t know. And there are things we don’t know we don’t know.” As a reminder, he cited the outcomes of DES and thalidomide, and argued that we must tread lightly. He asserted that using the techniques in question to treat infertility “should be taken off the table” and added that even using them to prevent the births of children with mitochondrial disease is a “very very slippery slope.” He pointed out that the US doesn’t regulate the fertility industry like the UK does, and that sick patients will put their trust in their doctors, who have a responsibility not to give them false hope.
Katharine Wenstrom reiterated that these patients are particularly vulnerable and that pregnancy for women with mitochondrial diseases can be extremely dangerous. She added that the inability to know whether the techniques had caused new problems for a child would be a huge burden for parents. John Gearhart expressed frustration over the term “mitochondrial manipulation or replacement” since technically it is nuclear replacement, or egg/embryo manipulation. Renee Reijo Pera commented that without first trying to develop techniques to see whether affected women might produce healthy eggs, we’re “over-engineering.” She noted the de facto “pact” against genetic manipulation of human embryos, and later told USA Today, "I just don't think that this is an avenue that we should pursue in humans."
In his summary remarks, committee chair Evan Snyder concluded that the discussion’s common theme had been the shared concern for the well-being of children born as a result of mitochondrial manipulation techniques. The sense of the committee, he said, was that there is not enough data either in animals or in vitro to move on to humans, and that these concerns involved both the preclinical data and the basic science. He asked: Are there better alternatives? What’s the unmet clinical need? And is this worth the risk? Acknowledging that some committee members found the data “very intriguing,” he went on to note that many felt that no one research model would be perfect. He added that long-term follow up in animal studies, of larger sample sizes, will be crucial; and that some studies may need to be mutation specific.
What will the FDA do next? The agency has not actually revealed whether it has received any formal proposals to approve clinical trials. And though it is not required to follow the guidance of its advisory committees, it often does. After the meeting, FDA press officer Jennifer Rodriguez told Reuters, “We have heard the concerns expressed at the advisory committee meeting, and will take the information back to consider whether we need to facilitate a public discussion and, if so, how best to do this.”
Chair Evan Snyder told reporters that he does not think the committee or the FDA will address the topic again within the year, though it will likely come up again after more animal research has been completed.
Craig Venter, the genomics and synthetic biology pioneer, launched a new company on March 4, Human Longevity, Inc. (HLI). The press release describes it as:
a genomics and cell therapy–based diagnostic and therapeutic company focused on extending the healthy, high performance human life span
HLI has raised $70 million, enough for 18 months of operations, partly from Illumina, which makes genome sequencing machines, two of which HLI has bought so far. The rest is from a few venture capital companies and/or individuals (details are sketchy), several of whom have invested in Venter's Synthetic Genomics company, which he will also continue to run.
Diamandis seems to be the main fundraiser, which may explain the investment of the noted transhumanist Martine Rothblatt, who inter alia was executive producer of the documentary The Singularity Is Near. Hariri is a trustee of the J. Craig Venter Institute and on the advisory board for the Archon Genomics X Prize, which is chaired by Venter and connects them both with Diamandis.
The new company already has partnerships with the Venter Institute, Metabolon Inc., whose Scientific Advisory Board is graced by Venter and his colleague Hamilton Smith, and the University of California, San Diego, which has four representatives on the HLI Scientific Advisory Board.
"Stay tuned for more announcements on the stem cell side."
HLI seems to be squarely focused on the growing contingent of aging, and sometimes affluent, baby boomers. According to The New York Times:
Dr. Diamandis said the goal was not to make people live forever, but rather to make "100 years old the next 60."
It's not entirely clear how they are going to do that, but genome sequencing certainly comes into it. Venter has spoken casually about sequencing everyone in the country, with one focus being to find protective alleles: he himself has a "slightly increased risk" for Alzheimer's but shows absolutely no sign of amyloid plaque buildup (about 5:00 in this video), so "obviously, I have genes that are protecting me from getting Alzheimer's disease."
Stem cells are somehow relevant, and HLI will be sequencing cancer tumors as well as whole genomes. However, when pressed by Science writer Elizabeth Pannisi (on the conference call) as to how they could legally and ethically make commercial use of patients' data gathered for research the best Venter could come up with was:
"We're still working out a lot of these issues."
They face some stiff competition, including:
BGI, the Chinese sequencing behemoth, which leaked plans for a partial $400 million IPO later this year, also wants to sequence the world (don't miss the movie); Venter claims that his Illumina machines are newer and better than BGI's Illumina machines but "we can't have enough players."
Editas, the genome editing company founded by, among others, George Church, may overlap with Venter's market. Church seems skeptical about HLI, whose plan he thinks is "all over the place."
Knome, a whole-genome-analysis company (founded by, among others, George Church) closed a $13 million financing round in January.
P5, a Sony-Illumina-M3 collaboration, was supposed to launch in February; it may be delayed but it seems to be part of a well-thought-out effort on the part of Sony to move heavily into the emerging high-tech medical market.
Venter, of course, is undaunted. He still firmly believes in the medical and commercial benefits of genomics. Asked if his vision for HLI was the same as his vision for Celera back in the 1990s, "where information from genomes would be sold to subscribers to lead to new therapeutics and diagnostic tests," he replied:
"This is Celera on steroids and cocaine."
Really? That's an ill-advised metaphor. How much better the company will do than its predecessor remains to be seen. Are Venter, Diamandis and Hariri talking themselves, as well as their investors, into a technophile fantasy of genetic omnipotence?
Posted by Osagie K. Obasagie on February 27th, 2014
The trial of former American exchange student Amanda Knox captivated much of America a few years ago – at least those who are fans of Nancy Grace. Her conviction for murdering housemate Meredith Kercher in Italy and subsequent acquittal were daily fodder for many newsfeeds. Thus, it should be no surprise that her retrial and recent conviction for the very same murder has rekindled the obsession that many have with this case.
Central to the inquiry is what, if any evidence, links Knox to the Kercher murder. Knox’s retrial led to new DNA tests on a knife that prosecutors said could be the murder weapon. But Greg Hampikian – founder and director of the Idaho Innocence Project – voiced serious concerns about this evidence. From the BBC:
some independent forensic scientists told the BBC this knife (which had been considered a possible murder weapon) should never have been given the importance it was because there was no evidence of blood found on it. . . . "I could see the problem with the case right away," says Dr Hampikian. . . .
A knife recovered from Sollecito's house was found to have Ms Knox's DNA on the handle and a small amount of DNA on the blade "consistent with the victim". . . . [Hampikian said] "That is significant because Miss Kercher had never gone to that house, so what is she doing on the blade of the knife? "While that may seem on its face to be evidence of a crime, in order to substantiate such a small amount of DNA you look for blood, and I can't emphasise enough how small this was - it was just a few cells." But there was no evidence of blood or any other body fluids found, the Boise State researcher points out. "You can't really wash the blood off and leave the DNA in any practical sense. That means that the few cells or molecules might have been from the laboratory after they amplified Miss Kercher's DNA," he explains. . . .
This concern was not his alone. There have been claims that the initial evidence was handled using dirty gloves and that investigators entered the crime scene without protective clothing. . . . To highlight how easily contamination in DNA evidence can occur, Dr Hampikian's team carried out a demonstration. They picked up used drink cans wearing clean gloves and then placed a new knife into an evidence bag without changing gloves. The knife was subsequently found to have tiny fragments of traceable DNA which had been transferred from the can.
The contamination of crime scene evidence has been known to falsely implicate suspects. While countless hours have been spent on this case, perhaps this is one area where the Italian courts should spend a little more time.
Posted by George Estreich, Biopolitical Times guest contributor on February 20th, 2014
The “distressed baby” Tim Armstrong blamed for benefit cuts. Photo by Deanna Fei
On Thursday, February 6th, Tim Armstrong, the CEO of AOL, justified a restructuring of the company’s 401(K) matching plan by citing the sick children of employees. Two sick children, to be exact. At an internal town hall meeting, Armstrong claimed, "We had two AOL-ers that had distressed babies . . . that we paid a million dollars each to make sure those babies were OK in general.” Unsurprisingly, the backlash was substantial. Tone-Deaf CEO is a tune we all know, and Armstrong’s improvisation on the theme, like others in the genre, was both memorable and inelegant. The complex discordance of Caring (“OK in general”), Slashing (the benefit cut), and personal wealth (Armstrong’s salary last year: twelve million dollars)—not to mention the blaming-the-infants thing—was answered by a disapproving choir, tweeting and talking and commenting, more or less in unison. Armstrong has since apologized and restored the matching plan to its previous form.
Rising above the other voices was a personal essay published in Slate, and written by Deanna Fei, the mother of one of the babies in question. Fei’s daughter was born months premature, weighing less than two pounds, and her narrative exposes the euphemism “distressed” for what it is:
We were too terrified to name her, to know her, to love her. In my lowest moments—when she suffered a brain hemorrhage, when her right lung collapsed, when she stopped breathing altogether one morning—I found myself wishing that I could simply mourn her loss and go home to take care of my strapping, exuberant, fat-cheeked son.
Since Armstrong’s announcement effectively compromised Fei’s privacy, she essentially had two options. She could remain silent, thereby accepting Armstrong’s characterization of her daughter as a “cost,” or she could out herself, then speak for her child. She chose the latter, replying to his numbers with a story. In doing so, she makes clear that numbers are not enough, that cost and value are not the same.
Jaws dropped around the globe last week when the U.S. Patent Office awarded Patent No. 8,647,872 to Hwang Woo-Suk and 15 Korean co-workers. The patent concerns a "human embryonic stem cell line prepared by nuclear transfer of a human somatic cell into an enucleated human oocyte." The astonishing part is that the whole world knows he faked it. More precisely, he faked some of the data in the papers originally published in Science in February, 2004 and May, 2005, both of which were formally retracted in January, 2006.
Hwang's motto at the time appeared to be "fake it til you make it," and he never withdrew the patent application. (He also committed numerous other ethical and financial crimes.) Indeed, he still claims that he succeeded in cloning human blastocysts and deriving embryonic stem cells.
By a strange coincidence, there are now swirling rumors about the STAP stem cells that drew attention earlier this month. The RIKEN research institute at which Haruko Obokata is based has launched an investigation into possible irregularities, following revelations of partially duplicated images, unearthed by anonymous bloggers.
That is exactly how Hwang's fraud was first discovered. Anonymous Korean scientists examined the images in his published work and noted anomalies on blogs. One is pictured, showing that a supposedly clonal stem cell was pictured in the same culture dish as one obtained from a fertilized egg. Soon, other bloggers picked apart the DNA analysis that purportedly proved the match with specific patients. Finally, Seoul National University (SNU) conducted a rigorous analysis that definitively established the frauds.
The STAP work is brand new, and at least some of the controversy may be normal post-publication review. Obakata and colleagues have admitted to "mistakes" with the images, but blamed late edits and her "extremely heavy workload." Still, other researchers do seem to be having difficulty duplicating the experiments, and informed opinion seems to be moving away from accepting the published results.
But what on earth is going on with the award of a patent for faked work? Jeanne Loring, the leading ESC specialist who has been deeply involved in challenging the stem cell patents held by the Wisconsin Alumni Research Foundation (WARF), explains:
My challenge of the WARF patents made me learn a great deal about patents and patent law, and trust me, the principles you cherish as scientists simply don't apply for patents.
The fact is that Hwang’s patent could impede further work on SCNT hESCs.
The patent owners may demand a licensing fee for use of any SCNT hESCs
and collect royalties on any commercial application of SCNT hESCs. This
is not out of the realm of possibility: those are the terms that WARF
imposed on blastocyst-derived hESCs, but at least those were real.
New Scientist (which is actually cited in the Hwang Patent) noted in 2006 that Hwang could still get his patent in some jurisdictions, or at least establish permanent prior disclosure. Indeed, Canada actually awarded Hwang a patent in 2011, though the general view, even in Korea, was that no other country would. Besides, if the method doesn't work, what's the point? That's part of the reason that SNU, which fired Hwang, dropped their efforts to patent the technology; they do not seem to have commented on the latest news.
But Hwang's incentive is much greater. As is his wont nowadays, he leaves the talking to others, in this case Prof. Hyun Sang-hwan at Chungbuk National University, described as "one of Hwang's closest aides." He told the Korea Herald:
"The patent is important because it officially confirms that the NT-1 is a human embryonic stem."
(Well, not really, but it certainly sounds good.) Getting to the heart of the matter, Hyun told the Korea Times:
"The USPTO acknowledged the technological edge of Hwang's team, which means something in consideration of the global scientific leadership of the U.S. Against this backdrop, I sincerely hope the government will allow Hwang to restart work on cloned human embryos. It's a pity that a scientist with very advanced technology cannot work on them."
A sign-on letter prepared by the Center for Genetics and Society and the International Center for Technology Assessment, a project of the Center for Food Safety, has been sent to the U.S. Food and Drug Administration (FDA) in anticipation of the agency’s discussion of a technique that would constitute a form of human germline modification.
The letter will be transmitted to members of the FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee, which on February 25-26 will hold a public meeting to discuss “oocyte modification in assisted reproduction for the prevention of transmission of mitochondrial disease or treatment of infertility.”
In just ten days, this letter garnered 255 signatures from 42 U.S. states and thirteen countries. From the Edmond J. Safra Center for Ethics at Harvard, to the Pro-Choice Alliance for Responsible Research, to Nurses for Life, to Friends of the Earth Nigeria, the respondents come from a broad array of affiliations and interests. The number and diversity of the signers speaks to the widespread public concern about experimental efforts to genetically alter humans.
N.B. We will continue to update the list of signatories (with a demarcation of who signed after the letter was sent to the FDA), so please consider showing your support for this effort and adding your name here.
Additionally, the FDA has released its background materials for next week’s meeting, which include a 35-page briefing document that discusses the scientific, technologic, and clinical issues related to “mitochondrial manipulation technologies.” The document is fascinating for many reasons.
It acknowledges that “ethical and social policy issues related to genetic modification of eggs and embryos… have the potential to affect regulatory decisions” but it puts these issues “outside the scope of this meeting.” Perhaps this bias was a foregone conclusion given the venue and the fact that none of the FDA committee members are social scientists, bioethicists, policy experts, women's health advocates, or children's advocates. However, even the document itself can’t fully disengage the clinical issues from the ethical ones, noting, for example, what would be needed to “ensure ethical conduct of long-term follow-up.”
The document notes, over and over, the difficulty of making a sound judgment about these technologies, given “the complexity of the science, the novelty of mitochondrial manipulation technologies, and the absence of a specific regulatory application.” It acknowledges that “the full spectrum of risks… has yet to be identified,” but does offer five categories of safety concerns for both the women involved and the potential resulting children, which include damage caused to the egg or embryo from the manipulations, nuclear-mitochondrial incompatibility, epigenetic modification of nuclear DNA, and the impact of the chemicals and drugs used at various points throughout the procedure.
The document also discusses the limited studies that have been carried out to date, noting, “Because most of these studies were not done with models of mitochondrial disease or infertility, it is not clear whether these data provide any support for the potential effectiveness if these methods in humans, for either prevention of transmission of mitochondrial diseases or treatment of female infertility.”
Given the many risks of these techniques, and the current paucity of data about them, it is hard to imagine that the FDA will eagerly usher in the world’s first human clinical trials of inheritable genetic modification. But, we will have to wait until next week to see what comes of this long-anticipated meeting. Live webcasts of the meetings will be available for both February 25 and 26.
Listen to the stories of the women in this documentary—Heather, Gail, Tanya, and Cindy, all white and American—and you will be struck at turns by their compassion, naïveté, and befuddled disempowerment. Heather, 20 years old with two children of her own under age 3, wants to help another family experience the same joy she has felt. Gail initially only wants to provide eggs for her brother and his same sex partner, but becomes convinced to serve as a surrogate. Tanya, who has found her previous pregnancies easy, intended to serve as a surrogate only for a gay couple, because she believed it would be easier to separate from the baby that way. Cindy proceeded under the assumption that she was going to bear babies with a friend of hers and help raise them, but not within the confines of a “normal” relationship.
Breeders serves as a necessary corrective to the rosy PR the surrogacy industry puts out. If you haven’t had occasion to land on surrogacy websites lately, suffice it to say that they frame the act of bearing children for other people for pay in entirely positive terms, deploying everything from sports analogies (become a part of “Team Baby”) to invocations of creating a “miracle.” Jennifer Lahl, founder of the socially conservative Center for Bioethics and Culture, which also produced Eggsploitation and Anonymous Father’s Day, about egg and sperm donation, and Matthew Eppinette, who with Lahl wrote, produced, and directed Breeders, provide a look at the realities behind the hype.
Spoiler alert: These are heartbreaking tales. Nothing turned out as planned. As Breeders unfolds, good turns to bad turns to worse.
The women in Breeders entered into surrogacy with various motives. Each, in telling her story, downplays the fiscal motive (although Lahl, who appears on screen, underscores the monetary driver, noting that many military wives and women from lower income brackets have been drafted into surrogacy). Each describes what happened as they encountered major physical and emotional problems with their pregnancies—we see and hear their distress—and as their relationship with the commissioning couples turned sour, yielding schisms and legal interventions. As Lahl remarks, “When money and contracts get involved in the creation of a child, what often happens when things go wrong is that the law has to step in.”
Breeders turns to O. Carter Snead, a law professor and the William P. and Hazel B. White Director of the Center for Ethics and Culture at the University of Notre Dame (and an outspoken opponent of abortion rights), for an overarching perspective on the legal issues involved in surrogacy. Snead notes that while surrogacy is not technically baby selling, the practice in many states circumvents the frameworks that have been put in place for adoption, which are meant to protect the best interests of children. “We don’t have a lot of good empirical evidence on the question of what are the harms, short-term and long-term, with respect to children or anyone who’s involved in this process,” he says. “And it seems to me if you’re confronted with the possibility of real, serious harms, the prudent thing to do for the legislature would be to try to pause for a moment, impose a moratorium, and conduct very serious and searching inquiry into what the harms are.”
Lahl and Eppinette explore the potential emotional harms to children born via surrogacy arrangements by interviewing psychotherapist Nancy Verrier, author of Primal Wound (1993). Verrier argues that pre- and perinatal bonding between mother and infant is disrupted by surrogacy. As a result, such children may be left questioning their identity within the family or suffering other long-term psychological impacts.
Breeders has a bias: The filmmakers chose only to include narratives of women whose experiences had been so negative in sum as to leave viewers shaken by a sense of sorrow and injustice. Even those entirely opposed to surrogacy must grant that not all such arrangements go so badly awry. The film does include segments with Darren Spedale, founder of Family by Design, which works in the “modern family space” and helps people form “parenting partnerships,” and with Joe Taravella, a clinical psychologist, both of whom talk about the benefits that surrogacy brings to couples straight and gay, and to single parents, and emphasize that it suits the modern redefinition of parenting. Says Taravella, “A family is love. And long gone are the days when we have a mom and a dad and two children.” Collin Smikle and Marlane Angle, the medical and IVF lab directors of Laurel Fertility Care in San Francisco also tell us how stressful building families outside normal channels is, and Angle admonishes us that it’s not anyone’s place to stand in judgment.
But the overwhelming message is that surrogacy poses grave social risks.
Lahl and others in her organization oppose abortion, though they keep that issue out of their films about assisted reproduction. And Lahl has worked with prochoice advocates who are also deeply disturbed by aspects of the fertility industry, including commercial surrogacy. In Breeders, Kathleen Sloan and MonaLisa Wallace, both on the board of directors of the National Organization for Women (NOW), emphasize that it is part of the ongoing trend whereby reproductive medicine commodifies women’s bodies. Sloan sees the fertility industry as having “huge profit generating capacity and [a] need for constant inputs, be that women providing their eggs or providing their bodies.” Wallace sees the surrogacy business as attempting to hide the fact that they treat women as mere means to an end: “Calling a mother a gestational carrier is a euphemistic way of dehumanizing her and taking away the relationship [with the child] by removing the word ‘mother.’” What results are “industrial human farms.”
In a film full of haunting moments, perhaps the most jarring comes when we hear from Jessica, who at age 26 found her birth mother. She says, “As much as I do believe that surrogacy can come from a compassionate place, as a product of surrogacy, it’s hard not to be aware that there is a price tag. There is an awareness that in essence you were bought by the family you grew up with. You are a product at the end of the day.”
Gina Maranto is Director of Ecosystem Science and Policy and coordinator of the Environmental Science and Policy program at the University of Miami's Leonard and Jayne Abess Center. She is the author of Quest for Perfection: The Drive to Breed Better Human Beings (1996).
Lonely this Valentine’s Day? Missing that je ne sais quoi with someone new? Thinking of signing up for an Internet dating service?
A new Canada-based startup, Instant Chemistry, was started by people who understand an important limitation to online dating: You can find the perfect match who checks off all the right boxes, but without chemistry, the relationship is likely to be DOA. The solution? Your DNA.
The company claims to have turned this elusive “chemistry” into a science. Apparently there are three genes in the Major Histocompatibility Complex that “play an important role in biological compatibility.” These genes are part of your immune system, and contribute to your particular body scent. So, Instant Chemistry can help set you up with someone who smells awesome to you! And there are extra perks, too,
Children born to couples with very different immune system genes are more likely to successfully defend themselves against a greater variety of infections. But not only do biologically compatible partners produce children with strong immune systems, these couples also enjoy more satisfying sex lives, greater marital stability, increased fertility rates – and they find each other more attractive!
Apparently, we’ve all been worrying about the wrong things! Who cares whether your partner is kind or adventurous or shares your world views? According to Instant Chemistry, “we now know the simple, stunning and provable fact: up to 40% of physical attraction can be determined through your genes alone.”
All you have to do is sign up for one of two pre-approved Matchmaker services (as long as you pass that criminal record check!) – at a cost of $675 to $2,700 depending on your package of choice, shell out an extra $500 for the DNA test, and then wait for a match to come in.
That may seem like a lot of cash to join a database with fewer people than are currently sitting at your local bar, but hey, if this Valentine’s Day goes badly, you can just blame it on your genes.
Scientists from the Model Animal Research Center of Nanjing University in China published a paper in Cell last week detailing their use of the precision gene modifying technique CRISPR/Cas9 to alter targeted genes in monkey embryos, resulting in the first birth of primates following the new technique. Other scientists are currently working on the same feat, but Xingxu Huang and his colleagues are the first to report a successful live birth.
The news has garnered a lot of attention, much of it focused on hopes for more accurate animal models for research on complex human diseases. Though transgenic mice are often used for this purpose, primates offer a substantial advantage, especially for neurological disorders.
Not all observers are convinced that this technology will in fact prove useful for studying human disease. The genes that were altered in the monkeys – Ppar-y and Rag1 – are not directly linked to a particular disease, though they are associated with some disorders. Additionally, the researchers have not yet ascertained whether the mutations occurred in all of the animals’ cells, and of course their impact on the monkeys as they grow remains to be seen. As stem-cell researcher Rudolf Jaenisch told Nature, the results say little on their own. "The next step is to see if we can learn anything from it," Jaenisch said.
Despite this rather large caveat, some people are already looking toward applying this technique to humans. Coverage in MIT Technology Review did not shy away from discussing the prospect of creating GM humans.
The fact that genome editing worked to create modified monkeys suggests it might also work to create genetically modified humans. Crispr is already used to modify human cells grown in labs, but it has not yet been tested on human embryos or adults. “We believe the success of this strategy in nonhuman primates gives lots of potential for its application in humans, but we think due to the safety issue, it will take a long way for expanding this strategy to human embryos,” says [study coauthor Wezhi] Ji.
Some coverage of the CRISPR monkeys identified experimental research on primates as the main ethical challenge raised by the research. The Guardian, for example, emphasized the concerns of animal rights advocates who warn that it could significantly increase the research use of non-human primates.
But scientists including George Church have already lined up the financing and launched a company called Editas that aims to use these precision gene editing technologies to treat a broad range of human diseases at the genetic level. Whether the company will also attempt to modify human embryos, leading to inheritable genetic modification, has not been clarified. In a February 6 webinar sponsored by Genetic Engineering & Biotechnology News, Church commented that human germline modification is “the ultimate in preventive medicine,” but that somatic modifications will likely be the focus for now, “until the safety and efficacy [of precision gene editing] is proven.”
We can recognize the beneficial potentials of CRISPR, and at the same time attend to its safety risks and to the door that it could open to eugenic enhancements. Acknowledging that prospect now is the first step toward ensuring that the social, ethical, and biopolitical implications of the work will guide, and not merely follow, the scientific research.
Two papers published in Nature on January 30 describe a new and remarkably simple technique for generating pluripotent cells: that is, cells that can, like embryonic stem cells, develop into many different kinds of cells. From the abstract of the first paper, by Haruko Obokata, Charles Vacanti and six colleagues:
Here we report a unique cellular reprogramming phenomenon, called stimulus-triggered acquisition of pluripotency (STAP), which requires neither nuclear transfer nor the introduction of transcription factors. In STAP, strong external stimuli such as a transient low-pH stressor reprogrammed mammalian somatic cells, resulting in the generation of pluripotent cells.
Slightly less formally, Andrew Pollack of TheNew York Timesexplained:
A surprising study has found that a simple acid bath might turn cells in the body into stem cells that could one day be used for tissue repair and other medical treatments.
The work was done on mice, but only a week later a photo was released apparently showing human STAP cells. This extension has not been peer reviewed but if confirmed "could be a paradigm changer," according to Robert Lanza. (Vacanti, according to a profile in the Boston Globe, is "not nearly as circumspect as many scientists, who are reluctant to speak about preliminary results or new research for fear of getting scooped or being wrong.")
But wait, there's more. From the abstract of the second Nature paper, by Obokata and ten colleagues, including Vacanti:
Here we report that reprogrammed STAP cells, unlike embryonic stem (ES) cells, can contribute to both embryonic and placental tissues … Taken together, the developmental potential of STAP cells, shown by chimaera formation and in vitro cell conversion, indicates that they represent a unique state of pluripotency.
These reports sent shock waves around the stem cell world. Can it be that iPS cells — so recently the subject of a Nobel Prize — have been outdated already? Are STAP cells in some way part of normal healing processes? (Is this what salamanders do?) Will they upend concepts of regenerative medicine? Or worse …
The authors carefully avoid using the term totipotent, but they do demonstrate that STAP cells (unlike iPS or ES cells) can form placental tissue. Theoretically, then, they could be transferred directly to a surrogate and develop as pure clones. New Scientist went so far as to suggest that:
This is enormously interesting scientifically, but has also raised concerns that STAPs might provide a ready pathway to animal, or even human, cloning.
That's almost certainly not going to happen soon, but such concerns serve as a reminder that proper regulation to prevent human reproductive cloning is urgently required, now more than ever.
All of the STAP results do need to be confirmed, though they have been a long time coming. Vacanti, who achieved notoriety in 1997 for the "earmouse," first published hints of it ("spore-like cells in adult mammals") in 2001, but had trouble getting support. Indeed, when Vacanti first met Obokata and her Japanese mentor, before suggesting that the isolation procedure might actually be creating these strange cells, he "asked them not to make fun of him" — only to find they already agreed.
Not everyone does. Paul Knoepfler, the UC Davis stem cell researcher and blogger, has been looking carefully at the papers (1, 2), has interviewed Vacanti, and ran an online poll, most of whose respondents are "not sure" though split almost down the middle on the significance of STAP cells. For the moment, he is skeptical:
I believe the odds are it won't work, at least not in a reasonably close fashion to what was reported in these Nature papers. Sure, we might see some people say to the media or even publish papers indicating that they can kinda sorta almost make STAP-like cells with certain stressors sometimes, but my prediction is that it still won't be very convincing.
I really hope I am wrong and if I am you'll read my happy mea culpa right here.
Knoepfler does note that "we'll know if STAP cells are the real deal within as short as two months because quite a few labs are now trying the technique."
That makes sense. Let's make sure the science is right. And begin figuring out how to apply it appropriately.
A new YouGov/Huffington Post poll on the use of genetic technologies provides a necessary corrective to excessive techno-enthusiasm. The public is clearly aware of the possibility of "breakthroughs" ahead but also concerned about "unforeseen dangers":
Which comes closest to your opinion about scientific research on human, plant and animal DNA?
I worry that this research poses unforeseen dangers – 11%
I'm excited that this research could lead to major scientific breakthroughs – 38%
Both of these – 33%
Neither – 6%
Not sure – 12%
This suggests that a solid majority (71%) is generically hopeful about biotechnology, but 44% are worried. When the questions get more specific, however, the concerns become significantly greater:
Would you approve or disapprove of scientists using DNA and cloning technology to bring woolly mammoths and other extinct species back to life?
Strongly/somewhat approve – 27%
Strongly/somewhat disapprove – 55%
Would you approve or disapprove of scientists using research on human DNA to produce children with unusually high intelligence or other special attributes?
Strongly/somewhat approve – 16%
Strongly/somewhat disapprove – 72%
How worried are you, if at all, that scientific research into human or animal DNA might lead to scientists "playing god" with things that should remain outside the realm of science?
Very/somewhat worried – 72%
Not very/not at all worried – 19%
Also worth noting (full details are here) is that strong disapproval, especially of "producing" high-intelligence children, far outweighs the weaker response; and mild support is more common than stronger. The distribution skews toward concern.
There is not a great difference among demographic groups, though older people tend to disapprove more than the young (who may of course change their minds), women more than men, Republicans more than Democrats, and Midwesterners more than those from the coasts. Even on cloning extinct species, no group reaches more than 40% approval (the highest is people from families with six-figure incomes).
All this is consistent with the polls that the Center for Genetics and Society has been collecting and tracking for many years (several date back to the early 1990s), on a variety of related subjects, mostly about US public opinion, but including some other countries:
This page includes polls on human genetics, specifically reproductive cloning, research cloning and inheritable genetic modification. Some of the polls are particularly useful because they show trends over time, notably Gallup, which has asked about the moral acceptability of human reproductive cloning every year since 2001 (answers range from 83 to 90% disapproval).
This page focuses on animals, including pet cloning and extinct and endangered species. Again, Gallup has surveyed on animal cloning every year since 2001, with 59 to 68% calling it "morally wrong."
On January 14, the preeminent DNA sequencing company Illuminarevealed its HiSeq X Ten, a machine that can reportedly sequence an entire human genome in a few hours, for under $1,000. The announcement of a “$1,000 genome” has long been anticipated as an important rite of passage for the field. In 2008, the same feat cost $350,000; the $1,000 benchmark is supposed to represent the point at which whole genome sequencing will move into the mainstream and trigger a “revolution in personalized medicine.” For now, however, its significance may be found primarily in its creation of good PR for Illumina.
However, the $1,000 price tag is actually somewhat misleading. The machine itself costs $1 million, and Illumina will only sell you a minimum of 10 machines. That’s $10 million upfront, so you have to be sequencing a lot of people to bring the cost down. As computational biologist Mick Watson put it, "I think they might be right in claiming the $1000 genome - if you do 18,000 human genomes per year for four years on each X Ten system. That's a lot of human genomes though." Furthermore, it turns out that this cost probably doesn’t include realistic labor costs, analysis, or commercial markup for providers of the test (see ‘Update’.) And finally, the price obviously does not include potentially substantial downstream costs such as over-testing and false positives.
Many people have argued that the real challenge with genetic sequencing is not in the sequencing itself, but in the interpretation and understanding of the results. A lot of the skepticism and criticism of the personal genomics field in the past few months has centered on exactly this point.
The PHG Foundation, an independent non-profit UK organization whose tag line is “making science work for health” recently released a new briefing note on whole genome analysis that highlighted a number of concerns with clinical applications. Most notably, PHG questions whether the lack of standardization in the interpretation of results rules out the possibility of information that is actually reliable or useful. The note mentions that one recent study found that 27% of the disease-associated mutations described in the published literature are incorrect, and another found a “43% mismatch between variants identified from a single sample processed by five common alignment and variant calling pipelines.” The note concludes that challenges to whole genome sequencing are not insurmountable, but that they will require care, time and resources to overcome.
Naming similar concerns, but coming to a somewhat different conclusion, an article in The Scientist last year argued that whole genome sequencing should not be used indiscriminately for all patients, even if the price does go down. The authors wrote, “in spite of an understandable narcissism regarding our own genomes, the reality for most of us is that our genomes are incredibly boring. Given our current understanding of how to interpret—much less apply—genomic information, the average person’s genome yields precious little knowledge that will lead to better health.”
Additionally, they continue,
~1 percent of us may find our genomes to hold rather terrifying information—mutations that strongly predispose us to disturbing diseases for which we currently have no preventive modalities and no treatments. Contrary to the usual trope that most people will “want to know everything” in their genome, actual data indicate that most people who are at risk of having mutations in such genes do not wish to know. We need to think very carefully before assuming that widespread genome sequencing will be universally useful or even desirable.
But the companies and universities that buy whole-genome sequencing machines will have a strong incentive to use them for many people, and to translate that mountain of data into information that at least seems meaningful and useful. One danger of so much front-end investment is that it could skew research interests toward a search for genetic explanations for diseases and traits that in fact have other etiologies. The causes and trajectories of most common diseases and traits are so integrated with environmental, social and lifestyle factors that an over-emphasis on genes could actually be counterproductive. Additionally, increased use of whole genome sequencing could encourage researchers, and marketing efforts, to promote theories of genetic determinism, potentially encouraging the disturbing resurgence of biological explanations for social ills.
All this considered, it is clear that the arrival of the $1,000 genome will not, on its own, imminently herald an age of personalized medicine. And although catchphrase-worthy goals can encourage speedy innovation, they can also overshadow pesky points such as the actual usefulness or desirability of the products themselves.
Posted by Amy Richards, Biopolitical Times guest contributor on February 4th, 2014
I always knew that I would be a mother. I was lucky to have been raised by a single mother, plus I had a godmother who adopted two children. This meant that from my earliest memories, I saw parenting as an individual choice and one not dependent upon biology or societal approval.
As I inched further along in my childbearing years, this personal perspective became more of a political directive. I wanted more women to free themselves from conventional thinking about parenting. I wished this not because I was secretly plotting for a feminist utopia, but because I worried about all of the women who were “waiting” to find a perfect partner – knowing that some of them would wait too long.
Tanya Selvaratnam, both a friend and a colleague, developed a similar calling; but hers came mostly as a consequence of her own journey, which included three miscarriages and many false promises. What Selvaratnam experienced personally also became political: how could she, a smart, well-educated, feminist have fallen prey to the false assumptions that pregnancy is within almost everyone’s reach (at least those who want it) – especially those with access to a world-class health care system and some extra cash to pay for interventions if necessary? Of course what Selvaratnam learned, and shares in her new book The Big Lie: Motherhood, Feminism, and the Reality of the Biological Clock, shouldn’t be anyone’s secret – even money and access can’t “get” some women what they desire most: a biological child.
The Big Lie isn’t a book about sharing personal disappointments, nor is it a book exclusively about pregnancy and biology. It’s more of a generational wake-up call – directed to those who have been raised to think that access has its privileges and that medical breakthroughs are always in humanity’s best interest. This book shames those (the media, the ART industry, politicians and patriarchs) who have preyed upon women’s vulnerabilities. But it also offers a personal cautionary tale: why have we forgotten to trust out own instincts? Selvaratnam’s goal isn’t to make women feel worse about not knowing what they should have known, but in true feminist spirit, about liberating women to think for themselves.
The best moments of the The Big Lie are when Selvaratnam buffers the statistics with her own personal experiences or supports her own feelings by quoting great feminist writers and thinkers. She uses women’s wisdom to bring forth more women’s wisdom. At times, it’s easy to forget you are reading a book, and instead to think you are hearing a good friend share her stories over a cup of tea. With humility and humanity, Selvaratnam reminds us that we are only human. She also helps readers to bring forth their own honesty: why do I really want a kid anyway – could it be because I’m supposed to want one?
The biological facts are clear – women have a harder time conceiving and carrying a child to term after a certain age. But that matters less to the author than discerning how these facts translate into the realities of our own lives. As is, we think the facts are about other people, not us.
The biggest truth of The Big Lie is that our society’s over-focus on women’s reproductive abilities is exclusively connected to babies. In fact, it’s also about the presumption that reproducing the next generation is a woman’s main function – and thus if you fail at that, you fail at being a woman.
Rather than looking at women’s lives only when they are in the midst of debating, planning, and trying to get pregnant, Selvaratnam sees reproduction as inseparable from what happens to us when we are 9 or 90. The Big Lie isn’t that women can wait indefinitely to get pregnant, but that women should trust anyone else about whether or not to become mothers, instead of trusting themselves.
Humans are one of the few species in which ovulation is isolated to a part of life, not continuing throughout a life cycle. To me that is proof that women exist for purposes far beyond reproduction. That might be one aspect of our lives, but it certainly doesn’t have to be.
The beleaguered defenders of direct-to-consumer genetic testing are now pressing their case in Nature. Robert Green and Nita Farahany complain that the FDA is "overcautious" and Virginia Hughes in National Geographic's blog Phenomena agrees. In this, they are following less temperate commentators who have used terms such as "outrageous" and "borderline absurd."
Critics of the FDA's move to require that 23andMe produce evidence that the health claims it makes about its DTC gene tests are warranted generally assume the technology works. (The moderates do include some caveats.) But in practice, it doesn't. Not reliably enough.
There have now been at least four experiments that involved having the same DNA analyzed by different companies, and in every case significant anomalies appeared. The classic report was the first, by David Ewing Duncan. In 2008, he had his DNA tested as part of his research for a book:
I was told by three companies — Navigenics, 23andme, and deCODE genetics — that my genetic risk for heart attack was high, medium, and low.
In 2009, Craig Venter and colleagues ran a similar experiment comparing the reports of Navigenics and 23andMe on five individuals. The full analysis is behind a paywall (Duncan wrote a useful summary for MIT Technology Review) but the abstract notes:
For seven diseases, 50% or less of the predictions of two companies agreed across five individuals
In 2010, the U.S. Government Accountability Office ran a similar comparison:
GAO's donors often received disease risk predictions that varied across the four companies, indicating that identical DNA samples yield contradictory results. One donor was told that he was at below-average, average, and above-average risk for prostate cancer and hypertension.
The GAO uncovered much more, including unethical and even illegal comments and advice. And yet this neither ended the story nor ushered in any significant regulatory changes.
By 2013, several companies had left the industry or required a doctor's referral, but Kira Peikoff repeated the experiment and published her results in the New York Times:
I Had My DNA Picture Taken, With Varying Results
23andMe said my most elevated risks — about double the average for women of European ethnicity — were for psoriasis and rheumatoid arthritis, with my lifetime odds of getting the diseases at 20.2 percent and 8.2 percent. But according to Genetic Testing Laboratories, my lowest risks were for — you guessed it — psoriasis (2 percent) and rheumatoid arthritis (2.6 percent).
Bernard Munos took a different tack. He had his whole family tested by 23andMe and wrote about the results in Forbes:
My daughter, as expected, got half of her genes from my wife and half from myself. My son, however, got half of his from my wife, but only 47.5% from me. Now, he is a crafty guy, but how did he pull that off?
He also found some (relatively trivial) projections that do not accord with his experience, for instance about lactose intolerance and metabolizing caffeine. In yet another case, Lukas Hartmann wrote about a more disturbing finding in Quartz:
Why 23andMe has the FDA worried: It wrongly told me I might die young
Hartmann's experience was caused by a bug in 23andMe's analysis that confused two unrelated heterozygous mutations with a potentially lethal homozygous mutation. Hartmann painstakingly examined the detailed data dump of his genetic analysis, and found the bug. The company confirmed and removed it, and now merely notes that he is at risk of passing on the mutations.
Craig Venter, quoted in Peikoff's New York Times article, commented on the contradictions she found:
Your results are not the least bit surprising. Anything short of [whole genome] sequencing is going to be short on accuracy — and even then, there's almost no comprehensive data sets to compare to.
Given the state of the science — and perhaps the state of reality — even full-genome analysis may not be definitive, since the risks of most common diseases are caused by complex interactions of genes, gene regulation, and environment. Certainly, almost everyone needs the assistance of trained professionals to understand the results of comprehensive genetic tests, let alone to make significant decisions based on them.
The anomalies detailed above were not uncovered by campaigners concerned about privacy issues and other social, economic, philosophical or political concerns. They were reported by people who actively want genetic technologies to succeed or are concerned about consumer protection. The inescapable conclusion is that the direct-to-consumer genetic testing industry is still, as one of the co-founders of Navigenics told Michael Hiltzik in December 2013, "not ready for prime time." Whether it ever will be ready is yet to be determined.
Update, 1/30: For an excellent analysis of how unreliable predictions based on DTC test results are, see this article by Cecile Janssens, whose research [pdf] was previously discussed by my colleague Jessica Cussins.
Many readers of Biopolitical Times will remember the stunning stem-cell fraud scandal that centered on Korean cloning researcher Hwang Woo-Suk. He won global fame in 2004–5, and equally newsworthy humiliation in 2005–6, leading to criminal conviction in 2009. Well, Hwang is back in the news — or perhaps that should be "news."
On Tuesday, January 14, Nature News & Comment ran a piece by David Cyranoski with this headline and summary:
Cloning comeback Ten years ago, Woo Suk Hwang rose to the top of his field before fraud and dodgy bioethical practices derailed his career. Can a scientific pariah redeem himself?
The article is long, and does not gloss over the fact that Hwang committed fraud and "gross ethical lapses." (Hwang is the surname; Koreans put it first but variants are common.) Overall, however, it does picture him as a penitent, now head of the Sooam Biotech Research Foundation and working to rebuild his reputation. Hwang is quoted after delivering cloned puppies, but not interviewed. Another scientist, named as Insung Hwang (no relation), did speak on the record.
Then on Wednesday, Science Insider published a piece by Dennis Normile, originally titled "After Fraud, Korean Cloner Seeks Redemption" but now (behind a paywall) headed:
The Second Act
After his first turn on the world stage ended in scandal, Woo Suk Hwang has quietly rebuilt his scientific career.
The article is long, and does not gloss over the fact that Hwang had a "central role" in fraud and "dubious" ethical practices. But it focuses on his success in rebuilding his career to the point where he is "in a position many researchers would envy" at the Sooam Biotech Research Foundation he heads. Hwang "declined to be interviewed" but allowed the reporter to witness him at work implanting canine oocytes and delivering cloned puppies. And In Sung Hwang (no relation) did speak on the record.
UC Davis stem cell expert, and blogger, Paul Knoepfler tweeted (Jan 15):
The story was cloned perhaps? ha ha
It's possible, I suppose, that Cyranoski and Normile were unaware of each other's presence at Hwang's lab (the caesarians each describes seem to be different), But once the first story was published, Science Insider could have written a very different account, such as:
Were Science and Nature manipulated to boost Hwang's reputation?
Nature writer Brendan Maher, on Twitter (Jan 16 & 17), wrote that Cyranoski had been asking for access, since the tenth anniversary of one of the retracted papers is imminent, and Sooam recently accepted. Quite possibly, Normile initiated contact too. But the visits were clearly, as Maher said, "carefully orchestrated." Hwang learned a lot from his media experiences ten years ago.
But is anything really significant happening? Hwang is cloning dogs and cows, big deal, he's done that for years. And he's talking about mammoths again. Why should we care? Cyranoski's reporting suggests the answer:
Woo Suk Hwang's greatest coup in terms of regaining legitimacy was establishing a partnership in March 2013 with BGI in Shenzhen, China — the world's largest sequencing facility and a powerhouse in scientific publishing (see Nature 464, 22-24; 2010). Together, they plan to look at modifications of chromosomes that determine how genes are expressed, a field called epigenetics. Analysing the variation between clones and how that may contribute to, for example, different coat patterns in dogs could be a powerful tool for such work.
Yang Huanming, BGI's co-founder, says that he was impressed by the level of involvement from Woo Suk Hwang after watching him deliver a litter of cloned pups. "Personally, I like him, how hard he works, and how passionate he is for science," Yang says.
Normile's reporting makes a similar point (why, they spoke to the same person at BGI!):
"For animal cloning, his team is one of the best in the world," says Yang Huanming, chair of the Chinese sequencing powerhouse BGI-Shenzhen. Eventually, Yang predicts, Hwang "will regain respect from the scientific community."
He's certainly been trying (see the list below of some of our previous posts). The ambitious old fraud who once dreamed of being the first Korean Nobel Prize winner is recasting himself as a scrappy underdog. He still wants to do cloning work with humans; he's had two applications turned down by Korean authorities. He is working with genetically modified cows to produce human proteins, and genetically modified pigs of organ transplants. He turned 60 last year, but has clearly settled in for the long haul.
Paul Ehrlich, author of the 1968 book The Population Bomb, and Stewart Brand, publisher of the 1968 Whole Earth Catalog, have taken to the pages of Yale Environment 360 (e360) to debate the idea of "de-extinction." They have known each other for half a century – Ehrlich was Brand's field work advisor at Stanford – but there is no discussion here, rather a contrasting pair of essays.
That's unfortunate, because they talk to an extent at cross-purposes. Brand presents his usual shtick in favor of de-extinction, but also takes it on himself to define the arguments against. He waves aside what Ehrlich sees as the most important, the "moral hazard" involved in anything that might reduce attention paid to a sixth mass extinction.
Ehrlich, whose wife Anne gets a contribution credit, is skeptical about the entire enterprise, and also raises issues about geoengineering to combat climate change. He closes with a call for "seeking ways to reduce the scale of the human enterprise," especially by promoting women's rights, in part to reduce birthrates.
Taken together, the essays provide an overview of the issue. But it's unfortunate that it's framed as a choice between techno-optimism and zero population growth.
DNA Dreams, a new documentary by Dutch filmmaker Bregtje van der Haak, could just as well be called DNA Nightmares. The scenarios it unfolds have a kind of eerie pseudo-logic that would be at home in a horror film. But DNA Dreams is a depiction of events happening right now, and that should make us all afraid.
DNA Dreams explores the inner workings of Shenzhen BGI (formerly Beijing Genomics Institute), which calls itself "The World’s Largest Genomics Organization." In addition to its tag line, the company boasts enormous sequencing and storage capabilities, thousands of scientists, and grandiose plans. In one scene, BGI chair Dr. Yang Huanming tells a spellbound crowd in a packed auditorium,
I have a dream. We have a dream. That we are going to sequence every
living thing on Earth, that we are going to sequence everybody in the
But sequencing isn’t all that BGI has up its sleeve.
DNA Dreams follows Zhao Bowen, a "science prodigy" in his teens who dropped out of high school and now leads BGI’s Cognitive Genomics Group, a controversial project working to uncover the genetic basis of intelligence. Over 4,000 bio-informaticians are undertaking whole genome sequencing of 2,000 particularly bright people using the world’s most powerful DNA sequencers. They believe that it is only a matter of time before the alleles associated with intelligence reveal themselves.
In one fascinating scene, a number of key BGI players are eating dinner together, discussing how their research will enable parents to screen their embryos and choose the one that will become the smartest child. One argues,
This isn’t even positive eugenics that we’re talking about, we’re not
encouraging smart people to have kids, we’re encouraging everyone who
has kids to have the best kids they possibly could have.
Amid nods of approval, another notes, "I would totally be willing to do it."
At another point, Michigan State University’s Stephen Hsu, who has been involved with the project, waxes lyrical on its potential,
The best humans have not been produced yet...If you want to produce smart humans, nice humans, honorable humans, caring humans, whatever it is, those are traits that are related to the presence or absence of certain genes and we'll have much finer control over the types of people that are born in the future through this.
We do it with cows, we have super cows and super chickens...We've pushed those animals in directions we want to push them, but we haven't really pushed ourselves, and I think people will push themselves.
There are plenty of reasons to believe that such control of human life won’t work technically – and that if it did, even a little, it would be disastrous socially. Yes, we’ve made cows that get bigger quicker (and genetic manipulation is not the only way this has been done). We haven’t made cows that are smarter, nicer, more honorable, or more caring.
And scientifically, the notion that complex human traits could be determined by "the presence or absence of certain genes" could well end up being nothing more than a DNA pipe dream (another alternative title for this documentary). A paper published in Science earlier this year, with over two hundred authors, reported on a genome-wide association study of over 100,000 people that looked for clues into the genetic basis of cognitive ability.
The grand conclusion? All the measured single-nucleotide polymorphisms (SNPs) account for about 2% of the variance in educational attainment and cognitive function. In other words, "fully 98% of all variation in educational attainment is accounted for by factors other than a person’s simple genetic makeup."
But BGI researchers are undeterred. They believe that the scale at which they can apply whole genome sequencing is unprecedented, and that this will provide them with answers others haven’t found. Bowen says,
It is generally assumed that intelligence is hereditary. Scientists such as Robert Plomin have been studying this for years. But so far they’ve only discovered one percent of that genetic basis. With confidence we can say that we’ll be able to get much further.
Other scientists also seem to have confidence in BGI's cognitive genomics approach. In an interview last spring, evolutionary psychologist Geoffrey Miller (who contributed his own DNA to the project) speculated that it could be only a matter of years before BGI's technology is used for widespread sequencing of human embryos. When asked if he thought the project could develop into something more sinister, he replied, "That same research does open up the door potentially to genetic engineering in the future."
Other BGI already projects could also help open that door. As DNA Dreams shows us, the company has extensive animal cloning and genetic engineering facilities. Its experimental farm produces multiple cloned pigs every day, some of them genetically engineered to glow in the dark, others to be prone to type II diabetes. The farm's 25-year-old director Lin Lin is proud of her work. Beaming at the camera with youthful enthusiasm, she says, "This is life that I created. It was made by my hands."
China, along with dozens of other countries (but not the US), currently bans human cloning and inheritable genetic modification. But BGI now has partnerships all over the world. If the technology improves and a country that hasn’t outlawed it wants to proceed, what would happen? Bowen, for one, believes that "people ought to be free to manipulate their children’s IQ. It’s their own choice."
Bowen is not the first to link the rhetoric of individual choice to a supposed "right" to genetically redesign future children based on personal preferences at a particular moment. But this is a spurious argument. As Nathaniel Comfort points out in a recent Scientific American post called "Is Individuality the Savior of Eugenics?,"
Individual eugenics, in other words, dissolves into a species of collective eugenics. Focusing on individual health does not absolve us of the evolutionary question, Whither humankind?
In an opening scene, DNA Dreams shows a clip from a 1962 film in which a man says about the power of DNA, "All the secrets of life are hidden in this substance. This bottle is
somewhat like Pandora’s box. It’s better to keep it closed, and we’ll
explain to you why."
DNA Dreams doesn't offer an explicit position on what DNA developments should be kept inside the box. It allows the fantastic and terrifying reality of BGI to speak for itself. If you can catch this provocative film at an upcoming festival, you’ll find a lot worth pondering.
The dubious business of selling so-called stem cell "therapies" seems to be gathering momentum, and some scientists are becoming quite alarmed.
One who is vocal on the subject is UC Davis cell biologist Paul Knoepfler, who wrote last week, in reference to a chain of clinics called Stem.MD:
I am extremely concerned about patient safety, the risks to the newly recruited physicians who are newbies to the stem cell world, and the huge risks to the entire stem cell field should there be major negative outcomes from these chains.
There have been fraud convictions in Nevada for selling "hope" that stem cell treatments would cure the chronically ill; exposés by 60 Minutes of phony labs in Ecuador and Mexico that cater to Americans; scandals in the Philippines (where the government is at least trying to regulate the industry); legal and financial difficulties for South Korea's leading stem-cell company; and the continuing saga of the Texas-based Celltex, which seems to be treating patients in Mexico.
But Italy tops them all.
There has been something of a mania in Italy for legalizing stem-cell therapies, on a scale that is reminiscent of South Korea at the height of the Hwang Woo-suk frenzy in 2005. Many Italian scientists were horrified by the government's decision last spring to authorize an unproven treatment, which was given to "more than 80 patients, mostly children, for a wide range of conditions, from Parkinson's disease to muscular dystrophy, before the health authorities halted its operations in August 2012."
Nature joined in with some investigative journalism that suggested plagiarism at least and possibly fraud. In the fall, an expert panel concluded that there was no scientific basis for the alleged treatment conducted by the Stamina Foundation, headed by Davide Vannoni. But the enthusiasts fought back and won a court order to reopen the question.
Now Nature has obtained and described the unpublished expert evaluations of the Stamina treatment, documents that it characterizes as "damning." Among other issues, the procedures involved would have been very unlikely to produce the cells claimed, the evaluations say, and even if they did the numbers would be too small to be efficacious. Moreover, there was no screening for pathogens; a proposed process made it likely that any clinical trial would be insufficiently standardized; there were conceptual errors in the clinical rationales; and some sections of the protocol had been copied from Wikipedia. Also, the patients that have been treated are not getting better.
Knoepfler, who runs a stem cell lab and remains a strong supporter of their therapeutic potential, is following this case closely. He comments:
I cannot fathom how Stamina could be good for the patients, including mostly vulnerable children.
Vannoni does have some scientists on his side, notably Camillo Ricordi, who is based in Miami, but he is also becoming controversial. Several leading Italian scientists have resigned from committees and foundations with which Ricordi is associated, because of his support for Vannoni. Moreover, Naturereports with evident concern:
Ricordi backs a controversial proposal that cell therapies should not be regulated as medicines, as US and European regulators insist, but as transplants. He argues that because transplants are not subject to strict regulation, novel stem-cell therapies could be introduced more quickly.
How potentially disastrous. There are already far too many scams being perpetrated on the unwary who are blinded by hope. New national and international regulations are desperately needed. As Dr Christopher Ceneno (an advocate of stem cell therapies, who himself has been the subject of criticism for over-optimism) wrote on Knoepfler's blog last June:
New procedures in medicine that take on a "Wild West" mentality are usually not regulated by some federal agency, but by the civil tort system. This then leads to guidelines that doctors must follow to get insurance and avoid law suits. So in the end there will be "regulation," just not the type we all planned.
Update 1/14/14: Nature has published even more damning evidence about Stamina; and the Oregon Medical Board has suspended a physician for conducting experimental stem cell treatments the board considers an "immediate danger to the public."
“The Gene Factory,” an article out earlier this week in The New Yorker, carries the subtitle, “A Chinese firm’s bid to crack hunger, illness, evolution – and the genetics of human intelligence.”
That firm is BGI, formerly known as Beijing Genomics Institute, a company with 4,000 employees working in a humble eight-story former shoe factory in Shenzhen, China. BGI single-handedly produces over a quarter of the world’s genomic data; it has sequenced over 57,000 people as well as many varieties of plants and animals. And it has no intention of slowing down. As New Yorker writer Michael Specter reports,
The company says the data will help explain the origins and the evolution of humanity, improve our average life span by five years, increase global food production by ten per cent, decode half of all genetic disease, understand the origins of autism, and cut birth defects by fifty per cent.
BGI’s immense, tireless sequencing (and labor) power enables it to undertake work about which other researchers can only dream. At least at the moment, BGI is eager to share its findings. When a deadly strain of E. coli bacteria appeared in Germany in 2011, BGI researchers managed to sequence the bacterial genome in just three days. They live-tweeted their work as it unfolded and made the final data entirely public. This novel approach produced results from researchers around the world that helped prevent a deadly outbreak.
BGI was formerly an affiliate of the Chinese Academy of Sciences, but in the words of its president, was “kicked out” for its “crazy” ideas. That’s when the company really began to flourish. After getting its bearings with minimal research on the Human Genome Project, BGI now has sequencing facilities all over the world, and says it will offer whole genome sequencing for less than a thousand dollars by the end of next year.
But many of the recent headlines about BGI have been about just one of its efforts, which it describes as a relatively small one: the Cognitive Genomics project, which aims to uncover the genetic basis of intelligence by poring through the genomes of thousands of people with extremely high I.Q.s. The project is of course controversial because of how often biological definitions of intelligence have been used to validate problematic and often horrific policies and practices.
Historically, biological explanations for human “fitness” or “superiority” have always been based on what is considered the best science of the time. But it’s likely that complex behavioral traits like intelligence will never be “found” in our genomes; studies so far have produced incredibly limited results.
BGI knows it is treading in socially and ethically treacherous waters with its intelligence project. A BGI press representative told Specter multiple times, without being prompted, that the company would never engage in eugenics. But a number of the researchers involved, including Stephen Hsu, a vice-president for research and graduate studies at Michigan State University, are explicit about what the findings of the project could do to “improve” human reproduction. They seem to welcome the prospect of a real-world Gattaca, in which embryos are extensively screened and carefully selected (and genetically manipulated, as Hsu envisions) prior to implantation.
BGI intends to be a trail-blazer with this project and in the field of genomics in general. Its managers have taken the attitude that their critics will come around when they see their results. Even if that’s not the case, BGI simply may not care. Jian Wang, the company’s president, told Specter,
In the United States and in the West, you have a certain way. You feel you are advanced and you are the best. Blah, blah, blah. You follow all these rules and have all these protocols and laws and regulations. You need somebody to change it. To blow it up. For the last five hundred years, you have been leading the way with innovation. We are no longer interested in following.
The FDA public meeting to discuss mitochondrial replacement that was postponed due to the government shutdown in October has now been rescheduled for February 25-26. This will be the first public meeting ever held by the FDA to discuss the feasibility and desirability of a form of human inheritable genetic modification.
The meeting will be held by the Cellular, Tissue, and Gene Therapies Advisory Committee and in their words, it will consider “oocyte modification in assisted reproduction for the prevention of transmission of mitochondrial disease or treatment of infertility.”
No official background materials have yet been published and may not be until just two days before the meeting. However, the FDA is encouraging public participation. Written comments may be submitted before February 18 to Gail Dapolito or Rosanna Harvey. Requests to make formal oral presentations may be submitted before February 10. If you previously submitted comments for the October meeting, I have been assured that they will carry over and be considered for the February meeting. Previous requests to speak should be confirmed. For those who cannot attend the meeting in person, a webcast will be available for both February 25 and 26.
CGS has written a detailed letter to the FDA to voice concerns regarding the safety, efficacy, and policy implications of allowing clinical trials of a technique under consideration.
The idea that poverty is the result of personal failure and inherent inferiority is relatively new, having taken root only a few centuries ago. But it is an insidious and enduring one. In “The Biological Inferiority of the Undeserving Poor,” University of Pennsylvania Professor of History Michael B. Katz sketches the history of this ideology and its various scientific justifications. The article connects past and contemporary understandings, showing that the argument that poor people are biologically inferior “rises and falls in prominence in response to institutional and programmatic failure,” but that such “hereditarian ideas always have been supported by the best science of the day.”
Katz takes us quickly through social Darwinism, Buck v. Bell, IQ tests, sociobiology, and The Bell Curve. He draws a jarring parallel between the current revival of notions of “faulty heredity” within bioscience and neuroscience, and earlier “ideas that ranked “races”; underpinned immigration restrictions; and encouraged compulsory sterilization.” Katz’s article provides an important reminder that scientific developments do not exist in a void, but are embedded in the cultural and social assumptions of their time, and can be used to “prove” all kinds of problematic ideas. “Indeed,” he states, “every regime of racial, gender, and nationality-based discrimination and violence has been based on the best “science” of the day.”
Katz also discusses how the new emphasis on epigenetics plays into this history with its promise “to move beyond the long-standing war between explanations for the achievement gap, persistent poverty, crime and other social problems based on inheritance and those that stress environment.” He makes the argument that although epigenetics provides “scientific sanction for early childhood education and other interventions in the lives of poor children,” it is still a biologically based theory of human behavior and is susceptible to over-simplifying complex social and behavioral traits to deterministic hereditary explanations. He warns that such research has the potential to “underwrite a harsh new view of the undeserving poor and the futility of policies intended to help them.” As such, his stated goal is to provide “a cautionary note from history about the uses of science and a warning to be vigilant and prepared.” It’s worth reading that note in full.
For better and worse, 2013 has been a year in which several related
issues familiar to those who follow human biotechnology moved into the
wider sphere of public discussion. Many involve genetic testing — at
every stage of life — and some explicitly raise issues of inheritable
genetic modification. The legacy of eugenics past, the horror of
sterilization abuse in the present, and the advocacy of genetic
selection for intelligence and other traits in the near future all hit
The U.S. Supreme Court issued a series of
important and yet strangely incomplete rulings whose implications are
still being unraveled. The commercialization of synthetic biology and
other newly developed technologies proceeded apace, with well-financed
businesses, partly crowd-sourced ventures and a number of outright
scams. The assisted reproduction industry continued its global spread,
and there were encouraging signs of academic interest in analyzing its
After the jump, much more on:
Testing, Testing …
“Three-Parent” Babies and Inheritable Genetic Modification
Eugenics: Past and Present as Prologue
IQ and Genetics and Education and Immigration
A Glowing Push for Synthetic Biology
The Global Assisted Reproduction Industry
California: Women's Eggs, DNA & Police Databases, the Stem Cell Agency
Following a Biopolitical Times tradition, we present some of
our favorite blog posts of the year, out of well over 100 by 15 different
contributors. Thanks to all the guests! In alphabetical order by title:
Advocating Eugenics in the UK Department of Education by Pete Shanks Dominic Cummings, a senior adviser to the UK Secretary of State for Education, provoked a flurry of complaints about his technocratic, effectively eugenic, definitely gene-focused approach to public policy.
Eight Misconceptions about “Three-Parent Babies” by Jessica Cussins Amid the talk about “mitochondria replacement” or “three-parent babies,” here are the top misconceptions proliferating about the efficacy, safety, public support, and societal implications.
Gene-ism and Mass Murder by Marcy Darnovsky Proposals to analyze the genes of a mass murderer have rightly drawn criticism from experts, including the editors of Nature.
Involuntary Sterilization Then and Now by Jessica Cussins North Carolina will be the first US state to offer compensation to victims of state-sponsored forced sterilization programs. The decision marks a milestone in the long struggle for recognition of this tragic history, but what about the questionable sterilizations still taking place today?
More Concerns Over Familial DNA Searching by Osagie K. Obasogie A recent paper by Rori Rohlfs et. al., and two accompanying videos, suggest that real concerns still remain with familial searching in California's DNA databases.
Predicting the IQ of Future People by Pete Shanks The resignation of Jason Richwine from the Heritage Foundation raised the profile of racist views about IQ. Expect new publicity soon for genetic claims about intelligence.
In 1998, a UCLA conference called "Engineering the Human Germline" brought together more than 1,000 people to discuss various emerging technologies and the challenges they faced. Gregory Stock, a co-organizer of the conference, toldNature at the time that, really, the goal of the event was to make the inheritable genetic modification (IGM) of humans “acceptable” to the public.
Over forty countries, and multiple international treaties, prohibit IGM due to the profound safety, social, and ethical implications of making permanent changes to the human germline. Opposition to IGM is widespread; the Center for Genetics and Society, for example, has long argued that “the case for allowing it is not compelling, and the potential harms of doing so are immense.”
Disturbingly, 2013 has seen a deluge of new efforts, more explicit than any since 1998, to ease public opinion towards allowing human germline engineering.
The big one for 2013, which I have written about before, is mitochondrial replacement. This is a technology that would in theory allow a woman with a particular kind of severe mitochondrial disease the chance to have a non-affected and mostly genetically related child. It would extract the nucleus from one of her eggs and insert it into an enucleated egg from a second woman, and then allow the resulting egg, containing nuclear DNA from the intended mother and mitochondrial DNA from a donor woman, to be fertilized. This crude technique poses severe risks to any resulting child, yet, with both the United Kingdom and the United States currently considering policy changes to allow clinical trials, it seems to be the world’s current forerunner for violating the international consensus against IGM.
But there are other developments worth keeping an eye on. One, a gene editing technique known as CRIPSR, has gotten a lot of attention recently because of its potential for permitting much more specific genetic alterations than can be accomplished with currently used methods. Researchers have had some success in mice and human stem cells, and a company called Editas that just launched intends to investigate and commercialize its human possibilities. Fortunately, the focus of CRIPSR is likely to dwell in the realm of gene therapy for critically ill consenting persons. Unfortunately, some scientists are also touting the possibilities of applying CRISPR to IVF embryos – in other words, of moving ahead to full-fledged inheritable genetic modification.
It is still too early to know how effective and safe CRISPR could be; so called “off-target mutations” caused by its high mutagenic efficiency could mean that the technique would fix one problem, but introduce others. Furthermore, epigenetic changes caused by this technique seem inevitable, and yet would be very difficult to understand or predict ahead of time. However, if it is found to be safe and effective, it would be the most powerful tool for producing “designer babies” the world has seen to date. Unlike mitochondrial replacement, with its crude wholesale swap of one woman’s mitochondrial DNA for another’s, CRISPR could make it possible at least to try to alter specific genes for specific purposes.
Another procedure that was recently in the news is a method to genetically modify sperm. Scientists from the Royal Veterinary College in the United Kingdom used a viral vector to insert genetic material into mouse spermatozoa and found that it was still functional three generations later. However, while this technique introduces another method for creating transgenic animals, it seems that any human applications are vague and hypothetical at this point.
All of these techniques are biologically extreme processes that carry unknown impacts. But it’s important to remember that, even if they can be made to work, none of them alleviate the illnesses of people alive today. Instead, they are proposals for creating new people. They are often justified as a way to help couples who desperately want a genetically related child, but are concerned about passing on a debilitating illness to their children. But people in this situation already have a powerful tool at their disposal: preimplantation genetic diagnosis. Though embryo selection also raises concerns about “designer babies,” its design capabilities have nothing on these engineering techniques, and it carries substantially fewer risks to the resulting children.
It remains to be seen how the policy cards will fall on these novel attempts at IGM, and whether technical limitations or the impressive outpouring of criticism from varied sources around the world this year could be enough to fight back this particular wave of enthusiasm.
Posted by George Estreich, Biopolitical Times guest contributor on December 18th, 2013
If you're interested in biopolitics, it's easy to feel off the radar. Prophets of climate change are at least vaguely familiar. They may often be dismissed, derided, or ignored, but at least they can assume that people acknowledge that there is such a thing as a climate, and have heard that it is changing. Notwithstanding writers like Margaret Atwood and Paolo Bacigalupi, whose visions of the future entwine catastrophic climate shifts and genetic engineering run wild, being interested in synthetic biology, or direct-to-consumer genetic tests, or the misrepresentation of disability in the age of prenatal prediction, can feel like being a prophet of the wrong disaster, on an abandoned street corner.
So it was with great interest that I read a piece in The New York Times a couple days ago, detailing the abuses of the pharmaceutical industry in selling treatments for attention deficit disorder – or, to be more precise, in quintupling the market for ADD drugs through a coordinated program of persuasion on every front, right down to shaping the science which is then cited as impartial support. The article interested me because the strategies it describes fit with what I've been seeing in the selling of prenatal tests. This, in turn, got me thinking about some of the concerns we may share with activists in other fields.
The parallels between the selling of ADD and the selling of prenatal screens are significant. Indeed, to say "parallels" may be misleading: both are phenomena of medical advertising, and both products are meant not to cure/prevent life-threatening conditions, but mainly or purely to address ability or achievement. Further, what's being sold is not only the product per se: it's also an idea of how to be, and in particular, what we want our children to be like. We want them, in short, to succeed.
I should say, in passing, that ADD is an actual thing. Though I think that the condition may be particularly noticeable in our achievement-oriented society, and in an educational system that emphasizes sitting, listening, and not disturbing the rest of the large (because largely underfunded) class, it is nonetheless true that ADD is real and the drugs are not placebos. Like antidepressants, they can help. The problem, as the article makes clear, is in the aggressive attempts to expand the market.
These attempts are, of course, precisely parallel to the vigorous marketing effort now underway with the new NIPS (noninvasive prenatal screen, a genetic test of very early fetuses based on a sample of the mother’s blood). As historian Alexandra Minna Stern pointed out recently at the Future Past conference, the market for these tests is vast: all women of childbearing age.
To convince people to adopt the test, you have to accomplish a number of things. You have to downplay any risk associated with the test itself. You have to establish the test as a "scientific" thing to do – hence the recommendations from professional organizations (some of which actually caution against misuse and overuse of the test, though the companies tend to ignore those passages), plus all the numbers, graphs, and general science-y feel of the websites. And you have to highlight the risk of not using the product. You establish a happy world on the product side, and a sad, anxious world on the not-product side, and then it's clear where the consumer should go.
Expanding a market is both a persuasive and an interpretive act. It involves a delicate balance between stigma and acceptance. If the condition is too stigmatized, people won't willingly admit they have it; conversely, if it's accepted as a normal part of being human, then people won't buy treatments for it. So, for example, you recruit a celebrity to be open and self-accepting about his ADD – and yet you portray children as hidden or obscured or weighed down by the condition. A delicate dance.
This balancing act is particularly important for a condition like ADD that is diagnosed on the basis of self-reported symptoms. In other words, absent an objective test, what people think they have shapes what they say about themselves to a doctor. Hence the importance, presumably, of self-administered questionnaires – which, as the Times reports, tend to indicate the possibility of ADD far above its actual occurrence in the population.
I was interested to read, too, that the selling of ADD drugs began with a bit of wordplay on the part of a pharmaceutical executive:
All. For A.D.D. A.D.D. for All. Adderall.
“A.D.D. for All” may be Pharma’s wishful thinking – but “ADD for many” is what they’ve managed to achieve. According to the article, “sales of prescription stimulants have more than quintupled since 2002.”
In the case of drugs like Adderall and Concerta, the interpretive act, the meaning-making achievement, is enabled by considerable financial muscle. Since corporations are people now, let’s call Shire (the company that sells Adderall) something friendlier, like Brad. Here’s what Brad can do: pay for research with a friendly conclusion; pay for doctors to be exposed to the research; cause millions of brochures to be written, printed, and distributed; take out state-of-the-art ads in mass-market, industry, and medical publications; sponsor parent advocacy groups; write and distribute comic books aimed at children; hire armies of sales representatives to pitch doctors directly; and hire Adam Levine (the frontman of Maroon 5, and celebrity judge on The Voice) to front your campaign.
The question that preoccupies me is this: How to respond? How does an actual person with an opinion – a person-person – respond to the sort-of person that is a corporation? When the sort-of person can spend millions not only to get a persuasive message out, but to alter the basis of fact from which we operate in the first place, how does a person-person respond?
Perhaps the first task would be to establish a taxonomy of error: to detail the standard abuses in the selling of new advances. Lots of work has been done on this, so I don’t expect to cover new ground here. But I would suggest, as a way of beginning the conversation, the following checklist, which could be used as a diagnostic tool when looking at advertising for a product.
Is persuasion being presented as information?
Are deep, irreducible human qualities being reduced to diagnostic categories? Are ways of being formerly thought to be part of life being pathologized? In what ways are the limits of “health” being expanded?
What would the world look like if everyone who possibly could use the product did use it?
In what ways is risk being portrayed? In what ways does the product on offer promise to reduce or eliminate risk?
In what ways are the risks of the product itself being minimized?
In the advertisement, is there anything that seems an absolute, inarguable good, like “a healthy child?” If so, what – or whom – does this good exclude? Or, to put it another way, with what other absolute, inarguable goods does the first good conflict?
Perhaps questions like these offer a partial solution to our lonely-prophet problem. To be interested in the effects of new human biotechnologies is at least in part to be interested in the way those technologies are sold.
On November 22, the Food and Drug Administration (FDA) ordered 23andMe to "immediately discontinue marketing" its direct-to-consumer genetic tests unless and until the agency grants it regulatory approval. This is the culmination of more than four years of discussion, in which it seems that the Google-backed company has become increasingly unresponsive.
The Center for Genetics and Society issued a press release welcoming the FDA's action. Executive Director Marcy Darnovsky said:
Our society regulates medical products to protect public health. Without strong public oversight, we're back to the era of snake oil.
Karuna Jaggar, the executive director of Breast Cancer Action (one of the plaintiffs in the successful Supreme Court challenge to the permissibility of patenting human genes), wrote in an article at Huffington Post:
[G]enetic testing is fraught with moral and medical complexity … [and] must adhere to medical rather than business ethics … the FDA has taken a welcome stand to protect public health by insisting that what is clearly a medical service be regulated as such.
Not everyone agreed. GenomeWeb has a roundup of initial reactions: two of the more forceful were "outrageous" (libertarian Ron Bailey of Reason) and "borderline absurd" (Misha Angrist, who used to blog as Genomeboy). Genomics Law Report has useful, and much less dramatic, summaries of the issues (1, 2). Bio-IT World offers a somewhat more speculative collection of opinion, which notes that 23andMe CEO Anne Wojcicki admitted in a blog post that "the regulatory process with the FDA [is] important" and asks pointedly:
If it's so important, why isn't 23andMe participating?
Stanford law professor Hank Greely wondered about that too, highlighting this sentence from the FDA letter:
You have not worked with us toward de novo classification, did not provide the additional information we requested necessary to complete review of your 510(k)s, and FDA has not received any communication from 23andMe since May.
This sounds as though 23andMe started down the FDA path but, six months ago, not only stopped communicating with the agency but started new and bigger marketing efforts. That sounds as though 23andMe did not just ignore the FDA, but, while walking briskly past it, quickly turned and spat in its face.
Similarly, Forbes' Matthew Herper supports direct-to-consumer genetic testing but headlined his piece:
23andStupid: Is 23andMe Self-Destructing?
That is possible. Less than a week after the FDA letter, a class action lawsuit was filed against the company, citing the letter, and accusing 23andMe of "falsely and misleadingly" advertising their service as providing health services it cannot justify. In the assessment of John Conley, of Genomics Law Report, this is "certainly a case with significant potential." His colleague Jennifer Wagner followed up with more analysis.
The attorney who filed the suit commented to the Associated Press about the 23andMe business plan:
"It seems to me to be a very thinly disguised way of getting people to pay them to build a DNA database."
CGS has suggested this repeatedly since 2007 (kudos to former staffer Jesse Reynolds). And Charles Seife, writing in Scientific American, sounded a similar note in an article titled "23andMe Is Terrifying, But Not for the Reasons the FDA Thinks":
The Personal Genome Service isn't primarily intended to be a medical device. It is a mechanism meant to be a front end for a massive information-gathering operation against an unwitting public.
Greely, who supports the FDA's move, suspects that the company is transitioning to whole-exome and whole-genome sequencing. That might be a reason that they were — and perhaps still are — stalling the FDA. But it could be a high-risk strategy. John Wilbanks put it succinctly:
I'm a deep believer that genetics generally, and personal sequencing in particular, will drive a marked and permanent change in health. But 23andMe are either there today or they aren't. They dealt the play last summer when they started this process, and advertised it. They've upped it by framing themselves as a daring company. But they're going after the FDA with this strategy. And if you come at the king, you best not miss.
This game is far from over, and the stakes are bigger and broader than the fate of a company that Silicon Valley techno-enthusiasts adore. The clamorous debate about 23andMe's troubles is surfacing questions about genetic hype and the geneticization of health; about the role of public policy in protecting public health; and about whether a glamorous and well-funded company will be permitted to make dubious marketing claims about its product, mislead its customers about its business model, and thumb its nose at the public agency that's mandated to regulate what it's selling.
A paper published in Nature early this week declared that learned fears can be inherited through multiple generations of mice.
Yes, this sounds an awful lot like Jean-Baptiste Lamarck’s long-discredited theory of the heritability of acquired characteristics, and yes, it is throwing scientists into disarray. Journalist Virginia Hughes captured some of the tweets that followed the news: “This is insane. Lamarckism, simply.” “Crazy Lamarkian shit.” “Astonishing if true.”
Here’s what happened: Emory University neuroscientists Kerry Ressler and Brian Dias trained mice to fear the smell of a specific chemical by exposing them to the scent while giving them small electric shocks; eventually the mice learned to fear the smell without the shocks. This kind of Pavlovian conditioning is routine. What is remarkable is that the learned fear reaction was passed down through two subsequent generations. Without ever having encountered the smell in their lives, the mouse pups exhibited the same reaction of fear around the scent, while a control group of pups did not.
What’s more, the brains of the mice were altered – they somehow had more neurons and bigger signal-receiving structures to help them detect the scent. According to Dias, “The overwhelming response has been 'Wow! But how the hell is it happening?'"
The answer to that question, Ressler, Dias and others believe, lies in “epigenetics,” the way in which traits can be inherited through changes in gene expression caused by mechanisms other than changes in the underlying DNA sequence.
There is, and will surely continue to be, a lot of skepticism about this kind of behavioral epigenetic research. The authors of the paper haven’t been able to identify a biological mechanism to explain how it actually works. But what would have simply been laughed at ten years ago is certainly gaining credibility as the field of epigenetics matures, and studies begin to mount.
The idea that the environment can modify how genes are expressed is fairly well accepted now. For example, surviving a famine as a fetus seems to increase the risk of getting certain diseases as an adult.
There have also been other studies that show transgenerational epigenetic changes in animals. A study of rats from the University of Texas, for example, suggests that exponential rises in obesity, diabetes, and autism in humans could be due to our grandparents’ exposure to chemicals in plastics, fertilizers and detergents. Other papers from 2010, 2011, and 2012 suggest that diet and stress can impact future generations.
But the inheritance of behavioral modifications could be the most controversial of all. And Ressler and Dias suspect that this phenomenon isn’t limited to mice.
The implications of this are pretty huge. It means that the experiences of our recent ancestors have left what could be called “molecular scars” on our DNA and on our lives, and that we will do the same to our children and grandchildren. This requires the reconsideration of much of what our biology textbooks taught us, and it will impact everything from medical research, to sociology, to neuroscience. As an article in The Telegraph put it earlier this year, “the idea is heretical.” But it seems to be one that’s here to stay.
The new novel by Dave Eggers, The Circle, is a provocative romp and a missed opportunity. It raises a lot of very interesting questions about many topics, some — but not all — of which are listed on the dust jacket, and at McSweeney's:
memory, history, privacy, democracy, and the limits of human knowledge
That's quite a list! Add in, oh, capitalism, anthropology, politics, class, the prevention of crime and the promotion of good behavior, generational struggles and problems of entitlement, among others, and we have a very ripe philosophical stew. To which, unfortunately, this page-turner does not do full justice. But it does have something to tell us about the culture of high tech; it's a dystopia with a purpose.
There are no major spoilers here (though you'll find some if you follow the links), because I do recommend you read The Circle. I have literary criticisms: the character development of the protagonist — Mae Holland, a new and talented employee at the story's start — is unconvincing; the secondary characters tend to topple over into caricature; some of the plot twists seem either predictable (I nailed the big reveal very early) or random. But the book's considerable interest lies in its setting.
The story takes place in the near future, where the Circle has become "the world's most powerful Internet company." It's a kind of combination of Google, Facebook, Twitter ("zings" are how Circlers recommend and comment on items), PayPal and more, with a dash of Apple and about 90% market share, globally. The Circle "has subsumed all the tech companies we know of now, linking users' personal emails, social media, banking, and purchasing with their universal operating system."
Eggers has been criticized, not unreasonably, for the phrase "universal operating system" and the assumed ease of the Circle's victory. A review in Wired was titled "What the Internet Looks Like if You Don't Understand It." But it does seem that the techies are protesting a little too much, perhaps because Eggers nails some of the major characteristics of their subculture. (He was even accused, before publication and apparently without evidence, of plagiarizing the memoir of an early Facebook employee.) Indeed, much of what Eggers describes, as several commenters have noted, is already here:
A lot of times I'd think of something that a company like the Circle might dream up, something a little creepy, and then I'd read about the exact invention, or even something more extreme, the next day. … But in general, I tried to write a book that wasn't so much about the technology itself, but more about its implications for our sense of humanity and balance.
Arguably, the real issue is not even the implications of the technology, but the culture of the people who develop it. In the real world, that means not just the likes of Mark Zuckerberg, Sergey Brin, Larry Page and the late Steve Jobs but many of the financiers behind them, many of the engineers they employ, and many of the eccentric talents they both respect and promote. It's the culture that produces Singularity University, the idea of Seasteading, dreams of immortality — all of which trumpet idealism mixed with a greed so assumed it's not even denied. And that is all well delineated in The Circle.
There is a long dialog near the center of the book (I have to be careful here for those who haven't yet read it) that expounds what is essentially a standard, and rather sophomoric, libertarian brief for abolishing privacy, filled with annoyingly glib generalizations. This is of course a set-up: Eggers is showing us what he doesn't buy, and hopes his readers will reject. But disappointingly, he never finds space in the book's 491 pages to rebut these ideas in any effective way. Instead, he provides separate, much shorter, emotional and vaguely hippie rationalizations for opting out of the technological system. I personally find them more appealing than the world of the Circle — but no more convincing. There is a serious lack of explicit critical analysis, even though the characters are there who could provide it.
And then there are the issues untouched by the book: privilege, primarily, in manifold forms. There are some almost offhand references to inherited class, and to racism (as history); there is a family struggling with healthcare in the modern United States; but nothing about the exploitation of overseas workers who do the bulk of the work for the techno-billionaires of our just-barely pre-Circle world.
All information, for the true believers in the Circle, should be completely available to everyone: secrets are lies, sharing is caring and privacy is theft. The assumption is that with that freedom of data will come liberation for all and the perfection of society. That's a large part of what Eggers is debunking, to the chagrin of some of his techie critics, though others are stimulated by the book, or even find it already passé. However, he fails to provide a critique that is likely to convince the techno-utopians. Whether that is due to the limitations of his novel or the impenetrability of the subculture he is trying to skewer is a question worth pondering.
Almost a month ago, as I noted here, there was a flurry of publicity about the "gene editing" technology known as Crispr that has been developed over the last couple of years. I put the media attention down to the self-interest of The Independent, a failing British newspaper, which used the threat — portrayed as promise — of germline engineering to publicize its latest relaunch.
But perhaps the paper was itself being played. Strangely, there seems to be no mention at The Independent's website of the topic of this press release (pdf):
Editas Medicine Created to Discover and Develop Novel Class of Genome Editing
Therapeutics Company Founded by Five World Leaders in Genome Editing; Secures $43 Million Series A Financing Led by Flagship Ventures, Polaris Partners and Third Rock Ventures
The basis of the company is indeed Crispr technology, which is said to be able to cut DNA at precisely defined positions and insert material to order. Its co-founders are Feng Zhang, George Church, Jennifer Doudna, Keith Joung and David Liu. The press release accurately says:
The company's five founders have published much of the foundational work that has elevated genome editing technology to a level where it can now be optimized and developed for therapeutic use.
Editas has not only lined up major financing, they already have a management team in place. Interim President Kevin Bitterman (of Polaris Partners) told Fierce Biotech:
"We think we're going to lead the way. We're making the big jump out of bacterium, where this machinery was discovered. And there's now a growing body of proof-of-concept that you can broadly target genes. We have the ability to essentially target any gene in the genome. And we have in our crosshairs any diseases with a genetic component. We can go in and fix the error."
Joung told the Boston Globe: "The way to think about it is molecular surgery." MIT Technology Review implied that Church pointed to Huntington's disease as a candidate, though the founders "won't talk specifically about the diseases they will try to address." Nature News checked with the competition, Sangamo BioSciences of Richmond, California, which uses a different technology, zinc-finger nucleases; Sangamo's chief scientific officer notes that technical issues with Crispr technology remain. But Editas will certainly be worth watching.
Adrienne Asch, bioethicist, scholar, and disability rights activist, died Wednesday morning at her home in New York City. Online tributes from her colleagues, students, and friends attest to the wide and deep impact she had on those who knew her work, and especially on those who were fortunate enough to know her personally.
Adrienne’s work and thinking about prenatal selection technologies and practices, a perspective on them grounded in both disability rights and reproductive rights, and what she termed markets in “genes and gestation” exerted a strong influence here at the Center for Genetics and Society. As one colleague put it, “Adrienne challenged our misconceptions, deepened our understanding, and inspired us to more inclusive perspectives.”
Two especially influential books that Adrienne co-edited are Prenatal Testing and Disability Rights (Georgetown University Press, 2000) and The Double-Edged Helix: Social Implications of Genetics in a Diverse Society (Johns Hopkins University Press 2002).
Adrienne was an opening plenary speaker at CGS’s 2010 Tarrytown Meeting. Her brief comments there, available on YouTube and below, showcase both her keen insight and the graciousness that she always tried – and often managed – to bring to discussions of intellectually and emotionally challenging issues. Here are a few roughly transcribed excerpts:
I don’t want to assume that all of us share everything I’m going to say. I hope part of what we’ll do is figure out what we share and what we don’t, and how to work with what we do share and how to deal with our differences.
Many of us here have spent considerable time trying to argue against what we see as dangers of extreme parental selectivity, or of markets in reproductive labor and genetic materials. Here I want to suggest three concerns for group discussion: a concern about selection [in which I include adoption, gamete selection and prenatal testing], a concern about markets – even if those markets don’t include selection – and a concern about the frequent dismissal of what are termed “symbolic harms.”
We have a difficult task: how to find the shared values and language to reach our philosophical opponents, and the millions of people in this country and worldwide who haven’t considered these questions at all. Why do we, and why should the rest of society, care about symbolic harms – and why are they more than symbolic?
Adrienne Asch at The Tarrytown Meeting, July 2012
Thanks to former CGS program associate Brendan Parent for sending a list of organizations to which you can donate in Adrienne's honor:
Disability Rights Education and Defense Fund, Berkeley CA
Lisa Jardine, the chair of the Human Fertilisation and Embryology Authority (HFEA), has announced that she will be stepping down from her position as head of the United Kingdom’s regulatory agency for assisted reproduction in January 2014. Since the announcement, she has been vocal about a number of important points.
In an interview with The Independent, Jardine argued that some IVF clinics have been over-using intracytoplasmic sperm injection (ICSI), a technique involving the insertion of sperm into eggs with micro-manipulation devices. She points out that although ICSI makes in vitro fertilization procedurally easier, it has limited utility and carries documented risks to resulting children.
In a commentary she wrote for the BBC, Jardine also warned that IVF still has a very high failure rate. “The world of IVF is a market, a market in hope,” she said. “Those who enter it deserve to be fully informed of its potential to deliver grief and a sense of failure, as well as success.”
However, for some reason, Jardine seems to be actively propagating highly dubious hope around extremely controversial and unverified mitochondrial replacement techniques. These would create an embryo through a biologically radical process that would combine genetic material from three people. The procedure has received extensive regulatory guidance from the HFEA. If the UK decides to carve out an exception to an existing law in order to allow clinical trials of mitochondrial replacement, it would become the first approved form of inheritable human genetic modification anywhere in the world.
While many people are alarmed and disturbed by that prospect, Jardine seems proud of her personal involvement with the issue. In a short press statement on her departure, she noted,
I am particularly honoured to have overseen the ‘Medical Frontiers: debating mitochondria replacement’ public consultation. It clearly demonstrated the specialised ability the HFEA has to engage, educate and communicate complex science and public opinion.
Jardine is disappointed she will not be able to see through the HFEA’s consultation on mitochondrial replacement – the so-called “three-parent” IVF babies who will receive their mitochondrial DNA from a donor egg.
Jardine apparently sees her work on this technique as a high point of her six years at the HFEA. Under her guidance, the HFEA certainly has played a critical role in advancing the potential change to UK law that could allow scientists to attempt human clinical trials as early as next year.
The trouble is that there are many reasons to believe that mitochondria replacement poses profound safety, social and ethical concerns, and there are a growing number of people, from scientists, to activists, to politicians, who have spoken up about them. But for some reason, Jardine has been extremely reluctant to accept these varied and widespread critiques. In an article she wrote for the BBC, she stated,
Over the past two years, the HFEA has carried out a consultation process with clinicians, scientists and the public in order to advise the present government on whether this technique - which has up to now only been allowed in the research laboratory - should be introduced into clinical practice. Perhaps surprisingly, the public supported the new technique, if it could prevent serious illness. They had little objection to its being approved for clinical use, as long as it was scrupulously overseen by an appropriate regulatory body.
Pete Shanks and I wrote a blog about the HFEA’s claim of "public support" shortly after its report came out. We were surprised to read – in the agency’s own report –that in what was by far the largest strand of the public consultation, and the only one open to everyone, the majority of people were against the introduction of any form of this technique, for a broad array of reasons.
We weren’t the only ones who noticed the discrepancy between the consultation’s data and what the HFEA reported to the public. But the HFEA responded defensively to the claim that they misrepresented their data, saying, “Our consultation was a more nuanced exercise than simply counting up votes for and against the techniques.”
I’m not sure what “nuanced” could mean other than that they seem to have considered the voices that agreed with them and disregarded the rest. I truly don’t understand why Jardine is comfortable saying that “the public supported the new technique.” At best, this is an over-simplification of an extremely socially and historically important moment. At worst, it is an example of exactly what she has decried: pandering to the market of hope, at the expense of desperate patients.
In early November there was what GenomeWeb accurately called "a media swoon" about one particular gene editing technology, and "in particular the question of whether this method may be used to improve people at the germ line level." Less than two weeks later, the brouhaha seems to have evaporated, but it's worth examining because it shows how media manipulation can distort scientific reality.
The story was launched (5 pages/month free; text also here) in London by The Independent, a roughly center-left newspaper that is by some distance the lowest-selling British national daily. Doubtless this explains why the editors keep fiddling with the paper's design. Originally a broadsheet, it switched to a smaller format in 2003-4, redesigned in 2005, with tweaks in the next few years before a major revamp in 2010, adjusted again in 2011 … and still the sales continued to fall. So on November 7, 2013, it changed again.
But even the greatest design needs content to sell. And what did they choose? The front page (pictured; larger here) featured a large picture of Yasser Arafat, separated by a modest horizontal line from the main headline:
The next genetic revolution
(Seriously, did no one notice this juxtaposition?) Arafat has been dead for 9 years, and the rumors about his poisoning had been floating around for weeks. The top of the page pushes a speculative piece about President Kennedy, the anniversary of whose death was still two weeks away. The other teasers discuss a Russell Brand interview that was already two weeks old, a TV show hooked to twerking (the October sensation), and two political thumb-suckers that could have run in any month this year or last.
In other words, they were not news. Nor is the so-called "genetic revolution," notwithstanding the Independent's headline:
Exclusive: 'Jaw-dropping' breakthrough hailed as landmark in fight against hereditary diseases as Crispr technique heralds genetic revolution
This front-page story by Science Editor Steve Connor was supported by a separate interview (also here) with Jennifer Doudna of UC Berkeley, a video explanation of the science, and an op-ed by Nobel laureate Craig Mello ("a triumph of basic science with huge implications"). The day after, the Independent featured a round-up of quotes ("Scientists call for more public debate") and the initial coverage was topped off with an editorial:
March of science: The 21st century will be the age of genetics. It is time to put our fears about 'designer babies' into perspective.
That's a lot of "exclusive" discussion. The development that underlies it all is a gene-editing technique that was hailed as "a Swiss army knife" — in August of 2012. Its cute acronym, Crispr (Clustered regularly interspaced short palindromic repeats), helps its media appeal, but the work is real and important.
Doudna, Emmanuelle Charpentier of Umea University in Sweden, and their colleagues identified an enzyme, CAS9, that could cut both strands of DNA at a specified location. From the interview:
"You can actually introduce new genetic information at the site of cleavage. So it has become a powerful way of doing genetic engineering. It's a fundamentally different way of recognising DNA target sites," Professor Doudna said.
Could this be done in human cells? Yes, that has subsequently been demonstrated by several teams, including Doudna et al. (pdf here) and — slightly earlier to press — in two papers published online in Science on January 3, 2013, by Feng Zhang et al. and by George Church et al., who note that:
Our results establish an RNA-guided editing tool for facile, robust, and multiplexable human genome engineering.
Cheap and Easy Technique to Snip DNA Could Revolutionize Gene Therapy
And does anyone have scientific doubts about the technique? Why, yes they do. In June, this letter was published in Nature Biotechnology:
High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells
In other words, the accuracy of the technique may have been overstated, leading to unexpected genetic alterations.
The Independent's recent series lacked any such context. It is, essentially, a magazine-style puff piece and that's all. It's admittedly based on genuine science, but that is still evolving, and subject to an entirely normal process of professional criticism. Moreover, Connor just had to add the designer-baby twist to his interview:
But perhaps the most intriguing and controversial application of Crispr-CAS9 will be the possibility of altering the genes of IVF embryos. Studies on mouse embryos show it is incredibly effective, and some IVF doctors may want to see if it can work on human embryos — which is illegal in Britain at present because it amounts to "germline" gene therapy.
Doudna, responding, downplayed this:
"Certainly, at this stage, I don't think we understand it well enough. Would you be correcting one problem but introducing others?"
But Connor had his story. Which caught the interest of the Daily Mail (circulation about 25 times larger than the Independent's) and Newstrack India, among others. Kate Henderson of the Las Vegas Guardian Express put together a pretty good selection of the notably enthusiastic quotes from the various articles. And thus talk of human germline intervention pings around the globe.
Fortunately, there was some pushback. BioNews ran a piece that included some mildly moderating comments, some of which seem to have been provided by the Science Media Centre (itself the subject of controversy for pro-GM publicity). The consensus was that there remains "a long way to go," the technology requires "a significant amount of work" and "the hype needs to be tempered with a little caution." Church, with his usual knack for the media-friendly quote, commented:
"Talking about the future is better than letting it sneak up on us. We need to do more of this or we will be left with very limited vocabulary in the space between positive and negative hype."
According to the Guardian (admittedly, an interested party), the Independent's re-launch boosted the its national circulation on day one by only 3,000, most of which evaporated the next day. But the hype may linger on.
Posted by Miriam Zoll, Biopolitical Times guest contributor on November 15th, 2013
Recently the American Society for Reproductive Medicine (ASRM) asserted that “60 percent of women who go through [fertility] treatments eventually end up with a baby.”
Those just entering the often-confusing and misleading world of assisted reproductive technology (ART) statistics, may mistakenly assume that out of 100 women randomly walking into a clinic, 60 will emerge with a baby in their arms.
Prospective patients deciding whether to invest precious time and resources toward reproductive medical services, or pursue adoption or foster care, need to understand what the ASRM’s statistic actually means and how it differs from, and is similar, to information provided by the Centers for Disease Control (CDC). That agency’s 2010 statistics found that, overall, 70 percent of cycles result in childlessness.
The two data sets are, to quote an old adage, apples and oranges. The difference between them has to do with how and what is being counted.
Analyzing data about pregnancies per cycle, a careful review of CDC statistics based on age found a 58 percent failure rate in women 35 and younger; 78 percent failure rate women 37-39; an 88 percent failure rate in women 40-42; and a 95 percent failure rate in women 43-44. The data cited by the ASRM is pulled from one study published in 2012 in the New England Journal of Medicine, “Cumulative Birth Rates with Linked Assisted Reproductive Technology (ART) Cycles.” It also confirms a 70 percent failure rate per cycle.
The study’s ‘best possible’ numbers scenario of 60 percent rests on pregnancy outcomes for 247,000 women who underwent no more than seven linked cycles over a four-year period. Approximately 25 percent of the women dropped out after the first cycle failed, and 33 percent after subsequent failed cycles. Roughly 50 percent of the women were younger than age 35—the age group consistently known to experience the highest ART success rates. Indeed, of the women in the study who were younger than 31 years of age, 63 percent experienced live birth. Among women 40 and older, there was an 81 to 93 percent failure rate––a failure rate consistent with the CDC data reported by age. Had half the study group been older than 40, the live birth outcomes would have been significantly lower.
Many women choosing fertility services never reach the IVF “cycle” phase. Some succeed with less invasive procedures while many others cannot afford to pay for multiple cycles. In addition, a ”live birth” does not necessarily mean couples bring home a healthy baby; multiple embryo transfers can often lead to premature births and expensive, prolonged stays in neonatal intensive care units.
When we think about how best to educate prospective patients/consumers, the NEJM study is important for a host of reasons. First, it confirms that those buying these services should plan for multiple cycles and all that they entail––including drug side effects, miscarriages, strained relationships, depleted bank accounts––and the debilitating grief that goes along with all of it. As someone who has run the gamut of IVF procedures without conceiving, I can attest that the psychological costs are immeasurable, while the long-term health risks remain largely unknown. Additionally, with so few insurance policies in the U.S. providing coverage for more than one or two cycles, the study’s findings reinforce the need for customers to budget anywhere from $40,000 for two cycles, all the way up to $200,000 for ten or more.
The study also verifies that older women using their own eggs experience the least success with IVF, signaling a greater demand for controversial egg donation. Infertility specialists obtain third-party eggs by injecting so-called “donors” with potent drugs that can cause serious side effects, ranging from dangerous swelling of the ovaries to infertility, stroke, and in rare cases, death.
ART services are packaged in hope, and can be very difficult to walk away from. There are serious emotional and physical risks involved––for women, their partners, donors and surrogates, and any potential offspring. This is all the more reason why those contemplating treatments should think very carefully about the notion of self protection, and determine ahead of time how many and what kind of interventions they plan to pursue before they begin.
Miriam Zoll is the author of the new memoir-expose, Cracked Open: Liberty, Fertility and the Pursuit of High-Tech Babies (Interlink-June 2013). She is a member of the boards of the global women's health and human rights organization, Our Bodies Ourselves, and Voice Male Magazine.
More than a hundred participants of diverse backgrounds and disciplines heard presentations from three panels, took part in facilitated small-group discussions, and watched a sneak-preview screening of a new documentary.
A number of questions inspired and illuminated the day: Why do the legacies and implications of eugenics matter now? How can we address them in teaching and pedagogy, in policy and activism, and in art? What are the social and ethical consequences of omitting eugenics from historical memory or misrepresenting it? What is the price of the pursuit of "human betterment" for reproductive and disability justice? What is being done – and what can be done – to increase understanding of the legacies of eugenics?
The participants were welcomed by SFSU Provost Sue Rosser and Catherine Kudlick, Director of the Longmore Institute. The symposium's three panels then framed the day:
WHAT? Eugenics and Disability, Past and Present
SO WHAT? The Consequences of Misremembering Eugenics
The National Institutes of Health (NIH) is accepting public comments until November 20 on a draft Genomic Data Sharing Policy “that promotes sharing, for research purposes, of large-scale human and nonhuman genomic data generated from NIH-supported and NIH-conducted research.” NIH provides an easy online form to fill out if you’d like to share your thoughts.
And therein lies the fundamental struggle facing genetic research. Genomic data is an extremely valuable resource; open access to large amounts of it could lead to improved understanding of the human genome and better ways to diagnose, treat, and prevent disease. But it could also pose risks to the individuals whose genetic information will be freely available. The NIH draft policy assures that provisions to protect privacy are included; for example, information will be connected not to a person’s name or date of birth, but to a random unique code. Research participants will also have some say over whether their data is available through open or controlled access.
However, a series of high-profile database hacks has shown that complete privacy or control is probably impossible. In June, Steven E. Brenner wrote an in-depth article in Nature warning, “It seems inevitable that there will be a major leak of genome information in the near future.”
Moreover, it doesn’t sound as though there will be much room for wary researchers to get around the NIH policy. It will apply to all projects involving large-scale genomic data funded in any way by the NIH, and failure to comply could lead to the withholding of funding. This may cause researchers to encourage participants to agree to share their data broadly, and could limit the likelihood that participants will choose to evade this pressure. The NIH says it will accept data derived before the policy goes into effect, and require any studies initiated afterward to inform participants that their genomic and phenotypic data will be shared broadly.
This policy could mark a critical shift in the landscape of genomic research. Importantly, it’s a move away from private efforts to monetize genomic data by limiting access. The NIH document emphasizes the Supreme Court decision that naturally occurring DNA sequences are not patentable and states that, “the NIH discourages the use of patents to prevent the use of or block access to genomic or genotype-phenotype data developed with NIH support.”
However, if genomic information does lead to the creation of drugs, tests, and treatments that are patentable, the people who provided the raw material will surely not be receiving any thanks. Furthermore, people giving away their genetic data should be aware that it is not only their personal privacy that is at stake; genetic information implicates entire families.
Not to disparage the lofty intentions of the NIH or genetic researchers, but the extent to which various organizations and companies are now vying for my DNA makes me somewhat uncomfortable. If the “open-access” model really does spread globally, people may feel that they’re a part of something important, even revolutionary, as the Personal Genome Project founder George Church likes to say. But, to me, it's all starting to feel a bit like a corporate colonization of our bodies, at the most intimate level.
ABC World Newsjoined other media this week in addressing the astonishing 74% rise over the past ten years in young women providing their eggs so that other women can create families. Correspondent Cynthia McFadden interviews egg “donors” and fertility practitioners to explore the risks of egg retrieval, and chats with anchor Diane Sawyer about the story. While the segment lets several misleading statements stand, it gets some important things right.
First, the report is clear about the point that young women, primarily college students, are recruited to become egg providers with offers of thousands of dollars (yet use of the term “egg donor” for what is a commercial transaction is misleading). Women who are considered better-looking are typically paid more, as are white and Asian women, and those who have higher SAT scores and/or athletic skills. More money also goes to “proven donors” – women whose eggs have been used by “intended parents” to achieve a successful pregnancy.
The story also correctly reports – and expresses appropriate surprise about – the lack of short- or long-term tracking of egg providers’ health and the fact that there is no national database for egg providers. As Dr. Jennifer Schneider points out in the segment, egg providers are “not considered patients – they’re considered more like vendors.” They essentially disappear as soon as the procedure is done.
Now let’s turn to the inaccuracies in the ABC World News story.
McFadden interviews Dr. Joel Batzofin, a reproductive endocrinologist, who states that although “nothing is risk free,” egg extraction is “essentially risk free.” He describes the short-term complication known as ovarian hyperstimulation syndrome or OHSS as “extremely rare” and says it occurs in less than 1% of cases. Unfortunately, his claim remains unchallenged in the segment, despite emerging evidence that OHSS occurs much more frequently than that. One prospective study analyzed OHSS rates in 339 women who produced more than 20 ovarian follicles. 49 (14%) were hospitalized due to OHSS, 13 (3.8%) needed intravenous fluids, and 9 (2.7%) needed to have fluid drained from their abdomens.
Egg providers are commonly stimulated to produce more than 20 follicles, and therefore appear to be at much higher risk for OHSS than is currently being reported. A recent study in theJournal of the American Medical Associationfound that more than 21 eggs were retrieved in 40.3% of the retrieval cycles performed on "oocyte donors." Furthermore, preliminary collaborative research on egg provider experiences by CGS and We Are Egg Donors has found numerous cases of women experiencing OHSS to the point