ScienceDebate.org was launched in 2007 with a goal of promoting a Presidential debate entirely on scientific topics. That hasn't happened yet, but the organization, which includes a broad selection of establishment figures and is co-organized by the National Academies, AAAS, and the Council on Competitiveness, is still trying.
Meanwhile, they set a perhaps more realistic goal of agreeing on 20 science-related questions and getting written answers from the candidates. The answers from Hillary Clinton, Donald Trump and Jill Stein are now online. Libertarian Gary Johnson has not yet responded.
Here’s what you get from the candidates for each question (illustrated with extracts from responses to the opioid problem):
From Clinton, three or four paragraphs that read as though they were drafted by a competent policy analyst and edited, or at least approved, by the candidate.
Sample: "We must work with medical doctors and nurses across the country to treat this issue on the ground, from how patients are accessing these medications to how we are supporting them in recovery."
From Trump, one paragraph that might have been extemporized by himself and then translated into a form of English.
Sample: "As this is a national problem that costs America billions of dollars in productivity, we should apply the resources necessary to mitigate this problem."
From Stein, short paragraphs (often several) that frequently make a lot of utopian sense.
Sample: "We will end the 'war on drugs' and redirect funds presently budgeted for the 'war on drugs' toward expanded research, education, counseling and treatment."
The Center for Genetics and Society’s core concerns about human biotechnologies are not explicitly covered. There are no references in either the questions or the answers to germline or other gene editing, or to genomics, stem cells, eugenics or precision medicine, to name but a few. Privacy is mentioned only in the context of the Internet in general.
Press reactions are listed on-site. Science had an anodyne but reasonably accurate summary. Lawrence M. Krauss in the New Yorker took a wry approach. Trump’s contributions were dissected at length by Martin Longman at Washington Monthly, who calls them variously “straight unresponsive pablum,” “almost unbelievable,” showing “no clue” and, on nuclear power, “positively Palinesque.” (Read the whole thing!) Michael Schulman at The Cubit blog (part of Religion Dispatches) has an entertaining summary that accurately concludes:
ScienceDebate.org asked questions about forces that will affect the basic well-being and survival of the United States’ citizenry. In theory, that’s the stuff of democracy. Not one of them, though, felt like something that will even remotely sway the election.
At almost the same time, Neal Lane and colleagues at Rice University issued a report arguing strongly that the White House Office of Science and Technology Policy (OSTP) and the position of science adviser should be retained by the next president, who should, as Science notes, "lay out priorities for science and innovation within the first 100 days of taking office.” The report is not specific on issues, but very strong on process.
On the lighter side, there are reports that Trump intends to nominate Peter Thiel, the notorious billionaire transhumanist, to the Supreme Court. Everyone involved denies this on the record, but the rumor is said to derive from sources close to Mr. Thiel. Someone allegedly close to the candidate confirms (on background) that there has been discussion but cautions:
Trump’s offers often fail to materialize in real life.
One set of CRISPR questions that poses hugely significant threats to future generations goes something like this:
Can we engineer human germ cells and embryos to re-wire genetic risk factors?
And if we think it’s safe enough, should we try to create genetically modified babies?
To address these questions, the video raises some helpful points. It notes the likelihood of market pressures and consumer incentives and how they might impact what sort of children and what sort of modifications become popular (”Buy two enhancements, get the third free!”).
It also illustrates the massive iceberg of unknowns facing those who are interested in pursuing genetic upgrades in the IVF clinic.
Yet the video is restricted in its ability to fully countenance the future of designer babies by its cheery optimism, by its unsupported claims that a new biological era of “intelligent design” is just inevitable, and by its assumption that people will naturally warm up to the idea as time goes on.
One of the video’s sanguine assumptions is that any social downsides are confined to scenarios of evil dictators and mad scientists. While North Korea’s current situation makes it easy to construe our own social and political context as reasonable by comparison, there is no shortage of social justice concerns that transcend crude state-sponsored violence.
The video also indulges in some anti-aging hype—a key cornerstone for much of the Silicon Valley collective's future-making projects, and a generator of headline gems like this recent one:
The company’s visuals bring to mind the TED Talk that entrepreneur Juan Enriquez gave in November 2015 entitled “We can reprogram life. How to do it wisely.” Enriquez's slides used emoji to describe the coming era of “intelligent design” in which humans “re-program” the “lifecode” of future generations. For all the policy wonks in the house, Enriquez has a super thorough plan for containing this GMO explosion:
We should take about a quarter of the Earth and only let Darwin run the show there. It doesn't have to be contiguous, doesn't have to all be tied together. It should be part in the oceans, part on land. But we should not run every evolutionary decision on this planet. We want to have our evolutionary system running. We want to have Darwin's evolutionary system running. And it's just really important to have these two things running in parallel and not overwhelm evolution.
Like Enriquez, Kurgesagt’s CRISPR video, for all of its unbound future visions, adopts an exceedingly narrow vision of democratic progress and governance. “The only thing we know for sure,” it asserts, “is that things will change irreversibly.”
By this logic, technology’s impending arranged marriage to biology is inevitable, and we might as well sit back and watch the Silicon Valley “cradle of innovation” unburden us from our human imperfections—one human birthing experiment at a time.
But before we give up on the current reproductive order, it seems only fair that we first admit our troubling assumptions about what it means to be human:
Departures from the optimum—and certainly most disease and disability—simply equate to abject suffering without individual or societal value, and should be de-selected, prevented, secluded, avoided, exterminated.
Some genes are just “bad”—or at least “inconvenient” in our society—and not worth bringing into the world. Some genes are just “good” and worth increasing in the population.
Each of us has a moral duty to cleanse our children’s genome before birth to maintain a superior human race—I mean, for the state’s interest in public health.
These assumptions are in fact the rationales of eugenics past. Do we really want to marry them to the angel-winged free market of Big Biotech?
Let’s be clear about what’s at stake. Let’s interrogate the assumptions that tell us our children must be bred from the finest stock available. Let’s challenge ourselves to forego conceiving of our children as value-enhanced property in a biopolitical marketplace. Let’s fight back against the politics and social pressures that tell us our bodies are the sole source of our value. Let’s ignore folks who say that we are internally deficient, that inequality is natural, and that we are each personally responsible when systems of power and oppression cut off our ability to thrive. Let’s allow all of us to be a little more human – imperfections, genetic variants, and all.
David Jensen, who writes the essential California Stem Cell Report blog, published a detailed front-page article in the Sacramento Bee on September 2 with the eye-catching headline:
Stem cell company paid $443,500 to former head of state agency that funds research
As has previously been reported, Alan Trounson joined the board of StemCells Inc. in 2014, about a week after he resigned from a six-year stint as President of the California Institute for Regenerative Medicine (CIRM) to return to Australia. CIRM, which is funded by California taxpayers, had previously allotted some $40 million of grants to the company, based just across the Bay from Stanford.
As Jensen recounts, some of those grants had raised questions; one was made despite having been twice rejected by the grant committee. In addition, Irving Weissman, the Stanford University-based co-founder of the company, has received research grants amounting to $30.5 million from the agency. Weissman notoriously appeared in 2004 television ads promoting the establishment of CIRM, while wearing a white coat and identifying himself as a doctor (which he also is), but not as a stem cell entrepreneur. Weissman’s academic institution, Stanford University, has received over a quarter of a billion dollars from CIRM, including over $40 million for a new building.
The new information that Jensen turned up in SEC filings was how much StemCells Inc. paid Trounson after he joined its board: $59,500 in cash over a year and a half (far more than any other board member) and nominally $384,000 in stock options. (The stock has since tanked completely.)
Did Trounson or StemCells Inc. do anything illegal? Quite likely not. Was this transaction appropriate? Absolutely not! It’s scandalous, but it’s the kind of scandal that was built into CIRM from its very inception. Nature, in September 2004, during the run-up to the state election that established CIRM, opened an article this way:
Opponents of California's $3-billion plan to fund embryonic stem-cell research say that the proposal would give researchers carte blanche to rewrite well-established ethical guidelines to suit their needs. They say the research institute planned under the initiative will be exempt from legislative supervision and, if established, will be able to make its own rules about conflicts of interest and informed consent.
Among those opponents was the Center for Genetics and Society, whose extensive pre-election analysis is archived here. In January 2006, CGS examined CIRM’s first year and published a detailed “report card” [pdf]. The overall grade we gave CIRM was C–, and on several issues, including minimizing conflict of interest, we handed out a D.
Jesse Reynolds, then Director of Project on Biotechnology Accountability for CGS, deserves particular credit for drawing attention to the conflicts of interest embedded in the structure of the stem cell agency. He attended numerous public meetings of CIRM, testified for investigations of the agency before the California legislature and the state’s “Little Hoover Commission,” wrotemanyop-eds, and helped to push for reforms.
CIRM was also scrutinized by the Institute of Medicine in 2012. Its report affirmed the existence and significance of the conflicts of interest and structural flaws that CGS and other public interest voices had identified even before the agency was approved by the 2004 ballot measure on which backers spent some $35 million. CGS’s invited testimony to the Institute of Medicine, and its press release welcoming the IOM’s report, provide details.
CIRM is now slowly running out of the $3 billion of public funds allocated to it in 2004, and is expected to wind up in 2020. It has provided an object lesson in how not to set up and run an independent public-funded agency. These latest revelations should end any speculation about extending its charter.
Posted by Emily Galpern, Biopolitical Times guest contributor on September 8th, 2016
The Center for Genetics and Society and allies are celebrating the demise of AB 2531, a bill that would have allowed payments to women who provide eggs for research, effectively expanding the commercial market for human eggs from the fertility sector to the research context.
The bill, which was sponsored by the American Society for Reproductive Medicine, died in the State Legislature last week, never making it to the Governor’s desk. Assemblymember Autumn Burke anticipated a veto from Governor Brown and decided not to bring it up for a vote in the Assembly when it was sent back for concurrence, after passing the Senate on August 29 with amendments that seemed to be a tepid response to opponents’ objections.
CGS and allied women’s health, reproductive justice and public interest organizations opposed the bill because of dramatically insufficient information about the health effects of egg provision; the impossibility of true informed consent given the lack of data; the likelihood that low-income women, women of color, and immigrant women would most likely be affected; and the bill’s conflict with national recommendations for federal policy and with state law. For a full explanation of these concerns, see the opposition floor alert and CGS’ letter to the Senate Health Committee.
The bill was covered by veteran journalist David Jensen in the Capitol Weekly (Senate eyes human egg business), and was criticized in a number of op-eds and columns, including one by former Senator Deborah Ortiz, author of a 2006 law that assured certain protections for egg providers:
We hope legislators have come to understand the complexity of this issue and, instead of bringing payment and undue incentive to the table, begin to call for long-term studies to provide the information women need to make truly informed decisions about their bodies and their health.
Emily Galpern works with the Center for Genetics and Society as a consultant.
Ruth Hubbard — prominent biologist, feminist scholar, multi-faceted social justice advocate, and critic of what she termed “the gene myth” — died on September 1 at the age of 92. Her scholarly and public interest efforts to track and shape the politics of human genetics were an important inspiration to many working on these matters today, including those of us who helped establish the Center for Genetics and Society.
Ruth took on a range of political and social challenges related to the politics of science, genetic determinism, race, and gender. Among these was human germline modification, which she strongly opposed. In 1999, she co-authored Human germline gene modification: a dissent with Stuart Newman and Paul Billings in The Lancet.
In 1993, she wrote in Exploding the Gene Myth:
Clearly, the eugenic implications of [human germline modification] are enormous. It brings us into a Brave New World in which scientists, or other self-appointed arbiters of human excellence, would be able to decide which are “bad” genes and when to replace them with “good” ones….We need to pay attention to the experiments that will be proposed for germ-line genetic manipulations, and to oppose the rationales that will be put forward to advance their implementation, wherever and whenever they are discussed.
The Boston Globe’s obituary for Ruth provides details about her long and influential life and career, as does an obituary written by her family that can be found here.
Maybe you haven’t heard of CRISPR-Cas9. To be honest, if I hadn’t previously worked at the Center for Genetics and Society, I probably wouldn’t have heard of it either. It’s a new genetic technology that brings modification of the human germline closer in reach than ever before.
Driven by the promise of allowing parents to avoid passing on incurable genetic diseases to their offspring, the use of CRISPR to engineer human embryos presents serious risks with particularly strong implications for people with disabilities—in the present and future. It’s been getting plenty of press. And yet, as someone who tries to stay up to date constantly with what’s trending in the disability social media scene, it has seemed to me that CRISPR has been more or less absent.
Why aren’t people in the disability community talking more about this?
Why should people with disabilities have to keep spending their time justifying their existence rather than just enjoying it at present?
I recall a conference I organized with the Longmore Institute in 2013, “Future Past: Disability, Eugenics, and Brave New Worlds.” Disability studies scholar and activist Marsha Saxton began her panel by sharing a memory of talking with a genetics counselor while contemplating getting pregnant. The counselor exclaimed, “Gee, if I’d have known Spina Bifadas turned out as well as you, I would not have recommended selective abortion as much as I’ve done!”
Similarly, a conversation comes to mind that I had with another disability activist, who previously focused on the neo-eugenic uses of genetic technologies but left because she was burnt out. As a person with a disability, she didn’t want to continue spending her life’s work validating her own existence, and moved into the arts instead to celebrate the beauty that disability brings.
Despite the disability rights movement’s progress, both of these stories help illustrate why people with disabilities might not want to waste their time thinking about these issues. Indeed it suggests that my own lack of understanding of why people with disabilities aren’t more interested in following this comes from a place of privilege as a nondisabled ally. It seems that for many, engaging in the debate is just too hurtful. Why should people with disabilities have to keep spending their time justifying their existence rather than just enjoying it at present?
Yet when it comes to CRISPR for human reproduction, disability is at the center of it all. Whether or not CRISPR takes hold in the fertility clinic, the scientific and philosophical debate is constantly centered on disability. So here are five reasons why CRISPR and disability are dangerously intertwined, exemplifying why we need the perspectives of people with disabilities weighing in on this debate, as unappealing as diving in may be:
Modern-day eugenics. For me, it’s pretty much that simple… and that scary. Advocates of using CRISPR for heritable genetic modification argue that we can distinguish to ensure this is only used for deselecting genetic diseases (“germline therapy”), rather than using the technology to select for more desired traits (“enhancement”). But even this binary presumes we can draw clean lines to eliminate diseases that don’t also suggest preventing disabilities. It brings up questions of what we should and shouldn’t value in future generations. Knowing that these choices are being made in a deeply ableist culture—where people like Marsha Saxton would likely not have been born because of fear of the “spina bifidas”—illustrates how hard it would be to draw lines about what genetic diseases “we” agree to engineer out of the gene pool and which are allowed to stay.
We are moving backwards. Even as opponents of CRISPR germline modification make their case, it often hinges on the idea that we don’t need CRISPR because we already have preimplantation genetic diagnosis (PGD) to allow parents to have children free from genetic abnormalities. However, disability advocates still contest PGD as socially harmful genetic selection and disability prevention. The Center for Genetics and Society’s Executive Director Marcy Darnovsky recently shared with me that when she points out this tension to the press, they rarely if ever include it.
It’s selling disability as tragic. This isn’t new. It’s how preimplantation genetic diagnosis was sold. It’s how stem cell therapy was sold. Before we even develop the technology, we develop the story: people with disabilities are living a sad, tragic existence, and only through progress in the genetic sciences can we spare their suffering in future people. This tragedy gets retold and retold, creating urgency for the technology in question: Forget the vibrant disability community. Forget the changes in technology, art, and culture that people with disabilities bring to our world from the insights of living with a disability. We don’t have time to worry about ethics or risks! Selling the need for the cutting edge technology comes on the backs of people with disabilities, so science policy and debates become one more place where the tired trope of disability as “the worst” thrives.
Nondisabled people won’t get it unless people with disabilities are part of the debate. Nondisabled proponents are arguing we need to use CRISPR to prevent disabilities. Nondisabled opponents suggest we should be wary of CRISPR for its threat to disability justice. Both sides are talking about disability, but the conversation would carry more weight if disability activists were involved.
This is why the work of disability activist and writer Harriet McBryde Johnson was so powerful. In a series of conversations with philosopher Peter Singer, one of the most outspoken advocates of preventing children with disabilities from being born, McBryde Johnson put a face to his theoretical exercises and argued that they had life or death consequences for people like her. (Still image via Vimeo)
When I share my interests in these sorts of debates, I often get this wave of enthusiasm from other nondisabled people who seem to find it fun to sit around and discuss how much better the world would be if we could prevent or cure all disabilities. They want to talk it out through thought experiments and philosophical exercises. I mean no disrespect to those who think that way. After all, I’m married to someone with a philosophy degree, and some philosophers with disabilities have made important contributions to the way disability is theorized in ethical debates (e.g. Adrienne Asch and Anita Silvers). However, I think the debate needs more perspectives and personal stories coming from people with disabilities who help us to attach faces and lives to the debate and to remind us what a loss it would be to live in a world with less disability.
(At the 2015 National Academies' International Summit on Human Gene Editing, the conversation did not include any featured speaker open about being a person with a disability. There were efforts to invite one or two, and Ruha Benjamin did give a wonderful presentation which you can view here, but the omission was startling.)
It impacts the fight for disability equity today. When cures and the end of disability are always cast as “just around the corner,” it continues to make it harder to fight for what we need today. We continue to invest millions of dollars on anything that might help us eliminate disability. Meanwhile people with disabilities struggle to implement things to make our society more accessible right now, as these social changes are always framed as “too costly.” This doesn’t mean that we need to be entirely anti-cure and certainly not anti-research, but again, we need people with disabilities to play a central role in this debate. A diversity of voices speaking to their experiences with disability can teach us that we don’t need CRISPR to “solve” the disability = tragedy equation. Social changes to the built environment and cultural changes to discriminatory attitudes are a safer bet with more widely shared impacts.
2017 will mark the 20th anniversary of GATTACA’s release, a film which brought to the big screen issues of genetic discrimination resulting from the effort to control human reproduction (for a great disability take on it, read here). The “not too distant future” imagined in the film grows closer with CRISPR. I wish I could just turn away from CRISPR to hope it’ll pass over—I far prefer spending my time on our disability film festival or promoting disability history. Yet disability culture and arts are more related to CRISPR than one might think. They provide a powerful illustration of how disability enriches our world. It just might be worth making time for the CRISPR debates (even though the emotional labor of doing so is huge), to help ensure a long-term future for disability as a creative and generative force.
Emily Beitiks is Associate Director of Paul K. Longmore Institute on Disability at San Francisco State University, and a former staffer at CGS. Beitiks earned her Ph.D in American Studies from the University of Minnesota with the dissertation "Building the Normal Body: Disability and the Techno-Makeover".
Posted by Gina Maranto, Biopolitical Times guest contributor on August 9th, 2016
Deep brain stimulation, image via Wikimedia.
Permit me a brief digression before I comment on the latest Pew Research Center survey of Americans’ attitudes toward biomedical technologies meant to “enhance” human performance.
I am married to a bioengineered man. Almost three years ago, after having been steadily eroded by Parkinson’s disease for over a decade, my husband Mark Derr braved deep brain stimulation (DBS) surgery. His incredible surgical team at Johns Hopkins implanted electrodes into his brain and a battery-driven stimulus device in his upper left pectoral, and the results seemed, at the time, nothing short of miraculous. With a mere incremental upping of the voltage during an initial adjustment session, the DBS instantaneously stilled Mark’s tremulous hand and foot, giving him relief that the standard drugs had only intermittently provided.
Much as DBS has improved his quality of life, Mark is far from cured. DBS cannot address the muscle stiffness, balance problems, and neurological pain he experiences daily. And the instrument requires constant attention. Mark’s days consist of frequent monitoring of his device; his weeks, of periodic adjustments of the voltage; his months, of consultation with his medical minders in Baltimore, where he travels every five months or so for “tweaking.” His latest technician there told him, “You are your own experiment.”
Based on direct experience, then, I would advise that heady promises regarding biotechnology should be viewed with a high degree of skepticism. DBS, for example, may eventually get better at addressing Parkinson’s symptoms, but cannot reverse the neuronal damage that lies at the base of the disease. Many other biotechnological interventions also carry with them an almost guaranteed set of deficits, inadequacies, inconveniences, and risks that are conveniently ignored in the valedictory narratives woven around them.
In some ways, the Pew survey, which looked at attitudes toward three hypothetical “enhancements” (although one, which would involve genetic enhancement of future children, is presented as a preventative medical measure), suggests that Americans get that biotech interventions raise profound social and ethical questions. In the chart below, more respondents said they were concerned rather than enthused about fiddling with babies’ genomes, following in the footsteps of Johnny Mnemonic, or engaging in blood doping squared. Not only did most of those surveyed expect that the cons would outweigh the pros of such interventions, a majority believed such interventions “could exacerbate the divide between the haves and have-nots in society…[and that] inequality would increase because only the wealthy could afford these enhancements.”
But Pew itself seems oddly disposed to undercut its own findings in the large accompanying piece probing “expert” opinion on enhancement in general. David Masci, in “Human Enhancement: The Scientific and Ethical Dimensions of Striving for Perfection,” seems to take the side of the pro-enhancement champions, giving ample play to the “sky’s the limit” point of view of self-avowed transhumanists and giving the final world to a futurist who says, “We’ll probably start by taking a human version of nirvana and creating it in some sort of virtual reality,” and then “we’ll transition to realms of bliss that we can’t conceive of at this time because we’re incapable of conceiving it.” Masci also strives to normalize enhancement, starting his piece with the claim that, “Human enhancement is at least as old as civilization.”
This claim, often advanced in pro-enhancement camps, suggests that education and exercise are equivalent to chips in the brain or performance enhancement through genetic alterations that would increase, say, fast twitch muscles. Call it argument by sleight of hand or by failure to make proper category distinctions. If we really want an accurate analogy, we should think about phase changes: water becomes colder and colder, and then becomes ice. A quantitative change leads to a qualitative change. Step by step, biotechnologists alter us; at a certain point, a qualitative change ensues. We cannot perfect the human; we can only push genes and protoplasm past a certain point—and no one quite knows where it lies, but many have agreed that the germline is certainly one clear and present possibility—and we will have crafted a new entity. But to what purpose is questionable.
Instead of leaving a person’s physical well-being to the vagaries of nature, supporters of these technologies contend, science will allow us to take control of our species’ development, making ourselves and future generations stronger, smarter, healthier and happier.
To this I say hooey and hooey again. Even the most exquisitely engineered of artifacts—take the Large Hadron Collider for example—are prone to error and screw ups. Surprise, chance, and unpredictability are hard wired into our universe. Whether breakdowns come from passing birds or wayward weasels, breakdowns will come. Even when our biomedical and bioengineering prowess achieves its best, there will always be downsides.
Gina Marantois a fellow at the Center for Genetics and Society. She is Professor and 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. Her articles, opinion pieces, and reviews have appeared inDiscover,The Atlantic Monthly,Scientific American,The New York Times, and other publications. She is the author ofQuest for Perfection: The Drive to Breed Better Human Beings.
In the past month, the media has reported seven patient deaths of subjects enrolled in separate gene therapy clinical trials being conducted by Juno Therapeutics and by Ziopharm Oncology, Inc., both aimed at immunotherapy-based cancer treatments that have sparked widespread hope. Despite these deaths, the trials continue to move forward.
Media coverage of trials related to gene therapy has portrayed the clinical research rollercoaster. Just this past week, The New York Times ran an unusually lengthy and high-profile series of articles in the Sunday paper about immunotherapy treatments for cancer, some involving genetic modification of immune cells. The articles describe the promising aspects of engineering one’s own immune system to fight cancer, including dramatic stories of tumors “melting away” and promises of complete remission.
Yet commentary on the ethical implications of these events has been scant, and these events raise a number of concerns about what bioethicists call “therapeutic misconception” – vulnerable patients seeking enrollment in a clinical trial with the mistaken belief that the gene therapy is approved by the FDA to be safe and effective. The clinical trial deaths also highlight lingering questions about transparent reporting of adverse events to the FDA and appropriately navigating financial conflicts of interest. Instead, numerous articles have focused on how these deaths impact the bottom line: corporate stock prices.
The excitement has been building for some time. In June 2015, MIT Technology Review described Juno’s experimental T-cell immunotherapy for leukemia as “Biotech’s Coming Cancer Cure” and profiled the “miracle” recovery of 20-year old leukemia patient Milton Wright III. Wright signed up for the clinical trial because “they hyped it up, like it was going to be amazing” and MIT Technology Review has characterized Juno’s immunotherapy trials as “remarkable.”
Some scientists are hopeful for a breakthrough, particularly for patients whose cancer has returned after multiple rounds of traditional chemotherapy. For vulnerable patients seeking a “miracle cure,” such characterizations blur the distinction between approved therapy and clinical research that may or may not produce a viable therapy. As a disclaimer, I have not seen any of the informed consent documents from Juno or Ziopharm. But whatever these documents say, media descriptions of a “coming cancer cure” make it challenging to fully convey the risks to sick people with few other options who are considering enrolling in clinical trials as a last-ditch treatment effort. This is precisely the kind of situation that the term “therapeutic misconception” addresses.
We must cautiously tread when describing Phase I and Phase II clinical trials to patients who are simultaneously acting as research subjects, and take care not to inflate our words when we discuss this research in the media. Despite the misleading name, these early gene therapy trials are not approved therapies, but experiments to assess safety, dosing tolerability, and effectiveness. The goal for this stage of research is not to provide a treatment for this specific person, but rather to contribute to generalized knowledge. It focuses on asking: Will this method of gene therapy work? Is it safe? Are there adverse risks so severe or frequent which constitute an unacceptable level of risk?
It is not clear whether the patients recognize the uncertainty of benefit, especially when measured against the magnitude of risk. Gene therapy poses a distinct, and an arguably riskier, profile of possible adverse effects compared to drugs alone because it can permanently alter the recipient’s cells and holds the potential for severe latent adverse effects such as cancer, immunologic, neurologic, and autoimmune complications.
When unexpected serious adverse reactions do occur that are related to the trial, the sponsor must report these to the FDA. Several months ago in May 2016, Juno reported one death to the FDA of a subject who was enrolled in one of its CAR-T protocols for leukemia, asserting: “It is not clear what caused the death, and a change at this time is not warranted.” In July, Juno reported two more deaths, this time stating that they resulted from compounding factors (a chemotherapy drug Fludarabine used in conjunction with the CAR-T protocol). Juno subsequently updated its statement, disclosing there have been four total deaths from its CAR-T protocols.
In response, the FDA temporarily (and very briefly) suspended the clinical trial, causing a fleeting plummet in Juno’s stock prices. Juno quickly submitted a modified protocol that removed Fludarabine, updated the trial brochure, and amended the patient consent form to the FDA. The FDA deemed these modifications acceptable and expediently lifted the hold within days, despite the alarming disclosure. Juno’s trial – and stock prices – were back in business. Articles (here and here) characterized these deaths and the corresponding swift response as a “bump in the road,” myopically questioning how it would impact the clinical trial progression and corporate financial outlook. Minimizing patient deaths that may have resulted from the gene therapy rather than their underlying illness is dehumanizing and ethically inappropriate, even if we reason that these patients were near the end of life.
One biotech analyst questioned FDA’s decision to quickly lift the clinical trial hold, observing, “They are trying to referee a game while the rules are still being written. And it appears to be causing some deaths that should have been avoided.”
Ziopharm made similar headlines in the past few months relating to its Phase I clinical trials designed for glioblastoma patients. Ziopharm partnered with the synthetic biology company Intrexon, and has been studying a gene therapy technique using a genetically engineered virus that is directly injected into the subject’s tumor. According to Ziopharm, the third subject died 15 days after beginning the trial of an intracranial hemorrhage. Prior to this report, two other enrolled subjects also died, albeit months after the initiation of one of the trials. According to a press release, Ziopharm maintains the intracranial hemorrhage death “is an isolated case” and the other patient deaths were unrelated, and attributed those outcomes to pre-existing illness, stating, “these patients are all, unfortunately, medically fragile.”
The problem with reporting adverse events, including deaths, to the FDA resides in a substantial loophole that awards discretion to the investigator to decide whether the adverse event is serious and whether it reasonably resulted from the gene therapy. Although the investigator theoretically stands in the best position to sort through the noise of the confounding variables of underlying illness or other drugs the subject may be taking, this nonetheless creates a troublesome reliance upon the corporation whose stock price and profitability are tenuously tied to clinical trial performance. This creates an undeniably powerful motivation to shift the blame of any adverse outcomes.
As Professor Osagie K. Obasogie has noted, profit motives remain entrenched in medical research, which can further complicate relationships where industry and medical care become intertwined. The arrangement between Ziopharm and MD Anderson Cancer Center exemplifies such enmeshment: Ziopharm and Intrexon executed a deal with MD Anderson to provide $100 million in stock, and recently appointed MD Anderson physician Dr. Laurence Cooper as Ziopharm’s newly minted CEO. Similarly, Science’s recent profile of competitor Dr. Carl June’s work at the University of Pennsylvania also flagged the potential conflict of interest arising from its partnership with Novartis to develop gene therapies for which June would hold a financial stake arising from related patents.
Despite assertions that these relationships will be managed according to institutional conflict of interest policies, such heavy financial ties heighten the stakes and necessarily raise concerns about independent judgment and transparency. The call to uphold ethical tenets of research is nothing new, particularly when there is a franticcompetition to bring an FDA-approved product to market. Back in 2007, Obasogie raised similar concerns after a patient death in a gene therapy trial for arthritis: “Time is money; in the rush to get products to market, patient safety can inadvertently take a backseat.”
These vulnerable patients have a stake, too. We must ask the right questions to see whether they appreciate the risks they decide to undertake. We must stop blindly accepting these dismissals of deaths and assurances that conflicts of interests are mitigated, especially when there is so much riding on clinical trials’ success.
Katherine Drabiak, JD is an Assistant Professor at USF Health in the College of the Public Health. You can follow her updates here: www.katherinedrabiakjd.com.
Posted by Jessica Cussins, Biopolitical Times guest contributor on August 3rd, 2016
Untitled DocumentPhilosopher Tina Rulli argues that three-person IVF is not a “life-saving therapy” or even a medical treatment at all. Rulli explains why the technology does not meet a plausible social value standard that would justify public research investment, and why other germline modification techniques may not either.
If you have seen any of the countless descriptions of three-parent or three-person IVF, also called mitochondrial replacement, as a “life-saving treatment,” you might find the question in the title confusing. How could any life-saving treatment not be of value?
As Rulli explains, the claim that this technology would save lives is “inaccurate and exaggerated.” Three-person IVF would not cure, treat, or save anyone. At best, it would allow women affected by a particular kind of mitochondrial disease to have an unaffected child who is mostly genetically related to her.
The experimental procedure works by genetically engineering an embryo to combine the intending mother’s nuclear DNA with another woman’s mitochondrial DNA. The choice a woman would make is not “do I save my child?” but “do I want to have a child in this way?” Rulli makes a strong argument that these are not morally equivalent, and that it is irresponsible to act as though they are.
How one thinks about this distinction between creating an unaffected genetically related child and saving lives may have implications well beyond three-person IVF. As Rulli points out, the creating-saving distinction probably holds for any form of germline genetic modification:
The argument here might provide a template for objections to other germline modifications or gene therapies that are valuable solely or primarily because they may enable prospective parents to have healthy genetically related children who would not otherwise exist.
For example, it would probably mean that the experiment carried out in April using CRISPR to introduce an HIV-resistant mutation into the DNA of embryos could also not be called a life-saving treatment, even if it worked well (it didn’t) and even if it was going to be used to generate a person with altered risk factors (it wasn’t).
Rulli further undermines the medical relevance of three-person IVF by pointing out that it isn’t the most effective way to reduce the transmission of mitochondrial disease. Only a small subset of mitochondrial disease could even hypothetically be addressed by this technology, since most cases involve mutations in nuclear DNA (instead of or in addition to mutations in mitochondrial DNA). And the procedure would only be accessible to women with far more financial resources than most have.
The alternative to three-person IVF – using an entire egg (rather than an egg that has had its nucleus removed) provided by another woman – would completely eliminate the risk of transmitting mitochondrial disease. In other words, the real value of the experimental procedure is not about health at all, but about the personal preference to have a genetic connection to one’s child. Rulli refers to this as “medicalization of a social preference” that works by “preserving the dominance of the bionormative family schema.”
Based on these points, Rulli asserts that three-person IVF lacks the social value that proponents have claimed for it, and that would be a necessary precondition of ethical clinical research, both in order to use limited health resources responsibly and to avoid human exploitation. She therefore concludes, despite the Institute of Medicine’s report endorsing the potential of “clinical trials,” that any public research investment in three-person IVF would be unethical.
Rulli reaches this conclusion even without addressing the multiple safety and efficacy concerns that have cropped up regarding three-person IVF. She takes it for granted that the technology will do what it says it will do. But she does note:
If the concerns about the safety of three-parent IVF for children and future generations are legitimate, then these considerations are not over-ridden by proponents’ claims about the great, life-saving potential of this technology. We know those claims to be fictional.
Throughout the push for legalization of these three-person IVF techniques, some advocates have painted any concern raised as anti-science or anti-technology. Rulli takes pains to point out that she is neither. Her argument is not against the technology per se, but whether to invest public resources in its development when the opportunity cost of that research includes, among other things, diminishing resources for investigating treatments for people suffering from mitochondrial diseases today.
Given the firestorm of attention to CRISPR, and the relative ease of genetically modifying an embryo versus an adult, we may well see arguments about germline gene editing as a “life-saving treatment.” Proponents are already pointing to three-person IVF as a pioneer technology that is paving the way for other forms of germline modification, so it is critical to set the record straight. Rulli’s report will be a useful framework to have on hand.