Lies, damned lies, and GWAS

[Blueprint cover]

Well, I provoked another kerfuffle in the pages of Nature. And it’s a troubling one, because it suggests a widening culture gap between the sciences and humanities—a gap I’ve spent a quarter-century-and-counting trying to bridge.

The piece in question is my review of Robert Plomin’s new book, Blueprint. I want here to give some context and fuller explanation for that piece, without the editorial constraints of a prestigious journal.

Plomin is a distinguished educational psychologist, American-born-and-raised, who works in the UK, at King’s College London. I have nothing for or against Plomin. I and my editors at Nature worked hard to keep ad hominem attacks out of the piece. Plomin’s book, however, is terrible.

  • “DNA isn’t all that matters, but it matters more than everything else put together” (ix).
  • “Nice parents have nice children because they are all nice genetically.” (83)
  • “The most important thing that parents give to their child is their genes.” (83)
  • “The less than 1 per cent of these DNA steps that differ between us is what makes us who we are as individuals” (9)
  • “These findings call for a radical rethink about parenting, education and the events that shape our lives.”(9)

I could go on—it’s teh Interwebs; people do—but you get the idea. However accurately he may represent the statistics, his statistics misrepresent the biology. With apologies to Benjamin Disraeli, there are three kinds of lies in genomics: Lies, damned lies, and GWAS.

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Unless you’re some sort of third-rate hack, riding out your tenure on the strength of your rotation in a genetics lab in the mid-sixties, you know better than to say things like this. I presume that you, Gentle Reader, are not such a person. Plomin is not a hack scientifically, but as a writer he is. On the page, he is all exclamation points and pom-pons, thwacking the bass drum with his heel as he dances for DNA. DNA is everything. DNA is the Word. DNA is Love.

That’s a weirdly retrograde view in the postgenomic world. Again, see the above mainstream sciences. Either:

  1. Plomin is such a poor writer that he fails utterly to get across his putatively more nuanced understanding of the genome’s role in biology
  2. Plomin is a cynic, writing things he doesn’t believe in support of a repressive ideology that he does believe; or
  3. He is naive and genuinely doesn’t realize (or care) how this powerful new science is used.

I went with Door #3. As a reviewer of his book I took him at face value as a writer. I take him at his word when he says he is center-left, politically. (No conflict there with eugenic values. There’s a long tradition of leftist eugenics, back to the 19th C.) And I decided it would be unproductive to simply brand him an ideologue. Instead, I took the middle road, presumed innocence but naïveté. I gave him the benefit of the doubt in presuming innocence of intent, although I do think it an odd negligence on his part, given his express interest in using PGS to shape social policy. Seems to me that if you’re engaging with social policy you should be capable of thinking in terms of social policy.

Why is it dangerous? Because it enables and encourages social policy of biological control. That shit scares me. And it should scare you. Plomin is so caught up in his DNA delirium that he says that environmental interventions toward human betterment are futile. Parents, teachers, government officials: Relax, there’s nothing you can do that really makes a difference. DNA will out. Kids will be what they will be, regardless, so don’t waste your money and time. Let’s take that apart.

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First, his statements on environment may be statistically accurate (I don’t know and don’t care), but biologically, they are just plain wrong. No one who knows the first thing about biology can be unaware of the profound changes over the last 30 years in our understanding of how genes work, how genomes interact, how DNA needs to be treated as a dynamic, ever-changing substance. Epigenetics, the microbiome, horizontal gene transfer, the 3-D (or 4-D) genome. While like any science there are debates within each of these fields, the basic precepts of the dynamic genome are mainstream knowledge.

I haven’t even touched upon gene-environment (GxE) interactions, which may swamp both purely genetic and purely environmental variables, and which Plomin also ignores. The importance or action of a given gene on a behavior depends upon its genetic and environmental context. Environment matters—and it makes a difference.

The book is full of ascertainment bias. For every study you can cite showing genetic contributions to complex behaviors, I can go head-to-head for quite a while, matching you with similar studies showing environmental contributions. Plomin makes no attempt to present the other side of his argument—a sure sign of polemic, rather than sincere inquiry. He makes the same argument that genetic determinists always make, claiming only to show that no complex traits are completely free of genetic influence—and then does a bait-and-switch, to argue that whatever environmental influences there may be, they can safely be ignored. He goes on to argue that, unlike environmental explanations of behavior (which, he says, are “random and unsystematic and so there’s nothing you can do about them”), the genetic correlations he discusses are causal. He literally confuses correlation and causation.

Some people are doing good science using polygenic scores to estimate environmental impact on behaviors. Comparing PGSs between environments or at different time intervals can be a way to measure the effect of changing the environment on the trait. But again, Plomin doesn’t talk about this. His is a simplistic message of “DNA is all.”

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Second, then, hidden agenda or not, Plomin’s argument is socially dangerous. Sure, genes influence and shape complex behavior, but we have almost no idea how. At this point in time (late 2018), it’s the genetic contributions to complex behavior that are mostly random and unsystematic. Polygenic scores may suggest regions of the genome in which one might find causal genes, but we already know that the contribution of any one gene to complex behavior is minute. Thousands of genes are involved in personality traits and intelligence—and many of the same polymorphisms pop up in every polygenic study of complex behavior. Even if the polygenic scores were causal, it remains very much up in the air whether looking at the genes for complex behavior will ever really tell us very much about those behaviors.

In contrast—and contra Plomin—we have very good ideas about how environments shape behaviors. Taking educational attainment as an example (it’s a favorite of the PGS crowd—a proxy for IQ, whose reputation has become pretty tarnished in recent years), we know that kids do better in school when they have eaten breakfast. We know they do better if they aren’t abused. We know they do better when they have enriched environments, at home and in school.

We also know that DNA doesn’t act alone. Plomin neglects all post-transcriptional modification, epigenetics, microbiomics, and systems biology—sciences that show without a doubt that you can’t draw a straight line from genes to behavior. The more complex the trait in question, the more true that sentence becomes. And Plomin is talking about the most complex traits there are: human personality and intelligence.

Plomin’s argument is dangerous because it minimizes those absolutely robust findings. If you follow his advice, you go along with the Republicans and continue slowly strangling public education and vote for that euphemism for separate-but-equal education, “school choice.” You axe Head Start. You eliminate food stamps and school lunch programs. You go along with eliminating affirmative action programs, which are designed to remediate past social neglect; in other words, you vote to restore neglect of the under-privileged. Those kids with genetic gumption will rise out of their circumstances one way or another…like Clarence Thomas and Ben Carson or something, I guess. As for the rest, fuck ’em.

These environmental factors are “unsystematic” in exactly the same way that genetic factors are: They do not act in the same way with every child. A few kids will always fall on the long tails of the bell curve: Some will do well in school no matter what you throw at them; others will fail, no matter what they have for breakfast. But the mean shifts in a positive direction. Same is true for genetics. That is literally the entire point of polygenic scores! Every single one of the many thousands of variables that shape something like educational attainment is probabilistic. Genes or environment, we’re talking population averages and probabilities, not certainties. There is no certainty—Plomin himself makes this point repeatedly (and then promptly jumps back on the DNA wagon). To venerate genetics and derogate environment on grounds of being “unsystematic” is at best faulty reasoning and at worst hypocritical.

Plomin is spreading a simplistic and insidious doctrine that says “environmental intervention is futile.” I don’t care whether Plomin himself, in his heart of hearts, wants to ban public education; he gives ammunition to people who do want to ban it. “Race realists” and “human biodiversity” advocates—modern euphemisms for white supremacy—read this stuff avidly. I watched them swarm around the discussion of my review on Twitter, many of them newly created accounts, favoriting tweets from my critics, saving those messages for later arguments.

“But does that mean that EVERYONE using PGS is a white supremacist?” people ask me, their keyboards dripping with sarcasm. No, dummies: It means it’s a risk. I’m giving you a qualitative risk score, a probability. Can’t you apply your own logic to other situations? Again, whether you critics are being disingenuous or naive, the effect is the same.

“So does that mean we CAN’T DO this science? Are you a fascist, trying to stifle scientific inquiry?!?” others gently query me. Again, no, dummies: I’m saying if you do this stuff, a) get your genetic bias out of the way and look at genes and environment, and b) be candid and explicit about your intentions and the risks of misinterpreting the data.

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The last point I want to make is about historical thinking. A lot of critics said and called me things that initially puzzled me. I had no evidence, they said. It wasn’t a review that I wrote, they complained. I didn’t engage with the book but merely promoted my ideology, they protested.

Eventually it dawned on me: These people don’t understand historical reasoning. They fail to see a historical argument as being evidentiary! After all these years, I still find it surprising that people with PhDs should fail to acknowledge an entire branch of knowledge, a fundamental way of explaining the world. But okay, communication, not war, is what I’m after, so let me lay it out, at least as I see it.

By and large, experimental science explains the world in terms of mechanisms, more or less eternal and independent of time and context. Historical reasoning explains the world through the three C’s: context, contingency, and cause-and-effect through time. Context means that science doesn’t occur in a vacuum. It mattered that Nazi Germany arose after Progressive-era Americans had advanced a scientific program of sterilization and institutionalization of the defective. The Germans, sensing the power of rigid social control founded on scientific authority and finding that authority in American eugenics, modeled their infamous sterilization law of 1932 on Harry Laughlin’s “Model Sterilization Law” of 1922. Contingency means that it matters who did what when. Contingency says, “It could have been otherwise: Why did things turn out as they did instead of some other way?” And by continuity and change I mean that when a historian tries to understand the present in terms of the past.

In short, my review used historical evidence to put Plomin’s book in historical and social context, rather than scientific context, and a number of critics cried “Foul!”, failing to even see historical evidence as evidence.

It’s not foul when a reviewer examines the central claims and aims of a book—you all (critics) just aren’t familiar with the way I did it. Especially with a field such as sociogenomics, which defines itself as interdisciplinary and aims to shape society. You may not read Plomin’s book in social context, but it’s a legitimate and—as attested by the many plaudits I’ve also received for the piece—an important one. Learn your damn history.

Historical thinking is not anti-scientific. Darwin was a historical thinker par excellence. Evolutionary biology, cosmology, geology, paleontology—these are historical sciences. To reason historically is by no means to refute the scientific method. In fact, I would wager that no person can get through life without employing historical reasoning). To do so is to refuse to learn from experience.

Because I did not primarily use scientific evidence in my review, some misguided and uncritical critics peg me as a radical relativist. You got the wrong guy, pal. I studied sociobiology and neuroethology as science for years, under some of the greats. Radical relativists do exist in the humanities and social sciences—I argue against them all the time.

Others, like Stuart Ritchie, bash away at me boneheadedly, picking at details of the piece that make no difference to my argument without the slightest effort try to understand what I am in fact saying. Playing “gotcha” is easier than real debate, but it wins you points with your yes-friends, I guess. Sad!

Historical thinking pulls your eye away from the microscope to look at science as an enterprise evolving over time. For really abstruse sciences, doing so may be mostly an intellectual exercise. But the more social salience a branch of science has, the more important it is to take the long view once in a while. And when you’re explicitly advocating using your science to shape society, it’s incumbent on you to do so.

I identify with distinguished, politically alert scientist-critics like Jonathan Beckwith and Richard Lewontin, who have critiqued their science (even their own science!) in order to make it better. I believe that in science as in politics, dissent is the sincerest form of patriotism.

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In short, I don’t think sociogenomics is wrong; I think it’s being done wrong, and written about wrong, by people like Plomin. Some people are doing it right. In a forthcoming piece in the MIT Technology Review, I discuss the work of Graham Coop at UC Davis. I won’t go into detail here, but for examples of honest, candid, historically sensitive discussion of PGS research, see this and this. This post is my attempt to do for my critique of PGS what Coop did for his own PGS research (which, for the record, I admire). By and large, I think the biologists have been doing better at avoiding deterministic talk than the social scientists like Plomin—although some social scientists, like the sociologist Dalton Conley at Princeton, do at least have complex positions worth taking seriously.

Plomin does none of this. Instead, he gives us a simplistic and distorted view of the role of heredity in behavior that causes much social mischief. We can watch some of that mischief in real time as the white supremacist trolls swarm around this debate like yellow-jackets around an open soda. Other risks we can infer from careful comparison with historical examples—looking at both the similarities and the differences between Blueprint and previous attempts to use heredity to shape social policy. The argument in Blueprint—that “DNA makes us who we are” and environment “is important but it doesn’t matter”—is an idea grossly wrong on many levels. It’s not supported by the evidence and it’s socially dangerous.

And someone’s got to call bullshit on it.

Major new cause of achievement discovered: studying

In a breakthrough discovery, researchers have identified a significant causal factor in educational achievement. It involves sitting one’s ass down at a table and opening books.

The problem of the underlying causes of educational achievement have stymied geneticists for years. Back in the Progressive Era, eugenicists attributed most of the variance in IQ, or intelligence quotient–a test designed to measure educational achievement–to a single Mendelian gene. Today, geneticists are just as obsessed with the genetic causes of IQ. After years of study, they have succeeded in spreading the effect out over several genes, while whittling the genetic basis down to under two percent of the variation. A recent study in Science magazine found that all known genetic variations combined explained 1.98% of the variation in achievement; the largest single effect of a genetic variant was 0.02%.

A different approach was taken by a researcher who prefers to be known simply as “Miss Perkins.” With her half-moon glasses, her hair done up in a tidy bun, and her sensible shoes, she is the picture of an elementary school teacher. Which she is. Collecting data over more than 20 years of teaching social studies to 3rd, 4th, and 5th graders at Martin Luther Malcolm Kennedy Roosevelt Elementary and Middle School, in Slippery Rock, Missouri, she has found that studying (STUH-dee-ying) explains a whopping 60% of the variance in educational achievement–no matter whether it is measured in grade-point average, standardized test scores, or subjective evaluations.

Another 30% of the total variation can be attributed to parents teaching their kids to put their butts in the chair and keep them there, without videos, music, or cell phones to distract them. A further 8% was attributed to nutrition.

The results have rocked the biomedical world. “I’m literally stunned,” said Dick Dorkins, of the Society for the Prevention of Intelligent design, Teleology, Or Other Nonsense (SPITOON), a biological think tank in Tumwater, Washington. “I feel exactly like I did last week when I accidentally got TASERED at the end of a bar fight.”

Not all scientists are convinced by the results, which involve 573 children and 1,719,000,000,000 base pairs. Nicholas Spork, a genomicist at Kashkow University, best known for its discovery of the “Republican gene,” said that Perkins’s “one-size fits all” approach was a “pedagogical dinosaur.” He was pioneering a personalized education approach, he said, that would tailor standardized tests to an individual’s genome. He also said he had applied for a federal grant to buy fourteen new high-speed sequencers that would identify 2 trillion base pairs in 93 seconds. “It’s just a hunch of course,” Spork said with a conspiratorial wink, “but I have every confidence that, with enough venture capital, in ten years we can double the amount of variance explained by single-nucleotide polymorphisms” (or “snips”). That would bring the total to around 3 percent.

Meanwhile, Miss Perkins continues her study—and her students continue their studying. She teaches about 60 students a year, in two classes. Her most high-tech tools are a globe, in the corner, a whiteboard (without a projector), and a terrific set of dry-erase markers, ranging from deepest violet through the spectrum to cherry red. But that’s not all. “Over the summer, a parent donated me a set of grays and blacks,” she said proudly during a quiet moment in class. “They were expensive, but oh, this will help a great deal. Nothing’s too good for my kids. Derek! What do you think you’re doing? Sit down and be quiet this instant, or you’ll have extra homework!”

Thalassophilia unmasked

There is no gene for thalassophilia—yet, anyway.

My satirical post last week about scientists finding a gene for love of the sea was intended to make a point about how we view genomics today—and a historical point about how we smugly congratulate ourselves on being so much more sophisticated than early human geneticists and eugenicists. Most people got that it was a spoof, but I thought it would be worthwhile to discuss some of the deeper issues at stake.

Charles Davenport was a real scientist, and the quotes from him are real. Davenport was a geneticist in the first half of the 20th century and the leader of the American Eugenics movement during the Progressive Era. He is often demonized as wrong-headed, misguided, and simple-minded. Indeed, he could be all of these things. Davenport really did believe there was a recessive, male-linked trait for the love of the sea. Thalassophilia has become a classic example of how eugenicists could ignore obvious environmental explanations in favor of the hereditary. When I told my 11-year-old daughter about Davenport’s thalassophilia, she immediately saw the fallacy: the sons of ship captains learn their love of the sea, they don’t inherit it.

My larger point is that simplistic analyses like Davenport’s can be masked by numbers and fancy technology.

For years, medical genetics involved the search for genes underlying genetic disease. Diseases that were caused by a defective gene, and not, say, by a germ or some other environmental factor. But that distinction has been erased. We used to think of genetic traits and non-genetic traits. Now, non-genetic traits are called “complex”—i.e., partly genetic and partly environmental. In other words, all diseases, and indeed all traits are understood as partially genetic.

There are sound reasons for thinking this way. I’m not arguing that those genes don’t exist. I don’t question the data—I’m happy to believe that there really is a genetic association with all of these traits. Indeed, I think it’s becoming possible to find a real, verifiable genetic basis for almost anything you like.

The advent of genome-wide association studies (GWAS) has made it vastly easier to examine traits with smaller and smaller genetic contributions. In essence, you can pick your trait, sample the DNA of a large group of people, and scan their genomes for bits of shared sequence.

As a consequence, we have the recent bloom of studies describing the genetic component of all sorts of “complex” traits, from religiosity to getting drunk and beating people up. We’re only limited by our imaginations, and by the kinds of traits we’re interested in today.

Thinking about these recent studies, it occurred to me that these traits were not fundamentally different from Davenport’s old favorite, thalassophilia. I bet, I said to myself, that if sailing were as culturally important today as it was in 1919, people would be doing GWAS to find the genetic basis of sea-lust. And I bet they’d find it.

Of course, there are big differences between human genetics in 2011 and human genetics in 1919. Davenport advocated sterilization laws and immigration laws to manage and shrink what he saw as the swelling populations of the “unfit.” That would be inconceivable today. I don’t think we’re returning to a “new eugenics” in any meaningful sense.

But cutting across the cultural differences are some continuities. One of them is the desire to believe there is a simple genetic explanation for our tastes and talents. That I think is a dangerous view. So on the one hand, I think we should be careful to evaluate 1920s science by the standards of the day, rather than by those of the 21st century. And on the other, we must not delude ourselves that modern science is completely objective. Mechanistic explanations are not proof against cultural bias.

My spoof was intended as a word of caution, a way to inject a note of skepticism about genetic explanations of human nature. C.M (“Call Me) Ishmael, the journal Genetic Determinism Today, MysticGene, the 4C (“for sea”) variant, the salt-stained polo shirts and the sailing widows—all that was pure balderdash. As the motto of this site goes, “Here lies truth”— in roughly equal measure.

So, keep your heads up, folks—and watch for the keyword “Satire” in the Categories section of this blog. Thanks for reading.

Scientists find gene for love of the sea

What did Thor Heyerdahl, Captain Ahab, and Odysseus have in common? They all may have shared a common variant of a gene for love of the sea.

Researchers at Mystic University in Connecticut have identified a gene associated with seafaringness, according to an article to be published tomorrow in the journal Genetic Determinism Today. Patterns of inheritance of the long-sought gene offers hope for “sailing widows,” and could help explain why the sailing life has tended to run in families and why certain towns and geographical regions tend historically to have disproportionate numbers of sea-going citizens.

The gene is a form of the MAOA-L gene, previously associated with high-risk behavior and thrill-seeking; another form of the gene, found last year, made news as the “warrior gene.” The current variant, dubbed 4C, was found by a genome-wide association study (GWAS) on 290 individuals from Mystic, CT, New Bedford, MA, and Cold Spring Harbor, NY—all traditional nineteenth-century whaling villages. Residents showed the presence of the 4C variant at a frequency more than 20 times above background in neighboring landlocked towns.

C. M. Ishmael, the lead researcher on the study, said the findings could be a boon to medicine. Although the International Whaling Commission outlawed commercial whaling in 1986, the research could benefit literally hundreds of “sailing widows” left alone for Wednesday-evening sailboat races up and down the East Coast. Each year, an average of 11 salt-stained Polo shirts wash up on the New England and Mid-Atlantic coasts, the only remains of lantern-jawed investment bankers and their half-million-dollar boats. Ishmael said he is trying to have the irrational urge to sail entered into the Diagnostic and Statistical Manual, standard reference for psychiatric diseases, in the next, fifth, edition.

“This receptor is an exciting potential target for new drug therapies,” Ishmael said in a phone interview. “We hope lots of companies will be interested in it. And venture capital, too.” Ishmael is himself CEO of a company, MysticGene, formed to develop such therapies. When asked about potential conflict of interest, he replied cryptically, “Well, duh.” Shares of MysticGene closed higher on Monday following the announcement.

The gene for seafaringness has long been an object of study for human geneticists. The trait was first described in 1919 by Charles Davenport, director of Cold Spring Harbor Laboratory, who named it “thalassophilia.” Using pedigree analysis and anecdotal correlation, Davenport identified thalassophilia as a sex-linked recessive gene and distinguished it clinically from wanderlust, or love of adventure. Although one might think naively that people living in towns with good harbors would tend to go to sea, Davenport suggested the reverse: those with the thalassophilia trait have tended to migrate toward regions with good harbors and found settlements there. The current study does nothing to refute Davenport’s analysis.

Further, a tentative expansion of the GWAS analysis to various racial groups largely confirms Davenport’s observations that thalassophilia is more prevalent in Scandinavians and the English, and less common in people of German ancestry.

Thalassophilia joins a rapidly growing list of complex behavioral traits that have been shown to have a genetic basis, thanks to GWAS. Besides the warrior gene, recent studies have found genetic links to promiscuity, aggressive behavior, especially while drinking, religiosity, and bipolar disorder, or manic depression—all traits that Davenport and other early human geneticists were deeply interested in. The difference is that modern science better understands the mechanisms involved.

“Seamen know very well that their cravings for the sea are racial,” Davenport wrote in 1919. “’It is in the blood,’ they say.” Today we know it’s not in the blood—it’s in the genes.

The true bits:

Garland E. Allen, “Is a New Eugenics Afoot?,” Science 294, no. 5540 (October 5, 2001): 59 -61. (http://www.sciencemag.org/content/294/5540/59.short)

Charles Benedict Davenport and Mary Theresa Scudder, Naval officers: their heredity and development (Carnegie Institution of Washington, 1919),http://books.google.com/books?id=EWESAAAAYAAJ&dq=naval%20officers%3A%20their%20heredity%20and%20development&pg=PP1#v=onepage&q&f=false.

Richard Alleyne, “A gene that could explain why the red mist descends,” Telegraph.co.uk,http://www.telegraph.co.uk/science/science-news/8219521/A-gene-that-could-explain-why-the-red-mist-descends.html.

Jeremy Taylor, “Violent-drunk gene discovered,”http://www.asylum.com/2010/12/23/bad-drunk-gene-discovered/.

Justin R. Garcia et al., “Associations between Dopamine D4 Receptor Gene Variation with Both Infidelity and Sexual Promiscuity,” ed. Jan Lauwereyns, PLoS ONE 5, no. 11 (11, 2010): e14162.

C. Frydman et al., “MAOA-L carriers are better at making optimal financial decisions under risk,” Proceedings of the Royal Society B: Biological Sciences (12, 2010),http://www.newscientist.com/article/dn19830-people-with-warrior-gene-better-at-risky-decisions.html.

 

 

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