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 pounds (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 webcast of the first day – particularly the afternoon session, 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 where they are bedridden for a week or more. Even though doctors and clinicians assure egg providers that OHSS is “rare,” no one is surprised when it occurs. When donors are in pain and bloated to the point where they look six months pregnant—after their eggs have been retrieved—they are told that this is “normal,” and to rest and drink plenty of fluids. These cases are not even diagnosed as OHSS, let alone reported or tracked, so there is no data to substantiate that it only occurs in 1% of cases.
The ABC World News segment is equivocal in its discussion of links between egg retrieval and cancer. McFadden reports that “there are no known long-term medical issues for donors,” but goes on immediately to say that this is “a world of difference from saying [that there are] no long-term issues.” In fact, some data does suggest that the synthetic hormones used in egg retrieval may increase risk of colon, ovarian, uterine and breast cancers, though it is difficult to prove the connection due to the delayed onset of cancers in former egg providers and infertility patients. One Dutch study published in Human Reproduction by Dr. Flora van Leeuwen followed over 19,000 women for 15 years and found that those who had undergone at least one IVF cycle were approximately twice as likely to suffer ovarian malignancies as women who had not undergone IVF treatment.
So how does the ABC World News report rate overall? We recognize that it is not possible in a three-minute segment to cover the entire gamut of egg retrieval risks and experiences but would have liked to hear a mention of the side effects of Lupron (which is used off-label and has been known to cause strokes and a variety of dangerous side effects) and Clomid (which has been linked to increased cancer risk in women who don’t go on to become pregnant). We would also have liked to see correspondent McFadden question the claims made by Dr. Batzofin, and point out that he and others in the infertility industry stand to profit from taking eggs from young women.
At the same time, we applaud ABC World News for its clear and explicit
call for follow-up studies of egg providers and for a national database
to track their short- and long-term health.
Synthetic biology has been attracting mainstream attention recently, most prominently in Foreign Affairs. The most significant advances, however, may not be the ones on which policymakers seem likely to focus. In October, there was a new indication of the practical power of the technologies being developed.
There are at least two broad schools of synthetic biology research that may lead to brand-new organisms. Until recently, the team headed by Craig Venter, the noted entrepreneur who made his name during the sequencing of the human genome, could claim to have the lead. But that seems to be changing.
Venter's team has been focusing on finding out how few genes are needed to make a workable organism. In May 2010 they announced what they called "the successful construction of the first self-replicating, synthetic bacterial cell." Many critics complained that it was not strictly synthetic since the work relied on the cytoplasm of a recipient cell to get the process started. Venter is not worried about that, telling New Scientist recently:
We're not trying to recapitulate the origins of life. Obviously, life evolved from much simpler systems, but in terms of trying to get to the next stages of evolution that is not very useful. … Understanding what a basic operating system looks like is essential. Then, we should be able to add components to evolve it into a new species.
Teams led by Farren Isaacs at Yale and George Church at Harvard have taken a very different approach. Theirs is to make changes to an existing genome, such that the resulting organism has a fundamentally new genetic code, which would therefore produce new proteins. They succeeded (Science papers 1, 2) and managed to make multiple changes simultaneously. This is a potentially huge step in the direction of creating brand-new life-forms. Isaacs explained:
This is the first time the genetic code has been fundamentally changed. Creating an organism with a new genetic code has allowed us to expand the scope of biological function in a number of powerful ways.
The feat was achieved using a technique called multiplex automated genome engineering, or MAGE, which involves designing fragments of single-stranded DNA that, with the assistance of viral enzymes, would replace existing UAG codons in RNA with UAA when E. coli cells were zapped with electricity.
There are several potential short-term advantages to this process, such as making the new organism incompatible with wild types, so they theoretically could not escape from the lab. Church likes to stress resistance to viruses:
If we make a few changes that make the microbe a little more resistant to a virus, the virus is going to compensate. It becomes a back and forth battle. But if we take the microbe offline and make a whole bunch of changes, when we bring it back and show it to the virus, the virus is going to say 'I give up.' No amount of diversity in any reasonable natural virus population is going to be enough to compensate for this wildly new genome.
These results might also open a whole new chemical toolbox for biotech production. For example, adding durable polymers to a therapeutic molecule could allow it to function longer in the human bloodstream.
Applications are of course some way off — but the technologies that allow precise, targeted alterations to existing genomes are developing fast. And in a general way, awareness seems to be growing.
The articles at Foreign Affairs are rightly concerned with bioweapons, crime, terrorism and accidents. (An overview by Laurie Garrett is reposted here and an article by Ronald K. Noble on "policing the new biological frontier" is behind the paywall here.) These are significant issues, but relatively easy to imagine: They are not truly novel. Yet the science really is pointing to new directions, whose implications imply vast disruptions to the economy, as well as to our entire relationship with the natural world.
There are dozens more signs of activity:
A recent article in the Washington Post described synthetic
"bio-factories" (reprinted memorably in the Santa Fe New Mexican as
"Creating life-forms: There's an app for that").
Venter has been talking up the emailing of novel vaccines in digital form.
Synthetic vanilla is on the agenda; Friends of the Earth and others are campaigning against it.
And, on a more hopeful note, a student project at the latest iGEM synthetic biology competition focused on the damage done to the field by gender bias.
The field of synthetic biology has been long on promise for a decade now, and relatively short on practical application. Meanwhile, regulators have barely begun to discuss how to conduct responsible oversight of these new technologies. If there is one single conclusion to be drawn from October's news, it is that we are running out of time.
On October 21, over 170 leading scholars from around the world submitted a letter to the University of Minnesota asking for a public, independent investigation of the 2004 gruesome suicide of 26-year-old Dan Markingson, a psychiatric research subject.
Researchers at the University enrolled Dan Markingson in an AstraZeneca-sponsored study of antipsychotic drugs despite it having been noted that the psychosis for which he was being treated at a state mental institution made him incapable of making his own medical decisions. His mother tried to get him out of the research study for months, warning the university that her son was exhibiting dangerous signs, but her pleas were ignored.
Why would the University of Minnesota avoid this basic responsibility toward her son? Why would it later file an action against her to recover costs, until she agreed not to appeal the court’s dismissal of her lawsuit against it? Disturbingly, a previous investigation into Markingson’s death by the St. Paul Pioneer Press revealed that psychiatrists at the university were paid significant amounts of money from the drug manufacturers who sponsored the study. Dr. Jerome Kassirer, a former editor of The New England Journal of Medicinestated, “There was an overt conflict of interest, and there is reason to believe that the boy's death was an indirect consequence of the financial inducements of the study.”
Carl Elliott, a professor in the Center for Bioethics and the Departments of Pediatrics and Philosophy at the University of Minnesota who has been advocating a thorough investigation for years, recently discussed the full extent of the conflicts of interest,
If the mutilated body of one of your research subjects is discovered in a blood-soaked bathroom, who should investigate the death? If you want to be cleared of blame, it’s useful if the investigation is led by a colleague from your own department. If you were being paid by a drug company to recruit that subject into a research study, it’s best if your colleague is getting a paycheck from the same company. Best-case scenario: your colleague is on the university’s “conflict of interest” committee, too, just in case anyone raises questions.
This should not be the status quo. Such overt conflicts of interest threaten the ability of public universities to conduct high quality medical research. A full and independent inquiry into this problematic case could shed light both on conflicts of interest in university research, and on concerns about enrolling vulnerable patients in potentially harmful research studies.
Writers at the pharmaceutical industry publication Pharmalotheard from Eva von Dassow, the vice chair of the University of Minnesota Faculty Senate. She said that she would request that the recent letter be brought before the Faculty Consultative Committee, and that she would urge the University to respond positively to it.
A new study in the Journal of the American Medical Association by Kawwass et al. uses Centers for Disease Control and Prevention (CDC) data to show that the number of IVF cycles using third-party eggs is rapidly increasing, and leading to higher "success rates." Significantly, the authors’ criterion of "success" is a full-term singleton birth. It is heartening that researchers in the fertility field are so explicitly acknowledging that multiple pregnancies and premature births are not results to be celebrated, since they carry notable risks for babies and mothers.
Nor would you learn by reading most news articles about the risks of egg retrieval, or the appalling lack of follow-up studies on the health of egg providers. An exception is this story by Melissa Dahl, which states that “some doctors and advocates worry that too little is known about the long-term health and psychological impacts on the egg donors themselves” and quotes We Are Egg Donors co-founder Raquel Cool.
I think in the 30 years that donor eggs have been used, that very few questions have been asked toward us donors about how we feel about the experience….It’s sort of dizzying and it can be very, very isolating.
Perhaps it’s unfair to blame the news media – or for that matter the authors of the JAMA study – for not including information about the effects of egg retrieval on young women who sell their eggs. After all, the study was based on CDC data, and while CDC collects data on how many eggs are retrieved from third-party providers, and how many pregnancies result from them, it gathers no information at all about what happens to the egg providers themselves. In other words, CDC data can tell us a fair amount about what the title of the JAMA study terms "Trends and Outcomes for Donor Oocyte Cycles," but nothing about the outcomes for the women who are the source of those "donor oocytes."
Another set of numbers in the JAMA study gives the number of eggs retrieved per IVF cycle. In 40.3% of the egg retrieval cycles performed on "oocyte donors," more than 21 eggs were retrieved. For women having eggs retrieved for their own use – "Patients Using Nondonor (Autologous) Oocytes" – 13.1% of the cycles produced more than 21 eggs. These are large numbers. In fact, a study presented at the annual meeting of the American Society for Reproductive Medicine that was held last week (see "ASRM Meeting: What to Know"), showed that retrieving more than 15 "leads to increased risk of complications."
The study’s authors might have remarked on this finding, or mentioned the lack of data about health outcomes for "donors," but did not. However, their article was accompanied by an editorial that did make the latter point, in clear terms.
Dr. Evan Myers, a professor in the department of obstetrics and gynecology at Duke University Medical Center, stated that current data "have an important limitation—no data on health outcomes in donors." He continued:
Donors are at risk for all of the complications associated with ovulation induction, including the potentially life-threatening ovarian hyperstimulation syndrome. In addition, there is uncertainty about longer-term issues such as effects on the donor’s own fertility or the need to inform recipients about the discovery of health issues not known at the time of donation. Current evidence on donor outcomes is limited to single centers or to small samples susceptible to selection bias….
More complete data on both short- and long-term outcomes of donation are needed so donors can make truly informed choices and, once those data are available, mechanisms can be put in place to ensure that the donor recruitment and consent process at clinics is conducted according to the highest ethical standards.
Dominic Cummings, a senior adviser to the UK Secretary of State for Education, recently provoked a flurry of complaints by allegedly claiming that "a child's performance has more to do with genetic makeup than the standard of his or her education." In response, he insisted that he had "warned of the dangers of public debates being confused by misunderstanding of such technical terms." Whatever you may think of that defense, it's worth looking a little more closely, because Cummings' technocratic, effectively eugenic, definitely gene-focused approach is dangerously close to affecting public policy.
Cummings has been called "arguably the most brilliant" special adviser in the UK government, but he also seems to be viewed as something of a loose cannon who has been blamed for leaks and criticized for the use of "colourful" language. He was awarded a First in History at Oxford, and has a background in activism against the UK adopting the Euro, and then controversial stints in the Conservative Party apparatus.
As an education adviser, he wrote what is called, oddly, a "private thesis" for the UK's Secretary of Education. What Cummings himself calls an "essay" runs 237 pages and is modestly titled "Some thoughts on education and political priorities" (10.3 MB pdf). It is a … remarkable document. From the third paragraph:
Less than one percent [of English school-leavers] are well educated in the basics of how the 'unreasonable effectiveness of mathematics' provides the language of nature and a foundation for our scientific civilisation. Only a small subset of that <1% then study trans-disciplinary issues concerning complex systems. This number has approximately zero overlap with powerful decision-makers.
That's the flavor of the thing; basically, baffle them with bullshit. It's full of name-dropping: in the first four pages, we find mentions of Murray Gell-Mann, Thucydides, Rudyard Kipling, Dean Acheson, Carl Sagan, E.O. Wilson, Mark Zuckerberg, Linus Torvald and many more. Later on, Malcolm Gladwell is solemnly criticized because he "downplayed the importance of genes" as demonstrated in a New York Times review by Stephen Pinker. (This amuses me since I suspect that the three of them thoroughly deserve each other's company.)
What provoked the fuss about this, beyond the frisson that comes from the document having been leaked by the Guardian, was Cummings' association of genes with IQ. He does indeed qualify his discussion of heritability, noting on page 196 that heritability "is a population statistic — it does not mean that for every individual x% of one's IQ score is accounted for by genes."
But that's not really the problem with his approach. Let's start with Cumming's full-throated endorsement of the BGI project to identify the genes for intelligence. He approvingly quotes the physicist Steve Hsu (linking to a Google Tech Talk):
Hsu says: 'I'm doing my best to increase the number of future humans who will be "fully awake". My current estimate is that one or two hundred common mutations (affecting only small subset of the thousands of loci that influence intelligence) are what separate an ordinary person from a vN [von Neumann].'
Most of Cummings' genetics comes, as he admits — nay, boasts — from Hsu and Robert Plomin (who is "much more cautious" than Hsu about "engineering higher intelligence"). This is summarized in a nine-page Endnote on "intelligence, IQ, genetics, and extreme abilities." The concluding sub-section on "Genetics, school achievement, 'added value' measures" includes the hackneyed trope, beloved of Victorian schoolmasters, that:
Instead of thinking about education as instruo (build in) we should think of it as educatio (draw out).
How true that is. Especially for … oh, you guessed it. From page 76:
We know (thanks to studies such as SMPY and Terman) that although cognitive tests are noisy, we can quite accurately identify the top ~2% in IQ on whom we rely for scientific breakthroughs and even crude tests at 13 predict differences within the top 1% [italics in original] in future scientific achievements … We should give this ~2% a specialist education as per Eton or Kolmogorov [see here and here], including deep problem-solving skills in maths and physics.
And there you have the blatantly eugenic association of genes with intelligence, intelligence with worth, and worth with the right to rule.
Steve Jones, Emeritus Professor of Genetics, critiqued Cummings based, it seems, on the first newspaper reports. What he wrote was fine, but Cummings did include enough caveats in his full document to wriggle out of the criticism and find points of agreement with Jones. Steven Rose, Emeritus Professor of Biology, offered a more detailed analysis in New Scientist, concluding:
Whatever intelligence is, these failures show that to hunt for it in the genes is an endeavour driven more by ideological commitment than either biological or social scientific judgement. To suggest that identifying such genes will enable schools to develop personalised educational programmes to match them, as Cummings does, is sheer fantasy, perhaps masking a desire to return to the old days of the 11 plus. Heritability neither defines nor limits educability.
At root, Cummings' simplistic genetics is not the issue. His technocratic eugenics emphatically is. And that deserves to be brought into the open and shredded.
Last week in Boston the American Society for Reproductive Medicine (ASRM) held its annual meeting, one of those mega-conferences with a 276-page program and reporters trolling for stories.
One story that generated coverage from high-profile outlets including CBS News, NBC News and Time was based on an ASRM press statement announcing that 5 million babies have been born worldwide as a result of assisted reproductive technologies. But this was not actually news; it’s a “best guess” that was released more than a year ago. Some reporters wound up elaborating on the statistic with stories about heart-warming IVF success stories or experimental IVF techniques. None mentioned the numbers cited by Miriam Zoll in her new book Cracked Open: Liberty, Fertility and the Pursuit of High Tech Babies showing that most IVF cycles fail to produce a pregnancy.
Here are some other notable news stories that came out of the conference, with brief comments:
Multiple Egg Donations May Not Affect Women's Future Fertility: Study The title of this story sounds better than what you learn when you read further: A study at Weill Cornell Medical College found that women could continue to produce a sizeable number of eggs per cycle, over multiple donations. News coverage of the study did not address other health outcomes for the women, the quality of their eggs, or whether any successful pregnancies resulted for others or themselves.
The seventh-graders at KIPP Bridge Charter in Oakland, CA, guided by science guy Tom McFadden, have put together a fabulous rap about Rosalind Franklin's role in the discovery of the double helix. Check it out:
Ain't nobody fresher than Watson and Crick (Crick, Crick)
That is, until Rosalind Franklin hits the screen …
Uh huh… that's my pic …
Oh yes, there's science in there — helical dimensions and phosphates on the outside — and there's also a sense of people doing science, mixed motives, prejudices and all. The lyrics (partly annotated) are here. McFadden's website has more, including links to other science rap battles, on the status of Pluto and on Wegener and continental drift, and background on making these videos.
The FDA public meeting that was scheduled to take place on October 22 and 23 to discuss mitochondrial replacement, a form of human inheritable genetic modification, was postponed due to the government shutdown.
The meeting has not yet been rescheduled, and FDA staff aren’t able to say when a new date will be announced. They have said that there will also be a new deadline for submitting written comments.
The postponement has an important silver lining: there is now more time to spread the word and get involved. To learn more about the germline mitochondrial replacement techniques being discussed by regulatory authorities both in the United States and the United Kingdom, please see these resources:
Posted by J. P. Harpignies, Biopolitical Times guest contributor on October 17th, 2013
David Epstein’s new book The Sports Gene is unfortunately named. Sports Genes? – with an emphasis on the question mark – would have been more accurate. Nonetheless the author, a former senior writer for Sports Illustrated, provides a thoughtful exploration of some very tricky terrain. The history of thinking about the possible genetic basis of athletic achievement has been littered with half-baked ideas, racist and sexist assumptions, and the propaganda of totalitarian governments. This tawdry legacy has, understandably, made many thoughtful contemporary scientists and social commentators hesitant about venturing into what can still be a minefield.
But the exploding study of genomes coupled with the relentless drive of elite athletes to rise to the top of their respective sports is bound to lead to attempts to boost performance through whatever “gene doping” methods might become available – some of them quite soon. It would be very surprising if, as the World Cup and Olympics approach, these issues don’t emerge into the larger public conversation as one scandal or another comes to light. Top-flight athletics will likely be one of the earliest and most obvious frontlines in the struggle over human enhancement, and fundamental questions about the genetic components of physical strength, endurance, and coordination are certain to rise to the fore.
In this context, Epstein provides a valuable service by exploring the current state of knowledge about the genetic factors involved in athletic success. He even-handedly looks at the eternal nature/nurture polarity, and immediately makes clear that environment, learning and culture play fundamentally important roles. He illustrates this in his amusing first chapter about how a leading woman softball pitcher easily struck out major league baseball’s top hitters because they weren’t trained to predict the behavior of softball pitches.
Epstein then leads us on a series of travels he took around the world to meet with researchers and extraordinary athletes from the U.S. to Kenya to the Arctic Circle to explore in depth such questions as why some specific ethnic groups excel at certain sports—e.g. Kenya’s Kalenjin in distance running; Jamaicans from a few parishes in sprinting; etc. He interviews the small number of leading researchers who are working on these questions and highlights the sometimes considerable differences in their conclusions and lines of inquiry, such as the possible link between malaria and muscle fiber composition that might help explain key differences between East and West African populations’ athletic propensities.
This is all far from settled science, but as one follows Epstein’s explorations, it becomes inescapably evident that there are clearly some genetic components involved in peak athletic performance. To cite one case, Epstein delves into the unusual family genetic mutation of Finland’s Eero Mäntyranta, who naturally has a 65% higher red blood cell count than average humans. This seems to have contributed to making him one of the world’s leading long-distance skiers of all time. Epstein also explores the breeding of Alaskan racing huskies and thoroughbreds to try to see what we can learn about the genetic factors in exceptional physical performance from work with those animals.
Epstein does not have an axe to grind. He wants to find out what we know in this domain, and he has literally gone to the ends of the earth looking for answers. He’s courageous to explore these emotionally charged topics, and he’s able to do it confidently because he is clearly not infected by racist ideas. He lets researchers with very different perspectives explain their work, and lets what evidence there is speak for itself without overstating any conclusions, which often leads to fascinating counter-intuitive insights.
The book delves into some technical genetic material, but it is geared to the literate general public and is well written by someone with an obvious passion for the material. It is a bit long and extensively detailed in parts, so finishing it requires a bit of stamina. But for someone with an affection for sports who is also interested in science and/or anyone involved in work on genetics issues, this is a very valuable contribution, currently the seminal text for the general public on this cutting-edge domain.
J. P. Harpignies, a writer/editor, conference producer and environmental activist, is an associate producer of the annual Bioneers Conference. A former program director at the New York Open Center, he is the author of three books: Political Ecosystems, Double Helix Hubris, and, most recently, Delusions of Normality.
As previously reported, an advisory committee of the US Food and Drug Administration is scheduled to hold a public meeting on October 22-23 that will discuss the technique known as mitochondria replacement. Headlines often refer to this as "three-parent IVF." It is also a form of inheritable genetic modification.
Because of the government shutdown, it is unclear whether the meeting will be postponed or held as scheduled. But it's not too late to submit written comments, and the meeting is starting to attract significant attention, both in the media and elsewhere.
On October 9, NPR's Rob Stein presented a report on Morning Edition that featured Marcy Darnovsky of CGS, stressing the established "bright line" against inheritable human genetic modification (IGM) and the reasons not to cross it. Bioethicist Ronald Green discussed both psychological effects on any resulting children and long-term dangers:
If mistakes are made, they won't just be mistakes in the child that is born. But if that child [is a girl and] has children down the line, those children will inherit the mitochondria from that child, and we'll have introduced new genetic diseases into the human population.
The segment also included advocates of mitochondria replacement and scientists working in the field.
Mothers for a Human Future has raised an alert (pdf linked here) on the new technology, which could be the first legally sanctioned form of IGM anywhere in the world. The alert lists ten reasons why we need a global moratorium on IGM "to allow for international public education, conversation, and decision-making on the appropriate global regulatory framework."
Peggy O'Mara is also mobilizing her connections to encourage public participation, and working with both Mothers for a Human Future and CGS to spread the word.
Written comments are due by October 15th, and should be sent to the attention of Gail Dapolito, whose e-mail is firstname.lastname@example.org; the fax number is 301-827-0294.
"Pride and Joy" is a series in six parts, plus ancillaries, by Natalie Stechyson that focuses on "the emerging world of gay parenthood and surrogacy" in Canada — and abroad. It's the product of her year as a Michelle Lang fellow; the award commemorates the first Canadian journalist to die in the War in Afghanistan.
Fellows spend a year learning their trade, on regular salary, at Postmedia News and the Calgary Herald, and also are encouraged to focus on a special project. Stechyson is the third fellow, and her project was published in September. The Leader-Post (part of the same conglomerate), where the series is hosted, has limited free access, and a 99-cent introductory offer if you want to read more than five pages. The series home page is here and a video introduction here.
The reports include photos, snippets of audio, and video (some pages come to noisy life), but are primarily solid, empathetic journalism. There are facts and statistics, and a video Q&A with a lawyer who specializes in reproduction issues and has pointed comments about the legal inconsistencies across provincial borders. Most of all, there are touching stories about various families trying in various ways to have children.
Part 4 of the series, Womb for Hire, focuses on surrogacy in Cancun, Mexico. Paid surrogacy is illegal in Canada, as are gamete sales and the use of sperm from sexually active gay men, and medical tourism companies such as US-based Planet Hospital are filling the commercial void. Of course, they charge for it: the surrogacy process in Mexico generally runs about $42,000, of which $12,000 goes to the surrogate. And then there are extras: $6,000 for sex selection; $9,000 and up for donors with specified qualifications (height, Ph.D, caucasian), plus travel and expenses.
If the sperm provider has HIV, there is a supplementary charge of $15,000, of which $6,000 goes to the surrogate. Chances of transmission should be very small if proper precautions are taken, and the semen is processed in Los Angeles before being flown to Cancun, but Dr. Mathias Gysler, the head of the Canadian Fertility and Andrology Society asks pointedly:
Why would you pay someone extra money for taking on a risk if there's supposed to be no risk?
Stechyson included this in her report, and also a fairly soft video interview with Planet Hospital's CEO Rudy Rupack, who was raised in Calgary and opened the Cancun site specifically for the US and Canadian markets. He claims that the Mexican surrogates are being paid about half as much as their U.S. counterparts, while Mexican Walmart cashiers make only a quarter of what U.S. cashiers do; so, no exploitation at all, in his view. The reporter raises a metaphorical eyebrow from time to time but lets him speak.
Other parts of the series include:
One family's story: It's a long road for Canadian gay and lesbian couples hoping to start a family
On September 24, the direct-to-consumer genetic testing company 23andMe was awarded a patent for "gamete donor selection based on genetic calculations." The idea is that people using sperm or egg providers would choose from the gametes on offer based on the probability of getting the kind of child they want. The examples given in the application of the traits of hypothetical children that might be of interest include:
Height, eye color, gender, personality characteristics and risk of developing certain types of cancer
There is a helpful flowchart (part shown here) to explain how the technology would be used to evaluate the possible matches between the client (recipient) and the available donors, and so to identify preferred donors, given that it would be dealing with statistical information rather than certainties.
That, of course, points up the biggest flaw in the process. Even a direct-to-consumer gene-testing company is compelled to acknowledge that there can be no guarantees. But they don't make clear that for the vast majority of "traits of interest," the associations between particular alleles and particular phenotypes are actually rather weak. (A few conditions, including single-gene ailments and some inherited forms of cancer, can be identified and avoided through pre-implantation genetic diagnosis or carrier screening, but they are rare.) The associations were weak four years ago, when the patent was filed, and they still are.
But the company is, after all, in the genetic prediction business, and the patent in question referred to a "hypothetical child." So it's hardly surprising that when news of this patent broke, most journalists made the same call. Nature News and MIT Technology Review had "designer babies" in the headline. Wired called it a "designer baby system." The Los Angeles Times labeled it a "designer baby patent." New Scientist referred to "planning a baby."
Perhaps the most thoughtful immediate response was published in Genetics in Medicine just before the media got hold of the story. Four European bioethicists (Sigrid Sterckx, Julian Cockbain, Heidi C. Howard and Pascal Borry) considered the patent under the title:
"I prefer a child with …": designer babies, another controversial patent in the arena of direct-to-consumer genomics
It's a short paper in which the authors largely restrict themselves to raising questions and noting controversy. They point out, for instance, that the U.S. Patent Office does not seem to have questioned whether such techniques "were appropriate subject matter for a patent" although it did invoke "morality" when considering the human/animal chimera patent application made by Stuart Newman and Jeremy Rifkin. (That was eventually rejected as too human to be patentable.) And the authors ask whether 23andMe's customers would be disconcerted by this use of their collected data; there was an outcry last year when the company was granted a patent for a test for Parkinson's disease.
As soon as the news stories began to appear and 23andMe realized that people were drawing the obvious conclusion, it began backtracking hard. It now claims that the patent relates to "one of the tools we offer individuals as part of their genetic exploration [which] offers an engaging way for you and your partner to see what kind of traits your child might inherit from you." Nothing there about choosing donors. The company's blog explains:
At the time 23andMe filed the patent, there was consideration that the technology could have potential applications for fertility clinics so language specific to the fertility treatment process was included in the patent.
To say "included" is disingenuous; the process description in the patent is entirely about the selection of gametes from strangers. The post continues:
But much has evolved in that time, including 23andMe's strategic focus. The company never pursued the concepts discussed in the patent beyond our Family Traits Inheritance Calculator, nor do we have any plans to do so.
So that's all right then. But wait, there is a kicker in that same statement:
23andMe believes that patents should not be used to prevent individuals from accessing their genetic data or its interpretation.
So would the company license that patent? It doesn't say. The Center for Genetics and Society has called on 23andMe to use its patent to prevent others from exploiting this technology. That's not unheard-of: the Newman/Rifkin application was explicitly intended to prevent development of chimeras. Thus far, 23andMe has not explicitly ruled out its future use.
Many of those who commented on the 23andMe patent, including CGS, law professor Lori Andrews, and geneticist Daniel MacArthur, expressed doubt about the practical feasibility of most trait selection. But even if scientifically dubious, the project of "breeding better babies" is, obviously, morally and socially fraught.
A few philosophers, such as Julian Savulescu, actively campaign for it as a moral imperative. In opposition stand CGS and many others. Harvard's Michael Sandel put it well when he said that trait selection "edges close to eugenics." This debate has up till now been theoretical. It's getting all too real.
A new report in Science offers a valuable pointer to “theory and experimental findings that appear to have been overlooked in the scientific and public forums” on controversial mitochondrial replacement (MR) techniques, which the media often refers to as “three-parent IVF.”
MR would combine the mitochondria of a healthy woman’s egg and the nucleus from the egg of a woman affected by a severe form of mitochondrial disease; this constructed egg would be used to try to create a healthy child. MR techniques are currently being considered for clinical trial in the United Kingdom and the United States.
The Science paper, written by evolutionary biologists Klaus Reinhardt, Damian K. Dowling, and Edward H. Morrow, provides a critical look at the scientific evidence behind MR and concludes “that it is premature to move this technology into the clinic.”
Reinhardt et al. explain why disruptions to the interaction between the nucleus and mitochondria could be problematic.
Energy production critically hinges on extensive cross-talk between genes dispersed across the nucleus and the mitochondria. Because phenotypes with less-than-ideal cross-talk are disfavored by natural selection, coordinated mitochondrial-nuclear interactions become highly specific over evolutionary time. If MR disrupts such specific, highly coordinated mito-nuclear allelic interactions, adverse health outcomes might occur.
They also problematize the notion that nuclear DNA is unaffected by this procedure.
Studies on model organisms, ranging from mice to fruit flies, indicate that MR can profoundly change the expression profiles of nuclear genes and affect a range of important traits such as individual development, cognitive behavior, and key health parameters. These studies also suggest that males of reproductive age are particularly sensitive to MR-induced effects.
The authors point out an important limitation to the only primate study carried out thus far, noting that the macaques born following MR need to be studied through to sexual maturity (they are only three years old currently) since, “the results from mice and invertebrates suggest that many deleterious effects of MR would not be revealed until adulthood.”
Their paper does not stress the fact that only one MR technique – maternal spindle transfer – has met with any success in primates. The other MR technique being considered in the UK – pronuclear transfer, which has been the focus of researchers at Newcastle University – did not work when researchers at Oregon Health and Science University (OHSU) tried it with macaques. When faced with that development, the Human Fertilisation and Embryology Authority (HFEA), which had previously required primate testing for pronuclear transfer, quietly dropped the requirement (page 21) earlier this year.
The Science paper states that these points “deserve careful consideration prior to any change in legislation,” but also that using this technique to allow women suffering from mitochondrial diseases to have a healthy child “is clearly an exciting prospect.” Despite giving the technology this allowance, the paper has stirred up some controversy and defensive responses.
In an article in The Conversation, Director of the Centre for Genetic Diseases at Monash University Justin St John said, “The authors of the Science piece mention that the research they are highlighting hasn’t been included in the public debate. It’s important to note that it has not been overlooked by the scientists working on the technology or the agencies involved.”
However, the press statement issued by the HFEA in response to the Science article admits that its panel did not analyze the four Drosophila studies Reinhardt et al. cited, despite the issue of interaction between nuclear and mitochondrial DNA being what HFEA termed “one of the key considerations in assessing the safety and efficacy of mitochondria replacement.”
Furthermore, scientists working on MR can’t agree (at least previously, and publicly) on the best way to handle these safety concerns. Each of the two major research groups involved has voiced its ideas about why the other group’s method won’t work. When the researchers at OHSU found that human eggs were more difficult to work with than monkey eggs (with a majority of the embryos created from the constructed eggs showing abnormalities), one of the lead researchers at Newcastle said,
The unfertilized egg has the complex task of remaining poised in readiness to halve its DNA content upon sperm entry. Given the biological complexities associated with maintaining this state, we have always held the view that manipulation of the egg at this stage would be rather precarious.
The Newcastle group has focused on a technique that transfers cellular material between embryos rather than between eggs. However, when the Oregon researchers tried that technique in macaques, they abandoned it after finding that “embryos fail early and no pregnancies [were] established.”
In a Nature paper on a third MR technique, nuclear genome transfer, researchers from Columbia University and the New York Stem Cell Foundation suggest reasons why both the methods used in Newcastle and in Oregon could create problems.
In fact, at least five articles have explored the potentially dire safety consequences of mitochondrial replacement:
“On Designer Babies,” Tufts Medicine, Sheldon Krimsky Ph.D, Professor of Humanities and Social Sciences at Tufts University and an adjunct professor of public health and community medicine
“Three person IVF,” Practical Ethics, Paula Boddington Ph.D, Lecturer in Philosophy at the University of Oxford
Most of the responses to the scientific, social and ethical critiques of MR, like the defensive response to the Science paper, have not been inspiring. The question is why critical opinions, coming from well-respected scientists, scholars, and advocates, are being dismissed and mislabeled?
I can’t help but wonder if the answer lies in Henry Gee’s recent article in The Guardian called, “Science: the religion that must not be questioned.”
Posted by George Estreich, Biopolitical Times guest contributor on September 24th, 2013
Some readers of Biopolitical Times may already have read Margaret Atwood's MaddAddam trilogy: Oryx and Crake, The Year of the Flood, and MaddAddam. Taken together, the books — "speculative fiction," as Atwood calls them — project a world where most of humanity, after years of sliding towards the abyss, has perished in the “waterless flood” of a genetically engineered virus. Remaining are a few surviving humans, and the Crakers.
As Atwood explains in a recent interview, the Crakers were engineered to avoid all the problems — notably uncontrolled lust and violence — that their creator, a brilliant genetic engineer self-named Crake, believed were the source of our human tragedies. Crake also engineers and releases the virus: literally Godlike, he both creates and destroys.
One of the main critiques of human genetic engineering is that things can go wrong with the end result. But the Crakers are gentle, childlike, stunningly beautiful, racially diverse. Their eyes are green and glow in the dark and they live on kudzu, and the men have extremely large blue penises, and the women turn blue when they are ready to mate. (These facts cause great misunderstandings with the surviving humans.) In the new society, the Crakers and the surviving humans have to get along and build a single civilization together; and indeed, MaddAddam is notable in narrating the slow fall of a single Craker child into knowledge, into the learning of writing and storytelling.
The paradox of the MaddAddam trilogy is that it is about starting over, about a new beginning, when a new beginning is impossible: human nature, whether genetically spliced or not, is unavoidable, and with their bickering and lusts and scars from the past, the new society wastes no time in reproducing the tensions of the old. It is, in fact, the false hope of a new beginning that is Atwood's satirical target. This is apparent in the third book’s palindromic title, in the trilogy’s multiple invocations of the Bible (no writing but rewriting: Atwood’s book is itself a splicing and resplicing of religious stories), and in the nonlinear approach of the narrative — the three books crisscross the same timespan, rather than narrating from beginning to end.
But most of all, the false hope of a new beginning is dramatized in the person of Crake. He is godlike, but not God. In his attempt to wipe out humanity and start anew, he not only fails — some humans survive, and by book's end, have begun to interbreed with the Crakers — but also enacts a central irony: his creation of gentle, peace-loving creatures is attended by an ultimate act of violence. Further, Crake's beliefs about what humanity is and should be, despite his terrifyingly equable, rational voice, are fueled by family trauma and betrayal. He has godlike power, but is human to the core; and his rhetoric of rationality is belied by his story.
For Atwood, the genome is pliable, but human perversity is ineradicable. In an essay on her website, she writes:
Like The Handmaid's Tale, Oryx and Crake is a speculative fiction, not a science fiction proper. It contains no intergalactic space travel, no teleportation, no Martians. As with The Handmaid's Tale, it invents nothing we haven't already invented or started to invent. Every novel begins with a what if, and then sets forth its axioms. The what if of Oryx and Crake is simply, What if we continue down the road we're already on? How slippery is the slope? What are our saving graces? Who's got the will to stop us?
Atwood’s emphasis — “it invents nothing we haven’t already invented or started to invent” — suggests that, though her work is fiction and not a tract, she also intends to do far more than entertain.
There is the technical critique of genetic engineering: that it won’t work, and that suffering or harm will result to the engineered. In Atwood’s trilogy, the problem isn’t that genetic engineering will go awry; it’s that it will work too well, and in doing so will amplify all that humans are, including our best impulses and our worst.
Time magazine just published a cover story (mostly behind pay wall) that is essentially a puff piece about Google. Most of the article focuses on Larry Page's tenure as CEO and the Google X division run by cofounder Sergei Brin. But it is hooked to the announcement of a company called Calico, which is so new that it doesn't even have a website. (Calico.org is the Computer Assisted Language Instruction Consortium; Calico.com is owned by Oracle, Calico.net by domaingrabber.com, calico.biz by an Indian outfit.) But it does have a CEO, and a mission, according to Page:
I'm excited to announce Calico, a new company that will focus on health and well-being, in particular the challenge of aging and associated diseases. Art Levinson, Chairman and former CEO of Genentech and Chairman of Apple, will be Chief Executive Officer.
Strangely, Levinson "was not immediately available for comment" to Time, but Page gave a strong clue about his own thinking in part of his interview that is available online:
"Are people really focused on the right things? One of the things I thought was amazing is that if you solve cancer, you'd add about three years to people's average life expectancy," Page said. "We think of solving cancer as this huge thing that'll totally change the world. But when you really take a step back and look at it, yeah, there are many, many tragic cases of cancer, and it's very, very sad, but in the aggregate, it's not as big an advance as you might think."
The New York Times did manage to get hold of Levinson, who is investing in Calico as well as running it. He's the only employee so far, and sees it as "more of an institute certainly than a pharmaceutical company." He's also "exploring a partnership with Roche" which might not be too difficult: he's been on Roche's board since they bought Genentech. He helpfully explained on his Google+ page:
Calico is an abbreviation for the "California Life Company," but if you're thinking about cats, we like the old saying that they have nine lives...
Immortality and transhumanist ideas generally have long been a source of fascination in Silicon Valley. Indeed, it's not unusual for billionaires to get interested in life extension. John Sperling did (and generated the pet-cloning business on the side). Larry Ellison did, and his Foundation continues to fund close to $50 million of research a year. And Google's commitment to what they see as the very long term — "ten or 20 years" — is certainly admirable, though the timescale seems a tad optimistic.
It's really not obvious just what Calico will be doing. There are vague speculations about computational power, and of course Google has genetic testing connections, but 23andMe doesn't seem to be involved. Nor it is clear how much of Google's $54 billion stash of cash the new company will use. Of course, if you have that much in your piggy bank, you can affect the course of research rather drastically. But Page is clear that Calico is not a core mission of Google, and strongly implies that its investment will be quite limited. On the other hand, Astro Teller (né Eric, and the grandson of Edward Teller, the father of the H-bomb), who runs Google X with Brin, told Time:
"If you make something a little bit better, people might pay you for it; they may not. But if you make the world a radically better place, the money is going to come find you, in a fair and elegant way."
Maybe this is not that important of a deal, to Google, just a long-shot bet that could come off. Perhaps it's even a hedge against the possibility of the Singularity not occurring. (That's the belief, with which Google has been connected, that "humans and machines will at some point merge, making old age and death meaningless.") But Levinson is a big-time player … so Calico certainly could be worth watching.
Meanwhile, if Vegas is making book on this fight, the smart bet might be on Death.
On September 5, the London Daily Telegraph ran not one, not two, but seven stories about sex-selective abortions (1, 2, 3, 4, 5, 6, 7). Why? Sarah Ditum suggested in the New Statesman on September 7 that
the campaign against sex-selective abortion is a cynical effort to take choice away from pregnant women.
The day before, however, Telegraph assistant comment editor Tom Chivers wrote,
Pro-choice feminists should be more appalled than anyone by the sex-selection abortion story.
Of course, both statements can be true. What happened, in short, was that in February 2012, the Telegraph conducted a sting that resulted in two doctors agreeing, on tape, to perform abortions for sex selection. These were never carried out, which seems to be the main reason why rather than starting criminal proceedings the Crown Prosecution Service decided to leave it to the General Medical Council.
Abortion politics in the UK are considerably different than in the US, and generally have a much lower profile. There is an anti-abortion rights lobby, which of course objected (and was quoted by the Telegraph, a conservative paper, and the Daily Mail, its down-market equivalent), and the Health Secretary asked the Attorney General to review the decision. But in most quarters this seems to have been treated as a minor matter. What seems blatantly obvious is that the newspaper was (again) trying to sell papers.
In the US, however, opponents of abortion rights have been working for years to use antipathy about sex selection as a weapon in their all-out assault on reproductive rights. Just this week, sex-selective abortion was thus wielded at a hearing of a Congressional subcommittee chaired by Chris Smith (R-NJ), a consistent opponent of abortion, who boasts a 0% rating from NARAL and a 100% rating from the NLRC.
The account of the hearing on Smith's website blames sex selection worldwide on Planned Parenthood and the Population Council. It cites Mara Hvistendahl, author of Unnatural Selection, as if she supports the anti-choice efforts, when in fact her book details the origins of the right-wing strategy to promote deceptive sex-selection abortion bans. This is not the first time the antis have actively tried to co-opt her work, as Hvistendahl explains in a 2011 Foreign Policy article titled "The Abortion Trap: How America's obsession with abortion hurts families everywhere."
Like Hvistendahl, many pro-choice groups and individuals are both deeply troubled by sex selection and alarmed by cynical efforts to use it to chip away at abortion rights. Since 2009, more than 60 federal and state bills have been introduced to ban abortions performed on the basis of sex or race. These efforts have been drawing increased attention, including a lawsuit in Arizona and a legal challenge in North Dakota. The National Asian Pacific Women's Forum has been taking a strong leadership position on these "thin-end-of-the-wedge" bills, arguing that sex selection is a problem but that abortion bans are not the solution:
We know the real solution to ending the preference for sons in some families is getting to the root of the problem: gender inequity. If lawmakers truly want to help us, we call on them to promote equal pay, access to education, health equity, and ending violence against women.
That description – which is the sum total of the information the FDA has so far released about the meeting – is a mouthful. What it apparently means is that the agency will, for the first time in over a decade, be considering a technique that would constitute a form of human inheritable genetic modification. It is the first time that the FDA has ever held a public meeting to discuss such a technique. That the agency is providing a forum for public comment seems like a good sign; the FDA surely realizes there are broad issues and profound societal consequences to consider.
The term the FDA has adopted – “oocyte modification” – is a new and somewhat strange framing. Though there is no way to be sure, oocyte modification for “treatment of infertility” may refer to a new in vitro fertilization technique being developed by a Boston-based company called Ovascience. The technique involves combining the egg of an older woman with mitochondria from egg precursor cells taken from her body. Ovascience had started enrolling women in a clinical trial, but this week the FDA sent the company a letter asserting its oversight and telling Ovascience it could not proceed without approval.
The FDA public meeting will almost certainly consider another technique – far more biologically extreme and socially consequential – known as mitochondrial replacement that is being developed by Shoukhrat Mitalipov and his research team at Oregon Health and Science University (OHSU). Unlike the Ovascience technique, mitochondrial replacement is a form of inheritable genetic modification. It is intended to allow a small number of women with a rare kind of severe mitochondrial disease to attempt to have a healthy and mostly genetically related child, but raises profound safety and societal risks.
The Mitalipov team’s version of mitochondrial replacement, called maternal spindle transfer (MST), works by inserting the nucleus of an affected woman into an enucleated egg – with healthy mitochondria – from another woman. This constructed egg is then fertilized with sperm from the father. Hypothetically, the resulting embryo could be transferred into the mother to create a healthy child, genetically related to his or her parents but not affected by the mother’s mitochondrial disease. Because the child would also carry genes from another woman, the media often refers to mitochondrial replacement as "three-parent in vitro fertilization" or as creating "three-parent babies."
The OHSU researchers believe their technique will work because they used it in rhesus macaques to produce four live offspring who after three years appear to be healthy and developing normally. Last year they were also able to generate embryonic stem cells from human blastocysts created with MST, which they view as a demonstration that the technique could produce a viable human embryo and child.
However, there are reasons to be dubious. A worrying difference was noted between the study of MST on the rhesus macaques and the trials so far on human zygotes: More than half the human MST zygotes had abnormalities that were not observed in the monkeys, leading the researchers to conclude that human oocytes are more sensitive to spindle manipulations than monkey oocytes.
MST can also introduce other kinds of errors. Genetic material can be lost during transfer; small amounts of mitochondrial DNA (mtDNA) from the unhealthy egg can be transferred; a mismatch between foreign mtDNA and nuclear DNA can occur; and the segregation of mutated mtDNA to specific tissues may lead to a significant accumulation of the mutant load. Negative effects caused by any of these would not be reversible, either in the child born as a result of the procedures or in any subsequent generations (if the child is female, since mitochondria are inherited only from mothers).
A number of scientists have voiced concern.
Joanna Poulton, Nuffield Department of Obstetrics, University of Oxford and others wrote a paper discussing nuclear transfer and noted that “huge problems need to be overcome.”
Stuart A. Newman, Professor of Cell Biology and Anatomy at New York Medical College, voiced strong doubt about the safety and efficacy of this technique in an article earlier this year, pointing out that it is extremely unlikely that billions of years of evolutionary complexity could be tweaked with any predictable outcome.
David King of Human Genetics Alert wrote a report on the dangers of epigenetic harm caused by the “crude excision process” of nuclear transfer. He noted that limited safety implications can be drawn from studies on human blastocysts because “only the most crude effects upon embryo viability are reflected in embryo death, and embryos can survive to the blastocyst stage with metabolic and gene expression abnormalities that will have profound effects later in prenatal development or postnatal life.”
Paul Knoepfler, Associate Professor of Cell Biology and Human Anatomy at the University of California, Davis School of Medicine, reiterated this point in an article that said, “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.”
The desire of the few women with mitochondrial disease who would be candidates for this technique to have a genetically related, healthy child is certainly understandable. But given that there is already a safe, available alternative way to accomplish this, why would anyone choose to subject a child to a highly risky experiment?
Back in 2002, the FDA stopped a number of fertility clinics from using a similar technique called “ooplasmic transfer” that was intended to help older women overcome infertility. The FDA’s communications at the time cited concerns about the genetic abnormalities (including Turner’s syndrome and Pervasive Developmental Disorder) found in several of the small number of resulting children, the lack of oversight, the paucity of safety data, and the resulting permanent changes to the human genome. As was noted by observers at the time, procedures that alter the human germline would violate the widely observed international consensus against inheritable genetic modification.
The same is true today. If the FDA gives the OHSU researchers a green light to move towards human clinical trials, it will be the first instance of regulatory approval for human germline modification ever, anywhere in the world.
Given the current regulatory void in the United States and the paucity of safety data, allowing scientists to experiment with creating permanent changes to the human genome is a genie that must be kept in the bottle.
The FDA is currently accepting public comments. Written submissions must be made before October 15; oral presentations must be confirmed before October 7. See here for more information, and spread the word.
U. of Washington researchers, sharing brain signals
The Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative announced by President Obama in April is attracting some much-needed notice.
Last week, the Presidential Commission for the Study of Bioethical Issues devoted Session 6 (of 7) of its formal Meeting Fourteen to a discussion of "Ethical Issues Associated with the BRAIN Initiative and Ongoing Work in Neuroscience." Video of that meeting is available, as are useful summaries at blog.Bioethics.gov (scroll down for several posts). Among the quotes listed:
"People who are developing the technologies are not thinking of ethics, they are engineers." — Henry S. Richardson, Kennedy Institute of Ethics
"We need to find ways to engage with social media and educate the public … that we did not have when the genome ELSI program began. … It's probably going to require a 20-year-old to figure out how to do it." — Thomas Murray, Hastings Center
"Working scientists and clinicians need to engage with the public directly, and at this point, there is no incentive to do so." — Anjan Chatterjee, University of Pennsylvania
Even more worrying, as noted in a comment, is that the representative from the Defense Advanced Research Projects Agency (DARPA) "stated that some of the brain research at DARPA would be classified for security reasons." Now there's a loophole …
The ethical issues are becoming pressing. On Tuesday, August 27th, researchers at the University of Washington claimed to have achieved a "Vulcan mind meld" — electrical signals in one human's brain caused another human's hand to move. (Yes, of course there is video.) It's a stunt that builds on previous work with rats and monkeys, it hasn't been peer-reviewed, the goal is to assist paralyzed people, and the data transmitted are "only simple brain signals, not thoughts, and cannot be used on anyone unknowingly." But it's an early signal of what is coming.
The Ethical, Legal and Social Implications (ELSI) program of the Human Genome Project, analyzed last week by Thomas Murray, who helped design it, is still controversial. Some biologists (usually off the record) see it as a waste of money and time; some ethicists see it as a convenient cover for researchers ("watchdog or lap dog?" [pdf]). But it did establish the concept of integrating such discussions into the research process. So far, the Presidential Commission is essentially discussing how to discuss the issues in relation to the BRAIN Initiative. A properly funded ELSI program seems like a good idea.
In 2004, the Havasupai tribe filed a lawsuit against Arizona State University for misuse of their members’ DNA samples. The legal action was prompted by the discovery that the Havasupai’s blood had been used to study conditions for which they had not given consent, after the original research that began in 1989 to investigate type II diabetes was unsuccessful. The case was settled in 2010; the university paid $700,000 to 41 tribe members, returned their blood samples, and provided funding for a clinic and a school. A headline in The New York Timesdeclared, “Indian Tribe Wins Fight to Limit Research of Its DNA.” However the issue, and the concerns it raises, have come roaring back, and are unlikely to disappear anytime soon.
Science writer Ricki Lewis stirred up the debate with an article provocatively titled “Is the Havasupai Indian Case a Fairy Tale?” Lewis argues that the wrongs claimed by the tribe “never happened.” She accuses the media of failing to look at primary documents and simply recycling false information. She seems to have talked in depth to the geneticist who carried out the work, Teri Markow, and uncovered some interesting information, but she does not appear to have spoken to, or quoted, a single member of the Havasupai tribe.
This omission is interesting given that just a week earlier, Lewis compared the Havasupai case to that of Henrietta Lacks’ cells being taken and used without her consent, which was in the news again precisely because her family members were finally being consulted by scientists. The family reached an agreement with Francis Collins, the director of the National Institutes of Health (NIH), that they would allow research on the cells to continue, but that from now on NIH projects will have to seek approval from a committee that includes Lacks’ family members.
Even though Lewis offered the disclaimer that she’ll “leave the HeLa news to the other bloggers,” there was something unsettling about her use of the announcement as a hook to discount the Havasupai’s claims and to defend Markow’s misuse of their DNA.
Evolutionary anthropologist Jonathan Marks has now explored Lewis’ points in detail. Marks is familiar with the original documents surrounding the case and notes that Markow has been unable to produce either the informed consents she claimed she had obtained, or her grant proposal, which according to the Hart Report (the document produced by Arizona State’s investigation in 2003) did request funds to research schizophrenia in the Havasupai.
Marks points out that though Markow may never have published specifically on Havasupai schizophrenia, the contention has been over whether she studied it without informed consent. Marks, Lewis, and Markow engaged in a heated debate on these issues until the PLOS BLOGS Network Community Manager closed further comments on the post. Markow defended herself, but never said outright that she didn’t study schizophrenia, which was the central question. Neither would she answer Marks’ question about whether the conclusion that can be drawn is that she has “received funding from an agency that focuses on schizophrenia, without any intention of actually studying schizophrenia, and ultimately performing no science related to that illness.”
For the Havasupai, informed consent was not merely a bureaucratic step. The implications of genetic research are particularly culturally sensitive. For example, migration studies can contradict origin stories, “inbreeding coefficients” can lead to stigmatization, and efforts to use DNA testing to determine membership and identity can problematize tribal sovereignty. In the initial lawsuit, the Havasupai claimed that the research carried out without their consent led to “misrepresentation, infliction of emotional distress, conversion, violation of civil rights, and negligence.”
Lewis told Marks that "science has nothing to do with belief, it is about data and evidence." But this is a problematic assertion. Like all endeavors, science must be understood as being integrated with its social, cultural and political context. As science journalist John Horgan recently wrote, “All truth claims–whether scientific, religious or political—reflect the prejudices and desires of those who make them.”
A perfect example of this can be found in a new study in Science, which Jonathan Latham covered in a fascinating article. The study found three gene variants that each contribute 0.02% to variation in educational attainment, and because the researchers were funded to find genetic explanations, this is what they reported. What they completely ignored is the much more striking implication of their research – that more than 98% of variation in education attainment is based on factors other than a person’s basic genetic makeup.
When scientists assert, as they did in the Havasupai case, that everyone would be on board if they only explained their research goals better, they overlook the fact that science is not neutral, and that progress is not merely a top down affair. Now that informed consent is mandatory (though its applications are oftenmurky), dissent from certain applications of biological materials must be respected. As Marks states, “The lesson we learned around the middle of the last century is that the progress of science is great, but when it bumps up against human rights, human rights wins, hands down.”
The high profile case concerning the arrest of Lonnie Franklin – aka The Grim Sleeper – in 2010 drew nationwide attention to a new tool in the DNA forensics arsenal: familial searching. This tactic is used when an unknown sample does not fully match anyone in a DNA database, but may partially match a known profile in a manner that may point to a close relative being the culprit.
The state of California has developed rather stringent guidelines for the use of familial testing that seem prudent. But a recent paper by Rori Rohlfs et. al. in PLOS ONE suggests that despite these guidelines, real concerns still remain. The study, which The Los Angeles Times covered in a news story, found that the methods currently in use misidentify distant relatives as being more closely related to the unknown sample than they actually are, potentially subjecting them to unwarranted police scrutiny.
The abstract explains:
Although the California familial search policy is likely to identify a first degree relative if his profile is in the database, and it poses little risk of falsely identifying an unrelated individual in a database as a first-degree relative, there is a substantial risk of falsely identifying a more distant Y- haplotype sharing relative in the database as a first-degree relative, with the consequence that their immediate family may become the target for further investigation. This risk falls disproportionately on those ethnic groups that are currently overrepresented in state and federal databases.
In other words, a partial match between a crime scene DNA sample and a profile in the DNA database might mistakenly suggest that the two people are siblings or father and son, when in fact they are much more distantly related. That could result, in a hypothetical example, in a police investigation of a second cousin who doesn’t even know the suspect whose DNA was found at the scene of a crime.
Click here to read the entire paper. The authors also prepared two videos to accompany their study. One is a clear technical summary – in three and a half minutes – of the paper’s methods and findings. The other is a wonderfully innovative dramatization of three high school students discussing familial DNA searches and their pitfalls, with narration by Cephus Johnson, the uncle of Oscar Grant.
Victims of forced and coerced sterilizations carried out under North Carolina’s decades-spanning Eugenics Board program finally received some good news earlier this summer: The state legislature has agreed to spend $10 million to compensate them for the abuse they suffered. Offering compensation to those who are still alive – 177 men and women have come forward and been verified so far – is an important recognition of the moral and practical failure of this eugenic practice.
North Carolina sterilized some 7,600 people between 1929 and 1974 for a range of reasons, including findings by authorities that they were lazy, promiscuous, or poor. State records have revealed the extent of the discriminatory nature of the program: “North Carolina's sterilization program zeroed in on welfare recipients. Over the last 15 years of its operation, 99 percent of the victims were women; more than 60 percent were black.”
The decision to compensate sterilization victims has been a long time coming. The state established the North Carolina Justice for Sterilization Victims Foundation in 2010, but the agency was temporarily forced to close its doors last summer when the Senate brought the compensation effort to a halt. Its ultimate success is in large part a testament to the passion of advocates such as Elaine Riddick, who was sterilized at the age of 14 after giving birth to a child that resulted from rape. She had no idea of what had been done to her until years later when she tried unsuccessfully to start a family with her husband.
North Carolina will be the first US state to offer compensation to victims of sterilization, but could inspire some of the other thirty states that had similar eugenics laws to follow suit. Coming to terms with this history is hugely important. It’s easy in hindsight to recognize what it was: in the words of medical reporter Elizabeth Cohen, a “horrific chapter in American history.” At the time, however, as she points out, “the programs were supported by some of the nation's most respected doctors, lawyers, and social workers.”
Most Americans are unaware of the country’s eugenic legacy. That is also true in California, where some 20,000 people, including a disproportionate number of Latinos, were sterilized under state auspices. As a group of California high school students pointed out in an online petition to incorporate this history into the curricula,
Learning about eugenics in California is not simply about being more informed, or redressing past wrongs, but about considering difficult questions about justice, equality, and human rights. We have seen how these questions are now more important than ever, as we move into an uncertain age of genetic science.
Unfortunately, involuntary sterilizations, as well as the ideology that informs them, are not behind us. They still occur today, often arranged by people who seem to genuinely believe they are helping society.
Guernica magazine recently reported that Kenyan doctors have been sterilizing HIV positive women, sometimes without their knowledge. Israel has admitted to targeting Ethiopian Jews for compulsory long-term contraception. Sweden only just changed a 30-year-old law that required transgender people to undergo sterilization before they could legally be recognized as another gender.
But involuntary sterilizations also occur much closer to home.
Just last month, an exposé by Corey G. Johnson of the Center for Investigative Reporting reported that 148 women in two California prisons were illegally sterilized between 2006 and 2010. Justice Now, a prisoner rights group that first uncovered evidence of this abuse, started a petition with Californians United for a Responsible Budget to demand that it end.
Thankfully, these efforts are having an impact. California legislators have just unanimously approved an audit of the doctors who carried out sterilizations of nearly 150 women without required authorizations.
Questionable sterilization efforts also continue today outside of prisons. A few years ago, a Louisiana state representative proposed paying poor people to get sterilized. A private organization, Project Prevention, pays crack addicts $300 to get sterilized. Wesley Strong recently wrote about its program:
Barbara Harris and Project Prevention are products of a post-1980s era where racism, sexism, and classism are far more nuanced, where eugenics programs can hide behind liberal notions of charity.
Looking from sterilizations of the past to those of today, it’s not hard to see all of the same racist, sexist and classist influences at play. However, as Nathaniel Comfort recently discussed in Scientific American, there are those who want to deny that structural discrimination still plays a role in modern eugenics. This “growing constituency of Drs. Jekyll within the biomedical community” argues that eugenic practices guided by individual choice are a clean break from the eugenics of the past. But as Comfort points out, “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?”
North Carolina’s compensation decision is a huge victory, and provides a valuable lens through which to see how easily eugenic practices can be viewed as valuable, progressive, social measures. Instead of waiting for the next generation to refer to our own “horrific chapter in American history,” let’s hope it signals an end to tolerance of all involuntary sterilization.
Wired recently ran a long story headlined "The Fall and Rise of Gene Therapy." The title is displayed with images of two viruses, captioned:
This virus laid waste to James Wilson's career.
This virus could bring him redemption.
That's just not true. James Wilson laid waste to his own career as a pioneer of human gene therapy. (He did remain a professor at the University of Pennsylvania.) He did not, however, single-handedly destroy the prospects of gene therapy, as the article implies, and we should be properly skeptical as to whether he might single-handedly restore the field.
The first virus pictured was used in an experiment Wilson ran in 1999 that resulted in the death of 18-year-old Jesse Gelsinger, a subject in a gene-therapy clinical trial whose own disease was mild and well under control. His death was a tragedy no matter what the surrounding circumstances.
At first, Gelsinger's father, Paul Gelsinger, supported the scientists. Paul's support continued even after he learned that monkeys had died during the pre-clinical work; he was assured that adjustments had been made. (His personal account is here [pdf].) Then he started learning about the conflicts of interest involving Penn and, in particular, Wilson.
Most damningly, Wilson specifically told Paul Gelsinger that he was an "unpaid consultant" to Genovo, the company that at least partly funded the research and had exclusive rights to license the related patents. That was disingenuous at the very least. Wilson held 30% of Genovo's stock, and eventually cashed in, reportedly to the tune of $13.5 million.
There were more problems concerning conflicts of interest, many of them detailed in this FDA letter, and in other links here. Wilson was indeed punished, and his gene-therapy career did indeed go "into free fall" as the Wired story by Carl Zimmer notes. But it was his own doing.
There are curious omissions in the Wired account. The FDA's investigation of Jesse Gelsinger's death revealed that ten other gene-therapy subjects had previously died, in four different labs, and not been properly reported. Indeed, NIH discovered (paywall) that less than 4% of "serious adverse events" occurring in gene transfer trials were being reported as required.
A couple of years later, two children who had gene therapy in Paris for a fatal auto-immune disease ("boys in a bubble") developed leukemia, apparently when the retrovirus used lodged the new gene in an unfortunate place. That led to a temporary halt to all gene therapy trials.
In 2007, a woman died in a gene therapy trial, but investigators ruled that it was not directly caused by the treatment (see 1, 2). In recent years, however, reports of successful gene transfer treatments suggest that the techniques may eventually prove useful for a limited number of conditions.
Meanwhile, Wilson has been trying to rehabilitate his reputation, which is understandable. He has also been doing what seems to be good science, which is laudable. But we should focus on the systemic failures and the human lapses in judgment, not on a simplistic narrative of tragic failure and redemption through hard work.
You know who really deserves our thanks? Paul Gelsinger. He has worked tirelessly, mostly with Citizens for Responsible Care and Research, in an effort to ensure than no one else suffers as his family did. He quite rightly added his brief comments to the Wired story. In 2008, after Wilson had published an article (paywall) about informed consent (discussed here), Gelsinger summed up his position:
So, my son, doing the right thing, was killed by a system and people rife with conflicts of interest, and real justice has been found to be very lax. It's essentially business as usual. You may think that I am bitter, but I am not. My son gave me the best possible example on how to be. The system showed me what everything is really all about. Hopefully, given enough time they'll fix this, but I'm not holding my breath. Anyone considering joining a clinical trial needs to be aware that they are dealing with a system that is seriously flawed.
Those concerned about the unregulated environmental release of organisms created with synthetic biology won a small victory on July 31, when crowdfunding website Kickstarter determined that its projects can no longer offer genetically modified organisms as a reward. The company quietly added this change to its guidelines after a project that promised to send its sponsors genetically modified seeds that would “likely” glow-in-the-dark became quite controversial.
The ETC Group launched a “Kickstopper” campaign in May to raise awareness about the dangers of releasing bioengineered seeds to thousands of people around the world – which, they pointed out, would constitute the first deliberate random release of synthetic seeds ever. It set up its own petition (on rival crowdfunding site, indiegogo), which raised a couple thousand dollars, but convinced Kickstarter to act only after it had handed over $484,013 to the glowing plant project.
Synthetic biology enthusiasts are not pleased with Kickstarter’s new rule, and have started an Avaaz petition to try to convince Kickstarter to reverse the ban on offering GMOs. The petition states that “lumping legal science in the same category as weapons or hate speech makes no sense.”
This point may have originated with Omri Amirav-Drory, one of the glowing plant project’s creators who made a very similar comment. But it’s not particularly convincing, since Kickstarter’s guidelines forbid plenty of completely benign things, such as cosmetics and sunglasses (for some reason). And while the US Department of Agriculture apparently does not consider the kind of genetic engineering used to create glowing plants to be in its purview, a lack of any regulatory framework should not be conflated with “legal science.”
Furthermore, putting synthetic biology in the same category as weapons does make some sense. Glowing plants might be a “frivolous” use, but some synthetic biologists have other applications in mind. Oxford University's Future of Humanity Institute recently announced that synthetic biology could be the greatest global threat to humanity.
The issue boils down to a question asked by Azeen Ghorayshi in the East Bay Express: “Should there be stricter rules governing the DIY bio community? And if not, what happens next?”
Posted by Judy Norsigian and Miriam Zoll, Biopolitical Times guest contributors on August 6th, 2013
Virtus Health chief executive Sue Channon
Virtus Health is an Australian company that owns and operates 36 fertility clinics, and provides more than a third of the in vitro fertilization (IVF) cycles performed in the country last year. Together with its partner, the private-equity firm Quadrant, Virtus Health made financial history recently when it became the world’s first IVF provider to go public – to the tune of nearly half a billion dollars.
Chief executive Sue Channon nonetheless has a tough job promoting Virtus’s business and medical portfolios. On the corporate front, Channon is quelling investors’ fears that improvements in assisted reproductive technologies might mean fewer cycles for clients – and therefore dwindling revenues. But she assures shareholders not to worry: To attract more customers, Virtus plans to reduce the costs of some fertility treatments, and to expand into new markets in the Middle East, China and India, where U.S. and European demand for commercial surrogacy, in particular, continues to grow rapidly.
On the medical supply side, Virtus, like most IVF companies, enjoys lucrative growth driven in large part by a steady stream of panicked women in their thirties and forties who, for a variety of reasons, believed it both safe and feasible to delay motherhood. They turn to clinics like Virtus’s for last-minute miracles, unaware that, for those beyond the age of 35 years, the vast majority of their IVF cycles will fail.
The customer base on which Channon and others in the fertility field rely for corporate earnings would undoubtedly shrink if more women were made aware of these high IVF failure rates, and were reminded of the natural limits of biological fertility. Most would likely reframe the trajectories of their educational and professional advancement, and plan for children much the way women did before the conversation about “biological clocks” was nudged off the table by sensationalized headlines touting the “miracles” of reproductive medicine. After three decades of overly enthusiastic media endorsements, millions of women have succumbed to the seductions of a science that purports to have trumped Mother Nature in the reproductive arena.
Research conducted among college students in Sweden (2005), Canada (2010), and Israel and the United States (2012) all point to a pervasive lack of knowledge about women’s fertility and over-estimations of the success rates of reproductive technologies (1, 2). A full one-third of the Swedish men thought a woman's fertility did not sharply decline until after the age of 45, and the Canadian study of undergraduate women found that “they significantly overestimated the chance of pregnancy at all ages and were not conscious of the steep rate of decline for women in their thirties.” In the 2012 U.S. survey, two-thirds of women and 81% of men believed that female fertility did not markedly decline until after the age of 40. One-third of women and nearly half of men believed this decline occurred after the age of 44 – an age at which an IVF cycle is almost certainly destined to fail.
The combined end result of these fertility misperceptions and high IVF failure rates is a growing population of older couples who are now coping with the emotional shock of involuntary biological childlessness. In August 2008, the U.S. Census reported that the number of women aged 40 to 44 without children had doubled in a generation, going from 10% to 20% in the 30 years since fertility treatments have come to be seen as a fallback option. Though some are perfectly happy without children, many others are still trying to conceive or to accept that they will not be able to do so.
Reproductive endocrinologists are experts in fertility and the efficacy of the treatments available in the marketplace. Many of them likely cringe at the level of inaccurate information streaming through the media. Yet few, if any, IVF doctors or clinics have stepped forward to protect patients’ interests by publicly countering this misinformation. Might conflicts of interest be playing a role here?
If the Virtus half-billion dollar public offering is any indication of things to come, we are likely to see less accuracy and transparency from clinics, not more. For an IVF industry at that scale, downplaying the real numbers helps to secure the profits that investors expect.
Judy Norsigian is the Executive Director of Our Bodies Ourselves and a co-founder of the California-based Pro-Choice Alliance for Responsible Research. Miriam Zoll is the author of the new book, Cracked Open: Liberty, Fertility and the Pursuit of High-Tech Babies (Interlink, June 2013).
A recent study published in Genetics in Medicine found that predictions of disease risk from different direct-to-consumer (DTC) genetic testing companies vary, sometimes dramatically. The research team at Emory University Rollins School of Public Health compared methods and results from 23andMe, deCODEme, and Navigenics by simulating genotype data for 100,000 people and predicting the risks of six diseases based on each company’s method.
They found that “predicted risks differed substantially among the companies as a result of differences in the sets of single nucleotide polymorphisms selected and the average population risks selected by the companies, and in the formulas used for the calculation of risks.”
This study is not the first to reveal an alarming degree of variation among different gene testing products.
In 2010, the U.S. Government Accountability Office put out a damning report on DTC gene testing. Its conclusion: Notwithstanding some good PR for the industry since the GAO’s last report, test results from four different DTC companies were still “misleading and of little or no practical use.” In fact, its investigation found that “identical DNA samples yield contradictory results.”
The Nuffield Council on Bioethics put out a report the same year which cautioned, “The powerful rhetoric used to promote these developments should be treated with caution, since it can downplay potential harms and exaggerate the usefulness of the technologies concerned.”
People may be willing to accept a degree of uncertainty in a burgeoning field, but the assumption is that the technology will improve over time. That this year’s results still yield the same conclusion is disconcerting.
More troubling, however, is an increasing monopoly in the DTC world. Two of the three companies in the recent study – deCODEme (bought by Amgen) and Navigenics (bought by Life Technologies) – have recently stopped selling their DTC tests. 23andMe is the only DTC gene test vendor left.
Sure, 23andMe has some competition. DNA Ancestry now offers its test for $99 too. But it only offers information about family origins. For the same price, 23andMe offers the largest DNA ancestry service in the world and information on more than 240 health conditions and more than 40 other inherited conditions. Its retail price was recently heavily subsidized by Facebook billionaire Yuri Milner, one of the investors in 23andMe’s $50 million round of new financing.
So what does this emerging monopoly do for accuracy? If 23andMe is the only player in the field, comparative studies will no longer even be possible. As the company sweeps up patents, and throws millions into a new television ad campaign, the possibilities for competition will only weaken, and patients could suffer the cost. As the controversy over Myriad’s patent on the BRCA genes has documented, monopolies and public health don’t mix too well.
The implications of a monopoly in the DTC field are not insignificant. 23andMe suggests radical life changes and choices based on its results, from which medications to take to how to responsibly procreate. What if they’re wrong?
Posted by Gina Maranto, Biopolitical Times guest contributor on August 6th, 2013
The surrogacy industry in India is both booming and changing. A new 168-page report from the Centre for Social Research, a women’s advocacy group based in New Delhi, finds that the industry appears to be shifting from towns like Anand and Amritsar to the megacities Mumbai and New Delhi, which are more easily accessible to international travelers and have higher quality health care facilities. Surrogate Motherhood: Ethical or Commercial documents a range of disturbing conditions: Although the government has guidelines for assisted reproduction clinics, regulation continues to be spotty and current law affords scant protection to the poor, largely uneducated women who are being drafted to serve as incubators, or to the resulting children handed over to primarily foreign clients.
Foreign scholars and journalists have probed the Indian surrogacy business for some years. Within the country, groups like the Sama Resource Group for Women and Health have drawn attention to the broader practices of ART clinics, as in their 2008 publication Cheap and Best, which puts the industry in the context of global medical tourism and examines the rhetoric deployed by Indian IVF websites and brochures competing for their share of the international pie. Sama also produced a report in 2012 based on interviews with a dozen surrogates in Delhi and Punjab, five physicians, two agents, and one set of commissioning parents. In addition, Sama has recently released a documentary, Can We See the Baby Bump.
To study the current situation, CSR expanded the sample size significantly and employed systematic methodologies, akin to the pioneering fieldwork of researchers such as sociologist Amrita Pandé. CSR researchers carried out structured and open-ended interviews with 100 women serving as surrogates, half in Mumbai, half in Delhi, and with 50 couples who had commissioned pregnancies. In addition, the Centre’s researchers convened focus groups that gathered information from,
the ART clinics, the doctors and the nurses who carry out the entire procedure, the immediate society and community members, family members, agents including travel agents who arrange for commissioning parent‘s arrival, stay, passport and departure with the child and guest house/hotel owners where foreign couples stay during the whole procedure and the maternity homes/shelter homes where at times surrogate mothers stay for nine months to maintain secrecy. (p.14)
The report begins with an overview of the legal and regulatory status of surrogacy in India and a literature review, both of which cover familiar ground and are notable chiefly for the authors’ eschewal of euphemisms: they define a surrogate as “one who is hired to bear a child that she turns over at birth to her employer,” refer to the child as a “saleable commodity,” and use similar market-based terminology throughout. CSR estimates that surrogacy accounts for $500 million of India’s total reproductive tourism market annually.
A committee of the California Institute for Regenerative Medicine (CIRM) has voted to postpone a decision on a proposal that would undermine protections for women who provide eggs for research by allowing researchers to use stem cell lines created with eggs for which women have been paid. CIRM’s leadership and staff had apparently intended that the Standards Working Group – the committee responsible for setting and upholding ethical requirements – would approve the broad policy change at its Wednesday meeting, and that the agency’s governing board would then adopt it the following day.
The push by CIRM leadership is one of two ongoing efforts in California to gut protections for women who provide eggs for research by creating a commercial market for them. The other is AB926, a bill sponsored by the fertility industry that has been approved by the legislature and now awaits Governor Jerry Brown’s decision to sign it, veto it, or let it become law without his signature.
Currently, California – like many countries – allows women who provide eggs for research to be reimbursed for travel, lost wages, child care and other expenses connected to the egg retrieval process, but not to be paid beyond that. Objections to expanding the market for eggs center on the significant but woefully under-studied health risks of the egg retrieval process, what bioethicists term the “undue inducement” of offering thousands of dollars to young women to undergo it, and the challenge to the very possibility of “informed consent” when risks are inadequately known.
The limitation on paying women to provide eggs for research was established twice in California. It was included in the 2004 ballot measure that created CIRM, the state’s $3-billion publicly funded stem cell program. The policy was extended to cover researchers not funded by CIRM in 2006 in a law that was authored by a Democratic Senator who was an early champion of embryonic stem cell research, supported by CGS and other women’s health and public interest groups, and passed by both houses of the state legislature almost unanimously.
AB926, now on the Governor’s desk, would reverse the 2006 law, allowing scientists to recruit women for the invasive and risky egg retrieval procedure with offers of up to $10,000 or more. Even if AB 926 becomes law, however, it would not override the law that prevents CIRM-funded researchers from using agency dollars to pay women directly. That’s why the agency’s leadership wants the Standards Working Group to approve what amounts to a giant loophole. Allowing CIRM grantees to use cell lines created with eggs paid for by non-CIRM funds would condone and encourage the practice and the commercial market.
With Wednesday’s vote by the Standards Working Group to delay consideration of the proposal, the next move is up to Governor Brown.
Posted by Grant Shoffstall, Biopolitical Times guest contributor on July 25th, 2013
Cryonic suspension, or “cryonics,” is the strange practice of freezing human corpses in hopes that scientists will at some future point achieve a level of medical technology so advanced that it will be possible to repair virtually any damage sustained by the human body, cure disease, halt and initiate a reversal of the aging process, and yes, rejuvenate and “reanimate” the “deanimated,” those who lay in cryonic suspension. The ethos of cryonics is summed up nicely by a quirky expression, coined in the tumultuous American 1960s, which has since become something of a hallowed commonplace among latter day cryonics advocates: “Freeze-Wait-Reanimate.”
As one might expect, cryonic suspension’s history is punctuated by episodes of controversy, misunderstanding, and accusations of fraud and pseudoscientific quackery – not to mention catastrophic disaster. Freezing People is Easy, an upcoming film by Zach Helm (Stranger than Fiction) and Academy Award winning director Errol Morris (The Fog of War), will to this end chronicle the plight of Robert F. “Bob” Nelson, a TV repairman, science-fiction enthusiast, and co-founder and former president of the long-since defunct Cryonics Society of California (CSC). The film will draw from Nelson’s 1968 memoir, We Froze the First Man, and “Mistakes Were Made,” the overwhelmingly popular “cryonics” episode of Ira Glass’s radio show, This American Life (1).
Freezing People is Easy (spoiler alert!) will offer an account of how Bob Nelson’s enthusiastic though remarkably amateurish toilings in cryonics during the 1960s and 70s conspired in producing the most disastrous and damaging event in the history of the practice – the abandonment, thawing, and decomposition of nine cryonic suspension “patients” interned in the CSC’s underground crypt at the Oakwood Memorial Park Cemetery in Chatsworth, California; what is infamously known in cryonics circles as the “Chatsworth Scandal.”
The macabre nature of the incident can’t be underscored too heavily. Bodies, and tens of thousands of dollars, went missing. In cryo-suspension capsules designed for one, Nelson had crammed two, three, even four “patients,” leaving scant room for liquid nitrogen. Questions were evaded. Visitations were denied. Relatives were kept in the dark. Rumors of something amiss at Chatsworth circulated among cryonics activists from coast to coast. When Valley News reporter David Walker finally ventured to the by-then abandoned CSC facility on the morning of Friday, June 10, 1979, he was overcome by the site: “the stench near the crypt is disarming, strips away all defenses, spins the stomach into a thousand dizzying somersaults (2).” Freezing people is easy; maintaining them in a frozen state over the long term, however, as Nelson found out the hard way, is another matter entirely.
What transpired at Chatsworth under Bob Nelson’s watch was so bizarre, so revolting, so tragic, it seems appropriate that Helm and Morris have opted to engage the scandal through stylistic conventions approximating those of the cinematic genre deployed to such masterful effect by Stanley Kubrick in Dr. Strangelove – nightmare comedy (3). Boasting a first-rate cast that includes Paul Rudd (as Nelson), Owen Wilson (as mortician Joseph Klockgether, Nelson’s collaborator), the one-and-only Kristen Wiig (as Nelson’s wife), and the legendary Christopher Walken (as Robert C.W. “Bob” Ettinger, so-called “father” of the cryonics movement), Freezing People is Easy will very likely make for a good laugh. I suspect, however, that Helm and Morris’s decision to portray Nelson as a naïve but otherwise good and loveable character who simply gets in way over his head will evoke howls of protest the from the contemporary cryonics fraternity, sizable factions of which regard Nelson as a con-man who perpetrated unspeakable evil at Chatsworth and beyond, forever trapping cryonics in the dreaded realm of “pseudoscience.”
Bob Nelson’s culpability in the events at Chatsworth will remain open to debate; Helm and Morris have simply made the most recent move. I am concerned, however, that their cinematic rehabilitation of Nelson, even though satirical, may incite discourses that end up concealing far more than they reveal about cryonics, Chatsworth, and Bob Nelson himself (4). This is not to say that the villainous Nelson of cryonics lore is somehow closer to the truth; that Morris and Helm’s portrayal is “biased.” No. The challenge is not to pinpoint Bob Nelson as a saint or the devil incarnate, but to recognize as dubious any attempt to “explain” a complex sociohistorical event like Chatsworth by attributing its horrific outcome to Nelson’s flawed moral character. While such a yarn is loaded with the sort of cinematic possibilities that tend to resonate so powerfully with the twin American cults of hyper-individualism and personal responsibility, it is also sociologically and historically anemic.
My concerns, of course, may prove to be unfounded. Like the nightmare comedy Dr. Strangelove before it, Freezing People is Easy may very well have the effect of inciting serious discourse about some of the most disturbing and destructive elements of postwar American culture: the denial of death, the denigration of the elderly, youthful hedonism, and a quasireligious faith in the destructive and regenerative power of modern technoscience. In the likelihood of such an outcome, we may then come to realize that we are not so very far removed from the world that gave rise to Bob Nelson’s strange ambitions in the first place.
Grant Shoffstall is a Ph.D. Candidate in the Department of Sociology and the Program in Science and Technology Studies at the University of Illinois at Urbana-Champaign, where he is completing his dissertation, Biomedicalization, Cybernetics, and the ‘Prospect’ of Immortality: Towards an Historical Sociology of Cryonic Suspension, 1958-1979. He has no intention of being placed in cryonic suspension upon deanimating.
This essay was originally published in the Spring 2013 issue of the University of Illinois’ Department of Sociology Newsletter.
1. Robert F. Nelson with Sandra Stanley, We Froze the First Man (New York: Dell, 1968). For a link to “Mistakes Were Made” and a take on Freezing People is Easy by a respected cryonics veteran, see Mike Darwin, “Freezing People is Easy,” Chronosphere: A Revolution in Time. 2. David Walker. “Valley Cryonic Crypt Desecrated, Untended.” The Valley News (June 10, 1979):11. 3. The comparison of cryonics to Dr. Strangelove is owed to Jill Lepore, Mansion of Happiness: A History of Life and Death (New York: Alfred A. Knopf, 2012), Ch. 10. 4. The present remarks are significantly indebted to John R. Hall, Gone From the Promised Land: Jonestown in American Cultural History (New Brunswick, NJ: Transaction Books, 1987), Introduction and Ch. 12.
Posted by George Estreich, Biopolitical Times guest contributor on July 23rd, 2013
Remembering Ethan Saylor
I’m just home from the annual National Down Syndrome Congress convention, and even given the fact that Down syndrome lands in the news with regularity, there were two big pieces of news during the week I was there. The first was a report that researchers have found a way – in a dish, at least – to “silence” the extra chromosome associated with Down syndrome, which “could help researchers to identify the cellular pathways behind the disorder's symptoms, and to design targeted treatments.”
The second was the release of a full report of the facts surrounding the death in January of Ethan Saylor, the twenty-six-year-old man with Down syndrome who – on refusing to leave a movie theater for a second showing of Zero Dark Thirty – was dragged from the theater by three off-duty sheriff’s deputies moonlighting as mall security, handcuffed, and held face down. He died of asphyxia. Before he died, he was crying in panic for his mother, who was en route to the theater. His death was ruled a homicide by the coroner, but a grand jury declined to indict the deputies. The case has gotten national attention, but the outrage has been mainly confined to what we would call, for lack of a better word, the Down syndrome community – those with Down syndrome, and those who care about them. It has taken months for the full record of facts to be released, and an independent investigation has finally begun.
At the convention, thinking about recent news and the people all around me, I thought a lot about invisibility. In Denver, for a few days, people with Down syndrome were unusually visible – not in the context of human interest features or stories about new prenatal diagnostic tools, which is the way they usually appear, but as family members of all ages. My own daughter was back home, though I had two suitcases full of copies of her story: I was selling my book about her, the one she calls “her book,” in the fluorescent, sunless caverns of the Convention Center. (Convention Center, a curious phrase, given the unconventional population.) But throughout the Center, and to a lesser extent in the streets and hotels nearby, people with Down syndrome were visible everywhere.
There are two kinds of invisibility: a literal one, abetted by new technologies, whose likely effect is to ease a population from sight; and a cultural invisibility, fueled by misunderstanding and fear. The two are interrelated. Misunderstanding and fear can fuel the demand for prenatal tests, which can in turn decrease the population; the resulting absence of contact can, in turn, drive further misunderstanding. More subtly, the very fact of prenatal testing drives the way we think and talk about people with Down syndrome: away from a discussion of citizens with rights, and towards a discussion of possibilities, potentialities, and risks. They occupy a kind of limbo of human value. They are discussed – often inaccurately – in terms of their effect on others, rather than in terms of their opportunities and hopes.
Last week, researchers at the University of Oxford announced that the first baby had been born after undergoing a technique which can sequence the entire genome of an embryo. The story was accompanied by a cute picture of baby Connor Levy, fast asleep on a fluffy white blanket wearing a shirt that reads: Made with love (where the ‘o’ of love is an image of an atom.)
No one could deny the claim. His parents, a couple from Philadelphia, had tried natural pregnancy for five years, then three rounds of intra-uterine insemination, and finally IVF in the hopes of having a child. They decided to take part in Oxford’s international study of next-generation sequencing (NGS) and sent cells from thirteen of their IVF embryos. A fertility specialist looked at the chromosomes of each and found that three had the right number. One was implanted into the mother and nine months later Connor was born.
In this instance, researchers used only the number of chromosomes as selection criteria. Chromosomal abnormalities account for half of all miscarriages and lead to conditions such as Down syndrome and Turner syndrome in the babies who survive to birth. Of course, not everyone sees this type of selection as wholly benign: Some question whether decisions to terminate pregnancies when Down syndrome is identified are typically made with full information; some consider the trend a problematic form of modern eugenics, rather than a medical necessity.
But this is obviously a happy occasion for the Levy family, and for many others who are struggling with infertility. Many fertility experts believe that new forms of genetic testing can greatly increase success rates and efficiency of IVF overall, particularly for older parents. Michael Glassner, the couple’s fertility specialist, firmly believes in the potential of NGS and stated, “In five years, this will be state of the art and everyone who comes for IVF will have it."
Genetic testing of embryos for the purpose of screening out disease does already occur. According to the Human Fertilisation and Embryology Authority, there are 263 medical conditions (and another 32 under consideration) that are considered serious enough to warrant the use of preimplantation genetic diagnosis (PGD), the genetic screening of embryos prior to implantation.
But NGS carries potentially broader implications.
This “revolutionary” process is capable of sequencing an embryo’s entire genome, providing an unprecedented degree of information about it prior to implantation. This would give parents much more (but often imperfectly understood) information, including about the child’s chance of developing certain diseases, as well as non-medical characteristics such as eye and hair color.
Is this what parents want? William Saletan at Slate is concerned that we’re only reporting the successes of embryo testing and warns that
We’re discarding embryos over the possibility of breast cancer, which rarely strikes before age 30, and early-onset Alzheimer’s, which doesn’t begin till 40 or 50. We’re rejecting them to avoid the risk of conditions such as rhesus blood disease, where onset is dubious (specific antibodies have to cross the placenta to the fetus) and the cure rate is 70 to 95 percent. We’re even chucking embryos just because their genes make them useless as tissue donors.
To move from testing embryos for specific genetic mutations based on family history to testing entire genomes no matter what would be a huge shift. Saletan seems largely concerned with the fate of the embryos themselves, but there are other reasons NGS would put parents-to-be in an uncomfortable position. How would people longing for a child weigh one abnormality or imperfection against another, or contemplate abstractions such as a 50-60% disease risk against a potential human life?
Nevertheless, there are already those with far broader hopes for the technology.
Zhao Bowen, the 21-year-old who oversees BGI Shenzhen’s multimillion-dollar research project searching for the genetic underpinnings of intelligence, explicitly hopes his research will be used to breed smarter babies. According to Wired, those on his team “expect that within a decade their research will be used to screen embryos during in vitro fertilization, boosting the IQ of unborn children by up to 20 points.”
Momentarily putting aside the fact that there is currently no evidence to suggest that genetic selection for intelligence is possible, if such research does pan out, it will largely be limited to the privileged elite. As Heather Long argues in the Guardian, “If we think the gap between the haves and have-nots is large now, just wait until this technology is used to pre-select characteristics for success.”
Of course, the process of selecting among existing embryos is somewhat limited in its design capabilities. It is important to note the difference between choosing traits based on selection, and actually modifying the germline of embryos in order to create a desired result.
An editorial in New Scientist noted that the announcement of Connor’s birth “brings the prospect of designer babies one small step closer,” but that “until it becomes possible to genetically engineer embryos rather than just select them, true designer babies remain in the realm of science fiction.”
The authors agree that we shouldn’t simply sit back and wait for that to happen. But they fail to mention how close this possibility truly is. The UK Government is preparing right now to draft regulations that would undermine the country’s ban (as well as international law and consensus) to allow embryo manipulations that would effect all subsequent generations. The justification is that this step would be a limited one aimed at allowing a small subset of the women with very serious mitochondrial diseases to have a healthy and mostly genetically related child. But it would provide the biggest push to date down this particular slippery slope.
RNL Bio is a Korean biotechnology conglomerate notorious for pushing the ethical, commercial and allegedly legal envelopes in pursuit of what seems to be the goal of becoming a multinational force in biotechnology. It has demonstrated a remarkable ability to combine real scientific expertise with a talent for headline-grabbing. They've done dog cloning (with an explicit goal of performing chimeric human research), sold stem-cell cosmetics, and established subsidiaries or partnered with companies in California, Texas, Germany, China and Japan.
Now RNL Bio is undergoing some major changes. How much difference they will make in the long run remains to be seen, but certainly the enterprise has suffered some significant setbacks:
The parent company was delisted from the Korean stock exchange in April.
RNL Europe went bust earlier this year and has been sold (according to the updated resume of former American Journal of Bioethics editor Glenn McGee, himself associated with a string of controversies).
In June, CEO Dr. Jeong Chan Ra (who last year pledged to donate 90% of his fortune to charity over the next decade) was arrested and charged with insider trading and also accused of sexual harassment.
The company has had legal issues for some time, not least because of its apparent attempts to circumvent Korean law by treating patients in Japan and China, perhaps with smuggled stem cells. In the U.S., RNL Bio used to be partnered with Celltex, the Texas company that became notorious for treating former and perhaps future Presidential candidate and Texas governor, Rick Perry. Then it set up a U.S. subsidiary, Human Biostar; Celltex is suing them both, and facing a countersuit. Meanwhile, Human Biostar is being sued in Los Angeles for fraud.
As recently as May, the Korean company filed an Investigational New Drug application with the FDA to begin clinical trials of an adult stem cell product for the treatment of osteoarthritis. At around the same time, RNL Bio and Human Biostar announced that they were offering direct-to-consumer adult stem cell banking in the U.S. — not treatments (that would be wrong) but storage for physicians whose patients request the service.
Confused yet? Fortunately, Leigh Turner and Paul Knoepfler have done remarkable work keeping up with all this. Turner's Health in the Global Village effectively broke the arrest story in English (with thanks to Dersu na Amure). Knoepfler's Stem Cell Blog is running a series on Celltex documents he obtained from the FDA via an FIOA request; apparently the most revealing letter is yet to come.
Contrary to some speculation, RNL Bio claims not to be going away. The company has appointed a new CEO, Hyoung Seung Lee, with strong connections to the old regime, who is reportedly planning to divest some divisions and focus on the stem cell business.
On July 1, the California Senate passed AB 926, which would overturn a current law that safeguards women’s health by limiting what researchers can pay for extracting their eggs. The bill, sponsored by the American Society for Reproductive Medicine, is about to land on Governor Jerry Brown’s desk. Once it does, he has 12 days to either approve or veto this bill; if he does nothing the bill becomes law.
If you agree that more research on short- and long-term risks is needed before expanding the market for women’s eggs, please act quickly. Contact Governor Brown and ask him to veto AB 926. You can reach him in any of these ways:
Fax: (916) 558-3160
Call: (916) 445-2841
Postal mail: Governor Jerry Brown, Attn: Lark Park, Deputy Legislative Secretary, State Capitol Suite 1173, Sacramento, CA 95814
For more about why AB 926 should be defeated, see these previous Biopolitical Times posts:
And over the last couple weeks, AB 926 has been receiving increasing media attention. The most recent and in-depth article is “Brown ponders sale of women's eggs for research” in Capitol Weekly. It’s also been covered by Nature, Southern California Public Radio, the California Stem Cell Report (1, 2, 3, 4), and in an hour-long interview on Mutiny Radio.
Corey G. Johnson of the Center for Investigative Reporting (CIR) published on July 7th a detailed exposé of unauthorized sterilizations of unwilling women in California jails from 2006 to 2010:
At least 148 women received tubal ligations in violation of prison rules during those five years — and there are perhaps 100 more dating back to the late 1990s, according to state documents and interviews.
Johnson's excellent and careful reporting has brought to national attention a scandal that some activists have already at least partially documented. Justice Now presented testimony [pdf] about it to a California Senate subcommittee on March 13, 2012, and discussed their findings at a conference in August (co-sponsored by CGS) called "Eugenics in California: A Legacy of the Past?" (video is available).
It is important to note that, as the CIR article says (links are provided to the relevant statutes), these sterilizations were illegal:
Federal and state laws ban inmate sterilizations if federal funds are used, reflecting concerns that prisoners might feel pressured to comply. California used state funds instead, but since 1994, the procedure has required approval from top medical officials in Sacramento on a case-by-case basis.
Yet no tubal ligation requests have come before the health care committee responsible for approving such restricted surgeries …
How could this happen?
Governor Gray Davis apologized in 2003 for California's twentieth-century sterilizations, 20,000 procedures carried out under an explicitly eugenic law. He did so quietly, via press release, and with no attempt to discover or compensate the victims. (Recognized experts on American eugenics were disappointed at the time: Paul Lombardo called it "premature" and Alexandra Minna Stern said it was "preemptive.") Now his statement seems like a sham. The fault is no longer the law, it's the failure to follow the law.
North Carolina is still struggling to pass a budget that includes compensation for its victims of eugenic sterilization. California has barely started the process of coming to terms with its troubled history.
The California state prison system is overcrowded — Governor Jerry Brown is appealing a federal court order to release inmates — and conditions are so bad that 30,000 are on hunger strike. If this report about sterilization helps to usher in a period of genuine reform, that would be wonderful.
We would still need to educate all too many people, inside and outside the jail system, about the moral and practical harm of modern eugenics. Based on some of the remarks by state officials that Johnson reported, and on some of the comments on coverage of his investigation, people slide right back into eugenic ways of thinking.
Update, July 11: Justice Now and Californians United for a Responsible Budget (CURB) have started a petition "demanding that the state end; make amends for; and prevent sterilization abuse, period." (See Comments below for more.) Meanwhile the California Legislative Women's Caucus is demanding answers. This would be a good time to put pressure on the legislature and the Governor.
Last month, the UK government announced it would move toward human trials of a risky, controversial and widely misrepresented technique known as “mitochondria replacement” or “three-parent babies.” The technique is currently prohibited by law in the UK (and in dozens of other countries), so final approval would require a legislative change. With another round of public consultation pending prior to legalization in the UK, here are the top misconceptions proliferating about the efficacy, safety, public support, and societal implications of mitochondria replacement.
Misconception 1: Mitochondria replacement “will save lives.”
It’s troubling when media accounts sloppily represent these techniques as “saving lives.” It’s worse when scientific and government officials mislead in this way. But it’s been far too common. Chief Medical Officer for England Dame Sally Davies, for example, claims that mitochondria replacement is a “life-saving treatment” and “will save around 10 lives a year.”
Fact: Mitochondria replacement will not save any lives; it is not a treatment for any of the people who are currently suffering from mitochondrial disease. Its aim is rather to create a prospective child who would be genetically related to a mother affected by the condition, and who would (if the new technique worked) be healthy.
Misconception 2: Mitochondria replacement techniques will eliminate mitochondrial disease in future children, which no other technique can achieve.
This is the fundamental premise and motivation for advocating these techniques, and it is repeated regularly. See examples here in the Telegraph and here in the Guardian.
Fact: Both aspects of this premise are misleading. First, even if the techniques were to work perfectly, they wouldn’t be able to guarantee a child free of mitochondrial diseasebecausein the majority of cases, the conditions are caused by anomalies in nuclear DNA. They can also occur due to spontaneous mutations or with age. Furthermore, the HFEA acknowledges that mitcohondria replacement may not even be effective at removing all of the mutated mitochondria from a future child.Annex VIII of its final report states:
The panel recommends that 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 this child or (if a female) subsequent generations at risk of mitochondrial disease. Thus, we recommend that any female born following MST or PST is advised that, should she wish to have children of her own, that her oocytes or early embryos are analyzed by PGD in order to select for embryos free of abnormal mtDNA. (page 5)
That leads to the second point – there is already a safe available technique (preimplantation genetic diagnosis or PGD) that allows carriers of mtDNA mutations the ability to have healthy children of their own. If the HFEA recommends that girls born after mitochondria replacement use the technology, then why wouldn’t a woman simply use it in the first place? Even women with high levels of mutations in their own mitochondria can produce eggs with very low levels; PGD can find those embryos and (with a high rate of success) implant them back into a woman to produce a healthy child.
Misconception 3: This technique would be in high demand because one in 200 babies is born with mitochondrial disease.
Many news articles (particularly early on) bought into this, likely because the HFEA’s website states that, “Around one in 200 children are born each year with a form of mitochondrial disease.”
Fact: This is an extremely misleading way to discuss the incidence of mitochondrial disease. The HFEA seems to be relying on findings that around one in 200 people in the general population have mutations in their mitochondrial DNA, but most of these people will not experience any negative impact. Estimates of the number of people who actually have mitochondrial disease run around one in 5,000-10,000. Their conditions run the gamut from very minimal to quite debilitating. But only about 15% of these cases are likely caused by mitochondrial DNA: the majority of mitochondrial disease is caused by interactions with nuclear DNA. Of this greatly reduced subset, it is only women with a very high level of mutations who would be potential candidates for using mitochondria replacement rather than PGD to have a genetically related healthy child. Officials at the UK’s Human Fertilization and Embryology Authority and at its Department of Health – both agencies that are advocating moving forward with mitochondria replacement – have estimated that perhaps 10 women a year would consider the procedure.
Misconception 4: The techniques have been proven to work in animals.
For example, the Guardian states here that “The procedure has been shown to work in animals.”
Fact: There were a number of studies done mostly in the 1990s using one kind of mitochondria replacement technique (pronuclear transfer or PNT) in mice (see footnotes 3 – 6). However, the HFEA required that researchers at Newcastle University test PNT on a non-human primate model, which they never did. A research team inOregon did try PNT on macaque monkeys, but found it to be unsuccessful, with embryos failing early, and thus abandoned PNT. They have shown success using another kind of mitochondria replacement (maternal spindle transfer or MST), although the monkeys are still young and no further generations have been studied. This knowledge has not deterred Newcastle,or the HFEA, from pushing for human trials of PNT. The HFEA’s response to the failed macaque experiments was to drop the requirement(see page 21) for non human primate testing.
Misconception 5: There is broad public support for mitochondria replacement techniques.
The HFEA put out a press statement on March 20 which cited “broad support for permitting mitochondria replacement” as the general conclusion of its public consultation on the techniques. This was consequently repeated by nearly every media report on the consultation.
Fact: By far the largest number of people (over 1,800) who took part in any of the different “strands” of the HFEA’s consultation were involved with the online open questionnaire. The majority of these participants wrote to say that theydisagree with the introduction of either mitochondria replacement technique (PNT or MST.) In its past consultations, the HFEA has presented this strand, as the only portion which is open to everyone, as the most important. In this case, the HFEA is downplaying it.
For more on the numerous ways in which the HFEA has misrepresented its own data by claiming “broad support” from the public, see this blog post.
Misconception 6: The genetic contribution of the donor of mitochondrial DNA is inconsequential.
This is another claim that has been made repeatedly. For example, Doug Turnbull, Professor of Neurology at Newcastle University said, "Mitochondrial genes only help produce mitochondria. They have absolutely no role in any other characteristics.”
Fact: This statement is quite misleading. It is true that mitochondrial DNA constitute only 37 genes, but that does not mean they do not have significant phenotypic effects. Mitochondrial DNA has an impact on cognition, aging and cancer, adult-onset diabetes and deafness, and interacts consistently with nuclear DNA. Among other things, mitochondrial DNA provides metabolic energy during embryonic development, which clearly has a large impact on phenotype.
Responding to Turnbull’s claim, New York Medical College Professor of Cell Biology and Anatomy Stuart Newman said:
If mutations in different mitochondrial genes affect different organs (which they do), how can it possibly be maintained that mitochondrial genes "only help produce mitochondria"? Impairment of mitochondria impairs development – that’s how the diseases are produced. Genetic variation (even within a normal range) leads to phenotypic variation. The inescapable conclusion is that normal variations in mitochondrial genes must have differential effects on developmental outcomes.
Misconception 7: Mitochondria replacement is just another kind of IVF
Numerous media accounts have referred to “3-parent IVF” or called mitochondria replacement an “IVF treatment,” and some have compared the initial uncertainty around the safety of IVF to the current uncertainty about the safety of these techniques.
Fact: There is a critical difference, which Stuart Newman sums up well in The Huffington Post:
Unlike in vitro fertilization (IVF) which generates embryos from the biological components that evolved to serve this function, the two methods under consideration by the HFEA de- and reconstruct the fertilized egg in radical ways, unprecedented in the history of life.
Misconception 8: The “slippery slope” argument is overstated; no one wants to modify nuclear DNA.
If human trials of mitochondria replacement are approved, it would be the first time that any government has authorized genetic changes that would affect future children and their descendants. Such procedures – known as human germline engineering – have been prohibited by dozens of countries because of concerns that they would open the door to a new form of high-tech eugenics, with profound societal consequences.
Some advocates of mitochondria replacement simply dismiss these concerns, rejecting them as a “slippery slope” argument.
Fact: If mitochondria replacement is allowed, there will almost certainly be increased pressure to permit modifying nuclear DNA in the name of preventing diseases. For example, Robin Lovell-Badge, head of developmental genetics at the MRC National Institute for Medical Research, told Wired that there’s no point in worrying about germline modification, but then went on to state,
I do not argue that germline genetic modification of nuclear genes should never be considered, for example, parents might accept modifications that would protect their child against diseases such as AIDS. However, we do not yet have the technology or knowledge to guarantee that any such genetic alteration would be safe.
Well, we don’t have the technology or knowledge to guarantee that PNT would be safe either. (In fact, Newcastle University did not submit any published material to the HFEA’s safety review.)
The reason there has been an international consensus against human germline modification is that it is incredibly hard to draw a line anywhere else. Lovell-Badge proves that point above. If this line is crossed for the prevention of certain kinds of diseases, there will be increased pressure to research and fund other kinds of genetic prevention – in spite of safer alternatives in very nearly every case, as there are with mitochondrial disease.
And if interest and money begin flowing into development of germline genetic modification, it is naïve to imagine that there would not be fertility clinics willing to offer couples the ability to choose “designer” traits of their liking, and some who would argue this is simply a matter of reproductive choice.
But when the facts are presented without misrepresentation, the case for mitochondria replacement – as for other kinds of inheritable genetic modification – is flimsy at best. For more information on mitochondria replacement and its implications, see the Center for Genetics and Society’s press statement or this detailed resource page.
Posted by Gina Maranto, Biopolitical Times guest contributor on July 3rd, 2013
By now it’s a familiar marketing tactic in the IVF industry: Pursue a dubious line of research and then manufacture a constituency that “demands” widespread access to the new technology. The latest campaign is being staged with the aim of normalizing egg freezing, thereby creating a new profit center for the industry in the form of otherwise fertile young women.
In the last several years, the message that egg freezing can help women defeat the biological clock has reached the mainstream press and blogosphere. This year, high- profile outlets published pieces in which women trumpeted their faith in the technology. Pieces by Sarah Elizabeth Richards in the Wall St. Journal and Amy Klein at Slate, provoked heated debate among both readers and the international community of scholars and activists concerned about the implications of the technique.
There has been pushback. Miriam Zoll, for example, challenged claims that egg freezing is implicitly safe and efficient in a response, also at Slate, to the Klein piece. And at The Feminist Wire, Lynn M. Morgan and Janelle S. Taylor tallied the negatives, calling the procedure “invasive, dangerous, unregulated, and insanely expensive.”
But a quick scan of the internet shows that the marketing of egg freezing to beat the biological clock is already well underway. See, for example, the Fertility Center of Illinois, the Extend Fertility website, and InVia Fertility. Once again, the industry is marketing a technology without first carrying out extensive studies to determine its safety.
What came first, the technology or the demand?
Originally, egg freezing was put forward as a response to the “complex ethical, social, legal, moral, and religious issues” surrounding the fate of excess embryos in the IVF clinic. In 1986, Christopher Chen made a preliminary communication to The Lancet reporting “the first successful attempt at deep freezing and thawing of the human oocyte.” [by subscription]. Chen reasoned that “oocyte banking, like sperm banking, should be more acceptable to the community than embryo storage, since it involves only the gamete.”
Within a decade, IVF researchers were expanding the circumstances in which they thought egg freezing should be carried out, advocating the technique as a means of maintaining the fertility of women undergoing radiation or chemotherapy for cancer (see, for example, Saunders et al. 1996) [by subscription]
By 2006, at the 54th Annual Meeting of the Pacific Coast Reproductive Society—the must-attend conference for top IVF researchers—a team led by Richard Paulson of University of Southern California was proposing egg freezing as “a promising strategy for circumventing the age-related decline in human fertility.”
DNA is the ultimate big-data dream. It can shed light on our health, ancestry, and family members. It can be used to solve crimes and exonerate the innocent, investigate diseases and treatments, advance basic scientific knowledge, and reveal certain aspects of our histories and potential futures.
But as genetic data is collected and used in increasingly varied contexts, issues of privacy, rights, access, justice, and innovation are poised to collide – and to intersect our lives in both positive and negative ways. The questions raised by this coming collision won’t be answered immediately, but we need to start now to tease out their complexities.
Many suitors are lining up to exploit the explosion of genetic information.
Local police agencies are creating their own databases – some call them “rogue” databases – and the Supreme Court recently determined that state and federal authorities can take DNA from people arrested (pre-conviction) for serious crimes.
Marketing and advertising gurus are looking to genetic sequencing as the next frontier of precision-targeted consumer data.
Developers are competing to create apps – many of dubious utility, and some potentially harmful – that will do everything from suggesting optimal nutrition for your genetic profile to offering good genetic matches as a dating service.
An artist is picking up stray hairs and using them to create 3D portraits of the owner.
Consumer genomics company 23andMe is now offering its genetic test for only $99 – knowing full well that the information you’re handing over is much more valuable than the information it’s giving you.
Each of these uses makes its own bevy of assumptions and raises its own array of ethical concerns. But certain themes resound: Who owns your genetic data? Who can access it? Who can profit from it? What does informed consent and privacy mean in different contexts? What control – if any – over your genetic information do you retain once it’s been collected? Who gets to and who is forced to have their genetic information profiled and stored?
In April, what appeared to be a tiny San Francisco start-up called Glowing Plant launched a Kickstarter campaign to raise $65,000 to create luminescent mustard plants. Its pitch was that anyone who contributed $40 or more would receive a packet of seeds and full instructions for growing their own glowing plant. For $150, you would get the plant itself. Also for sale, of course, are T-shirts and stickers and vases and planters and even a photo book.
The promoters blew past their initial goal in a few days, and added further premiums, in the form of glowing roses. They haven't done the engineering work yet, for either mustard or roses, but it seems technically plausible. (The image above, used in their publicity, is of a tobacco plant.) By June 7, the funding deadline, they had raised $484,013 from more than 5000 people.
It will take them a year or so to complete the project, they estimate. But then they threaten to release somewhere between 5000 and half a million experimentally modified plants to completely unknown sites, with absolutely no oversight or reporting requirement. This, they claim, is legal.
Glowing Plant is not (just) a stunt. The principals have close ties to Genome Compiler and Cambrian Genomics, which in turn are linked to major funding, in the form of Silicon Valley venture capital. Some serious scientists are also involved: George Church endorsed Glowing Plant and co-founded Cambrian with, among others, John Mulligan of Blue Heron Biotechnology, which worked on Craig Venter's synthetic bacterium project.
Glowing Plant and Genome Compiler's Omri Amirav-Drory and Austen Heinz of Cambrian like to talk about "democratizing creation" and to position themselves as champions of the little guy. But it looks as though they hope to jump-start commercial synthetic biology — and perhaps to become the billionaires of what they see as the coming Synthetic Biology revolution. They bear watching, and this project is just crying out for proper regulation.
How the unanimous Supreme Court decision that human genes may not be patented will affect our lives continues to be somewhat unclear. Some industry sources claim that it won't make much difference in the long run, others that biotech will overall benefit, and some that it will be damaged. Generally, the expectation seems to be that consumers of genetic tests will find them cheaper and more available. However, Eleonore Pauwels wrote in a New York Times op-ed:
The Supreme Court's unanimous ruling ... was a wise and balanced decision that clears away a major barrier to innovation in the areas of biotechnology, drug development and medical diagnostics. But the decision is just a first step toward finding the right balance between protecting legitimate intellectual property and securing an open future for personalized medicine.
In other words, no one is quite sure how it will all play out. Here are some more responses, with capsule pointers to the attitude in each:
Posted by Gina Maranto, Biopolitical Times guest contributor on June 18th, 2013
In 2004, after years of impediments to stem cell research imposed by the federal government, California voters approved a ballot referendum that created a $3 billion workaround, the California Institute of Regenerative Medicine (CIRM). Supported by tax revenues and reporting to a governing body called the Independent Citizens’ Oversight Committee made up of representatives from the biotech industry, patient advocacy groups, and academic and not-for-profit labs, CIRM’s mission is to
support and advance stem cell research and regenerative medicine under the highest ethical and medical standards for the discovery and development of cures, therapies, diagnostics and research technologies to relieve human suffering from chronic disease and injury.
In that statement, and in its frequent public pronouncements, CIRM gives no recognition to the controversies that accompanied its foundation, nor to any ongoing conflicts surrounding stem cell research.
For a full account of these issues, we can turn to Ruha Benjamin’s nuanced and incisive investigation, People’s Science: Bodies and Rights on the Stem Cell Frontier, published this month by Stanford University Press. Benjamin, assistant professor of Sociology and African American Studies at Boston University, carried out extensive fieldwork for the project, attending CIRM hearings; studying patients and physicians in a sickle cell clinic; visiting prime movers behind Proposition 71, the referendum that established CIRM; and interviewing politicians, healthcare activists, social justice and women’s rights advocates (including members of the CGS staff), legal specialists, and researchers in the biotech industry. In this way, she was able to identify and illuminate the tensions at play in the formulation of CIRM’s standards, policies, and research aims and protocols.
Benjamin views stem cell technology through a co-production lens, seeing the application of the technology, and the results it yields, as shaped by an ongoing process in which both scientists and various publics participate. Indeed, the very structure of the California initiative, coupling citizens’ oversight with a granting arm, seems designed to embody co-production and signal it as a primary value. But Benjamin repeatedly reveals how power relations have skewed the process in favor of technological elites, and how problematic assumptions about race, ethnicity, gender, and class have undercut the likelihood that the fruits of CIRM-funded stem cell research will reach segments of the California population already underserved by the healthcare industry. Writes Benjamin,
Compared with the old, cloistered model of science, the initiative and its governing structure appear radically inclusive: approval is by the voters, funding by taxpayers, and governance by representatives of the public. Yet it still does not fully address the concerns and expectations characteristic of the participatory trend in science development.
In fact, Benjamin argues, conflict over research priorities and access to the technology has been suppressed through a “pro-cures” bias that emphasizes the benefits of stem cells to individuals and families, without including broader social concerns. By conducting a campaign that encouraged Californians to identify with – or identify themselves as members of – biological groups defined by disease type (that is, Parkinson’s, sickle cell anemia, diabetes, and so on), proponents of Proposition 71 effectively discouraged public discussion of alternative framings that involve, among other things, injustices surrounding access to medicine in the state and concerns of various disability communities.
Benjamin views this “strategic fabrication and mobilization of a particular kind of consenting public” as problematic. CIRM has sought to minimize attention to risks, to alternative research priorities, and to scientific profit motives in order to “insulate the science of stem cell research from impinging political values.” In other words, “public participation” has been a shell game meant to misdirect attention so that the stem cell industry could pursue its agenda.
Benjamin provides insights especially into how the oversight committee conceptualized the role of one essential constituency: women who would provide eggs for use in crafting embryos for use in stem cell research. She writes that, “depending on who one imagines women are in this context – bioworkers who supply eggs for research, or a protected class of female research subjects – how one seeks to implement ethical research shifts dramatically.”
Benjamin’s excerpts from multiple discussions by CIRM’s ethical standards committee demonstrate how demand for a steady stream of eggs and embryos for research was recast in terms of the right of all women to participate in human subjects research. Diversity and equality were held up as goals dictated by the logic of rights, leading to lengthy discussions in which some committee members voiced paternalistic and classist views about how to ensure participation by a diverse pool of women. At the same time, as Susan Fogel of the Pro-Choice Alliance for Responsible Research pointed out, the committee’s focus on the “right to donate” came at the expense of discussion of “how women could provide ‘informed consent’ to participate [in egg harvesting for stem cell research] when not even the researchers were fully informed about all the possible effects of the procedure.”
Benjamin concludes that for medical technologies to become truly beneficial, it is imperative that researchers expose, rather than attempt to conceal through rhetorical framings, the shortcomings, risks, and uncertainties surrounding their work, and acknowledge the structural inequalities inherent in American healthcare. Ethical arguments that center on individual rights can obscure the larger social realities of who actually receives the benefits of technologies. Benjamin calls for more widespread application of social justice principles in decision-making and greater power-sharing.
Such shifts ultimately can come about only with significant revisions to the view of science and technology as inevitable and as operating above or outside social spheres. In the final chapter, “Toward Real Utopias,” Benjamin marshals a number of thinkers, including political scientist Langdon Winner, educator Farzam Arbab, sociologist Erik Wright, and law professor David Winickoff, who have thought deeply about how to develop more inclusive and responsive mechanisms for social deliberation and change. Here, notwithstanding the worth of her sources, one wishes that Benjamin had devoted more space to her own synthesis of the issues.
That said, the frameworks for action she lays out are based on a recognition that scientific values should not ipso facto prevail over social ones; that institutions must reconfigure themselves as “learning organizations” rather than agents of the prevailing socioeconomic status quo; and that collective well-being should be privileged above paradigms of scientific “progress” – and in this regard, she suggests inspiring ways forward.
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).
A bill that would overturn protections for women undergoing egg harvesting for research is making its way through the California legislature, and was unfortunately passed yesterday by the Senate Health Committee. If AB 926 is approved by the full Senate and then signed into law by Governor Jerry Brown, researchers would be permitted to pay women upwards of $5,000 for their eggs. It would overturn a 2006 law that was passed nearly unanimously by both the Assembly and Senate.
Supporters of AB 926, sponsored by the American Society for Reproductive Medicine and authored by Assembly member Susan Bonilla, argued that California’s current law, which limits payments to reimbursement for expenses, constrains researchers from acquiring the eggs they need; that loosening the payment policy could help women with cancer and promote other scientific advances; and that the bill promotes “equity” for women because it treats them like other research subjects.
Testimony opposing the bill was offered by CGS Associate Executive Director Diane Tober; Dr. Jennifer Schneider, whose daughter, a former egg donor, died of colon cancer; and Dr. Sindy Wei, a former egg donor who almost bled to death when a prominent infertility specialist retrieved over 60 eggs from her ovaries and in the process nicked an artery. Their main points included the health risks of the drugs and procedures used in egg retrieval, which are significant but under-studied; the impossibility of getting truly informed consent from women because research is so inadequate; and the pressing need for an egg donor registry that would permit further research and tracking donors to ensure the procedures are safe.
They also pointed out that egg providers are actually in a very different position than research subjects, whose reactions to a drug or procedure being studies are the object of study. In the case of egg providers, researchers are interested in what are essentially raw materials for research; the impacts on the health of egg providers are not germane to their work.
Jennifer Schneider’s testimony included the story of her deceased daughter, and the associations her subsequent investigations uncovered between egg retrieval and colon cancer. Sindy Wei recounted her injuries during egg retrieval and the callous treatment she received from the infertility specialist responsible for it. She also described the dramatically different way she was treated when she was an egg donor (“just a vendor”) versus the care she received when, years later, she was unable to conceive naturally and sought infertility treatment.
Distressingly, many of the senators present at the hearing paid little attention to these accounts, talking among themselves while opponents of the bill were testifying. Yet they gave supporters of the bill their full attention.
Today's unanimous Supreme Court decision [pdf] that human genes may not be patented was greeted with unbridled enthusiasm by the large coalition of plaintiffs and supporters. Early reactions concurred that the decision is indeed a momentous one.
The Center for Genetics and Society response is here. For background, the amicus brief that CGS and allies filed with the US District Court in 2009 is described and linked here; the 2012 follow-up brief to the Supreme Court is covered here and here. Similar briefs were filed by many others.
Myriad tried to spin the decision as a victory, by highlighting the Court's explicit refusal to rule on "method claims" or "the patentability of DNA in which the order of the naturally occurring nucleotides has been altered," and asserting that its cDNA claims were upheld. Possibly as a result, Myriad's shares initially rose. However, Mark Lemley, a Stanford law professor, told Nature News that "cDNA may not end up being the subject of valid patents after all."
Some commentators called the ruling a "mixed decision" (Fierce Biotech, Bloomberg), or "scientifically inaccurate" (Forbes) and filled with "genetics errors" (PLoS blog) and "ignorance" (New Republic). In this, they seemed to be building on the brief concurrence by Justice Scalia, who was "unable to affirm those details [of molecular biology] on my own knowledge or even my own belief." However, in broad terms Scalia unequivocally agreed with the decision's key finding:
It suffices for me to affirm, having studied the opinions below and the expert briefs presented here, that the portion of DNA isolated from its natural state sought to be patented is identical to that portion of the DNA in its natural state ...
Legally, any scientific quibbles seem unlikely to become significant. Lori Andrews, of the IIT Chicago-Kent College of Law, who has been involved in these issues since the early days of the Human Genome Project, and helped to craft the lawsuit, has no doubt. From her excellent analysis of today's Supreme Court ruling:
If I spend a lot of money on a telescope to discover a new planet, I can't own the planet. A brief filed by the Department of Justice said that it was an error to let Myriad have the patents in the first place. So, paying Myriad nearly $4000 for each look at your breast cancer genes was like having to pay a car thief for the right to drive your own car.
Applause to the Supreme Court for getting this one right!
The Supreme Court's unanimous ruling against Myriad Genetics is a triumph for common sense and the common good, and for scientific research and legal fundamentals as well. The decision means that all of the existing patents on human genes – some 15,000 of them – are no longer valid. It affirms a century of legal precedent that prohibits patents on “products of nature.” And it puts US law in line with the assertion of UNESCO, the World Medical Association, and the Human Genome Organization that the human genome is part of the “common heritage of humanity.”
The Supreme Court cut through a tangle of legalistic confusion to assert that “a naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated.” The Court explicitly avoided ruling on “method claims” or “new applications of knowledge” [italics in the judgment; PDF here]. This seems reasonable – researchers can freely investigate isolated DNA but can presumably only patent something they invent.
However, the Court said that patents on so-called cDNA may be allowable, as long as these synthetic copies of DNA are not “obvious.” The interpretation of this aspect of the decision may take some time to clarify.
The ruling in the lawsuit, argued by the ACLU and Public Patent Foundation on behalf of a group of plaintiffs including researchers, genetic counselors, women’s health organizations, and breast cancer patients, should significantly bring down the bloated cost of Myriad’s test for genes that elevate the risk of breast cancer. And it will reassure scientists doing basic genetic research that they won’t be sued for patent infringement.
It is not immediately clear what the broader effect of the ruling will be on the gene testing industry, and on public understanding of what gene tests can and can’t do. The publicity about the gene patent case and Angelina Jolie’s revelation about her own BRCA status may have obscured the fact that these alleles account for only about 10% of breast cancers. The Supreme Court ruling by no means implies that most people should feel more inclined to rely on a gene test to predict their chances of developing cancer or other common diseases.
Moreover, gene testing companies, including Myriad, are already moving toward techniques that remain eligible for patent protection. Myriad has announced a “next-generation test” (to be launched this fall) called myRisk. This “will include a 25-gene panel that is focused on clinically-actionable cancers including: breast, colon, ovarian, endometrial, pancreatic, prostate and melanoma.” The test “will have a turnaround time of 14 days or less and a list price between $4,000 and $4,500.”
But the genetic links to risk for these other cancers are not nearly as clear as for the BRCA association with breast and ovarian cancer.
The battle to reap the benefits of genetic technologies – and avoid their misuses – is in its early days. But make no mistake about it: The Supreme Court decision is a hugely important step toward reclaiming biotechnology for the common good.
In “Tinkering with DNA,” C.S. Soong of KPFA Radio’s Against the Grain talks with Stuart Newman about the deeply problematic nature of inheritable genetic engineering. Newman argues that its proponents misunderstand the nature of living things and the process of human evolution. Listen here.
Shoukhrat Mitalipov and his colleagues at the Oregon Health and Science University keep trying to dissociate their research cloning work from human reproductive cloning. Unfortunately, not everyone is willing to cooperate.
Here's the reaction by the Center for Human Reproduction (CHR) to the recent news about research cloning:
In a more controversial clinical application, this research, however, also potentially points towards the possibility of creating human embryos for infertility treatments in this way. While current U.S. law prohibits human cloning for reproductive purposes, laws, can, of course, change over time, should the safety of this cloning process be established.
CHR is a long-established New York-based fertility clinic, with a history of pushing boundaries. Founder Dr. Norbert Gleicher has been an advocate of human cloning for many years. He detailed his objections to any restriction on human cloning in a 2005 article in the Journal of Assisted Reproduction and Genetics [pdf], in which he insisted that "government has no place in that process." He has held that position consistently since at least 1998: while disparaging the self-promoting efforts of Richard Seed, he stated, with no apparent qualms, "I believe that human cloning will probably be done at some point."
Gleicher hit the headlines in 2001-2 by trying to persuade the American Society of Reproductive Medicine (ASRM) to endorse the use of embryo screening (known as preimplantation genetic diagnosis or PGD) for sex selection. The controversial acting chair of the ASRM Ethics Committee, John Robertson, initially approved the procedure, but soon reversed the decision, and CHR then agreed to abide by the revised ASRM recommendation. It's not clear how long that lasted: CHR, like many other fertility clinics, now disregards the ASRM guideline and explicitly offers "elective gender selection."
In 2003, Gleicher experimented by inserting cells from a three-day-old male embryo into a female embryo and let the resulting "human chimera" develop for six more days. The results were reported at a conference of the European Society for Human Reproduction and Embryology, and caused a stir. As Boston University's George Annas told the Washington Post:
It's one thing if the right-to-life community has problems with your work, but if scientists hear you talk about your work for the first time and say it's outrageous, that says something.
CHR claims to be "the fertility center you turn to when nobody else will help" (see YouTube video). Gleicher and his colleagues clearly have no fundamental qualms about the ethics of reproductive cloning, and they seem at least to accept that Mitalipov's work is a significant step in that direction. They accept that cloning is presently not legal in the United States, but leave the strong impression that they'd do it in a minute if they believed it was predictably safe — and they think that development is, at least, on the horizon.
In fact, there is no federal US prohibition against human reproductive cloning, though the FDA has asserted that it would step in to stop any such effort. Unfortunately, the FDA's position is on less than solid legal ground; it's been called "a stretch." Cloning is at present regulated as part of "a new class of human somatic cell therapy products" and the FDA claims authority over "clinical research using cloning technology to clone a human being." That was enough to deter Seed and the Raelians, but it may no longer be sufficient.
The severity of the dangers to possible children and their mothers is clear from work with animals; the attempt can only constitute unethical human research. Besides, any scheme to "revive" any particular person would inevitably be bound to failure, due to the nature of the developmental process — the result of conception and pregnancy is inherently unpredictable, even with identical DNA. Many religious people consider cloning sinful; many secularists consider it shameful. The attempt to define and control the very existence of another in this way is rejected by large majorities of people, who find cloning morally unacceptable.
Human reproductive cloning is prohibited in more than a dozen states and some 60 countries. Every scientific and medical organization that has adopted a policy on the issue opposes it. In response to the recent news, UC Davis stem cell scientist Paul Knoepfler has called for reproductive cloning to be made explicitly illegal. So has Wesley Smith, a Christian conservative. And so has the Center for Genetics and Society, in our initial response.
President Obama, while restoring federal funding for embryonic stem cell research, stressed that
we will ensure that our government never opens the door to the use of
cloning for human reproduction. It is dangerous, profoundly wrong, and
has no place in our society, or any society.
Thoughtful people from many different political perspectives can agree: It's time to get a law on the books, before someone tries to break the social consensus.
Posted by Abby Lippman, Biopolitical Times guest contributor on June 11th, 2013
And yes, the double entendre is intentional. This is about size as well as about why size matters. And it all has to do with age and aging.
When we were kids, many of us were regularly lined up against some wall or door with a pencil leveled on the top of the head so a mark could be made to show how tall we were. We were probably excited to see how the mark on the wall kept moving higher and higher, a sign that we were growing that was more "real" than any dot placed on a paper growth curve in a doctor's office to see what percentile we were tracking.
Now that we are older, our kids or grandkids may be sharpening their pencils (do younger folks still use them?) to make marks on walls about our height. If so, these will likely document how we are going in reverse and, with age, getting shorter and shorter. (And perhaps these marks will only confirm what is revealed daily by bathroom mirrors that may now only reflect our faces from about the eyebrows up, not the best view for checking the state of our teeth.)
But our height isn't all that's going away. So, too, are the ends of the chromosomes in all of our cells, the parts of DNA at the tips called telomeres. And the only ones who may be excited about this phenomenon are those developing yet more new screening tests to predict our fate, from length of lifespan to maybe even risks for breast cancer.
Basically, telomeres are bits of DNA that protect the chromosomes on which they appear and which become shorter with each cell division. When telomeres get too short, a cell loses the ability to divide and either dies or becomes inactive. For those who like pictures, these multiple images offer a sense of what telomeres look like in a wide range of presentations.
We get shorter with age and so do telomeres; this is all quite normal. But because telomere shrinkage can be visualized with the right equipment, a new commercial opportunity seems to be opening up, with clever genetic capitalists applying what they can measure and developing a new gizmo to define where we stand on the mortality scale in comparison to others. Specifically, some researchers are working to perfect a "genetic thermometer" that will "assess a patient's (sic) health in relation to other individuals of the same age" by measuring telomere length to predict what shape we are in. In fact, direct-to-consumer telomere testing is already on the market, with more products on the way, though some experts call it “premature” and “not supported by scientific data.”
Even if there really is a way to use telomere length to predict lifespans, however, this mirror into our inner workings raises some troubling questions. How might this information be used? By whom? When? Why? What occupational options might be foreclosed if someone is predicted to have a shorter working life? How could insurance policies be applied in a discriminatory way? Might this create a height-ocracy? And, as for all screening tests that provide only statistical averages, what will be the actual predictive value of telomere length for any particular individual? (That’s an issue no one ever seems to address.)
Genetic predictions have always been dangerous when used as crystal balls to tell individual fortunes. This danger only increases with the refinement of the tools to look at chromosomes and genomes, which we really know so little about yet believe in so much. So caveat emptor: be wary of buying into this latest fortune telling hype.
If shorter size is a problem, perhaps a better investment would be yoga, or other ways to improve posture so we stand and sit up straighter — even wearing shoes with higher heels or working in chairs that have liftable seats.
As for lengthening lifespan, well, there may even be a "fix" for this: the ancient practice of meditation. Lately, this practice seems to be appearing as the preventive for problems ranging from depression to high blood pressure and — yes, the shortening of the telomeres! This is not to suggest that researchers have finally found the "fountain of youth" some have long sought, from which the transhumanist death defeaters want to drink. But at least meditation probably has no adverse side effects — and even if it doesn't extend the length of telomeres, it may extend the quality of the years we have. Better to stretch and bend our bodies than to stretch the profit lines of Pharma and the biotech industry.
Posted by Nanibaa’ A. Garrison, Rori V. Rohlfs, and Stephanie M. Fullerton, Biopolitical Times guest contributors on June 11th, 2013
A shorter version of this was published in Nature Reviews Genetics [abstract].
In July 2010, California police used a new forensic technique called familial searching to capture the “Grim Sleeper,” a serial killer who had evaded them for a quarter century. With DNA obtained from a discarded pizza crust, investigators found in the state’s offender database not the profile of the killer himself but instead, through a partial genetic match, that of his son. Based on the identification of a close genetic relative, a principal suspect was identified (1).
Forensic familial searching is practiced in some US jurisdictions and a number of other countries, and its use is increasing. Not surprisingly, this has raised significant scientific and social concerns. Careful consideration of these issues is especially urgent now, in light of the recent Supreme Court decision allowing the collection of DNA from arrestees prior to conviction (2,3).
How does familial searching work? In most forensic cases, investigators analyze DNA from a crime scene at 13 genetic markers determined by the federally managed Combined DNA Index System (CODIS) (4). They compare this genetic information to profiles stored in large databases, in an attempt to identify a complete 13-locus match.
In familial searching, analysts instead search the database to find profiles that are partial matches to a crime scene DNA sample. These partially matched profiles may come from genetic relatives of the person whose DNA was found at the crime scene. Police can then investigate these family members in an effort to identify the suspect (5).
In the Grim Sleeper case, familial searching led police to the suspected killer. But it is also expected that database searches for partial matches will find profiles of one or more unrelated individuals that coincidentally partially match the crime scene sample. Depending on the likelihood of these coincidental partial matches and the follow-up investigative procedures used, the relatives of those people would then be investigated, exposing innocent individuals to unwarranted criminal justice attention and posing risks of unjustified search and seizure.
Three main concerns surround the increasing use of partial matches and familial searching in criminal investigations.
First, familial searching is, by definition, less certain than DNA matching at 13 loci.
Second, the increased uncertainty, and hence greater extent to which an otherwise unrelated individual may be erroneously identified as a relative, makes familial searching more prone to errors. Potential errors are related to assumptions underlying the methodology (described below), which may render some individuals more vulnerable to being wrongly implicated than others.
Third, because current forensic state and federal databases over-represent individuals of certain racial backgrounds, particular ethnic groups and/or communities are disproportionately exposed to errors associated with familial searching.
These features of familial searching and database demographics threaten to unjustly expose many innocent individuals to unwarranted surveillance from the criminal justice system. This essay elaborates on our recently published work (6) about these concerns.
The Supreme Court ruled on Maryland v. King Monday in a split-party 5-to-4 decision, echoing national ambivalence, but ultimately determining that police can take DNA samples from people who are arrested for serious crimes, prior to conviction. This is a far-reaching decision: Justice Samuel Alito, part of the majority, called Maryland v. King “perhaps the most important criminal procedure case that this Court has heard in decades.”
The case was based on the experience of Alonzo King, who was serving a reduced sentence for which no DNA sampling would have been required, when his DNA (which had been taken at arrest) was linked to an unsolved rape case six years prior. This evidence was used to sentence King to life in prison.
The Supreme Court determined that the practice of taking a DNA sample from an arrestee is no different from fingerprinting: a minimally intrusive means to determine identity. This is a useful analogy for people in favor of rampant DNA sampling; one can compare the easy act of taking a mouth swab to giving a fingerprint, and this seems to side-step the Fourth Amendment’s prohibition of unreasonable search and seizure.
However, arrestee identification is almost never what DNA sampling is actually used for. And DNA holds much more information than a fingerprint; the intrusiveness it represents occurs when database searches are conducted, not when an arrestee’s mouth is swabbed.
DNA samples are entered into a national database and used for solving cold cases – previous, unsolved crimes. Using a potentially innocent person’s DNA for this purpose clearly violates the Fourth Amendment, which forbids searching for evidence for an unrelated crime without reasonable suspicion.
Justice Antonin Scalia accused the majority side of “sleight of hand” for using the fingerprint analogy, noting that DNA testing can take months to process and is rarely used strictly for identification purposes. His extremely vocal dissent stressed the negative impact of the decision:
Make no mistake about it: because of today’s decision, your DNA can be taken and entered into a national database if you are ever arrested, rightly or wrongly, and for whatever reason.
Many are shocked by the court’s decision. Michael Risher, staff attorney for the ACLU of Northern California, called it “a serious blow to genetic privacy.” The Council for Responsible Genetics called it "a serious blow to human rights.”
is a landmark because it represents a major step toward a “Gattaca” world. This means that evidence of a crime can be collected without any particular suspicion, avoiding the pesky requirement of a warrant that the Founding Fathers thought would give us liberty and privacy.
Walter Olson asks on The Daily Beast, “How long before you’ll be asked to give a DNA swab before you can board a plane, work as a lawn contractor, join the football team at your high school, or drive?”
Jacob S. Sherkow, a Fellow at Stanford Law School, who actually agrees with the decision, nevertheless finds fault with the legal analysis. He wrote:
The spotlight will likely now turn to California, where the state’s Supreme Court and the U.S. 9th Circuit Court of Appeals have been holding a decision on the state’s use of arrestees’ DNA until after the Maryland v King ruling. In 2004, California passed Proposition 69, which allows police to collect DNA from people arrested of a range of crimes, and enter it in a database that is accessible to all local, state, national, and international law enforcement agencies.
The Supreme Court’s decision in Maryland v. Kingdoes not guarantee that California’s much broader program will also be allowed to continue unobstructed. Maryland only takes DNA from those arrested for violent felonies and burglaries, and if the person is acquitted, the DNA sample is automatically removed from the database. But in California, anyone arrested for a felony (which includes drug possession and joy riding) is required to give a DNA sample and if the charges are dropped, the person has to apply to have his or her sample removed. The ACLU filed a lawsuit against the Proposition in 2009 and will continue to challenge the California program.
The fundamental fight – that data from potentially innocent people should not be used to connect them to unrelated crimes – has been lost. Nonetheless, there is a chance that California will become an example of going too far. Hastings law professor David L. Faigman noted, “To the extent that the California law is broader in a pertinent way, meaning that it leads to appropriating the DNA and using it in a broader and more invasive fashion, it might still be vulnerable to 4th Amendment challenges.”
California already has the third largest DNA database in the world. Despite this, it generates comparable numbers of matches as states with much smaller databases. This is because it has been shown (repeatedly) that solving crimes is less about the number of DNA samples collected from people than the amount of evidence collected from crime scenes. DNA databases already face debilitating backlogs, with the number of samples submitted far greater than the ability of laboratories to analyze them.
Surely the wave of DNA collection that the court unleashed Monday will catch some future McVeigh. But processing all that information may gum up the works, proving overall to be a big and misguided distraction. This is the kind of cumulative cost that’s harder to see.
Furthermore, since racial minorities are disproportionately targeted by police in most jurisdictions, the impact of heightened genetic surveillance will also disproportionately impact these communities. The practice of familial searching, which is currently allowed in California, Colorado, Texas and Virginia, only further exasperates this problem.
Justice Scalia warned of a “genetic panopticon” in his dissent, referring to Jeremy Bentham’s idea of a prison in which inmates knew they could be watched at any and all times, but never knew if they were actually being watched at any particular time. This was designed to lead the inmates to internalize the surveillance and monitor themselves. Nearly one third of the United States population is arrested before the age of 23. As of April 2013, the National DNA Index contained a total of 12,247,200 DNA profiles. If DNA collection continues this exponential expansion, a “genetic panopticon” doesn’t seem so farfetched.
Stanford University hosted a one-day conference on May 31 titled "De-extinction: Ethics, Law & Politics" that featured scientists, lawyers, civil servants and the most prominent advocate of the concept, Stewart Brand. Including Hank Greely, the master of ceremonies, there were fifteen speakers and perhaps 35 others in the audience. The event was cosponsored by the Center for Law and the Biosciences and the U.C. Irvine Center for Land, Environment, and Natural Resources. Video should be available later.*
The meeting was largely dominated by a sense of inevitability, though there was more cautionary talk than at similar meetings in Cambridge, UK in April or in Washington, DC in March. The USA Todayreport rightly highlights the murky legal status of the enterprise. Chuck Bonham, of the California Department of Fish and Wildlife (but speaking as an individual), in particular emphasized the need to "to start figuring out how to regulate it now."
The most widespread concern, stressed by Jamie Rappaport Clark, now with Defenders of Wildlife and previously with the Federal Fish and Wildlife Service, was that extremists who want to destroy the Endangered Species Act (ESA) will use vague promises of revival to do so. Why bother saving any particular species, they will likely ask, if we can always bring it back later? This prospect clearly horrifies conservation biologists.
Matthew Liebman of the Animal Legal Defense Fund expressed outright opposition to the de-extinction project on grounds of cruelty. But the tone stayed mostly within the promotion-to-resignation range until three philosophers showed up to discuss "Justice, Hubris, and Moral Issues." Hilary Bok took a pragmatic approach, involving benefit analysis as well as cost analysis. She identified animal welfare risks, and said that damage to the ESA would be a game-ender, if true. She concluded [from my notes]:
We could be repeating the sin that led us to drive them to extinction in the first place: We don't undo the sin of hubris that led to killing the passenger pigeons by recreating them without at the least working out in great detail how to do it right. If we do it the "how cool would it be to bring back the Neanderthal" way, then we are simply repeating the sins of the past.
Jay Odenbaugh, who tended to raise rather than definitively answer questions, noted the almost-instant deaths of two cloned individuals, an extinct bucardo (tissue samples had been preserved) and a gaur (technically, vulnerable but sometimes described as endangered), and wondered:
How many painful, two-minute lives are worth it?
Ronald Sander found the rationales presented to be "less convincing than they may first seem" and the concept to be "rather peripheral to conservation." He said he had not argued against de-extinction, but concluded, rather like Bok, that
the justification for de-extinction is human-oriented. It's really about the amazing thing we want to do and the cool species we want to see back.
That is a devastating rebuttal to the arguments put forward for doing it. If "de-extinction" is not about species conservation but simply about helping people feel less bad about destroying the environment, then surely we should instead be putting our time, effort and human resources into developing a more sustainable way of living on the planet.
Cloning and controversy seem to go well together. The recent news that Oregon researchers have created human stem cell lines through cloning was thrown into doubt after an anonymous submission on PubPeer reported several errors in their paper. It notes that two different images are slightly cropped and duplicated throughout the paper although all four instances are supposed to show different phenomena. Additionally, it calls attention to two scatterplots that are identical and two more that are almost identical. Are these just sloppy mistakes?
Shoukhrat Mitalipov, who leads the research team, immediately replied that the errors were simply careless slip-ups made in a rush to publish, and that they do not impact the validity of the results: “The results are real, the cell lines are real, everything is real.”
Cell, the journal that published the paper, backed him up, calling them “minor errors.” But the editors clearly should have caught them. This is particularly the case because of the notorious fraud by Korean scientist Hwang Woo-suk, whose claims about having successfully created stem cells from cloned human embryos were first cast into doubt by the realization that they included duplicated and manipulated images. As Paul Knoepfler noted,
Given the 2004/2005 cloning papers by Hwang Woo-suk that proved to be bogus and the highly sensitive nature of human therapeutic cloning, an intense review of the paper before publication would indeed seem like it should have been a no-brainer, eh?
Former Nature senior editor Natalie DeWitt commented that all this “unnecessary turmoil” could (and should) have been avoided. “I and my Nature editorial colleagues recommended that for critical cloning papers, since it’s so easy to verify, they should submit verification from a separate lab when they submit the paper.”
The authors are now in the process of fixing the errors, and giving other researchers access to their cell lines so that they can replicate their results. Presumably, confirmation from these researchers will come shortly. What will be missing, however, is a response to the objections about cloning techniques that have nothing to do with careless errors.
David King, director of UK watchdog group Human Genetics Alert, wrote a scathing article for CNN disparaging Mitalipov’s research for being irresponsible “zombie science.” He noted that people have incredibly high hopes for the possibilities of therapeutic cloning due to inordinate amounts of hype over many years, but that there’s little scientific substance or logic to back up the claims.
We are told that there will be great medical benefits and that the risks that there will be cloned babies are small, but in truth it's the other way round… What the Oregon scientists have done is to deliver the baby that the would-be human cloners have been waiting for 15 years – what looks like a reliable technique for creating cloned embryos. I think it was irresponsible to publish their research before there is a comprehensive global ban on cloning, with tough sanctions.
The current controversy makes it very clear: It really is time for the United States to join every other developed nation and ban human cloning. Marcy Darnovsky of CGS explains this need in a recent televised debate for CCTV.
In another telling debate on Al Jazeera, King and two other commentators, including a stem cell scientist who previously supported research cloning, found themselves in agreement: Given that there are less controversial ways already available to produce disease-specific and patient-specific stem cells, Mitalipov’s cloning technique is unnecessary.
Perhaps the errors in the Cell paper are just a useful reminder that there is better work out there.
Posted by Alliance for Humane Biotechnology, Center for Genetics and Society, Our Bodies Ourselves, and Pro-Choice Alliance for Responsible Research on May 30th, 2013
Updated August 1, 2013
AB 926, initiated by the American Society for Reproductive Medicine (ASRM) and authored by Assembly member Susan Bonilla, seeks to permit payment to women providing eggs for research. ASRM is a fertility industry organization whose members have for decades had a financial interest in expanding the availability of eggs, but that has not responded to repeated calls by women's health groups for research to firmly establish the health consequences of egg retrieval.
The state of California acknowledged the dangers to women’s health of paying for eggs for research by passing SB 1260 in 2006. Authored by then-Senator Deborah Ortiz, an acknowledged champion of women’s health, SB 1260 prohibited paying for eggs for research beyond compensation for direct expenses. It was approved by near-unanimous votes in both the California Senate and Assembly.
AB 926 would repeal this law, and would also be at odds with the similar prohibition included in Proposition 71, which established California’s stem cell research program. AB 926 is problematic for a number of reasons:
AB 926 states that it promotes “equity for women” as “research subjects.” This language is misleading. Research subjects are recruited for clinical trials to study the effects of a drug or procedure. Providing eggs for research does not resemble a clinical trial; the short-term and long-term effects of the egg-harvesting drugs and procedures on healthy young women are not being studied, collected, reported, or followed. In the case of egg providers, researchers are interested in what are essentially raw materials for research. The impacts on the health of egg providers are not germane to their work. Egg providers are thus quite different from research subjects.
Supporters of AB926 argue that the bill creates “equity for women,” so that those who provide eggs for research would get compensated at the same rate as women who provide eggs for fertility purposes. The bill does not promote fairness, however. It is primarily about helping researchers compete for eggs to be used in their research. Given that many young women providing eggs for reproductive purposes have experienced serious complications and infertility due to their “work” as egg providers, it would seem prudent to collect adequate safety data before expanding the market for eggs to include eggs for research.
AB926 supporters contend that existing laws and regulations are adequate to protect women from being unfairly exploited or enticed by compensation. Yet they provide no evidence or analysis to back this assertion. The bill states that “[c] oncerns that women will be exploited if compensated for providing human oocytes for research have not borne out in the states where compensation is allowed.” But in fact there is no published information about the outcomes there. Low-income women may feel particular pressure to risk their health in order to pay living expenses, tuition, etc.
AB 926 states that “all women undergoing ovarian stimulation and oocyte retrieval have another layer of regulation as all cycles are reported to the federal Centers for Disease Control and Prevention.” In fact, fertility clinics report the number of IVF cycles that use third-party eggs and the number of resulting live births to the CDC – but no information about the women who undergo egg retrieval as paid providers, the number of eggs retrieved from them, or the number or severity of adverse reactions they experience.
Supporters of AB926 assert that research is suffering due to “lack of needed tissues” and that research using women’s eggs will ultimately help women with cancer and help improve infertility treatment. However, there is substantial evidence to suggest that the drugs and procedures used for egg harvesting and retrieval actually increase cancer risks and infertility in previously healthy women. At least 10 scientific studies have found increased cancer rates among women who have undergone ovarian stimulation. While some studies have not found an increase, they typically acknowledge that the period of follow-up is insufficient to rule out the possibility.
Egg harvesting uses powerful drugs (including some unapproved by the FDA for these purposes) to both suppress and hyper-stimulate a woman’s endocrine system to produce large numbers of mature eggs. The most well documented side effect of egg harvesting is ovarian hyperstimulation syndrome, which can cause organ damage, ovarian rupture, and in rare instances death.
AB926 supporters contend that current laws deny a woman’s “fundamental ability to make informed decisions.” This is not the case. Without sufficient information or studies on the short-term and long-term health risks of egg harvesting and retrieval – including the use of potentially dangerous hormones – it is not possible for women to make an “informed decision.” Before proceeding with a potentially dangerous bill, adequate research needs to be conducted on the risks of egg-harvesting and retrieval.
In March, the American College of Medical Genetics and Genomics (ACMG) released a report on "incidental findings" in genetic tests [pdf, discussed here], which is continuing to attract the wider discussion it deserves. Essentially, it said that doctors ought to tell
patients about some (not all) unexpected genetic results. This proved so controversial that ACMG has released a formal "Clarification" [pdf] of its position, which has not fundamentally changed.
This debate involves issues at the heart of the implementation of genomic medicine. It raises major questions of patient consent, and challenges established principles about testing children for late-onset conditions. It also suggests the possibility of unnecessary medical interventions, and perhaps even difficulties in obtaining a medically needed genetic test if a patient is unwilling to be presented with findings that are not directly relevant. Some initial reactions were detailed in our April 2nd post, and GEN had a summary of the debate as it stood in early May.
Then Science published a pair of articles on the subject, one essentially supporting the ACMG position (abstract; two of the eight co-authors were also members of the ACMG Working Group), the other describing it as misguided (abstract; by Susan Wolf, George Annas and Sherman Elias). John Lauerman of Bloomberg interviewed several of the authors, among others, for a discussion of the controversy.
Meanwhile, even broader issues about genome sequencing are attracting attention. The European Society of Human Genetics (ESHG) is taking a more cautious stance than the ACMG. Professor Martina Cornel, chair of the Professional and Public Policy Committee, is quoted in the press release:
It is preferable to use sequencing or analysis specifically targeted at a particular health problem to avoid unsolicited findings, or those that cannot yet be interpreted, which can cause considerable anxiety to patients and their families. Clear guidance on how to deal with such findings is needed.
The emphasis in the current ESHG recommendations on "Whole-genome sequencing in health care" (available, free, at the European Journal of Human Genetics) is more on developing than promulgating guidelines. For instance, Point 5 (of 11) reads:
Guidelines for informed consent regarding diagnostic testing need to be developed. Patients' claims to a right not to know do not automatically over-ride professional responsibilities when the patient's own health or that of his or her close relatives are at stake. Patient groups could provide important input into how this should be handled.
The background document ESHG developed (same journal) is titled:
The 'thousand-dollar genome': an ethical exploration
This covers the topic quite broadly, and seems likely to be a valuable resource for analyzing what it calls "potentially far-reaching consequences, not only for future developments in healthcare, but also for individuals and society as a whole." As if to emphasize the importance of this topic, the BMJ just published another pro-and-con pair of articles: "Should we sequence everyone's genome?" Yes or No.
One final important point was raised by Megan Allyse, who co-wrote a critical analysis of the ACMG recommendations with Marsha Michie [pdf], and told GEN that that "there is already a significant shortage of qualified genetic counselors in the U.S. and it is by no means clear that the existing supply could meet this additional demand." Indeed, according to GEN:
At press time, the American Board of Genetic Counselors counts 3,026 certified professionals among its ranks. For the sake of comparison, the U.S. National Cancer Institute estimates that 232,340 women will be diagnosed with breast cancer this year.
Under any likely scenario, we're going to need a lot more counselors.
Angelina Jolie’s New York Timesop-ed about her preventative double mastectomy continues to generate news and commentary. For those who somehow missed the many headlines, Jolie decided to undergo these surgeries because a genetic test determined that she carries mutations in the BRCA1 gene, purportedly leading (in her case) to an 87% chance of developing breast cancer. She felt that a mastectomy, which will greatly lower her risk, was the way to be proactive and take control of the situation.
As many have noted, baring such intimate details to the world took courage, and may inspire women to be more proactive about their health. But the information she shared can also easily be misunderstood.
Jolie states that breast cancer kills about 458,000 people around the world each year and that gene testing should be a preventative priority. But fewer than 1% of women in the U.S. have harmful BRCA mutations, and not all of them will get cancer. And most people who get cancer don’t have any genetic disposition toward it. The uncomfortable truth is that cancer is caused by many things; 70% of people diagnosed with breast cancer do not have any of the known risk factors, let alone the BRCA genes. Genetic testing is a valuable preventative tool, but only for a very few.
[W]omen who might be likely to have the mutations – those whose family histories suggest they have an elevated chance of having the harmful versions of the genes – should then be referred to genetic counseling for further evaluation and discussion of the risks and benefits of testing. Only after such genetic counseling should DNA testing to look at BRCA variations be warranted.
This conclusion, unlike Jolie’s, takes into account the potentially negative impacts of testing – the fact that inconclusive results are common and can lead to unnecessary treatment and stress. It is somewhat disconcerting that Jolie brandishes gene testing as a powerful tool of preventative care for all women.
Jolie does address the fact that the BRCA test is prohibitively expensive for most women (the list price is close to $4,000), but she does not explain why this is the case. The reason is that one company, Myriad Genetics, effectively owns the BRCA genes. Never mind the fact that every one of us has them in our bodies, or that they are naturally occurring phenomena, Myriad has been steadfastly defending its patent on the BRCA genes for years. A lawsuit against the patents was heard by the Supreme Court in April, and a decision is expected in June.
As it stands now, no other companies can research the BRCA genes without Myriad’s permission and no one can offer a different test, even though it’s widely acknowledged that a better test could be made available for less. As CGS executive director Marcy Darnovsky and Breast Cancer Action executive director Karuna Jagger point out in an op-ed in the Los Angeles Times, Myriad’s monopoly has a disproportionately negative impact on low-income women and women of color:
Since Myriad's test focuses on the variants that have already been identified, some women, especially women of color, are more likely to get ambiguous results. They are told they have a genetic variant but that Myriad doesn't know whether it increases their risk of cancer.
At a time when we desperately need new insights into cancer prevention, diagnosis and treatment, the human BRCA patents stops vital scientific research and medical care connected to breast and ovarian cancer. One company serves as a gatekeeper for all research into these genes and therefore sets the research agenda—which is driven by corporate earnings from testing as well as future earnings based on all the bio-data they collect (and hoard) from women’s bodies.
David B. Agnus notes in The New York Times that there is absolutely no reason for Myriad’s test to be as expensive as it is. Molecular scientists can now sequence an entire genome for around $1,000. Myriad’s defense – that insurance companies cover most of the cost – isn’t good enough. As Agnus points out,
lost in this answer is the fact that somebody — private insurance companies, Medicare, Medicaid — pays much of the rest. Ultimately, that means that all of us are paying in the forms of higher insurance premiums, co-payments and deductibles as well as higher taxes.
Given that there is only one available test, priced prohibitively high, and with definite limitations, many women may not feel that Jolie’s “choice” is one that is really available to make.
However, all women who have a preventative mastectomy will face a different choice, one which Jolie completely passes over in her op-ed. This is the choice of whether to undergo reconstructive surgery, wear a prosthesis, or leave their body as it is. Jolie normalizes her own decision of reconstructive surgery by defining it as the last stage of treatment, as though it is medically necessary and just happens to have a cosmetic result. She states,
The final surgery is completed with the reconstruction of the breasts with an implant. There have been many advances in this procedure in the last few years, and the results can be beautiful.
Speaking of her kids, Jolie explains her decision further: “It is reassuring that they see nothing that makes them uncomfortable. They can see my small scars and that’s it. Everything else is just Mommy, the same as she always was.”
Silicone implants provide an option valued by many women. Jolie’s status as an international sex symbol may have made her decision almost inevitable. But not all women with mastectomies feel that an outward presentation of “sameness” is necessary, and it is worthwhile to know that there are other options, and strong, smart women who have chosen them.
Audre Lorde, a self-described “black woman warrior poet” described her own struggles with breast cancer and mastectomy in her 1980 book The Cancer Journals. She wrote,
It is not my intention to judge the woman who has chosen the path of prosthesis, of silence and invisibility, the woman who wishes to be ‘the same as before.’ She has survived on another kind of courage, and she is not alone. Each of us struggles daily with the pressure of conformity and the loneliness of difference from which those choices seem to offer escape. I only know that those choices do not work for me, nor for other women who, not without fear, have survived cancer by scrutinizing its meaning within our lives, and by attempting to integrate this crisis into useful strengths for change… When other one-breasted women hide behind the mask of prosthesis or the dangerous fantasy of reconstruction, I find little support in the broader female environment for my rejection of what feels like a cosmetic sham. But I believe that socially sanctioned prosthesis is merely another way of keeping women with breast cancer silent and separate from each other. For instance, what would happen if an army of one-breasted women descended upon Congress and demanded that the use of carcinogenic, fat-stored hormones in beef-feed be outlawed?
Other women have also found strength in embracing the new look of their bodies. After her double mastectomy, three-time cancer survivor Kelly Davidson got a tattoo of fairies and butterflies in the place where her breasts used to be. She exclaimed, "It is my badge of honour and strength, a piece of beautiful art that I wear with pride because it represents how I kicked cancer's ass and how breasts don't define who I am as a person or a woman." When she posted an image of the tattoo on Facebook in April, it went viral in just 48 hours. Tattoos after mastectomy have been an important form of dissent and expression for many women.
Despite these counter-narratives, Jolie’s op-ed is already having an outsized impact. The day it was published, for example, Myriad’s stock went up 3%.
The ugly reality is that cancer is a highly profitable business. Lorde wrote about what she termed “Cancer Inc.” back in 1980. And as feminist G. Arunima notes in a recent blog post,
Having been reduced to being a “consumer”, like millions of others, my response to these trends is primarily one of bewilderment, accompanied by mistrust of a medical system that’s clearly making huge profits whilst subtly introducing anxieties about possible health risks that one might embody, utterly unbeknownst to oneself… I would suggest we hit back by asking feminist inspired questions to the scientific establishment about access, costs, and the necessity of specific forms of treatment. That may be the way forward towards not only accountability to ‘consumers’, but actually for equitable health-care for all.
Shoukhrat Mitalipov and his research team at Oregon Health and Science University (OHSU) are back in the news with a big announcement: They have become the first scientists to create human embryonic stem cells using a cloning technique called somatic cell nuclear transfer or SCNT. Scientists have been unsuccessfully attempting this feat for over a decade; indeed, many had given up in favor of work with induced pluripotent stem (iPS) cells. The success raises questions about which kind of stem cells will drive research on regenerative medicine, as well as significant concern about human reproductive cloning and the use of women’s eggs that cloning requires.
Mitalipov and his team were recently in the news for their research on mitochondria replacement techniques, which raises serious concerns because it involves a form of inheritable human genetic modification. The media however paid more attention to yesterday's announcement. The cloning paper, published in Cell on Wednesday, prompted a range of assessments. It was called a “landmark” discovery here and here, but scientists quoted here and here were far more restrained.
A stem-cell showdown
Much of the news coverage reflects surprise that scientists are still investigating cloning techniques at all, since iPS cells appear to provide disease-specific and patient-specific lines while avoiding many of the technical difficulties and ethical quandaries of SCNT. Unlike cloning-derived ESCs, iPS cells don’t necessitate the retrieval of eggs from women, or the production of cloned embryos that could be misused in efforts at reproductive cloning. Understandably, many comparisons are now being made between the two methods (Nature called it a “showdown”).
New Scientistreported that tissues made with iPS cells have tended “to accumulate mutations and suffer abnormal patterns of gene activation.” But not everyone is convinced that making stem cells through cloning will soon – if ever – become medically useful. Carolyn Johnson at the Boston Globecommented that “the discovery would no doubt be a bigger deal if in 2007, scientists had not discovered that there was a different, simpler way to create stem cells that bear a patient’s own genome and are pluripotent, possessing the capacity to develop into any of the myriad cells and tissues in the body.” David Brown of the Washington Post also noted that “few experts think that production of stem cells through cloning is likely to be medically useful soon, or possibly ever,” and quoted MIT biologist Rudolf Jaenisch’s opinion that the study “has no clinical relevance.”
George Daley, a stem cell expert at Children’s Hospital Boston, notes that, “it’s essential to compare the cells from the two methods.” According to Nature, Mitalipov and his team are already doing exactly that – conducting a study of comparisons between iPS and SCNT cells derived from the same donor cell. There will certainly be ongoing updates on this front.
Reproductive human cloning?
The Center for Genetics and Society raised the issue of human reproductive cloning in a press statement, and pointed out that the United States – unlike some 60 other countries – still has no federal prohibition against it. “If we're going to be having cloned embryos in laboratories around the country, said CGS’s Marcy Darnovsky, “we really need to get our act together and have a law that prohibits human reproductive cloning.” GenomeWeb picked up this argument here, and NPR looks at the prospects on the policy landscape here.
Many other news outlets also voiced concern that the SCNT work could be used to attempt reproductive human cloning. Paul Knoepfler provides a useful diagram that illustrates the “elephant in the room” of the close relationship between research and reproductive cloning. He acknowledges that cloned babies will not “be bouncing out all over the place anytime now,” but says that “yesterday’s story does of course relate to human reproductive cloning and it is a real, deeply serious concern longer term. Some crazy person will try to clone humans.” Dr David King of Human Genetics Alert raises similar points and says that the OHSU research is an "irresponsible" project that has created "the baby that would-be human cloners have been waiting for: a method for reliably creating cloned human embryos".
Mitalipov’s team is understandably eager to dissociate their work from the possibility of reproductive cloning. Nature reports, “Mitalipov has tried without success for more than a decade to produce a monkey by cloning. [Co-author] Tachibana says that an upcoming publication will explain why reproductive cloning of humans is not possible using their SCNT technique.” Professor Robin Lovell-Badge, head of developmental genetics at the National Institute for Medical Research, similarly reiterates that years of cloning work with animals has affirmed that it would be unsafe to try in humans, so: “For this reason alone it should not be attempted."
More demand for women’s eggs?
Relatively few news stories explored how the SCNT success might affect the demand for women’s eggs and the health of the women who undergo invasive procedures to provide them, though a number mentioned that Mitalipov’s work used fewer eggs than previous cloning experiments. As Chris Mason of University College London told New Scientist, "Mitalipov clearly has very high efficiency ... However, it still boils down to needing to get human eggs."
Payments to women who provide eggs for research are controversial because of concerns that they encourage women to overlook the significant health risks of egg retrieval. Many women’s health advocates point out that because follow-up studies on egg retrieval have been so inadequate, getting “informed consent” to take the risks is challenging if not impossible.
Another troubling aspect of the OHSU study is that at least five of the authors of the Cell article work as practicing reproductive endocrinologists, raising concern that some may have themselves overseen the egg retrieval procedures. It is therefore unclear whether the study followed the recommendations of the International Society for Stem Cell Research that in order to avoid conflicts of interest, “wherever possible, the treating physician or infertility clinician should not also be the investigator who is proposing to perform research on the donated materials” [pdf].
The OHSU study reports some troubling findings about egg retrieval protocols, including the fact that one of the hormonal drugs typically used for ovarian stimulation results in “sub-optimal quality oocytes,” and that “premium quality” eggs are produced when fewer are retrieved in a stimulated cycle. This suggests that the hyper-stimulation protocols frequently used in fertility procedures are not only dangerous for the women who undergo them, but may also be hazardous to the health of their prospective children.
As the CGS press statement points out, these adjustments to standard IVF protocols “were made in order to obtain ‘optimized’ eggs for research, not to protect women from adverse effects” of egg retrieval. The focus, ironically, is “on the quality of the eggs, not on the well-being of the women.”
Jason Richwine was forced to resign from the Heritage Foundation by a media storm about his offensive comments on race and IQ. That's remarkable, and perhaps significant, but there are likely more and bigger headlines to come.
The background in brief: Richwine co-authored a Heritage position paper titled "The Fiscal Cost of Unlawful Immigrants and Amnesty to the U.S. Taxpayer," clearly published to oppose immigration reform.The paper was unwelcome to all but right-wing extremists, for various reasons, and it soon came out that Richwine's 2009 doctoral thesis included such statements as (on p. 66):
No one knows whether Hispanics will ever reach IQ parity with whites, but the prediction that new Hispanic immigrants will have low-IQ children and grandchildren is difficult to argue against.
His dissertation proceeded to explore "the proposition that immigration policy should select for IQ" (p. 123). That wasn't explicitly in the Heritage study, but it certainly provided a handy cudgel. The report was released on Monday May 6, his thesis was reported on Wednesday, and he "resigned" on Friday. One of Richwine's mentors was Charles Murray, of The Bell Curve infamy, who promptly tweeted:
Thank God I was working for Chris DeMuth and AEI, not Jim DeMint and Heritage, when The Bell Curve was published. Integrity. Loyalty. Balls.
From Murray's perspective, he has a point. For the rest of us, it's actually heartening that such opinions have become toxic. And the dust-up has provoked some insightful commentary (e.g., Ta-Nehisi Coates at The Atlantic, Ari Rabin-Havt at Media Matters, Diego von Vacano at The Monkey Cage).
However, it's also important to note that "respectable" politicians have always been willing to jettison those that go too far. William Shockley, for instance, was effectively shunned in the 1970s, but Murray and Richard Herrnstein had no trouble putting their work into the public sphere in the 1990s. And indeed the backlash to the backlash may already be starting, as Andrew Sullivan (who, as editor of The New Republic, published excerpts from The Bell Curve) detects "red flags about intellectual freedom."
Race and IQ may now be a dangerous combination, but the combination of genetics and IQ is definitely on the rise. China's BGI has for a while been running a research project on "genius genes," headed by Zhao Bowen, who claimed in February that it would produce results in three months. That would be now. Well, we don't have the data or the analysis, but we are seeing a burst of publicity.
An article in the London Times on May 14 (unrelated to the news about Richwine) includes more caveats than previously:
"The reality is that the genomics of IQ will be much more complex than saying: 'Look, here are the genes for genius.' We will be talking about hundreds, possibly thousands of genes and mutations, each with a tiny effect on IQ. Will someone somewhere want to try to engineer intelligence in embryos? Will someone claim they can make your unborn child more intelligent? Of course they will. But it's not technically possible now and won't be for decades," Zhao says.
Sure. But the caption to one of the accompanying photos reads:
If Zhao Bowen discovers the intelligence gene, he may be able to determine a baby's IQ from a blood sample
A simultaneous article in Nature News says that the project "is slated to begin data analysis in the next few months." It reports that BGI is "halfway through its sequencing" but the rest of the work might take as long as a year. It also includes a noteworthy comment from Harvard geneticist Daniel MacArthur:
If they think they're likely to get much useful data out of this study, they're almost certainly wrong.
That's likely true—but no real reason for comfort. The researchers will find something. And someone will abuse the findings. History tells us that's a given. The fallacy may not be that Hispanics (who, ahem, are a cultural community not a race) are dumb, or Jews (essentially a religious group) are smart, or Asians (a broad geographical set) are good at math, or any such nonsense. But suggesting that this embryo has brilliance while this one does not … that could become a very significant problem.
Talking Biopolitics began in 2011 with webinars on synthetic biology and assisted reproductive technologies. It continued in 2012 with interviews of Bill McKibben, Dorothy Roberts, and Harriet Washington. We are excited to announce that Talking Biopolitics is back for 2013, featuring conversations with Miriam Zoll, George Estreich, Ruha Benjamin, and Donna Dickenson that are open and free for everyone.
Each of these cutting-edge thinkers has recently published a book that engages with different facets of the challenges raised by human biotechnologies. They address provocative questions about assisted reproduction, personalized medicine, prenatal gene sequencing, stem cell research, and much more. Their work provides invaluable insights into the new biopolitics we need.
The 2013 series kicks off on May 21 with a live web interview by the Center for Genetics and Society’s Associate Executive Director Diane Tober of Miriam Zoll, award-winning writer and international public health and reproductive rights advocate. Miriam’s new book, Cracked Open: Liberty, Fertility and the Pursuit of High Tech Babies, gives a moving and unblinking account of the emotional anguish, health complications, ethical quandaries and financial costs of her own fertility journey. She also delivers vital insights into the consequences of our failure to adequately understand and regulate the business of assisted reproduction. Find more information and RSVP here.
The second event on June 3 features George Estreich, who will be interviewed by the Longmore Institute on Disability’s Emily Beitiks. George’s book, The Shape of the Eye: A Memoir, is an award-winning account of his family and life with daughter Laura, who has Down syndrome. He asks how the new non-invasive fetal gene tests are affecting women’s experiences of pregnancy and childbearing, and how they might change our personal and social feelings about disabilities such as Down syndrome. The Shape of the Eye is a powerful and moving contemplation of what it means to be human and what it means to be different. Find more information and RSVP here.
In the third event on June 25, CGS Executive Director Marcy Darnovsky interviews Ruha Benjamin, assistant professor of Sociology and African American studies at Boston University. Ruha’s new book, People’s Science: Bodies and Rights on the Stem Cell Frontier, delves into stem cell research, arguing that public engagement must be considered in controversial scientific advances. She particularly advocates for the voices of people with disabilities, African Americans, and women, showing that citizens have the power to influence science, and not merely the other way around. Find more information and RSVP here.
On July 16, we hear from author, activist and scholar Donna Dickenson, interviewed by Osagie Obasogie, Senior Fellow at CGS and Associate Professor of Law at the University of California, Hastings. Donna’s new book, Me Medicine vs. We Medicine: Reclaiming Biotechnology for the Common Good, is an essential read for anyone trying to make sense of personalized medicine. She makes a powerful case for taming "me-centeredness" and market domination of medicine, and for renewing our commitments to public health and the common good. Find more information and RSVP here.
Posted by Gina Maranto, Biopolitical Times guest contributor on May 9th, 2013
The print edition of the May 4/5 issue of the Wall Street Journal devoted almost two full pages to a piece by Sarah Elizabeth Richards, author of the new book from Simon & Schuster, Motherhood Rescheduled, published May 7. They also ran an accompanying piece by Christine Rosen, senior editor of the New Atlantis, on "The Ethics of Egg Freezing," but gave it so little space it seemed like an afterthought. (The online versions are here and here.)
Richards' piece, accompanied by a huge photograph, spanned the whole front page of the Review section, and most of page 2. The visual rhetoric suggested nothing so much as triumphalism: Richards is posed in ¾ frontal position standing against a black background wearing a scarlet sweater and camisole set matched by her fingernail polish. On her face is a look of either bemusement or smugness, or maybe both. She's looking offstage with steely eyes and the fingers of her left hand clutch a white stuffed lamb by the belly—rather too tightly for the lamb's comfort, it seems to me. In white type, the caption reads, "It was the best investment I ever made.” That investment was having her eggs retrieved and cryopreserved.
The headline is pure sales: “Why I Froze My Eggs (And You Should, Too),” while the pull quote under it invokes both present and past discourses regarding working women: “Amid the talk of ‘leaning in,’ and ‘having it all,” we’ve ignored the most powerful gender equalizer.” The first allusion suggests that Richards thinks she can go Cheryl Sandberg one better. The second allusion seems dated, but introduces the essential element of childbearing, which is, after all, Richards’ paramount goal.
Now, Richards says, women can achieve biological parity with men by using technology to provide themselves with the reproductive equivalent of a time machine: their bodies might be old, but their frozen eggs will be forever younger. The implication is that in the business arena, the only thing that matters is being able to compete in one's youth—to fight it out on the lower corporate rungs, where the battle is most intense, in order to rise in the ranks. Only then can one take a breath and think about one's personal life. Richards buys into this world view, and in the process, renders motherhood just one more CV item.
The lack of sentimentality in Richards’ whole description of the enterprise of freezing eggs is pronounced: that cuddly little lamb, clutched so tightly, seems to advertise that a desire for motherhood should not be confused with having warm and fuzzy feelings (those might render one vulnerable in the workplace, after all). Richards discloses some emotional responses regarding her quest to freeze her eggs, but they have mostly to do with control: when she awakes from an egg retrieval procedure she feels heartened, but she also feels empowered, freed of the "punishing pressure to seek a new mate." (At least in this piece, Richards never mentions the possibility of single parenthood and frequently invokes online dating.) The tales she recounts of other women who have also frozen their eggs read like descriptions of partners in some supply chain relationship ensuring that a product moves to market.
At the same time, Richards is singularly naïve in her acceptance of the rationales and arguments offered by the industry. She cites the American Society of Reproductive Medicine’s recent recategorization of egg freezing as non-experimental without mentioning that ASRM is referring to medical applications (such as chemotherapy) and explicitly disagrees with her:
“Marketing this technology for the purpose of deferring childbearing may give women false hope and encourage women to delay childbearing. Patients who wish to pursue this technology should be carefully counseled.”
Richards deploys straw men, such as an argument supposedly advanced by "critics of 'social freezing' ... that biological deadlines serve a purpose in life: Without them, a woman would have little incentive to sit through dozens of Match.com dates to find a partner and father for her children.” Surely, no reputable critic of egg freezing has suggested that oocytes evolved the way they have in order to ensure that women would get with the program and take mating seriously.
In fact, critics have challenged the procedure on numerous grounds, including risks involved in egg retrieval, side effects from the drugs used to stimulate the ovaries to produce multiple eggs, potential complications from the surgical removal of the ripened eggs, and possible development of ovarian hyperstimulation syndrome. Christine Rosen mentions other legitimate criticisms in her piece on ethics, including the ways in which “egg freezing could undermine arguments for greater workplace accommodation and flexibility for women and children,” and the ways in which egg freezing furthers the march toward ever more manipulation of human eggs, sperm, and embryos under the neo-eugenic banner.
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).
Posted by George Estreich, Biopolitical Times guest contributor on May 9th, 2013
If our entertainments reveal what’s on our collective minds, then we seem to be thinking quite a bit about human modification. Spider-Man, X-Men, the Aaron Cross of the most recent Bourne thriller: all have powers, and all are genetically different, whether bitten, mutated, or engineered.
The Twilight books, and their subsequent movie adaptations, aren’t usually thought of in this vein. But despite the air of romance, Stephenie Meyer’s four-book series, in which a human girl (Bella) falls in love with a pale yet hot vampire boy (Edward) is really about superheroes. And like the hyphenated superheroes of recent movies, Meyer’s vampires are genetically different: they have a superabundance of chromosomes. (The vampires have twenty-five pairs, unlike our twenty-three.)
In our fang-free human life, having extra chromosomes is not usually seen as a plus. Aneuploidies, including Down syndrome, have been targets of prenatal testing as long as such testing has existed. As such, those conditions attract a host of polarizing questions, not least about abortion. In Breaking Dawn—the last book in the Twilight series—these questions come to the fore. Bella, still a mortal, becomes pregnant with a half vampire child thought to be a risk to her life, and a danger to the society around her. Edward wants her to abort, and she wants to keep the child.
The quarrel, and indeed the book, is framed by genetics. The high chromosome count signifies both ultimate superpower (in the case of the vampires) and the undesirable child (in the case of Bella’s fetus). The Twilight series, in other words, evokes both our fears about human modification and our anxieties about reproduction.
Today marks the nine-year anniversary of 26-year-old Dan Markingson's premature death. His story, covered previously here at Biopolitical Times, illustrates the medical-industrial complex at its worst: greedy university professors who put pharma profits before their patients' well-being, combined with ongoing institutional support from the University of Minnesota.
Many alumnae, myself included, have declared our disappointment at our alma mater. And recently, a number of important people of international reach have been motivated by Markingson's story and are demanding justice on his behalf. A change.org petition, initiated by Markingson's friend Mike Howard, implores Minnesota Governor Mike Dayton to investigate the case. Despite ongoing efforts by the U of M to bury the issue, advocates for Markingson continue to demand answers and are gaining increasing support.
High-profile signatures have already come from:
three former editors of the New England Journal of Medicine
Vera Sharav, the founder of the Alliance for Human Research Protection
and many other prominent bioethicists, health practitioners, academics, and community members (see the list here).
I encourage Biopolitical Times readers to learn more about Markingson's story. If you do, you will almost certainly want to sign the petition.
It’s important to bring attention to this issue to help prevent further cases like it. But equally important, the petition helps honor the memory of Dan Markingson, a real person, not just a symbol, whose family is hurting deeply today.
With political dividing lines carved deep into the collective consciousness, wading through the ethical minefield of embryo creation and destruction is a challenge. A recent New England Journal of Medicine (NEJM) article, “Made-to-Order Embryos for Sale — A Brave New World?” by I. Glenn Cohen and Eli Y. Adashi tackles the controversial issue of for-profit embryo creation. Possibly in an attempt to come out on a particular side of the political line, it sweeps what is truly novel about the practice under the rug.
The issue gained prominence last November, when the Los Angeles Timescovered a Davis fertility clinic, California Conceptions, and their falsely named Donated Embryo Program. “Donated embryos” typically refer to the gift of embryos left over from a couple’s IVF procedure to another, infertile couple. The embryos belong to the people whose gametes created them, and they make the decision about whether, when and to whom they should be given.
What California Conceptions does is completely different: It creates batches of embryos from donated sperm and eggs, keeps them in an embryo bank on site, and divvies them up to sell to multiple parties for a profit. As the LA Times reporter put it, “The clinic, not the customer, controls the embryos, typically making babies for three or four patients while paying just once for the donors and the laboratory work.”
The news about California Conceptions’ program caused a surge of public outrage (well chronicled here by Dr. Craig Sweet, medical and practice director of Embryo Donation International.) Andrew Vorzimer, a Los Angeles fertility lawyer said,
Make no mistake, this is commodification. These are not donated embryos. Rather, they are embryos created from donors hand-selected by California Conceptions. It is one step removed from a mail order catalog. The only difference is that the product being sold is nascent human life.
Cohen and Adashi do not share this concern. They compare the practice of creating and selling embryos to the sale of gametes and to the use of gametes and embryos for stem cell research. They conclude that, “viewed through a legal and ethical lens, the concerns raised by this potentiality appear to be similar to those associated with widely accepted and more common reproductive technologies.”
But made-to-order embryos present a different set of questions. Reverting to the reasoning behind other technologies or practices does not address what is troubling about this.
For example, they make the argument that embryo destruction for the purpose of stem cell research raises concerns about “respect for personhood” comparable to those raised about “made-to-order” embryos. But this is only the case if you believe that embryos inherently have a claim to personhood. If you do not share this view, then the authors are leaving out the crucial difference: the embryos used for stem cell research will never become people. However, the creation of an embryo that is implanted into a woman (with a pregnancy-or-your-money-back guarantee) is about “respect for personhood” because it turns actual nascent life into a commodity, sold for a profit just like any other.
That is what is unique about this practice. But the NEJM article dismisses this and concludes that there is really only one important difference: “the lack of clear legal guidance as to the parentage of the embryos in question.”
“Parentage” is plainly not the real issue. As is the norm with gamete donation, the sperm and egg donors that were used to create the embryo would not be likely to have any claim to parenthood. The embryos will actually not have any kind of “parentage” at all. They will rather be owned by the fertility clinic, until a woman implants one into her womb.
California Conceptions markets their service as cheaper than using third-party eggs and IVF, and less time consuming than adoption. But it’s important to note that along with the heightened element of commodification, an additional imperative for “design” has seeped into their approach. To offset their costs, they have to produce embryos that multiple couples will find desirable as products. Cohen and Adashi may not find these “eugenic overtones” worrying, but acknowledging their existence is telling enough.
There is no federal law governing the sale of embryos and Cohen and Adashi note that it “appears to be legal in all but two states.” Indeed, this was the justification offered by Jennalee Ryan, who gained notoriety several years ago after advertising “the world’s First Human Embryo Bank” online. That turned out to be a failed business plan, run from her living room, but she explained, “You know how it works? If there is no law against it, it’s legal.”
It’s one thing for eccentric business entrepreneurs to try to exploit a poorly regulated system. The fact that established scholars have made the case that we should accept selling embryos as ethical is much more troubling.
A bill being considered in the California legislature would allow researchers to pay women cash for their eggs. If passed, it would overturn established policies including guidelines from the National Academy of Sciences, the rules of the California stem cell agency, and a 2006 California law authored by then-state Senator Deborah Ortiz, known as a champion of women’s health and medical research. All these policies state that women who undergo egg retrieval for research can be compensated for their expenses, but not paid beyond that.
The new bill, AB 926, is sponsored by the American Society for Reproductive Medicine, which instigated the proposed legislation and is lobbying hard for it. Misleadingly worded to suggest that the bill promotes equity for women by offering “fair compensation,” the bill is really about trying to increase the number of eggs for research—where there is a perceived “shortage” of eggs and competition with the infertility industry—and has nothing to do with a concern for women. AB 926 in fact would have serious short-term and long-term health implications for women, especially college-age and low-income women, who may be enticed to put themselves at risk by selling their eggs out of financial need.
A fact sheet by the bill’s author, Assembly member Susan Bonilla, argues that women who provide eggs for research should be “treated equally to all other research subjects.” But these women are not at all like traditional research subjects in clinical trials. Their reactions to experimental drugs or procedures are not under study. Nor are the researchers in this situation investigating the health implications of egg retrieval. Instead, they are seeking raw material—women’s eggs—for their work.
Further, if researchers are paying thousands of dollars for each cycle of egg retrieval, they will likely be tempted to try to obtain as many as possible from each woman, and may consciously or sub-consciously make decisions from an economic position. Unfortunately, the more eggs retrieved in a procedure, the greater the risks to women’s health.
Although many women undergo egg retrieval for their own or other people’s fertility treatment, the procedure involves high doses of powerful hormones, some of them being used off label, and carries risks that are both significant and under-studied. Despite efforts by women’s health advocates, follow-up studies to determine the procedure’s effects on women are inadequate. Attempts to encourage assisted reproduction clinics to take part voluntarily in a registry of women who have undergone egg retrieval have mostly been ignored by the fertility industry. Without that information, women cannot possibly make an informed decision about the safety of providing eggs even for fertility treatment, let alone for research purposes.
AB 926 claims to be motivated by concerns for women’s equity and for advancing responsible medical research. Those are worthy goals. But, unfortunately, this bill undermines both.
Current status of the bill: AB 926 was passed by the Assembly Health Committee on April 16. It will go next either to the Appropriations Committee or straight to the Assembly floor. If approved by the Assembly, it will go to the Senate, where it will be voted on again.
Last week, some 15 French activists in chimpanzee masks disrupted a Forum on Synthetic Biology at the National Center for Arts and Crafts in Paris. This was the first public event held by the "Observatoire de la biologie de synthèse," a body set up by the government to monitor and debate the technology and its social implications. The meeting was effectively shut down. The only reports available are in French (by protesters here, by organizers here) but this placard speaks for itself:
To participate is to accept
I have to admit, my first reaction to seeing pictures of this protest was to laugh out loud and cheer. It's easy to agree with slogans such as "Non à la Vie Synthetique." (Translation is inexact but that's roughly "No to Living Synthetically.")
But are they right to claim that to engage in debate over how to implement synthetic biology is to concede the thin end of the wedge — to trade in your principles for a seat at the table — or is this counter-productive flamboyance?
In this particular case, critics of synthetic biology have in fact been part of the private discussions that preceded this public event. I have no idea if they managed to change the dynamic or to raise significant questions in the minds of civil servants, let alone representatives of industry. But the reaction to this disruption might be to drive all discussion away from public view, and it's hard to see how that could be helpful.
Conversely, it is vital that policymakers understand the depth of feeling on the issue. Opinion polls tell a nuanced story, according to research conducted by the Wilson Center (abstract here). The public is skeptical, and capable of making fine distinctions. But that doesn't mean that industry can rely on passive acquiescence by any means. The kind of drama enacted in Paris does show that opposition is not only mild and general but also intense. That's worth something.
The relationship between campaigners and negotiators is often fraught with suspicion, as a couple of other current controversies illustrate. Some of those who worked hard on California's GM labeling proposition last year are skeptical about the value of the new federal labeling bill (which the Center for Food Safety is supporting). Will it "pre-empt anything any of the states will be doing?", one asked me in a private communication. Will the big food companies make sure that "any federal bill passed will be way gutted"? Such cynicism is easy to understand, and important to factor into activist strategizing.
By coincidence, I just received an announcement from the Global Justice Ecology Project (GJEP), which works at multiple levels, nationally and internationally, to stand up for native forests and promote climate justice, among other issues. The latest email was about the Stop GE Trees Campaign, which includes planned public protest at the the Tree Biotechnology 2013 Conference in Asheville at the end of May.