Nathaniel Comfort

I’ve been offline for a few weeks, but I’ve had good reason this time: I got married and went on a cross-country honeymoon!

But naturally, my work follows me, even into the County Clerk’s office. My bride and I got married in California, and when we applied for a marriage license, as required by law they handed us a booklet entitled “Your Future Together: Health Information You Need to Know.”

We need to know, apparently, a wide range of health information, spanning general nutrition, domestic violence, sexually transmitted diseases, and birth control, and that government services are available to prevent, treat, or enable each of them as appropriate. But the largest number of pages in the booklet is devoted to genetic disorders, screening, and counseling. My bride and I were struck immediately by the fact that genetics would be so front-and-center in a booklet on the public health of marriage.

Should we cue the sinister-music soundtrack? Not necessarily—but the booklet does raise questions about the similarities and differences between contemporary genetic public health and that good ol’ time eugenics.

The booklet is produced by the Genetic Disease Screening Program, a branch of the California Department of Public Health. The program’s published mission is “To serve the people of California by reducing the emotional and financial burden of disability and death caused by genetic and congenital disorders.” As a historian of genetics and eugenics, I find this more than a little troubling. In the Progressive era, eugenicists such as the Yale economist Irving Fisher used “financial burden” as an important justification for promoting sterilization and sequestration of “defectives”—those with genetic diseases, either physical or mental. Serving the people of California by reducing the financial burden of genetic disease is a form of population improvement, full stop.

As it has ever been, the segment of the population that most needs improving is the poor, which in California is largely Latino. California’s “PACT” program (“Planning, Access, Care and Treatment”) provides comprehensive family planning services to low-income residents, including:

• birth control
• pregnancy testing
• sterilization (male and female)
• STI testing and treatment, including HIV
• hepatitis B vaccine

Wait…what?

Yep, state-sponsored sterilization. Now, of course, that sterilization is not compulsory. California repealed its compulsory sterilization law…in 1979. That reversal was prompted, the year before, when 10 Latinas sued the state of California for sterilizing them, without informed consent or simply against their will. Although they ultimately lost their case, historian Alexandra Stern argues that the suit had a significant impact on the required stipulations for sterilization. She also highlights the issue of race, pointing to the long history of anti-Mexican sentiment and the relative dearth of information on genetic screening and testing in Spanish. I searched in vain for a version of the brochure en Español. “Your Future Together” is in English only.

The booklet also presents the reader with an extremely simple-minded introduction to genetics—basically a 1930s view of genetic disease:

Genetic disorders are not contagious. That is, they cannot be “caught” like a cold. They can only be passed down to your children through genes. Genes are tiny bits of information contained in the father’s sperm and the mother’s egg that form a blueprint for the baby.

Infectious diseases are spread “horizontally” through the population, while genetic diseases spread “vertically.” In 1933, the medical geneticist and avowed eugenicist Madge Macklin helped bring genetics into medicine by declaring,

It makes no difference whether the disease with which they are afflicted came to them by way of germs or germ plasm, the disease is transmissible, and so comes under the category of public health.

 I call this the “germ theory of genes.” Genetic diseases may not be contagious, but like infectious disease they have “silent” carriers, and in both cases you can stop their spread by isolating the carriers. The brochure goes on to list several genetic diseases that one’s baby will automatically be tested for:

• Sickle cell disease
• Thalassemia
• Tay-Sachs
• Familial dysautonomia
• Cystic fibrosis

These diseases behave in a more or less Mendelian way. You can identify carriers (heterozygotes) and make predictions of likelihood (although not severity) of onset. But these are just a few of the 77 genetic diseases every child born in California is screened for. As the panel is expanded, it will include increasingly “complex” diseases—diseases more common in the population but with less straightforward patterns of heredity. As the genetic component in a given disease gets less and less, the predictive value of a genetic test goes down. And the difficulty of adequately informing a layperson about their genome goes way, way up.

This combination of an obsolete, simplistic presentation of genetics with an expanding, state-mandated panel of genetic tests places undue emphasis on heredity and leads to an overinflated view of the role of genes in health. Adequate health information needs to accurately reflect what we know of biology.

The next section is on genetic counseling. You should “definitely” talk with a genetic counselor, the booklet advises, if you answer “Yes” to any of a list of questions, including these:

• Is anyone in your family or your partner’s family mentally retarded?
• Have you had two or more miscarriages?
• Have you been diagnosed with diabetes or with seizures (epilepsy)?
• Are you related to your partner (for example, cousins)?

As I show in The Science of Human Perfection, these same questions were being asked a century ago by people we now brand as “eugenicists.” And they were eugenicists. They explicitly advocated the improvement of the race by genetic means, and happily referred to that practice as eugenics—while also being interested in relieving human suffering right there, right then, in their patients.

A Progressive-era eugenicist such as Charles Davenport, frozen and revivified, say, by the California-based American Cryonics Society, would find nothing to disagree with in “Your Future Together.” The understanding of the gene, the emphasis on intelligence and inherited diseases, the importance of avoiding inbreeding are all points that have been emphasized throughout the history of medical genetics, during the entire 20^th century and now into the 21^st. Davenport would have been pleased to find that so many diseases had been identified and tested for, and delighted that the state mandates screening for them. He would of course hope that individuals, properly educated by brochures such as this, would make the “right choices”—namely having many children if the tests come back negative, and abstaining from reproduction if they have bad genes.

Davenport would be disappointed, of course, in the lack of compulsory measures available to the state in the case of recalcitrant or incapacitated individuals. But eugenicists have long contented themselves with reliance on slow progress through education, and hoped for a future with a more enlightened and far-sighted reproductive policy. This view, of the relief of suffering in the short term and the elimination of disease and ideally the enhancement of positive traits in the long term, has also been the goal of medical genetics, from Madge Macklin forward. Medical geneticists have seen nothing wrong with population improvement so long as it didn’t trump the relief of suffering; on the contrary, they have believed that relief of suffering through the prevention of hereditary disease would lead to the gradual elimination of disease and human betterment. Eugenics, in short, was not wrong; it was just done wrong. Are we ready to come to terms with that view?

“Your Future Together” is not eugenic, then, if by “eugenics” you mean state-mandated compulsory reproductive behavior. It veers pretty close at points, but ultimately it aims, imperfectly, at giving individuals access to information and permitting informed reproductive decisions.

However, most medical eugenicists and medical geneticists have hewed to a more inclusive, Galtonian definition of eugenics, in which education is the preferred means of achieving both the the short-term relief of individual suffering and the long-term goal of human improvement. Eugenics and medical genetics have always shared these two aims. And this to me is the central dilemma of contemporary genetic medicine.

Just got this nice review of The Science of Human Perfection in Publishers’ Weekly!

Here’s the link, and here’s the text:

In this intriguing history of medical genetics, Comfort, associate professor of the history of medicine at Johns Hopkins, makes a bold and rather uncomfortable assertion: that together with the compassionate drive to reduce individual suffering, the eugenic drive to improve the biological trajectory of the human race overall has always been central to the practice of genetic medicine, despite attempts to separate the discipline from its racist reputation after WWII. Comfort supports his assertion through carefully tracing the development of ideas about heritability and how they became manifest in academic, medical, and governmental contexts in America from the early 1900s to the present. Two strains of thought in particular come together: the Garrodian influence, focused on individual biochemical variation and the interaction between a particular patient’s natural constitution and environment; and the Galtonian influence, tracing traits across large populations, with a focus on social implications and human engineering. As we move from treating manifest disease to predictive and preventative medicine based on “latent disease” detected only in an individual’s genes, Comfort provides some complex food for thought about the balance between creating good for individuals and for the human species, and about the ways we define the methods we use.

In today’s New York Times, Ross Douthat writes about Irving Fisher and Progressive-era eugenics, comparing it to today’s “liberal eugenics.” His faith in universal human goodness may be questioned, but he is right about the fundamental similarities between eugenics old and new. This–including Fisher–is the subject of chapter 2 of The Science of Human Perfection.

It’s been a busy week for genetic oversell.

Benjamin et al. examined the genetic architecture of economic and political preferences in PNAS. They conclude that “molecular-genetic-based heritability estimates…partially corroborate evidence of significant heritability from behavior genetic studies,” i.e., there is some evidence from molecules that there is some evidence from behavior genetics that political preference is genetic. And also, their analyses “suggest that these traits have a polygenic architecture, with the heritable variation explained by many genes with small effects,” i.e. that although behavior is mediated by proteins and therefore somehow involves genes, there is no single gene for being a bleeding liberal or an evangelical Republican.

Chris Mooney discussed the paper, recognizing that “finding a single ‘liberal gene’ or ‘conservative gene’ just ain’t gonna happen. The studies that we’ve heard about so far focusing on individual “political” genes may be suspect, and much larger samples will be needed. In all likelihood, there isn’t going to be any one gene that does a lot of work to explain ideology–the phenomenon is going to be polygenic…and very tough to study.”

All true, but we need to go deeper than this. Since the middle of last century it has been clear that there is no single gene for any complex behavioral trait. Granted, the headlines continue to scream this stuff (see below), but we need to go beyond refuting simple genetic determinism. The larger question is why the genetics of politics gets so much play, when all it concludes ultimately is that lots of genes plus lots of other stuff go into complex qualities of temperament.

A minor dust-up over personal genomics raised similar issues. Over at The Awl, Russell Brandom wrote a trenchant critique of personal genome tests. He points out that items on a personal genome screen such as, “Your odds of heroin addiction are 2.9X higher than average” are hard to interpret. Does he get a bigger than average reward from opiates and so is more likely to keep doing them if he tries them? Or does he get less reward, and so would have to do more and more to keep the sensation?

He points out that a large percentage of a low risk is still a low risk. Going from a 2.4% risk to a 3.2% risk doesn’t mean much for the average person. The public health geneticist Tony Holtzman has been collecting data and making this argument since the early days of PKU, sickle cell, and Tay Sachs screening in the 1970s and 1980s, and it’s still true.

Complex traits have many contributing factors, each of which contributes a tiny fraction of the total variation. No one argues this, not even 23AndMe. However, the fashionable emphasis on genes—the dizzying fact that we can now identify a gene that contributes, say, to IQ, or to left-handedness, or for crying out loud to a preference for pork, enhances the genetic component, making it seem more important.

“They don’t have any straightforward truths to offer users,” Brandom observes, “just a flood of vague and often frightening ambiguities. But wherever there’s a gap between what they promise and what they can deliver, 23andme fills it with social media.” All the Facebook- and Foursquare-style features are designed, of course, to keep users on the 23AndMe site, to create a sense of identity and community.

There’s nothing illegitimate about that, but there is something insidious. To the extent that one buys in to this scene, one enters Gene World, where your genes are You. Your identity is determined by your DNA. The complexity of gene-environment interactions that every sane person acknowledges is stripped away, and we slide back to the genetic equivalent of the Ptolemaic earth-centered cosmos: a simplistic, gene-centered universe that seems to account for more than it does.

Misha Angrist responded to Brandom with an impassioned and well-informed defense of genetic testing, in which he pointed out ways in which he has indeed gotten useful information from his genome. He brings up one of the best examples: BRCA1. No argument that knowing your BRCA1 status is useful; however, for cost and other reasons it is not recommended to have yourself tested for BRCA1 unless you have a family history of breast cancer. However, Angrist’s argument that some genetic testing is medically useful does not really refute Brandom’s central claims, that DTC testing risks over-simplifying and overselling the genetic basis of disease and personality.

Razib Khan then totted up the score and decided that personal genomics won this round. It’s not clear why. He emphasizes that a “non-trivial minority of people receive actionable information” from personal genomics—although by his own estimate, 90–99% of those who undergo thise sort of testing will not receive useful medical information—and that the recreational side of personal genomics deserves to be explored. Again, his points are valid but not salient as criticisms of Brandom’s piece.

The comments under Khan’s brief post are more interesting. Several readers seemed to put their arms round each other’s shoulders and say, “Why is everyone always hating on personal genomics?” They saw no reason to do so unless you were an anti-determinist, which they used the way an evangelical uses “pro-choice.” They suggest that skepticism of personal genomics reflects a lack of curiosity and even, bizarrely, a lack of interest in participating in scientific research. One reader suggested that authors such as Brandom who are skeptical of DTC testing are “wedded to a Blank Slate view” and “ideologically oppose any form of genetic determinism.”

It is, rather, the ideology of genetic determinism that Brandom and I and others are concerned about: the troubling attitude that anyone who is wary of some of the implications of molecular soothsaying must be an extreme environmental determinist. Paired with a refusal to consider ways in which, unchecked, the profit motive may corrupt the dissemination of medical data, this is a dangerous view.

There are good reasons to be skeptical of DTC genome testing, and those reasons have nothing to do with one’s general support of science, one’s curiosity, or one’s interest in genetics. DTC genome testing is a large and potent social experiment. It has already brought some benefits, and we can expect it to bring more. However, it also has associated risks, which can and sometimes do mitigate those benefits.

Let me just take two examples, which in my mind encompass many of the smaller criticisms and risks. First, there is a creeping genetic determinism in much of the information on the relationship between genes and disease and behavior. This occurs at several levels. First, it’s worth contemplating why papers like the Benjamin et al. article even get published. There’s a man-bites-dog quality to them. Consider the converse, a paper that purported to show that political and economic preferences had a cultural basis. Ho-hum. But if you find a gene that correlates with such a complex “trait” you have a paper in PNAS. In other words, novelty creates a kind of ascertainment bias that makes it easy to think genes are more important than they are. A slight lapse in one’s critical thinking is all it takes to go from that paper to thinking, “Political and economic preferences just are genetic.” That’s a risk.

That risk is magnified by the publication process, from article authorship all the way to headline-writers. At each step, the contrast of the conceptual image is enhanced, in order to attract the notice of readers. Eventually, you end up with blog posts entitled, “Your IQ depends on a single gene,” and “Can a single pill save your marriage?” While everyone up to speed on genetics understands it doesn’t no, it can’t—that many genes and many environmental variables contribute to any complex biological trait—that complexity tends to get lost when the information is translated into accessible language.

Or consider 23AndMe’s page on “variation.” Using physical performance as an example, they begin modestly:

What does it take to become an Olympic champion? Hard work and perseverance are no doubt part of the equation, but DNA may play a role too.

Nothing to argue with there. The next paragraph introduces ACTN3, alpha-actinin skeletal muscle isoform 3, a protein associated with so-called “fast-twitch” muscle fibers. One form of ACTN3 has been correlated with stellar athletic performance. Its role in athletic performance, the 23AndMe page continues, “has led some to dub it the ‘gene for speed.’” Who is this “some”? Some scientists? Some journalists? Some nutjob bloggers? Some evidence.

At any rate, the page continues in a sweet vein, noting a long-jumper with two non-working copies of ACTN3 as a “testament to the fact that genes are not destiny.”

But the page concludes by asking, “Want to know if you have the ‘gene for speed’? 23andMe’s Health and Traits reports can tell you what versions of the ACTN3 gene you have in your DNA. You can also learn about how your genes may influence a variety of other traits, including your risk for certain diseases. Join 23andMe now!”

The potential customer is left with a clear if implicit message that there is a gene for speed and that for $299 you can find out if you have it. The discussion of variation and the importance of training and other factors is lost.

Where it gets lost, not surprisingly, is in the sales pitch, which brings up my second risk: commercialization. 23AndMe is not a charity. Although I have no reason to doubt the humanitarian impulses of anyone at the company, it’s no secret that their first allegiance is to their shareholders. Their primary task is making money. This of course does not immediately invalidate it as a socially beneficial enterprise, but it does and should make us alert to potential conflicts between profit and benevolence. As an advocate for patients, one feels responsible for raising questions and maintaining transparency so that the medical benefits Angrist rightly emphasizes don’t get lost in the commercialism Brandom exposes.

DTC testing is a fascinating, perhaps revolutionary development in medicine. It democratizes medical diagnostics, putting the first step in prevention and treatment into patients’ hands. It has the potential to empower patients, and thus to begin to counter the twentieth-century trend toward an ever more hierarchical healthcare establishment, in which objectification of the patient was justified on grounds of therapeutic potency. DTC testing may be one of those developments that medical historians a century hence will note as pivotal, the beginning of a new model of more participatory healthcare.

Advocates of DTC testing need to address concerns about hype, creeping genetic determinism, and commercialization in order for DTC testing to flourish. Waving away critics as anti-intellectual, anti-science, or blindly ideological merely deepens concerns about overselling this potentially transformative technology.