Fast Forward-Pause-Stop: The 3-Speed Human Germline Debate
Posted by Lisa C. Ikemoto, Biopolitical Times guest contributor on September 10th, 2015
Researchers borrowed a tool from the bacterial immune system toolkit, and developed a genetic modification technique called CRISPR/cas9. CRISPR’s rapid uptake by biologists in nearly every field demonstrates the technology’s utility and potential. Its use for deliberate species modification, and human germline modification in particular, has spurred vociferous debate.
The debate has three buttons – Stop, Pause, and Fast Forward. Or so it seems.
Steven Pinker grabbed headlines and staked out the Fast Forward position with his Boston Globe op-ed. His central point – that taking dignity, social justice, health and safety into account will cost millions of lives – expresses technological optimism at its extreme. His central pitch, “get out of the way,” targets those who would Pause or Stop CRISPR’s use to address those concerns. “Get out the way” functions like recent accusations of “scientific authoritarianism.”
Big Tobacco called researchers and public health experts “Nicotine Nazis,” in its campaign to fight tobacco regulation. More recently, opponents of environmental protection measures have accused climate scientists who support such measures of scientific authoritarianism. Here, Pinker’s “Get out of the way” in effect charges those who support moratoria or regulation of CRISPR with being human, rather than scientific.
There is nothing inherently wrong with technological optimism. Nor is technological optimism incompatible with principled caution. A 2012 study by Hochschild, Crabill & Sen shows that a majority of the 4,300 Americans they surveyed holds coherent views that pair technological optimism and support for regulation of genomic science. Hyper-optimism paired with scientific authoritarianism, on the other hand, makes any other position seem oppositional, and creates both a false sense of polarization and a false divide between science and human values.
Leading scientists and ethicists, including David Baltimore, Jennifer Doudna, Hank Greely, Rudolf Jaenisch, Paul Knoepfler, and most recently, The Hinxton Group, have called for hitting the Pause button. Others would hit Stop. Eric Lander, and Edward Lanphier, for example, have advocated prohibiting human germline modification altogether. The proposed moratoria vary considerably. Most, if not all, are moderate and take seriously risks to human health, life, and status arising from efforts to implement germline genetic changes.
Most are also narrowly tailored, subjecting only human germline modification to scrutiny. The combination of the Fast Forwards’ efforts to characterize moratoria as extreme, and the Pause and Stop supporters’ sole focus on modifying the human germline, effectively edits out other pressing issues that genetic modification techniques like CRISPR raise.
Jasanoff, Hurlbut and Saha have pointed out that the 1973 moratorium on recombinant DNA research and the subsequent meeting as Asilomar bracketed off “three serious concerns: environmental release of engineered organisms; biosecurity; and ethical and social aspects of human genetic engineering.” The proposed moratoria may have the same effect.
Social stratification by wealth, race, and disability patterns technology use; technology does not by its very existence erase stratification. That fact alone should temper our optimism. Yet the Fast Forwards tend to overlook history and social reality in projecting the effects of new technology.
Only a few observers, including Hank Greely, have raised concerns about the environmental consequences of using CRISPR and a technique known as “gene drive” to re-engineer organisms. Some scientists have also pointed to risk that releasing modified mosquitoes may have unintended consequences, as have importation of nonindigenous plants and animals.
The CRISPR debate is just getting started. The issue of genetic modification is not new. Nor is human germline modification a stand-alone issue. While I support a moratorium and rigorous discussion, we need more than an ad hoc response. It is time to develop a participatory governance approach to the many issues that technologies like CRISPR raise.
Lisa C. Ikemoto is a fellow at the Center for Genetics and Society. She is Professor at the University of California, Davis School of Law. She teaches bioethics, health care law, public health law, reproductive rights, law & policy, and marital property. Her research areas include reproductive and genetic technology uses, health care disparities, and public health law. Her recent work addresses reproductive tourism, the ways in which human gamete use links the fertility and biotechnology industries, and the privatizing effects of informed consent. She will interview George Annas in the upcoming installment of the Center for Genetics and Society's Talking Biopolitics series.
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Composite image via Pixabay and Flickr/Shaury Nash
"Moonshot Medicine": Putative Precision vs. Messy Genomes
Posted by Gina Maranto, Biopolitical Times guest contributor on September 9th, 2015
Like so many medical terms, “precision medicine” is a combination of both wishful thinking and obfuscation. In this case, it also carries a somewhat unsettling suggestion: if medicine has not up until now been precise, then what has it been?
Precision medicine started being touted in the specialized journals in the late aughts as part of a “new era” being ushered in by coordinated and integrated care, fiscal transparency, and patient-centered practice. It was one of a suite of approaches that promised to bring costs down while improving outcomes. The idea was that by looking at drugs and other therapies according to how they succeeded (or didn’t) in people sharing particular gene variations and similar physical traits, physicians could make more intelligent choices patient-by-patient, selecting the treatment with a greater chance of working.
Big Pharma saw promise in the approach and made strategic partnerships (Pfizer and Medco Health Solutions in 2011, for example, and Novartis and Genoptix that same year); startups and researchers rushed to secure patents; while medical groups such as the American Society of Clinical Oncology devoted sessions at their annual conferences to precision medicine’s potential benefits now that speedier gene sequencing was bringing costs down sufficiently to make it possible to contemplate tailor-making cancer drugs.
At the same time, some in the burgeoning field saw major structural hurdles. For example, most work on biomarkers—the substances or physical signs that a disease is present or a drug is working—is done in university and government research labs, and it takes time for any given biomarker to be proven accurate, as well as to be adopted by physicians in the clinic. Finding biomarkers that not only show whether a drug is present but whether it is affecting the target cells to reduce disease presented a further challenge.
Soon enough, though, proponents were touting precision medicine in scientific meetings as “revolutionizing oncology,” and medical programs launched courses in whole genome sequencing. Dean Dennis Charney of Mt. Sinai School of Medicine gave the rationale for their decision to start offering an elective course “Practical Analysis of Your Personal Genome” in 2012, "For precision medicine to become a routine in the medical clinic, we need to train the next great generation of physicians to harness sequencing-driven medical genetics."
Genome sequencing, though, wasn’t enough, argued some. That same year, Peter Taylor, director of the Victorian Life Sciences Computational Institute at the University of Melbourne, wrote in The Australian,
Medicine today is as much about statistical literacy as it is about bedside manner or learning about anatomy. As the world heads towards the field of personalised, or, as I prefer to put it, precision, medicine where treatments are designed for individual patients based on their genetics, cancer type and family history, the next generation of doctors need to know about statistics, errors and measurements so they can understand how the almost daily announcements of breakthroughs, recalls of medicines and clinical trial results impact on their patients.
In addition to advocating a renaming of the field by replacing the previously used word “personalized” with “precision,” and championing the value of statistics for future physicians, Taylor delivered a zinging backhand indictment of the med school status quo: “These tools they will be using will be produced by mathematicians and bio-statisticians, not just the anatomists of old.”
Precision medicine made the leap out of medical circles and into the mainstream around this time. Google Trends shows the term emerging onto the interwebs in March 2012 with 11 news headlines and then blipping along at about the same level until February 2015, when it leaps to a new plateau of about 100 in the wake of President Obama’s announcement of a $215 million precision medicine initiative in his State of the Union address.
Critics offered a raft of objections to the announcement. Even those in favor of increased use of genetic testing predicted it would be years before there were enough sufficiently trained physicians and genetic counselors to ensure that patients received accurate readings; until then, the complexities of genomics would likely result in an unsettlingly large number of faulty diagnoses. Others said it would just bring about more problems related to genetic privacy.
Writing in The New York Times, Mayo Clinic physician Michael Joyner leveled a much more sweeping critique of the entire precision medicine effort, one that can’t be answered better privacy protections or more doctors with training in genetics. Joyner argued that Obama's plan, which he dubbed "moonshot medicine" is unlikely to prevent disease and a misdirection of effort. He cites the “unexpected findings” emerging from the Human Genome Project, including the growing scientific consensus that genetic variants don't account for most common complex diseases, and the “missing heritability” problem. His advice:
We would be better off directing more resources to understanding what it takes to solve messy problems about how humans behave as individuals and in groups. Ultimately, we almost certainly have more control over how much we exercise, eat, drink and smoke than we do over our genomes.
As a colleague said to me recently, precision medicine is also a non-starter when it comes to social justice: in the U.S., dollars could be better spent on providing primary and preventive care to more people who, even with the Affordable Care Act still cannot access medical treatment on a regular basis.
But the hype, with its hopeful but unlikely message, is so much easier to sell than the not-terribly encouraging reality. And in research and medical circles, the funding being directed at gene-based health care is a powerful lubricant of enthusiasm. So the megaphones will likely be blaring the precision medicine tune for some time to come.
Gina Maranto is 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 in Discover, The Atlantic Monthly, Scientific American, The New York Times, and other publications. She is the author of Quest for Perfection: The Drive to Breed Better Human Beings.
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The Moral Imperative for Psychologists
Posted by George Annas, Biopolitical Times guest contributor on September 9th, 2015
Steven Pinker was one of the first to have his genome sequenced, and he wrote a long essay about the experience in the New York Times magazine in 2009. He sensibly concluded that your genome could tell you some things, but that there were more direct ways to find out about yourself. In his words: “If you really want to know yourself, consider the suggestion of François La Rochefoucauld: ‘Our enemies’ opinion of us comes closer to the truth than our own.” Pinker seems to have gained a whole new group of “enemies” with his recent Boston Globe op-ed calling on ethicists to leave scientists alone to pursue their research with new gene editing technologies. But it’s at least possible, if not entirely plausible, that Pinker actually agrees with his critics that genetic editing requires regulatory and bioethics oversight, and that he believes that such regulation needs more, not less, attention.
Pinker understands the power of language to shape beliefs. In his 2009 book How the Mind Works, he noted that “in everyday life” we will need language (and humor) to “undermine the pretensions of countless blowhards, blusterers, bullies, gasbags, goody-goodies, holier-than-thous, hotshots, know-it-alls, and prima donnas.” I’ll let him decide which one he most closely represents when he “claims authority on a pretext of beneficence and competence” (a strategy he says he despises in How the Mind Works).
In his recent op-ed, Pinker is, of course, beneficent, promising that science will slay premature death and disability. His promise, however, comes at a high price: we must ignore human dignity and social justice.
But if morals are not to matter to scientists, why should they matter to bioethicists? How can Pinker suggest as a matter of importance that bioethics should “get out of the way” of research because this is (or should be) “the primary moral goal” of today’s bioethics? Maybe this is because he has always mistrusted morality as being too dependent on philosophy (rather than science?). As he argued in How the Mind Works,
Maybe philosophical problems are hard… because the mind of Homo sapiens lacks the cognitive equipment to solve them. We are organisms, not angels, and our minds are organs, not pipelines to the truth.
The argument seems to be, if psychologists think that the human mind cannot solve a problem, humans should not waste their time trying to deal with it.
The ability to ignore human dignity was on display when Pinker’s own profession of psychology, through the American Psychology Association (APA), decided post-9/11 that it was “ethical” for psychologists to ignore human rights, and to participate in torture at Guantanamo Bay and at the CIA’s black sites. Of course they thought they were being beneficent and saving lives. As the playwright Arthur Miller observed, “to perceive somehow our own complicity with evil is a horror not to be borne.” Only this summer did the APA unequivocally denounce its pro-torture “ethics” and adopt a human rights framework for the profession. Psychiatrists’ organizations, in contrast, consistently refused to permit their members to join in the torture, even in the ticking-time-bomb scenario where thousands of lives could theoretically be saved.
It is worth asking whether this is because psychiatrists are physicians with a “do no harm” moral tradition; whereas psychologists, who are non-physicians, have no such tradition. Similarly, most genetic researchers are not physicians, and there is no equivalent of the Hippocratic “do no harm” morality in science.
Since Pinker knows all this, it is worth at least considering his essay as a cry for help from bioethics to aid in the rehabilitation of his own profession, and to prevent the perversion of science in general. This is not as far-fetched as it seems since Pinker praises bioethics for setting up safeguards “for the safety and informed consent of patients and research subjects.” He has to be able to see this contradiction which can be resolved only with more, not less, attention to ethics.
So here’s the real question Pinker raises: should there be a scientific exception to our laws against committing crimes against humanity? This is (or should be) an easy question regarding genocide, murder, torture, or slavery. But mostly what is at stake in the new gene editing techniques is what I have called a “type 2” crime against humanity: altering humans in such a way as to either irrevocably transform the species itself or to put the human species at risk of extinction (e.g. through a novel pathogen, a risk at the core of “gain of function”—ferret flu type—research).
Put another way, if researchers really, really want to do good, should society simply let them decide among themselves whether the risks to humanity are acceptable? Can we (morally?) say to our scientists, if you can give us all an extra decade of disease-free life (plausible) by killing all the members of a tribe that lives in a remote jungle of Brazil in some necessary experiment (implausible to be sure), you have our blessings? To answer this question in the affirmative—it seems to me—means we have already given up the ethical values that make our species worth preserving. I think the (new) American Psychology Association would agree, and perhaps Steven Pinker would too.
George Annas is Warren Distinguished Professor and Director of the Center of Health Law, Ethics & Human Rights at Boston University School of Public Health, and Professor in the Boston University School of Medicine and School of Law. He is a member of the Institute of Medicine, a fellow of the American Association for the Advancement of Science, and vice-chair of the American Bar Association’s Committee on Health Rights and Bioethics (Civil Rights and Social Justice Section). His most recent book Genomic Messages: How the Evolving Science of Genetics Affects our Health, Families, and Future (with Sherman Elias) will be featured in an upcoming Talking Biopolitics conversation.
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Biotech Imagination: Whose Future is this?
Posted by Jessica Cussins on September 8th, 2015
PLOS Biology, a peer-reviewed open-access journal, recently asked “eight leaders” for their predictions about the next ten years in genetics and genomics. Many responses acknowledge that this task may be impossible; nonetheless, the answers do not waver: “All are optimistic and predict enormous positive impact.”
Is this insider enthusiasm warranted? Should the rest of us be so optimistic?
One thing we can count on is uncertainty – both in the biological systems and with regard to the power of emerging technologies. Contributors Laura F. Landweber of Princeton University and Ian Dunham of European Molecular Biology Laboratory and Wellcome Trust Genome Campus each underscore how much more we have to learn of vast and complex “genome architectures.” They highlight how new findings from more sophisticated whole genome sequencing and data mining are “eroding traditional notions of a gene,” moving us ever further from the “classical reductionist examples from early molecular biology and the idea that molecule X ‘does’ function Y.”
Aside from such concessions of uncertainty, the overall tenor of the commentaries is near-utopian.
None of the contributors mention even widely acknowledged challenges of the genetic future such as data overload, let alone the potential for much more difficult social and legal problems such as new modes of surveillance or lawsuits due to “gene editing” gone wrong.
Meanwhile, examples of the boons of genetic advances range from the practical to the conceptual. Routine genetic sequencing of tumors to provide more precise cancer treatment is mentioned. There is also a prediction that we will soon have precise, personal “miniaturized genomic monitoring” devices capable of reading our bodies for signs of sickness and disease, causing the whole of healthcare to shift from primarily reactive to primarily proactive.
In addition to revolutionary new products on the personalized healthcare market, predictions meander briefly into social implications, maintaining an oddly optimistic gaze. Bartha Knoppers, director of the Centre of Genomics and Policy at McGill University, suggests that genetic information could move us away from today’s contentious human classifications such as gender and ability towards “destigmatized” “subpopulations of risk or resistance” revealed by genomic profiles. It’s an interesting idea, but the trend so far has moved us in the opposite direction: toward genetic information being used to underscore the “biological reality” of human difference.
It seems quite likely that we will have to continue struggling to avoid reifying social categories like gender, race, and ability. In addition, we may have to fight discrimination at newly imagined sites of difference – say for example, against carriers of a particular gene mutation who can suddenly no longer purchase life, disability, or even health insurance.
Unwittingly straining against Knoppers’ colorblind destigmatization prediction, BGI-Shenzen director Huanming Yang predicts that we will sequence “most, if not all, of the species identified on earth” as well as “most, if not all, ethnic groups.” He asserts that this knowledge will help treat diseases and restrict the births of those deemed genetically “abnormal,” and that we will manage to simultaneously honor individual privacy, intellectual property rights, and free access to genome sequencing data because “the future is brilliant and is now.”
But whose future is this?
Missing from these short exploratory essays is discussion of the forces that will be shaping this biotechnological future. There is no mention of societal mechanisms such as regulation or democratic participation. Nor is there any mention of the impact of money, global collaborations among biotech giants, or competing national agendas. This notable absence of actors supports the insidious storyline that biotechnology is an unguided force leading inevitably to human progress; a kind of cellular manifestation of destiny, unstoppable and un-shapeable in its trajectory.
In this view, biotechnology itself is protagonist: an unrelenting [bio]power that asserts itself on all forms of life. The people, the structures, and the money that do in fact guide the specific research goals and ultimate direction of biotechnology are made invisible.
The question posed by PLOS – “But how will society view such developments?” –positions us as passive observers and receivers of exciting advances coming our way. Importantly, the phrasing of the question suggests that while society may view developments in a negative way, the developments themselves could not actually be negative. In other words, it asserts the judgment that people could only feasibly be concerned about the future of biotechnology if they misunderstand. After all, the “leaders” are all in agreement: Utopia is around the (research funding) bend.
It is only this telling of the biotechnological future that makes it possible for one to consider the most ethical option for bioethicists and concerned bystanders to “get out of the way.”
To meaningfully consider the future requires imagination, but the story of biotechnology as heroic protagonist is a fairytale. We must make visible the monetary, social, and political forces determining the direction of genetics and genomics. If we fail to enrich the stories we tell with the context of our times, we risk becoming a footnote to our own future.
Jessica Cussins is a consultant and former Project Associate at the Center for Genetics and Society, currently earning a Master's in Public Policy from the Harvard Kennedy School. She is a regular blogger at Biopolitical Times, Psychology Today, and the Huffington Post.
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