Posted by Jessica Cussins on October 31st, 2014
|Prometheus Brings Fire by Heinrich Friedrich Füger|
About a year ago, Steven Brenner posed this question in Nature,
How long will it be until an idealistic and technically literate researcher deliberately releases genome and trait information publicly in the name of open science?
We now seem to be well on our way.
For just $5 and your acknowledgement of the fact that DNA variations offer limited information (so you really ought to discuss the findings with a doctor or genetic counselor), an online venture called Promethease will provide you with the full explanation of your 23andMe health data in just 15 minutes, FDA be damned.
Promethease acknowledges that “For now, consumers have to fend for themselves in a thicket of scientific information—and make their own decisions about risks.” Apparently, people are happy to do so; the site averages 50-500 reports each day. But the trend to gain access to genetic data isn’t merely coming from “consumers” curious about their own data; it’s also coming from researchers and companies looking to greatly expand their databases to find statistically relevant genetic variants.
Many trait-affecting alleles can only be identified by analyzing huge amounts of data, because each one has a tiny effect. For instance, some 697 variants have been identified that are linked to height, but they are only thought to represent an estimated "16% of the genetic contributors to height.” Other researchers are trying to find genes affecting intelligence (one-twentieth the influence found with height), as well as rare mutations leading to or preventing diseases (hopefully to fare better.)
For example, the Haplotype Reference Consortium was unveiled in San Diego last week at the annual meeting of the American Society of Human Genetics. The consortium includes data collected by 23 other research collaborations and has identified 50 million genetic variants in two years.
While anyone can make use of their haplotype reference panel to expand upon their own data, the Exome Aggregation Consortium, unveiled on the same day, goes even further. This resource has made the entire exome sequencing data of 61,486 unrelated individuals, from “a variety of large-scale sequencing projects,” available to anyone “for the benefit of the wider biomedical community.”
Harvard biologist and prolific blogger Daniel MacArthur’s tweet about the announcement received over 100 “retweets” and was “favorited” nearly as many times. In the comments, people referred to the consortium as a “beautiful resource” that is “simply a game changer.”
Another effort, the Personal Genome Project (PGP) has been leading the charge to develop an open source database of genetic information for years, though their model is on the far end of the spectrum. Every participant not only volunteers their genetic data to the entire world, but their date of birth, gender, weight, height, blood type, race, list of health conditions, medications, allergies, zip code, other family members enrolled, answers to surveys, and even whether they can carry a tune. The fact that one’s full name is omitted is really only a formality, since anyone who wanted to know could easily find it out.
Another critical player in this trend is the Global Alliance. In just over a year, the alliance has expanded to include more than 170 organizational members in a “public-private partnership” representing over 25 nations. Their stated goal is to “unlock the great potential of genomic date,” by sharing all of their data and making “comparisons across millions of human genome sequences.”
Importantly, the trend to “free the data” is a significant antidote to Myriad’s “trade secrets,” but huge challenges remain.
The Personal Genome Project does a pretty good job of outlining the risks involved with sharing your genetic data with the world in its consent form. These include the acknowledgement that you are foregoing privacy, and the acceptance that this means your data could be used as a barrier for you or your family to obtain employment, insurance or financial services; to implicate you or your family in criminal activity; or even to make synthetic DNA based on your genome and plant it at a crime scene to frame you or your family.
But while those who send their sequence to the PGP explicitly consent to these risks, the merging of research databases presents a critically different reality. According to New York Times writer Gina Kolata, “There are no common procedures for assuring that patients consent to sharing their information.” The initiatives have simply moved forward anyway. While some people are pleased to share all of their personal and health information, obviously not everyone is privileged enough to afford that luxury.
Furthermore, with all the talk about “the greater good,” it can be easy to overlook the fact that this information is poised to become really big business. When all of these noble efforts to promote open-access lead to the creation of drugs, tests, and treatments – these findings will be patented, and the wealth that flows from them is unlikely to be quite so “open.”
Previously on Biopolitical Times:
What Good is a Scientific Meeting If You Dismiss the Science?
Posted by Jessica Cussins on October 29th, 2014
I want to be wrong about this.
Based on the evidence hearing held by the UK Parliament’s Science and Technology Committee last week, it is apparent that there is ample enthusiasm among many in Parliament for changing the UK law against human germline modification to allow what’s called “mitochondrial donation” into fertility clinics. The technique would combine genetic material from two women and one man into a single embryo.
Perhaps naively, I am still shocked by the hubris of some proponents of this technique. I really thought that mounting evidence of the risks to resulting children would encourage more people to question the advisability of this path.
But if the upcoming Parliamentary vote isn’t informed by a more realistic approach, it seems likely that women will be offered this technique by their fertility specialists as early as next year, making the UK the only nation in the world to explicitly allow a form of human inheritable genetic modification. Importantly, this would not be attempted as a closely controlled clinical trial, but in the open market of the fertility industry (with guidance from the HFEA, but no required follow-up).
I sincerely hope that any children born via this technique do not have to pay the price for our desires and curiosity. To reiterate, I really want to be wrong about this. But unlike many at this “evidence hearing,” I cannot so easily dismiss the evidence.
Dr. Edward Morrow, an evolutionary biologist at the University of Sussex, was the sole panelist out of nine to raise a single concern about the state of the science. Dr. Morrow is hardly alone in his concerns; numerous scientists, fertility specialists (pg. 36), and public health advocates have questioned the safety and efficacy of these techniques. But Morrow’s fellow panelists were remarkably unmoved.
Every concern that was raised – either from Morrow or as a question from others in the room – was dismissed as a “theoretical concern.” This worked rhetorically to marginalize those urging caution, and to make the proponents the keepers of the “practical reality” of the matter. But the possible benefits of this technique are no less theoretical than the possible risks.
In fact, if you stack the evidence side by side, the chance that “mitochondrial donation” will actually lead to a healthy child seems like the greater leap of imagination.
Since the hearing at which he was effectively sidelined, Morrow has taken the trouble to enumerate some of the evidence for us. He has compiled numerous papers that highlight problems that can occur from mito-nuclear mismatch here. He has also provided a link to a new meta-analysis in the Journal of Evolutionary Biology that reviews 66 publications showing evidence of significant effects on a variety of traits from the interaction of the nucleus and the cytoplasm (which includes the mitochondria). What this all suggests is that if even a single one of the complex interactions that occur continuously between the nucleus and mitochondria are disrupted by “mitochondrial donation,” it could lead to a range of adverse outcomes in a resulting child.
At the hearing, Morrow’s claims were dismissed as being irrelevant to humans because they took place in inbred animal tests. But as Morrow pointed out, that is only the case in one of the studies reported above. Furthermore, there is all of the following additional evidence of possible health risks for resulting children, though they got no real attention at the meeting:
- When pronuclear transfer was attempted in macaques, researchers couldn’t get a single embryo to implant; moreover, human embryos have been shown to be more sensitive to manipulations than macaque embryos
- Even a tiny amount of carryover mutated mitochondria can lead to disease if preferentially replicated
- Epigenetic harm can be caused by the removal and reinsertion of a nucleus from one egg or embryo into another
- The reagents used could pose risks of toxicity to any resulting child
In addition to dismissing all this evidence, proponents relied on another move: they repeatedly downplayed the novelty of what is at stake.
Doug Turnbull, Director of the Wellcome Trust Centre for Mitochondrial Research, said that mismatches between nucleus and mitochondria can be compared to what happens naturally after multiple generations of not breeding with our cousins. Similarly, he insisted that the fact that there is no greater rate of disease among mixed-race babies tells us that this technique will be safe.
This kind of argument often pops up when new technologies are being promoted… Don’t worry! We’ve been doing (basically) this for forever! But at least in this case, the reassurance just isn’t based in reality. There is obviously a desire to placate a nervous public, but mixing DNA from three people into a single embryo is not the same as having a child with someone from a different ethnicity than you, and frankly, the notion that it could be is insensitive and insulting.
The patronizing effort to appease an “irrational,” “fearful” public extended to the HFEA’s Orwellian redefinition of genetic modification to specifically exclude mitochondrial manipulation techniques. The growing body of evidence that mitochondria impact traits means that despite the insistence of UK Chief Medical Officer Dame Sally Davies, this re-definition is neither “based on science” nor “reasonable.” Morrow has a great post on this point here.
One participant at last week’s hearing asked about the fact that the UK would be going against international law if it moves ahead with this, pointing to international treaties stating that germline modification is incompatible with human dignity. Conservative MP Jane Ellison’s response avoided the question altogether. Rather than admitting to any concern about the UK becoming an outlier, she stressed that she is “extremely proud” that Britain is a “pathfinder” and “innovator” in this respect, and happily referred multiple times to the country’s “well-respected regulatory regime.”
The effort to change UK law in order to permit this biologically extreme procedure has been in the works for more than six years. There have certainly been a lot of documents, meetings and consultations. But I can’t help but wonder the same thing as Morrow:
Advances in genomic medicine are thrilling. I look forward to improved gene therapy treatments for consenting individuals who are currently suffering from diseases. But the deliberate creation of a new human being through an experimental technique that puts the most fundamental mechanisms of human biology at jeopardy is an entirely different calculus. Who will be responsible if this doesn’t work out?
Previously on Biopolitical Times:
Posted in Assisted Reproduction
, Biopolitics, Parties & Pundits
, Biotech & Pharma
, Egg Retrieval
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, Inheritable Genetic Modification
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Why We Should Teach the History of Eugenics
Posted by Jonathan Chernoguz on October 28th, 2014
|Source: Miles Cole|
This month, New York University and University College London have both launched initiatives to focus on the history of eugenics. Students and faculty at UCL hosted an event to encourage their institution to face up to its complicity in constructing unjust racial hierarchy through its support of Francis Galton’s research on eugenics. At NYU, a new exhibit, “Haunted Files: The Eugenics Record Office,” opened at the university’s Asian/Pacific/American Institute.
At both universities, these initiatives acknowledge that advances in modern genetic technologies make education about the history of eugenics increasingly important.
Galton’s legacy at UCL is extensive. It began 110 years ago this month, when he contributed funds to establish a position there for a “research fellow” in “National Eugenics,” which he defined as “the study of the agencies under social control that may improve or impair the racial qualities of future generations either physically or mentally.”
The NYU exhibit brings to life the physical offices and paper archives of Cold Spring Harbor Laboratory on Long Island, the center of the eugenics movement in the United States between 1910 and 1939. According to The New York Times, the exhibit’s curators relied heavily on Cold Spring Harbor’s online Image Archive on the American Eugenics Movement:
David Micklos, executive director of the laboratory’s DNA Learning Center, applied for a government grant to scan files from the office and display them in an online archive, which opened in 2000. “It was a hidden part of American scientific history — people didn’t like to talk about it,” said Mr. Micklos, who added that he was inspired by ethical concerns surrounding the Human Genome Project.
Other educational projects have also aimed to bring to light the history of twentieth-century eugenics. An ambitious online effort called Living Archives on Eugenics in Western Canada, “directly engages communities in developing accessible resources to bring to light the history of eugenics in Canada.” Two public events have been co-organized by the Center for Genetics and Society – Future Past: Disability, Eugenics, and Brave New Worlds in 2013 and Eugenics in California: A Legacy of the Past? in 2012. The motivations behind these efforts included concerns about misuses of new and emerging genetic technologies.
Many educational institutions still avoid discussing the history of eugenics, and many are reluctant to confront their own complicity in the abuses it facilitated. But studying eugenics in the twentieth century is important not just as a matter of learning history, but as part of what we need to know in order to thoughtfully consider the responsible uses of genetic technologies today.
How Should the U.S. Regulate Genetic Testing?
Posted by Jessica Cussins on October 16th, 2014
Stanford Law School’s Center for Law and the Biosciences held a conference Monday to tackle the increasingly important question, ‘How Should the U.S. Regulate Genetic Testing?’
I attended the conference along with some hundred others to hear experts address the question from various perspectives: government, professional, payor, industry, and academic. Notably, social and ethical perspectives were not explicitly included, and only inched in at the peripheries.
Nonetheless, the conference was fascinating and incredibly informative. The biggest take-away of the day was that better regulation of genetic testing is certainly needed, but that it is a hugely complicated problem, from every perspective.
Center Director Hank Greely asserted that population-wide, next-generation sequencing will be the future and asked how we can maximize the benefits of this coming sea change while minimizing the harms. This may be obvious, but it’s actually critical, since in some cases people are receiving life-changing information of relevance to the whole family from these tests.
The timing of the conference couldn’t have been better, since the FDA just released its draft guidance on laboratory developed tests (LDTs) for comment last week, and will be holding a webinar October 23 to address questions. While not all genetic tests are LDTs, an awful lot are, and the FDA has good reason to cast light on this opaque world:
The FDA has identified problems with several high-risk LDTs including: claims that are not adequately supported with evidence; lack of appropriate controls yielding erroneous results; and falsification of data. The FDA is concerned that people could initiate unnecessary treatment or delay or forego treatment altogether for a health condition, which could result in illness or death.
Concerns about genetic tests are often described as three-fold: do they provide analytical validity, clinical validity, and clinical utility (or patient validity, as Greely put it)? In other words, do genetic tests accurately report the sequences they say they’re analyzing? Do they actually correspond to a given health condition? Is there any clinical benefit of knowing this information? And what should we do with the information we get? The current lack of over-arching regulation, oversight, or independent review of genetic tests makes it nearly impossible for anyone to answer even the first of these questions, let alone the others.
There was broad agreement among the speakers that the interests of patients (or “patients/consumers” in the case of 23andMe) need to come first. Multiple people noted inadequacies or irregularities among CLIA certified labs and tests and welcomed more comprehensive regulation. For example, Megan Grove, a genetic counselor at Stanford, pointed out that genetic counseling does not scale up to genomic counseling and insisted that counselors need more guidance on how to communicate an onslaught of (quickly changing) information to their patients.
Kathy Hudson from the NIH argued that we need a “nimble and risk-based regulatory system.” She pointed to President Obama’s recent remark that “we’re going to have to change how we regulate some of this stuff,” and advised us to “watch this space.” Pamela Bradley from the FDA echoed this sentiment, insisting that we need a framework of oversight in the interest of public health in order to realize the promise of personalized medicine. She stressed the FDA’s desire to hear from the public on the agency’s new guidance, as well as its desire to improve what can be a dangerous marketplace, while continuing to encourage innovation.
A couple speakers from the “professional perspective” were vocal in their disagreement. They strongly rejected “dual regulation” by the FDA and CMS (Centers for Medicare & Medicaid Services, which administer CLIA), asserting that if the agencies don’t communicate well enough with each other they will end up caught in the middle, with increased burdens and costs for their labs.
However, John Richardson of the National Society for Genetic Counselors pointed out that he is seeing 30% of tests being ordered inappropriately and that too often there are pressures coming from heavy marketing to primary care physicians, at the expense of the best interests of patients.
The sole voice from the “payor perspective,” Wade Aubry, formerly of the Philip R. Lee Institute for Health Policy Studies, said he believes payors will be happy with the FDA’s efforts because they want to see more evidence of validity so they know they're only paying for tests that are clinically useful.
The “industry perspective” was remarkably diverse. Mya Thomae of Illumina was happy with the FDA’s willingness to be flexible with her company in allowing their sequencer to gain fast approval, and felt that CLIA regulations aren’t “cutting it” because not all labs are compliant. Ethan Knowlden of Complete Genomics (recently acquired by BGI) had a very BGI-esque dream of the “ultimate genetic test,” which could be compared to a vast whole-genome sequencing database. Jill Hagenkord of 23andMe smiled a lot and insisted multiple times that 23andMe is “working with the FDA to move forward.” Regarding the new FDA regulations, she said she agreed with the agency’s concerns, but wanted to see them balanced against the costs to innovation, access, and cost.
Ken Song of Ariosa was impressively honest, stating that his new company has not done everything right and that oversight is definitely needed, though he was concerned about whether it could keep pace with the evolution of testing processes. Importantly, he pushed back against the notion that more is always better, pointing out that without a high degree of accuracy and complex counseling, this notion can be dangerous in the realm of genetic testing. John West of Personalis, whose whole business model is based upon providing accurate genomic medical information, went so far as to suggest further regulations from the FDA to monitor the quality of tests instead of merely whether they do what they say they will.
From the “academic perspective,” Stanford Law’s Jacob Sherkow argued that patents are yet another kind of regulatory tool. He shared his concern that they will increase costs and decrease competition, noting that there are countless patents right now blocking ways of looking at and manipulating genetic data, and turning valuable information into “trade secrets.” Bob Cook-Deegan of Duke University also talked about gene patent problems, particularly of the Myriad variety, which have really impeded information flow at the expense of researchers and patients. He suggested three possible solutions to this problem: That payors insist they’ll only pay for tests that have independently reviewable data, that consumers demand access to their own data, or, that we build a system that enables this flow of information from the outset. Cook-Deegan made a strong case for moving away from the language of ownership of genetic data so that we can work towards improved access, transparent analysis, and collaborative science.
After a healthfully heated concluding discussion among all speakers about the appropriate degree and kind of regulation, Greely joked that he wasn’t sure whether the conference had managed to really get a handle on its central question, but that he felt gratified to see everyone wanting to “do the right thing.” I’m not sure I would be quite as generous, since notions of the “good” or “ethical” played such a supporting role to the “practical” and "innovative" throughout the day. But I wholeheartedly agree that there is a real need here, and found it heartening and invigorating to see so many intelligent people, from so many perspectives, working to address it.