Tag Archives: sterilization

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.

Alex Stern on California’s recent nonconsensual sterilizations

Just a quick note to let you know about Alexandra Minna Stern’s recent interview on Capital Radio, discussing the California sterilization case. Her work appears frequently on Genotopia—she’s one of the smartest historians discussing this important case.

 

Thursday Eugenics Roundup

“Eugenics is old history, kind of scary to read about but reassuringly far in the past. We don’t really need to know about that, right, professor? Right???”

Sorry kids. It’s going to be on the exam. The discussion over the California prison sterilizations continues. Today, the Huffington Post carries a compassionate and well-informed historical essay by Alexandra Stern, who Genotopia readers know as a distinguished historian of eugenics and genetic counseling. “Many of the stereotypes that fueled 20th century sterilization abuse remain in vogue today,” she points out.

Dr. James Heinrich, who performed tubal ligations of women in prisons, stated that this practice saved the state money because his involuntary clients were likely to have “unwanted children as they procreated more.” Such a callous attitude could have been uttered by superintendents in the 1930s, who worried about the economic burden of “defectives,” or by the obstetrician at USC/LA County who purportedly spoke to his staff about “how low we can cut the birth rate of the Negro and Mexican populations in Los Angeles County.”

She concludes, “It is time to break the cycle of reproductive injustice in California, and to challenge the continuing potency of eugenic rationales of cost-saving and societal betterment that have undergirded compulsory or unauthorized sterilizations. The 21st century calls for a new era of human rights, institutional oversight, and the protection of vulnerable populations.” I should also point out the two excellent posts on the California sterilization fiasco over at Nursing Clio, one by Tina Kibbe, the other by Adam Turner.herndon small Thursday Eugenics Roundup

At the other end of the country, North Carolina lawmakers are currently finalizing this year’s budget plan, and it includes $10M for victims of the state’s eugenic sterilization program, which reached its peak in the 1940s and 1950s. Claude Nash Herndon, a physician and medical geneticist who I feature in my book, was one of the leaders of the program. He was by all accounts a kind man and a good doctor. He also had the beliefs common to prosperous white people in the South in that period, and the paternalistic attitudes common to physicians then. The North Carolina sterilization program was a point of pride for the state. The definitive sources for this chilling story are the Winston-Salem Journal’s series of news articles “Against their Will,” and Johanna Schoen’s thorough, scholarly, and chilling account, Choice and Coercion.

Debate of course rages about this program. Some say money won’t undo the damage, while others say hell yes, it will help. Some ask where the money is going to come from, while others ask why such a small sum is being set aside. There were an estimated 1,800 people sterilized against their will under the program. Tribtown.com shows that if 1,000 come forward with legitimate claims, they will receive $10,000 each. How do you put a price tag on your fertility? Some choose not to have children voluntarily, while for others the prospect of having children is one of the things that gives life meaning.

I personally can never do the math of converting morality into money. But I do believe a cash settlement provides some compensation, gives the victims at least a small sense of justice, and exacts a penalty of public shaming–however late–on a governing body that could have known better.

Is public shaming a valid reason? Does that justify all this attention and money? You bet. Shame should never be used vindictively, but a proper sense of shame is an essential check on antisocial behavior. Aversion to shame is one of the things that ensures civility. Sadly, in the real world, that often involves money, difficult thought it may be to calculate the exchange rate.

The gene for hubris


A recent post by Jon Entine on the Forbes website leads with a complimentary citation of my book– and then goes on to undermine its central thesis. He concludes:

Modern eugenic aspirations are not about the draconian top-down measures promoted by the Nazis and their ilk. Instead of being driven by a desire to “improve” the species, new eugenics is driven by our personal desire to be as healthy, intelligent and fit as possible—and for the opportunity of our children to be so as well. And that’s not something that should be dismissed lightly.

510938342e29b The gene for hubrisWell, first of all, as the recent revelations of coerced sterilization of prisoners in California shows, “draconian, top-down” measures do still occur. Genetics and reproduction are intensely potent, and wherever we find abuse of power we should be alert to the harnessing of biology in the service of tyranny.

Second, there’s more than one kind of tyranny. Besides the tyranny of an absolute ruler, perhaps the two most potent and relevant here are the tyranny of the commons and the tyranny of the marketplace. The fact that they are more subtle makes them in some ways more dangerous. The healthcare industry does much good in the world, but it is naive to treat it as wholly benign.

Further, putting human evolution in the hands of humans, means accepting long-term consequences for short-term goals. The traits we value–health, intelligence, beauty–are the result of the action of many genes interacting with each other and with a dynamic environment. The entire system is contingent, inherently unpredictable. Yet we treat it as simple and deterministic. Until now, technology has been the major obstacle to guiding human evolution. It may be that now the major obstacle is our reasoning ability, our capacity for grasping contingency and probability and change. We’re tinkering with the machinery of a system whose complexity is still unfolding before us. The probability of unforeseen consequences is 100%. The only question is how severe they will be. We will only know in retrospect.

If we now have the tools to meaningfully guide our own evolution–as eugenicists have always wanted to do–we cannot take a blithe and Panglossian attitude. We have to be alert to the risks and take them seriously. That is not traditionally science’s strong suit. The public face of science is sunny, optimistic, fun. It strides boldly into the future, laughing and making striking promises. The industries behind science and health are wealthy and politically powerful. Not everything they do is benign.

To be a critic of that public-relations machine–of hype, in other words–is not to be a critic of health or knowledge or progress. Genetic science has the potential to bring us enormous benefits in health and well-being, and as they do, I stand in line with my fellow humans for my fair share. But that science also carries huge and unforeseeable risks, the root of which, perhaps, is arrogance. It’s one whose consequences are painfully evident in the historical record.

 

Eugenics? In California?

latinos Pacific Colony Eugenics? In California?

Pacific Colony hospital in California, where they used to perform the sterilizations.

[UPDATE: Changed the link from the Sacramento Bee article to the longer report from cironline. h/t Alex Stern.] A quick note on today’s report from the Center for Investigative Reporting that at least 150 pregnant inmates in prisons in Corona and Chowchilla, CA, were sterilized against their will. Between 2006 and 2010. That’s TWO THOUSAND six. Another hundred or more may have been sterilized in the 10 or so years before that. (See also this HuffPo piece from last month.)

In an earlier post, I noted that when I applied for my marriage license in California, my betrothed and I received a state-sponsored booklet called “Your future together.” It was heavily gene-centered and mentioned that one can obtain free birth control and sterilization, paid for by the state. The historian Alexandra Minna Stern has written about the racial politics of California sterilization (see my review of her latest book–and then buy the book). Not surprisingly, the largest number of people sterilized are poor Mexicans, often illegal immigrants. Those surgeries, however, are at least nominally voluntary. Involuntary sexual surgery on prisoners sounds like something from the 1910s, not the 2010s.

In my book, The Science of Human Perfection, I note that eugenics is alive and well, though it often travels under an assumed name. The principles of informed consent can be–and as this report shows, are–used to mask persuasion. When that persuasion includes being made to “feel like was a bad mother if I didn’t do it,” it grades into coercion. Further, the ethics of sterilizing minority women in prison are even more complex than doing it outside—one wonders, for example, how many of those women were impregnated by prison guards. We should not let the drawing of apparently bright ethical lines allow us to become complacent about the gray, unlit areas where that good ol’ time eugenics can still flourish.

DNA Day and Body Modification

The scientific study of human heredity has and has always had two types of practical application: relief of suffering and human improvement. Research programs with those ends in mind have existed at least since the beginning of the 20th century—maybe earlier, depending on how you define things. But by the Progressive Era (roughly 1890–1920), research in human heredity and genetics explicitly sought to reduce or eliminate human disease, raise the average level of our intelligence, beauty, and longevity, and improve our character.

For a long time, the only way to accomplish those goals was to regulate behavior. At the highest level—i.e., the least invasive of bodies but the most invasive of liberty—you regulate the relationship between people who might have children together. In the Progressive Era, many states passed laws prohibiting marriage between two people who were mentally retarded, or certifiably insane, or had tuberculosis (though its infectious nature was recognized, researchers also understood that there was an inherited predisposition). Immigration restriction laws, too, were a form of regulating behavior in the supposed interest of the national heredity (at least in part). They can’t breed if you don’t let them in in the first place.

Many people at the time saw surgical sterilization as much less invasive than marriage or immigration restriction. Advances in surgical technology and practice shifted the target of modification from the relationship to the individual. Modify the individual body and you can afford to be unconcerned with who that person marries or lives with or next to. From our perspective today, sterilization is an appalling invasion of autonomy, but in the 1930s, the heyday of eugenic sterilization—worldwide, by the way, not just in Germany—many people saw it, like abortion, as a way to loosen restrictions on the behavior of the sick, imperfect, and impure while still working toward improving society.

For a long time, then, “applied” human genetics was synonymous with what we think of as the worst excesses and sins of eugenics. Science historians and historically minded scientists have often written that human genetics got “tangled up” with eugenics because the researchers back then did not have sufficient knowledge. Now that we understand the science better, the argument runs, we can avoid the kinds of simplistic fallacies that drove the eugenics movement—fallacies such as the idea that there is a single gene for “feeblemindedness.” Or, ahem, the love of the sea.

But that argument gets it backward. Eugenicists resorted to marriage laws and sterilization for the same reason that there was so little reliable data on human genetics: genetics required sex. Because human geneticists couldn’t carry out breeding experiments, they couldn’t do backcrosses, self-fertilizations, and all the other kinds of matings that other geneticists could do. They could, though, control who mated with whom to some degree on a broad social scale.

The significance of DNA is that it made it possible to do genetics without sex. It wasn’t just DNA, of course—cell culture as well as lots of advances in biochemistry and microbial genetics also contributed—but by the 1960s DNA had emerged as the emblem of a “new genetics.” From the beginning, the DNA double helix had an iconic aspect. The first published image, in Watson and Crick’s first paper (the anniversary of which is the impetus for DNA Day), had a stripped-down, cartoonish quality, and was described in the figure legend as “purely diagrammatic.” Everyone understands DNA, then, to mean much more than “deoxyribonucleic acid.” It stands for the relationship between heredity and health.

The new, DNA-based, molecular genetics finally made it possible to do genetics without sex. Reducing or preventing disease no longer required controlling who married whom, or (more theoretically) even which babies got born. Technology made it possible to select which genomes made it into the next generation, and even, in principle, to alter and “correct” genes in the individual.

“DNA” thus solved the fundamental ethical problem of eugenics. State-level involuntary coercion of reproductive behavior simply makes no sense in a developed country with sophisticated biomedical facilities. It is pointless and paranoid to fear a “return to eugenics” if what you mean is that good ol’ time Progressive eugenics.

In the DNA era, human genetics is still about relief of suffering and human improvement. The NIH touts the disease side of things, but what counts as a disease is heavily freighted with subjectivity, cultural bias, gender, and racial prejudice. Further, at the molecular level, the difference between preventing disease and genetic enhancement dissolves. If you up-regulate transcription of the gene for Human Growth Factor, for example, it makes no difference technically whether you do it in a dwarf, a short person, or a person of normal stature. And the moral distinction between remediation and enhancement relies on soft, unsatisfying philosophical arguments that basically amount to “Ugh!”—in the same way that a conservative parent reacts when his child comes home with blue hair and a lip piercing.

In 1957, Julian Huxley—grandson of Darwin’s bulldog, a distinguished biologist in his own right, and an articulate, politically liberal eugenicist—coined the term “transhumanism.” He wrote, “The human species can, if it wishes, transcend itself —not just sporadically, an individual here in one way, an individual there in another way, but in its entirety, as humanity.” This is what he defined as transhumanism, and he intended us to accomplish it by a variety of means, but of course at the root of it would be the conscious, deliberate manipulation of the human germ line. Throughout the 1960s, geneticists fantasized about using the new knowledge of the genetic code to control human development and evolution, to tinker with the design of human beings. The overwhelming majority of this fantasizing was done with the noblest of intentions. Huxley, JBS Haldane, HJ Muller, Joshua Lederberg, Edward Tatum—these were not ignorant fools but rather some of the greatest, most sophisticated minds in biology. They wanted not to rule the world but to reduce suffering and improve happiness, compassion, and noble achievement.

Muller’s eugenic scheme was called “germinal choice.” We’ve all heard of the Nobel sperm bank that William Shockley (inventor of the transistor) wanted to establish—that was Muller’s germinal choice. Present-day transhumanists prefer Muller’s term to “eugenics,” which is irritating because it requires so much explanation about how their eugenics isn’t the same eugenics as the bad old eugenics. But it’s eugenics. The only reason to deny it is the bad publicity the term gives you.

Transhumanists such as Gregory Stock and ScienceBlog’s own Eveloce tend to argue that genetic enhancement is coming whether we drag our feet or not, and they may be right. The sociotechnical power of contemporary biomedicine is astonishing—and on the rise. I’m not yet sure how I feel about this. I am inherently suspicious of any structure with such a concentration of technological and economic power, and power leads to hubris. It is a truism that 21st century DNA science has the potential for enormous benefit as well as catastrophic harm.

The problem is that the largest benefits tend to be long-term, while the largest risks are in the short term. It is not paranoid to be worried about such a situation, nor is it inconsistent to enjoy and admire positive results as they come out while maintaining a healthy, grouchy skepticism about the larger project.

I’m actually encouraged by the fact that transhumanism has a significant overlap with the blue-dreads-and-lip-piercing set. I’m more comfortable with tweaking our genes to, say, be able to grow horns or have Mr. Spock ears than to make everyone tall, white, and smart. Sure, it can be trendy and pretentious, like other body modification subcultures such as the “modern primitives,” but at bottom these folks are interested in it as a form of expression, not social control. Anything that breaks down barriers rather than reinforcing them gets my vote.