Tag Archives: genetic counseling

23andMe, FDA, and the history of hype

Yesterday I and seemingly everyone else interested in genomes posted about the FDA letter ordering the genome diagnostics company 23andMe to stop marketing their saliva test. FDA treats the test as a “medical device, because “it is intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or is intended to affect the structure or function of the body.” The company first issued a bland, terse statement acknowledging the letter and then company president Anne Wojcicki signed a short post affirming the company’s commitment to providing reliable data, promising cooperation with FDA, and reasserting her faith that “genetic information can lead to better decisions and healthier lives.” (I say she “signed” it because of course we have no way of knowing whether she composed it and she’s no fool: surely the text was vetted by Legal.) In other words, the company followed up with a bland, less-terse response, carefully worded to reassure customers of the company’s ethical stance and core mission. Reactions to the FDA letter range from critics of the company singing “Hallelujah!” to defenders and happy customers are attacking FDA for denying the public the right to their own data. The 23andMe blog is abuzz and, hearteningly, a few sane souls there are trying to dispel misinformation.

I am doing history on the fly here. If journalism is the first draft of history, let’s take a moment to revise that first draft—to use the historian’s tools to clear up misconceptions and set the debate in context as best we can. The history of the present carries its own risks. My and other historians’ views on this will undoubtedly evolve, but I think it’s worth injecting historical perspective into debates such as these as soon as possible.

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We must be clear that the FDA letter does not prohibit 23andMe from selling their test. It demands they stop marketing it. The difference may not amount to much in practice—how much can you sell if you don’t market your product?—but the distinction does help clarify what is actually at stake here. FDA is not attempting to instigate a referendum on the public’s access to their own DNA information. They are challenging the promises 23andMe seems to make. This is, in short, not a dispute about access, but about hype.

The company seems to promise self-knowledge. The ad copy for 23andMe promises to tell you what your genome “says about you.” “The more you know about your DNA,” they trumpet, “the more you know about yourself.” On one level, that’s perfectly, trivially true: your genome does have a lot to do with your metabolism, body structure, how you respond to disease agents, and so forth. The problem is, we as yet know very little about how it all works. The 23andMe marketing exploits a crucial slippage in the concept of “knowledge,” which FDA correctly finds misleading. In short, the marketing implies a colloquial notion of knowledge as a fixed and true fact, while the science behind the test is anything but.

Historians and other scholars of science have thought a lot about the concept of scientific knowledge. In 1934, Ludwik Fleck wrote about the “genesis and development of a scientific fact,” namely the Wasserman test for syphilis. It is a pioneering classic in a now-huge (and still growing) literature on how scientific facts are created. Science claims to gather facts about nature and integrate them into explanations of natural mechanisms. A moment’s reflection reveals that very few scientific facts last forever. Most, perhaps all, undergo revision and many are discarded, overthrown, or reversed. They are historical things, not universal truths. A surprisingly small amount of what I learned in science courses 20 and 30 years ago is still true. As that great philosopher of science John McPhee wrote, “science erases what was previously true” (Oranges, p. 75). Because scientists search for universal, timeless mechanisms, they easily slip into language suggesting that they discover universal, timeless truth. But there is uncertainty, contingency, malleability built into every scientific fact.

This goes double for genome information. The 23andMe product, like every genome test, provides probabilities of risk, not mechanisms. Probabilities are messy and hard to understand. They carry an almost irresistible tendency to be converted into hard facts. If you flip a coin 9 times and it comes up heads every time, you expect the next flip to come up tails. And if you get heads 49 times in a row, the next one has got to be tails, right? Even if you know intellectually that the odds are still 50:50, just like on every previous flip. You can know you have a particular gene variant, but in most cases, neither you nor anyone else knows exactly what that means. Despite the language of probability that dots the 23andMe literature, their overall message—and the one clearly picked up by many of their clientele—is one of knowledge in the colloquial sense. And that is oversell.

Human genetics has always been characterized by overstatement and hype. In the early 1900s, the rediscovery of Mendel’s laws persuaded many that they now understood how heredity works. Although every scientist acknowledged there was still much to learn, prominent students of human heredity believed they knew enough to begin eliminating human defects through marriage and sterilization laws. We now view such eugenic legislation as almost unbelievably naive. Combine that naivete with race, gender, and class prejudice and you obtain a tragically cruel and oppressive eugenics movement that resulted in the coerced sterilization of many thousands, in the US and abroad—including, of course, the Nazi sterilization law of 1933, based on the American “model sterilization law,” which culminated not only in racist forced sterilization but euthanasia.

Human-genetic hype hardly ended with the eugenics movement. In 1960s, as human diseases were finally being mapped to chromosomes, it seemed transparent that if a chromosomal error that produces an individual with an XXY constitution feminizes that individual (which it does), then an extra Y chromosome (XYY) must masculinize. Such “super-males,” data seemed to suggest, were not only taller and hairier than average, but also more aggressive and violent. It was, for a while, a fact that XYY males were prone to violent crime.

The molecular revolution in genetics produced even more hype. When recombinant DNA and gene cloning techniques made it possible to try replacing or augmenting disease genes with healthy ones, DNA cowboys hyped gene therapy far beyond existing knowledge, promising the end of genetic disease. The 1995 Orkin-Motulsky report acknowledged the promise of gene therapy but noted,

Overselling of the results of laboratory and clinical studies by investigators and their sponsors…has led to the mistaken and widespread perception that gene therapy is further developed and more successful than it actually is.[1]

Soon after this report was published, Jesse Gelsinger died unexpectedly in a gene-therapy trial, patients in a French gene-therapy trial for adenosine deaminase (ADA) deficiency unexpectedly developed leukemia, and the gene-therapy pioneer W. French Anderson was arrested, tried, and convicted on charges of child molesting—in other words, abusing and overestimating his power over the children whose health was entrusted to him. The risks of failing to heed warnings about genetic oversell are high.

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Like gene therapy, genome profiling has great promise, but the FDA letter to 23andMe is a stern reprimand to an industry that, like gene therapy and the entire history of human genetics, blurs the line between promise and genuine results.

The current controversy over commercial genome profiling has two qualities that distinguish it as particularly serious. First, unlike previous examples of overselling human genetics, it is profit-driven. The “oversell” is more literal than it has ever been. Although 23andMe presents as a concerned company dedicated to the health of their clientele, they are also—and arguably primarily—dedicated to their stockholders. In a for-profit industry, oversell is a huge temptation and that risk needs to be made transparent to consumers.

Second, the 23andMe test is being sold directly to individuals who may not have any knowledge of genetics. The tendency to convert risks into certainty is higher than ever. The knowledge they sell is a set of probabilities, and further, those probabilities are not stable. The consumer may not—indeed probably doesn’t—appreciate how much we know, how much we don’t know, and how much we don’t even know we don’t know. The company claims to be selling knowledge but in fact they are selling uncertainty.

In a characteristically insightful and clarifying post, the geneticist (and 23andMe board member) Michael Eisen doubts whether the 23andMe test will ever meet FDA’s definition of a “medical device.” It is not an MRI machine or a Wasserman test. It’s something new. Adequate regulation of products such as the 23andMe genome profile will require rethinking of what exactly the company is marketing.

Putting this controversy in context, then, illustrates another critical risk: the risk of failing to acknowledge the uncertainty underlying the science. In some sense, the more we learn, the less we know.

 


[1] Orkin, S. H., and A. Motulsky. Report and Recommendations of the Panel to Assess the NIH Investment in Research on Gene Therapy.  Bethesda, MD: National Institutes of Health, 1995.

Is There Any Malevolence to Procreative Beneficence?

John Belmont has asked a question that deserves a separate post. This is necessarily brief and should not be mistaken for a general survey of this concept, but the concept is so general that it deserves a somewhat fuller answer than I can (or should) give in the comments. Here is John’s question:

Can you discuss Savelescu’s Procreative Beneficence in the context of these new genetic screening technologies? (Screening that then often triggers definitive diagnostic testing)
It seems normal for parents to desire healthy offspring. Is it evil or morally suspect for a couple to choose healthy offspring?

In 2001, Julian Savulescu advanced a principle he calls “procreative beneficence,” which states that “couples (or single reproducers) should select the child, of the possible children they could have, who is expected to have the best life, or at least as good a life as the others, based on the relevant, available information.” It is of that species of ethical principles called “intuitive”: on the face of it, who could argue on behalf of not providing the best possible conditions for one’s child, whether they be environmental or genetic? So no, of course it’s not evil to choose healthy offspring, so long as one is morally okay with disposing of “unfit” embryos or young fetuses. But its morality is less straightforward.

Savulescu’s idea has spawned a sizable secondary literature, especially among bioethicists, most of whom have tried various tacks to destroy his principle. A full discussion and evaluation of this literature is more than I can undertake here, but i’ll provide a starter bibliography at the bottom.

Few–including Savulescu himself–deny that PB is an element of the “new eugenics.” By this is meant an “individualized” or “liberalized” (or even “commercialized”) eugenics, rather than a state-controlled eugenics. This distinction is entirely appropriate. State-controlled eugenics is part of a specific historical context, whereas I see eugenics as a trans-historical principle (what I have more colloquially called an “impulse”). The eugenic impulse goes beyond notions of “old” or “new” eugenics: eugenics is just there, manifesting in different ways in different periods. Empirically, we appear to be driven to take control of our own evolution.

On the surface, Savulescu’s principle, like arguments in favor of “new” eugenics generally, appears not to be concerned with control over human evolution. It refers only to choices about specific individuals—a couple’s (or individual’s) choices about the genome of an embryo or fetus, it doesn’t concern the well-being of the population. However, <a href=”http://www.ncbi.nlm.nih.gov/pubmed/20047587″ target=”_blank”>Elster</a> shows that procreative beneficence is impossible to fully separate from “General Procreative Beneficence”–the idea that “couples ought to select children in view of maximizing the overall expected value in the world, not just the welfare of their future child.” Most literature advocating the new eugenics treats the individual and the population as wholly distinct, yet of course what is a population but a collection of individuals? These two principles–concern for the individual and concern for the population– are by no means mutually exclusive; indeed, the thrust of my book is that they have always coexisted. It’s naive (or cynical) to act as though one can be separated from the other.

Under this view, PB is in fact an indirect means of directing the evolution of the population. My position is that state control is not what makes a practice eugenic. What makes a reproductive practice eugenic is whether it includes a decision about the welfare of the population; whether it is subject to social (including economic) pressures. If one is “merely” choosing the “best” possible child, few of us have the luxury of ignoring racial features, for example. The “best” child is the best in a particular or anticipated environment. The literature on PB that I have read does not take this fully into account.

If the “best” environment is truly adapting, shifting, and local, then we have Darwinian conditions, in which the population is “evolving itself” with no particular end. This is morally less troubling than a Spencerian goal-directedness. I make no claim to being a moral philosopher, but as a historian, it seems morally less responsible to deny parents that freedom than to allow it. In sum, I am not persuaded by moral arguments against PB.

But I have rational arguments against it. They are two: What if it doesn’t work?; and What if it does?

What if it doesn’t work? We can tinker with genomes long before we understand them, the way one can learn a few Unix commands without fully comprehending the operating system. I worry we will make bad choices. I worry we will uncouple biological systems that have evolved together for millennia. I worry that our technology outstrips our wisdom.

What if it does? I worry that corporate control–via market pressures, advertising, and so forth–may prove even more potent than government control. I worry that PB will instantiate in our very DNA ideas of normalcy that may transcend local conditions and become general principles of human perfection. I worry that it will encourage the idea that genes are all; that we can simply “dial in” the child we want; that we will rob poorly funded social programs to pay for already amply funded research programs for the elite. Historical examples do not provide a comforting set of models for human behavior in these areas.

In short, then, it may not be “evil” to choose the genetic constitution of a child, but in doing so we are making many more choices than we are aware of.

 

Some references on procreative beneficence:

Savulescu, J. “Procreative Beneficence: Why We Should Select the Best Children.” Bioethics 15, no. 5-6 (Oct 2001): 413-26.
Savulescu, J. “In Defence of Procreative Beneficence.” J Med Ethics 33, no. 5 (May 2007): 284-8. doi:10.1136/jme.2006.018184.
Savulescu, J., and G. Kahane. “The Moral Obligation to Create Children with the Best Chance of the Best Life.” Bioethics 23 (Jun 2009): 274-90. doi:10.1111/j.1467-8519.2008.00687.x.

Herissone-Kelly, P. “Procreative Beneficence and the Prospective Parent.” J Med Ethics 32, no. 3 (Mar 2006): 166-9. doi:10.1136/jme.2005.012369.
Bennett, R. “The Fallacy of the Principle of Procreative Beneficence.” Bioethics 23, no. 5 (Jun 2009): 265-73. doi:10.1111/j.1467-8519.2008.00655.x.
Elster, J. “Procreative Beneficence: Cui Bono?”. Bioethics 25, no. 9 (Nov 2011): 482-8. doi:10.1111/j.1467-8519.2009.01794.x.
Herissone-Kelly, P. “Reasons, Rationalities, and Procreative Beneficence: Need Hayry Stand Politely by While Savulescu and Herissone-Kelly Disagree?”. Camb Q Healthc Ethics 20, no. 2 (Apr 2011): 258-67. doi:10.1017/S0963180110000903.
Bourne, H., T. Douglas, and J. Savulescu. “Procreative Beneficence and in Vitro Gametogenesis.” Monash Bioeth Rev 30, no. 2 (Sep 2012): 29-48.
Herissone-Kelly, P. “Wrongs, Preferences, and the Selection of Children: A Critique of Rebecca Bennett’s Argument against the Principle of Procreative Beneficence.” Bioethics 26, no. 8 (Oct 2012): 447-54. doi:10.1111/j.1467-8519.2010.01870.x.
Hotke, A. “The Principle of Procreative Beneficence: Old Arguments and a New Challenge.” Bioethics (Jul 29 2012). doi:10.1111/j.1467-8519.2012.01999.x.
Bennett, R. “When Intuition Is Not Enough. Why the Principle of Procreative Beneficence Must Work Much Harder to Justify Its Eugenic Vision.” Bioethics (Jul 10 2013). doi:10.1111/bioe.12044.

 

Taking counsel (Review of Stern, Telling Genes)

I just read Alexandra Stern’s fine new history of genetic counseling, Telling Genes (Johns Hopkins, 2012; $40 cloth/$25 paper/ $15 Kindle). Though Alex is my friend, I review her book here because her subject relates so closely to the themes of Genotopia. Alex and I played leapfrog around some of the same archives as we researched. Telling Genes and The Science of Human Perfection are complementary—and I mean that in the nicest possible way. With that warning of possible conflict of interest, I want to examine her history of genetic counseling with the same “critical and sympathetic” analysis (3) that she applies to the history of genetic counseling itself.

Like medical genetics, the history of genetic counseling is intimately bound to that of eugenics. And like medical geneticists, genetic counselors have been trying to shake off these eugenic associations for many years. Stern, though highly sympathetic to today’s genetic counselors, won’t let that historical firewall stand. Unflinchingly, she drives home the eugenic connections in every chapter.

One of the most contentious issues in this history is where the history begins. Almost all genetic counselors today are Master’s level professional GCs. A Whig history of genetic counseling, then, might argue that the history began in 1969, with the founding of the first Master’s degree program in genetic counseling at Sarah Lawrence College. In contrast, a radical interested in showing the continuities with the darkest side of eugenics, might argue that the history began in 1910, with the founding of the Eugenics Record Office at Cold Spring Harbor. ERO staff advised people about many of the same things—likelihood of disease, of perpetuating family traits, of a particular racial parentage—that GCs still do today.

Stern takes a middle ground, beginning the history in 1941, with the founding of three independent research and counseling institutes for medical genetics: the Heredity Clinic in Ann Arbor, MI; the Family Record Office and Department of Medical Genetics at Wake Forest, and the Dight Institute of Human Genetics, in Minneapolis. These were conceived as Eugenics Record Offices attached to medical schools; collectively, they are known as the heredity clinics. At one of them (the Dight), the term “genetic counseling” was coined, by director Sheldon Reed, in 1947. Beginning here with these hybrid institutes—part ol’ time eugenics office, part modern genetic counseling facility— allows Stern considerable interpretive room. She allows the ambiguity and the tensions between individual and population to hang in the air, creating that kind of awkward pause in a conversation that makes a reflective person stop and think.

GC timeline.001 Taking counsel (Review of Stern, Telling Genes)

A (very) rough chronology of major events in the history of genetic counseling.

Stern does not, however, narrate the history chronologically. Rather, the history unfolds in a series of oscillations and resonances, in a series of analytic chapters organized by central concepts and problems in genetic counseling. Taking a thematic rather than chronological approach buys her a great deal of analytical substance, but it sacrifices narrative continuity. The arc of genetic counseling over the second half of the twentieth century doesn’t emerge until the end, and the reader must do the work of pulling out the major events and arranging them chronologically. Although the first chapter is titled “History,” it covers mainly the debate in the 1970s over the professionalization of the field. This is the only significant misstep in the book. A brief narrative account of the field—from the establishment of the Heredity Clinics in the early 1940s through the neo-eugenic 1950s, the emergence of genetic screening in the ‘60s, with the first Master’s level program at the end of the decade, through the profesionalization of the 70s and ‘80s, would have set the stage better for her later thematic analysis. I read the book with two graduate students, and both of them felt the lack of a chronological narrative to be a hindrance.

The remaining chapters cash in marvelously, often brilliantly, on the thematic organization. Chapter 2, “Genetic Risk,” looks at Huntington Disease, tracing the “shifting risk calculus” of the disease “as it crossed the transom of genetic testing and genetic counseling” (31). Stern notes that in lieu of effective therapies, more information and more precise diagnostics do not lessen—and perhaps increase—apprehension about the disease. Chapter 3, “Race,” focuses on questions of the population and the individual. Thinking in terms of populations, she argues, carries many tacit racial considerations into human genetics: “Population was never a neutral biogeographic term.” A harrowing and perceptive section on the methods of “racial matching” at the Dight Institute of Human Genetics in Minnesota and the Heredity Clinic in Michigan excavates a remarkable series of notebooks from the director, Sheldon C. Reed. Stern observes Reed simultaneously advocating publicly a liberal stance toward miscegenation as a solution to racial tension and advising adoptive parents on the goodness of fit of mixed-race children into a white family. Reed used an implicit “one drop rule,” At Michigan, James V. Neel—one of the pioneers of noneugenic medical genetics—also classified babies, according to a sort of Pantone series of skin tone. Stern allows this ambiguity to hang in the air, neither damning nor defending their inconsistency. These medical-genetic pioneers helped bring the field forward, but they were flawed, and Stern makes no apologies for them.

Chapter 4, on disability, focuses on the evolution of Mongolism to Down syndrome. In the 1940s, she shows, genetic counseling was built around a code of prevention (97). Gradually that code shifted to focus more on adaptation and adjustment, as families and patients’ rights groups have pressed for the acknowledgment of the disabled. These groups have understandably expressed concern over reproductive technologies and prenatal genetic screening, perceiving mandatory screening laws as an attack on the very existence of the disabled.

In chapter 5, “Women,” Stern relates the history of the founding of the Sarah Lawrence program in genetic counseling. Established in 1969 by Melissa Richter, it was brought to maturity by Joan Marks, who ran the program from Richter’s death in 1974 until 1998. Though mythologized as a moment when genetic counseling at last threw off its eugenic shackles, here too eugenic concerns mingle with sure-footed movements toward autonomy and informed consent. Richter, for all her sunny optimism and prescience, was a “neo-Malthusian,” couching her program proposal in the language of population explosion and mounting genetic “load,” Hermann J. Muller’s term for the accrual of mutations. Richter’s signal contribution was in establishing women as the foundation of modern genetic counseling—a startling echo (unnoted by Stern) of the long tradition of female “field workers” at the Cold Spring Harbor Eugenics Record Office in the teens and twenties. The medical community fought bitterly against the establishment of Master’s level genetic counseling, but the persistence of Richter and others persuaded physicians to cede jurisdiction over this critical but “softer” aspect of genetic medicine.

Chapter 6, on ethics, focuses on the shift from directive disease-centered eugenic counseling to nondirective, client-centered counseling. Here Stern takes us back to before the Heredity Clinics, to the psychologist Carl Rogers, who coined “nondirectiveness” in developing a new approach toward counseling victims of violence and abuse. She brings forward much fascinating and new material here, although her inference that Lee Dice and other Heredity Clinicians were borrowing directly from Rogers is circumstantial and, to me, not entirely persuasive. However, her analysis of the erosion of the concept of nondirectiveness is fascinating. She shows, surprisingly, that “nondirectiveness” has had a relatively short life. It didn’t enter the genetic counseling lexicon until the 1980s, and already by the 2000s it had begun to recede as the discipline’s gold standard, in favor of a more nuanced discussion about the strengths and limits of autonomy and consent.

The final chapter shifts categories to look at a recent methodological development: prenatal genetic diagnosis and its uneasy marriage with genetic counseling. This provides her with a vehicle for examining developments in genetic counseling since the 1970s. Her analysis of the rise of amniocentesis is a valuable contribution to literature by Rayna Rapp, Ruth Schwartz Cowan, and Robert Resta, among others. A conclusion briefly examines current-day practices and, in an original analytical move, closes by considering the possibility that the history of genetic counseling may be drawing to a close. As genomic medicine works to treat all disease as genetic in origin, the concept of genetic disease is gradually eroding. If genetics dissolves into biology, what exactly will genetic counselors counsel about? Stern closes with a call for genetic counselors to examine their history as a means of ensuring their future.

Yet if the juggernaut of geneticization continues unabated, there will always be a need for a medical-genetic middleman—or middle-person. Someone with serious genetic training but also skilled in psychology, ethics, and education. Someone whose time is not metered in quarter-hour increments (and billed in C-notes). Telling Genes is unflinching in tracing our hereditarian past, but sympathetic toward and highly supportive of those compassionate professionals who guide the rest of us into an ever more genetic future. It should be widely read, by genetic counselors, by clinicians, by future parents, and by anyone who is or knows someone who is affected by genetic disease.

Sign me up

Check out the delicious spoof over at The DNA Exchange. It’s a program for the “National Education Conference of the National Society of Genome Service Specialists.” Sponsored by the likes of “UneedaTest, Inc.,” “Twist-of-Fate, Inc.,” and “BraveNew Analytics,” the conference program features panel discussions such as “Clinical trials—a barrier to patient uptake of new genetic tests” and “Fear of genetic disease—your best marketing tool.” Breakout counseling sessions include “How To Appear To Promote Autonomy, Empower Patients, And Seem Non-Directive – But Still Increase Hospital Revenue.”

No conference is complete without awards. This one includes the Huntington Award for most TestAll tests ordered for adult onset diseases in a pediatric setting and the GATTACA award For Strongest Advocate of the TestAll! Really, Really Expanded Newborn Screening Panel.

At day’s end, conferees can hoist a few at the Uneeda Party, “an evening of food, drink, fun, and clever sales pitches” by the sponsor, “not intended to influence your choice of genetic testing laboratory.”

It’s a wonderful send-up of some troubling potential conflicts of interest that may be brewing in the genetic counseling profession. Or is it?