Learning can hurt

This essay, from 2007, summarizes how progress in genomics came to confront convenient but incorrect views on the genetic clustering of human populations. The vast majority of people, even scientists, are still confused about this subject. See also Human genetic variation, Fst and Lewontin's fallacy in pictures.

The flipside of serendipity: human genetics rediscovers race

... In this paper I investigate the recent re-emergence of genetic race in more detail, and endeavour to ascertain how, after a half-century hiatus, a young team of population geneticists could casually rediscover race in 2002. Was it happenstance? Or was it opportune timing? My tentative conclusions are: (a) the flipside of serendipity is sociopolitical context; and (b) in the first few years of the new millennium, on the face of it, the time was indeed ripe for genetic race to re-emerge within the scientific mainstream.

IT ALL STARTED WITH A CLUSTER ANALYSIS ...

'We have sequenced the genome of three females and two males, who have identified themselves as Hispanic, Asian, Caucasian or African American ... to help illustrate that the concept of race has no genetic or scientific basis. In the five Celera genomes, there is no way to tell one ethnicity from another.'--J Craig Venter, White House press conference, June 2000. (4)

Craig Venter was the 'maverick' geneticist who founded Celera Genomics--a private biotech company that, in the late 1990s, took on a trans-national network of publicly and privately funded researchers in a frantic race to sequence the human genome. In June 2000, at the White House press conference that heralded the completion of the 'first assembly' of the genome, standing next to his public-sector adversary Francis Collins, United States President Bill Clinton, and (via satellite feed) United Kingdom Prime Minister Tony Blair, in a triumphal moment for Big Science and liberal humanism Venter announced: 'the concept of race has no genetic or scientific basis.'

In saying this, he reaffirmed evolutionary biologist Richard Lewontin's oft-cited claim that racial classification is of 'virtually no genetic or taxonomic significance'. (5) He also echoed a gaggle of other geneticists and an army of anthropologists who, since the middle of the twentieth century, have similarly sought to deny that the 'race concept' has any basis in biology. In short, he took up what might be termed the 'race as social construct' position--a position that has come to function as a default setting within the social sciences in recent decades. Never mind that his assertion was based on an analysis of only five individual genomes and thus a statistical fallacy; the important thing was that it befitted the hyperbole of the occasion and had the aura of incontrovertible truth.

[[ Who could have possibly accepted these results as decisive? See Bounded Cognition. ]]

Over the next few years the incontrovertibility of the 'race as social construct' position began to erode. Just four years after Venter's speech, in the pages of a Nature genetics supplement dedicated to the issue of race in genomics, Francis Collins--who had shared both podium and Time magazine cover with Venter on that aforementioned momentous day--offered this cautious qualification: 'As ancestral origins in many cases have a correlation, albeit often imprecise, with self-identified race or ethnicity, it is not strictly true that race or ethnicity has no biological connection.' (6)

... Collins ... is the director of the US National Human Genome Research Institute, a renowned medical genetics researcher, and by all accounts not a racist. So why is a distinguished geneticist, not some racist crackpot on the margins of academia, suddenly making the claim: 'it is not strictly true that race or ethnicity has no biological connection'? What happened in those few short years that separate Venter's exultant assertion and Collins's wary disclaimer?

Ostensibly, the answer to these questions can be found in Collins's paper, for he cites evidence to support his claim: a population genetics study conducted by Noah Rosenberg and his team of researchers that was published in Science in December 2002. Drawing on samples from the Human Genome Diversity Cell Line Panel, (8) these researchers investigated the 'correspondence of predefined groups with those inferred from individual multilocus genotypes'. (9) They used a complex computer algorithm to sort 1,064 genome samples, from fifty-two different populations, on the basis of 4,199 different alleles, at 377 highly variable 'junk-DNA' loci, into varying numbers of statistically significant genetic clusters, and then compared the clusters with the geographical origins of the populations from which they were drawn. Put simply, they took the labels off the samples and tried to see if the computer could sort them back into meaningful groups based solely on their genetic similarities.

They found that 'predefined labels' (such as 'Yoruba', 'Italian' or 'Japanese') were 'highly informative about membership in genetic clusters'. (10) Further, when asked to identify five clusters, the computer grouped the samples into sets roughly corresponding to five geographical regions: (i) sub-Saharan Africa, (ii) Europe and West Asia, (iii) East Asia, (iv) Oceania, and (v) the Americas (see the row marked 'K=5' in Figure 1 below for a graphical representation of these clusters). Curiously, these regions are roughly geographically concordant to those occupied by the 'black', 'white', 'yellow', 'tawny' and 'copper-coloured' 'varieties' outlined in Johann Friedrich Blumenbach's seminal eighteenth-century racial typology. (11)

These results should have come as no surprise to most population geneticists, as it had long been assumed that human groups separated by physical, environmental, linguistic, and/or cultural barriers would display some degree of genetic differentiation. (12) Nonetheless, they were quite significant, as it was the first time that human populations had been comprehensively shown to cluster together on the basis of genetic likeness in a 'blind' test.

Still, Rosenberg and his colleagues were relatively circumspect in their conclusions. Their point was not to show that old anthropological conceptions of race are genetically 'real', but to argue that differentiating between human populations is both methodologically and statistically valid, and that such distinctions can be legitimately used for tracing the origins and migrations of peoples, as well as for medical and epidemiological purposes.

The words 'race' and 'ethnicity' never appeared in their paper, only 'population' and 'ancestry', and they were careful to choose neutral colours to code the continental clusters they identified--sub-Saharan Africa was orange, Europe and West Asia pale-blue, East Asia pink, Oceania green, and the Americas purple (not black, white, yellow, tawny and copper-coloured). Here they seemingly followed a convention established by the father of human population genetics and the prime mover behind the Human Genome Diversity Project, Luigi Luca Cavalli-Sforza, whose co-authored magnum opus, The History and Geography of Human Genes (1994, abridged 2006), featured a colour-coded atlas on its cover (Figure 2), with the caption: 'Four major ethnic regions are shown. Africans are yellow, Australians red, [Mongoloids blue] and Caucasoids green.' (13) A reviewer from Time magazine described Cavalli-Sforza's book as 'a landmark global study' that 'flattens The Bell Curve, proving that racial differences are only skin deep.' (14) Similarly, the Rosenberg study was lauded for its 'humanitarian' findings and adjudged 'paper of the year' by The Lancet in 2003. (15)

On the surface the consensus was that nothing much had changed. Population genetics had proven racial differences were only 'skin deep', and the Rosenberg findings only served to further confirm this incontrovertible fact. Everyone was content to repeat the familiar mantra: 'no race here ... nothing to look at ... move along'. However, beneath the 'race as social construct' ideological edifice a fuse had been lit and a 'race as biological reality' powder keg was about to go off.

THE MESSY FALLOUT

Even before the Rosenberg paper appeared, a group of belligerent geneticists headed up by Neil Risch from Stanford University had published an opinion piece in Genome Biology defending 'the validity of race/ethnicity categories for biomedical and genetic research' on the basis of cluster analyses similar to that used by the Rosenberg study.

[[ See Neil Risch, Portrait of a mathematical geneticist. ]]

The following year A W F Edwards, who had pioneered the statistical techniques behind cluster analysis with Cavalli-Sforza in the 1960s, penned a curt refutation of Lewontin's 1972 claim about the insignificance of racial classification, citing the Rosenberg study to buttress his argument. (17)

Following on from Edwards's assault, over the next few years several review essays appeared in major journals, (18) and the issue exploded onto the pages of the major broadsheets. Two articles from The New York Times tell the story of this re-emergence quite well: in August 2000 the headline read, 'Do races differ? Not really, genes show', with the author quoting Venter and others; (19) by July 2006 another headline read, 'Imperfect, imprecise but useful: Your race', and the article discussed the utility of racial classifications for biomedical research. (20)

A further twist in the plot of this recent race potboiler began on 14 March 2005, when evolutionary biologist Armand Marie Leroi published a now infamous op-ed piece, again in The New York Times (seemingly the arbiter of all things genetic), entitled 'A family tree in every gene'. (21) Taking up the Rosenberg study bait, he heralded their findings as suggesting: 'the consensus about social constructs was unravelling', and 'looked at the right way, the genetic data show that races clearly do exist.' (22) Further, he celebrated new advances in genetics that will soon mean, 'we shall no longer gawp ignorantly at the gallery [of racial differences]; we shall be able to name the painters.' (23)

Of course, more than a few people took exception to this talk of 'genetic painters' and 'racial galleries', and Leroi's article prompted a swift multi-pronged rebuttal. Within a month the US Social Science Research Council (SSCR) had sponsored a web forum collecting together critical responses from many of the usual 'social construct' suspects, including Alan Goodman, Evelynn Hammonds, Joseph Graves, Ruth Hubbard, Richard Lewontin and Jonathan Marks (many of whom also appeared in the 2003 PBS documentary series 'Race--the Power of an Illusion'). (24)

Labouring valiantly to plug the holes emerging in the epistemic dyke separating old race pseudoscience from modern human genetics, these ageing anti-race activists accused Leroi of 'reifying' race, and argued that race is most certainly not a biological category but rather an all-too-real social category that should be kept as far away as possible from the objective realm of science. ...


... This is what more sophisticated constructivists mean when they say race is a social construct--that the social and political aspects of race cannot easily be disentangled from the biological. (28) However, some constructivists want to go as far as to suggest that there is no biological dimension to race at all, with Richard Lewontin being a notorious culprit. Lewontin's research in the 1970s did not show that racial classifications were genetically insignificant, only that differences between racial groups were less significant than within groups. (29) His denial of the genetic significance of race is a non sequitur.

Putting aside Lewontin's fallacy, the major mistakes that unsophisticated social constructivists make are: (a) to suggest that being bound up with social and political concerns renders race 'unscientific' (as if scientific knowledge about human subjects could ever be separated from society and politics); and (b) to believe that by replacing race with the term population we can somehow escape this problem. The latter move just 'purifies' the concept of race, allowing geneticists to investigate racial groups such as 'Yoruba', 'Japanese', 'Caucasoid' or 'Australian' under the rubric of population, whilst denying that their research has anything to do with race. ...

Genetic basis for race

[See more recent posts on this topic here.]

The essential tension between science and political correctness on this issue is discussed in the Sunday Times.

We were told long ago that there is no scientific basis for race. Yet, it would be surprising if the distribution of individual genes were the same in all ethnic groups, with their different evolutionary histories of the last tens of thousands of years. In fact, mtDNA tests can readily identify which of a few dozen matrilineal lines any modern human belongs to. Each of these lines can in turn be traced to certain geographical regions to which early humans migrated from Africa, and correspond reasonably well to conventional racial categories.

Researchers last week described a new drug, called BiDil, that sharply reduces death from heart disease among African-Americans. ...But not everyone is cheering unreservedly. Many people, including some African-Americans, have long been uneasy with the concept of race-based medicine, in part from fear that it may legitimize less benign ideas about race.

...The emergence of BiDil, described last week in The New England Journal of Medicine, is a sharp reality test for an academic debate about race and medicine that has long occupied the pages of medical journals. Is there a biological basis for race? If there is not, as many social scientists and others argue, how can a drug like BiDil work so well in one race?

...This month, in a special issue on race published by the journal Nature Genetics, several geneticists wrote that people can generally be assigned to their continent of origin on the basis of their DNA, and that these broad geographical regions correspond to self-identified racial categories, such as African, East Asian, European and Native American. Race, in other words, does have a genetic basis, in their view.

...Some African-Americans fear that if doctors start to make diagnoses by race, then some in the public may see that as a basis for imputing behavioral traits as well. ''If you think in terms of taxonomies of race, you will make the dangerous conclusion that race will explain violence,'' says Dr. Troy Duster, a sociologist at New York University.

Portrait of a mathematical geneticist

An interesting PLoS interview with Neil Risch (via the blog Gene Expression.)

Neil Risch (Caltech BS in math; PhD in biomathematics from UCLA) is the Lamond Distinguished Professor in Human Genetics and Director of the Center for Human Genetics at the University of California, San Francisco, California, United States. He has held faculty appointments at Columbia, Yale, and Stanford Universities.

I have a strong problem with the way politicians use this information. [Former President] Clinton, for example, when the first draft of the human genome sequence came out, made a statement about how all people in the world, in terms of their genetic makeup, are 99.9% the same. His intent—to reduce conflict among peoples—is noble. People on the left, anthropologists and sociologists, do the same thing. They use the 99.9% figure as an argument for social equality. But the truth is that people do differ by that remaining 0.1% and that people do cluster according to their ancestry. The problem is that others could use that information to create division.

From NYT, March 20, 2003:

A view widespread among many social scientists, endorsed in official statements by the American Sociological Association and the American Anthropological Association, is that race is not a valid biological concept. But biologists, particularly the population geneticists who study genetic variation, have found that there is a structure in the human population. The structure is a family tree showing separate branches for Africans, Caucasians (Europe, the Middle East and the Indian subcontinent), East Asians, Pacific Islanders and American Indians.

Biologists, too, have often been reluctant to use the term "race." But this taboo was broken last year by Dr. Neil Risch, a leading population geneticist at Stanford University. Vexed by an editorial in The New England Journal that declared that race was "biologically meaningless," Dr. Risch argued in the electronic journal Genome Biology that self-identified race was useful in understanding ethnic differences in disease and in the response to drugs.

Race corresponded broadly to continental ancestry and hence to the branches on the human family tree described by geneticists, he said. Expanding this argument today, Dr. Risch and nine co-authors say that ignoring race will ‘retard progress in biomedical research.’ Racial differences have arisen, they say, because after the ancestral human population in Africa spread throughout the world 40,000 years ago, geographical barriers prevented interbreeding. On each continent, under the influence of natural selection and the random change between generations known as genetic drift, people would have diverged away from the common ancestral population, creating the major races. Within each race, religious, cultural and geographical barriers fostered other endogamous, or inbreeding, populations that led to the ethnic groups.

Genetics and Group Differences: David Reich (Harvard) in NYTimes

Harvard geneticist David Reich writes below in the New York Times. The prospect that human ancestry clusters ("races") might differ in allele frequencies, leading to quantifiable group differences, has been looming for a long time. Reich writes

I am worried that well-meaning people who deny the possibility of substantial biological differences among human populations are digging themselves into an indefensible position.

See Metric on the space of genomes (2007), Human genetic variation and Lewontin's fallacy in pictures (2008), and What's New Since Montagu? (2014).

How Genetics Is Changing Our Understanding of ‘Race’

By David Reich

March 23, 2018

In 1942, the anthropologist Ashley Montagu published “Man’s Most Dangerous Myth: The Fallacy of Race,” an influential book that argued that race is a social concept with no genetic basis. A classic example often cited is the inconsistent definition of “black.” In the United States, historically, a person is “black” if he has any sub-Saharan African ancestry; in Brazil, a person is not “black” if he is known to have any European ancestry. If “black” refers to different people in different contexts, how can there be any genetic basis to it?

Beginning in 1972, genetic findings began to be incorporated into this argument. That year, the geneticist Richard Lewontin published an important study of variation in protein types in blood. He grouped the human populations he analyzed into seven “races” — West Eurasians, Africans, East Asians, South Asians, Native Americans, Oceanians and Australians — and found that around 85 percent of variation in the protein types could be accounted for by variation within populations and “races,” and only 15 percent by variation across them. To the extent that there was variation among humans, he concluded, most of it was because of “differences between individuals.”

In this way, a consensus was established that among human populations there are no differences large enough to support the concept of “biological race.” Instead, it was argued, race is a “social construct,” a way of categorizing people that changes over time and across countries.

It is true that race is a social construct. It is also true, as Dr. Lewontin wrote, that human populations “are remarkably similar to each other” from a genetic point of view.

But over the years this consensus has morphed, seemingly without questioning, into an orthodoxy. The orthodoxy maintains that the average genetic differences among people grouped according to today’s racial terms are so trivial when it comes to any meaningful biological traits that those differences can be ignored.

The orthodoxy goes further, holding that we should be anxious about any research into genetic differences among populations. The concern is that such research, no matter how well-intentioned, is located on a slippery slope that leads to the kinds of pseudoscientific arguments about biological difference that were used in the past to try to justify the slave trade, the eugenics movement and the Nazis’ murder of six million Jews.

I have deep sympathy for the concern that genetic discoveries could be misused to justify racism. But as a geneticist I also know that it is simply no longer possible to ignore average genetic differences among “races.”

Groundbreaking advances in DNA sequencing technology have been made over the last two decades. These advances enable us to measure with exquisite accuracy what fraction of an individual’s genetic ancestry traces back to, say, West Africa 500 years ago — before the mixing in the Americas of the West African and European gene pools that were almost completely isolated for the last 70,000 years. With the help of these tools, we are learning that while race may be a social construct, differences in genetic ancestry that happen to correlate to many of today’s racial constructs are real.

Recent genetic studies have demonstrated differences across populations not just in the genetic determinants of simple traits such as skin color, but also in more complex traits like bodily dimensions and susceptibility to diseases. For example, we now know that genetic factors help explain why northern Europeans are taller on average than southern Europeans, why multiple sclerosis is more common in European-Americans than in African-Americans, and why the reverse is true for end-stage kidney disease.

I am worried that well-meaning people who deny the possibility of substantial biological differences among human populations are digging themselves into an indefensible position, one that will not survive the onslaught of science. I am also worried that whatever discoveries are made — and we truly have no idea yet what they will be — will be cited as “scientific proof” that racist prejudices and agendas have been correct all along, and that those well-meaning people will not understand the science well enough to push back against these claims.

This is why it is important, even urgent, that we develop a candid and scientifically up-to-date way of discussing any such differences, instead of sticking our heads in the sand and being caught unprepared when they are found.

To get a sense of what modern genetic research into average biological differences across populations looks like, consider an example from my own work. Beginning around 2003, I began exploring whether the population mixture that has occurred in the last few hundred years in the Americas could be leveraged to find risk factors for prostate cancer, a disease that occurs 1.7 times more often in self-identified African-Americans than in self-identified European-Americans. This disparity had not been possible to explain based on dietary and environmental differences, suggesting that genetic factors might play a role.

Self-identified African-Americans turn out to derive, on average, about 80 percent of their genetic ancestry from enslaved Africans brought to America between the 16th and 19th centuries. My colleagues and I searched, in 1,597 African-American men with prostate cancer, for locations in the genome where the fraction of genes contributed by West African ancestors was larger than it was elsewhere in the genome. In 2006, we found exactly what we were looking for: a location in the genome with about 2.8 percent more African ancestry than the average.

When we looked in more detail, we found that this region contained at least seven independent risk factors for prostate cancer, all more common in West Africans. Our findings could fully account for the higher rate of prostate cancer in African-Americans than in European-Americans. We could conclude this because African-Americans who happen to have entirely European ancestry in this small section of their genomes had about the same risk for prostate cancer as random Europeans.

Did this research rely on terms like “African-American” and “European-American” that are socially constructed, and did it label segments of the genome as being probably “West African” or “European” in origin? Yes. Did this research identify real risk factors for disease that differ in frequency across those populations, leading to discoveries with the potential to improve health and save lives? Yes.

While most people will agree that finding a genetic explanation for an elevated rate of disease is important, they often draw the line there. Finding genetic influences on a propensity for disease is one thing, they argue, but looking for such influences on behavior and cognition is another.

But whether we like it or not, that line has already been crossed. A recent study led by the economist Daniel Benjamin compiled information on the number of years of education from more than 400,000 people, almost all of whom were of European ancestry. After controlling for differences in socioeconomic background, he and his colleagues identified 74 genetic variations that are over-represented in genes known to be important in neurological development, each of which is incontrovertibly more common in Europeans with more years of education than in Europeans with fewer years of education.

It is not yet clear how these genetic variations operate. A follow-up study of Icelanders led by the geneticist Augustine Kong showed that these genetic variations also nudge people who carry them to delay having children. So these variations may be explaining longer times at school by affecting a behavior that has nothing to do with intelligence.

This study has been joined by others finding genetic predictors of behavior. One of these, led by the geneticist Danielle Posthuma, studied more than 70,000 people and found genetic variations in more than 20 genes that were predictive of performance on intelligence tests.

Is performance on an intelligence test or the number of years of school a person attends shaped by the way a person is brought up? Of course. But does it measure something having to do with some aspect of behavior or cognition? Almost certainly. And since all traits influenced by genetics are expected to differ across populations (because the frequencies of genetic variations are rarely exactly the same across populations), the genetic influences on behavior and cognition will differ across populations, too.

You will sometimes hear that any biological differences among populations are likely to be small, because humans have diverged too recently from common ancestors for substantial differences to have arisen under the pressure of natural selection. This is not true. The ancestors of East Asians, Europeans, West Africans and Australians were, until recently, almost completely isolated from one another for 40,000 years or longer, which is more than sufficient time for the forces of evolution to work. Indeed, the study led by Dr. Kong showed that in Iceland, there has been measurable genetic selection against the genetic variations that predict more years of education in that population just within the last century.

To understand why it is so dangerous for geneticists and anthropologists to simply repeat the old consensus about human population differences, consider what kinds of voices are filling the void that our silence is creating. Nicholas Wade, a longtime science journalist for The New York Times, rightly notes in his 2014 book, “A Troublesome Inheritance: Genes, Race and Human History,” that modern research is challenging our thinking about the nature of human population differences. But he goes on to make the unfounded and irresponsible claim that this research is suggesting that genetic factors explain traditional stereotypes.

One of Mr. Wade’s key sources, for example, is the anthropologist Henry Harpending, who has asserted that people of sub-Saharan African ancestry have no propensity to work when they don’t have to because, he claims, they did not go through the type of natural selection for hard work in the last thousands of years that some Eurasians did. There is simply no scientific evidence to support this statement. Indeed, as 139 geneticists (including myself) pointed out in a letter to The New York Times about Mr. Wade’s book, there is no genetic evidence to back up any of the racist stereotypes he promotes.

Another high-profile example is James Watson, the scientist who in 1953 co-discovered the structure of DNA, and who was forced to retire as head of the Cold Spring Harbor Laboratories in 2007 after he stated in an interview — without any scientific evidence — that research has suggested that genetic factors contribute to lower intelligence in Africans than in Europeans.

At a meeting a few years later, Dr. Watson said to me and my fellow geneticist Beth Shapiro something to the effect of “When are you guys going to figure out why it is that you Jews are so much smarter than everyone else?” He asserted that Jews were high achievers because of genetic advantages conferred by thousands of years of natural selection to be scholars, and that East Asian students tended to be conformist because of selection for conformity in ancient Chinese society. (Contacted recently, Dr. Watson denied having made these statements, maintaining that they do not represent his views; Dr. Shapiro said that her recollection matched mine.)

What makes Dr. Watson’s and Mr. Wade’s statements so insidious is that they start with the accurate observation that many academics are implausibly denying the possibility of average genetic differences among human populations, and then end with a claim — backed by no evidence — that they know what those differences are and that they correspond to racist stereotypes. They use the reluctance of the academic community to openly discuss these fraught issues to provide rhetorical cover for hateful ideas and old racist canards.

This is why knowledgeable scientists must speak out. If we abstain from laying out a rational framework for discussing differences among populations, we risk losing the trust of the public and we actively contribute to the distrust of expertise that is now so prevalent. We leave a vacuum that gets filled by pseudoscience, an outcome that is far worse than anything we could achieve by talking openly.

If scientists can be confident of anything, it is that whatever we currently believe about the genetic nature of differences among populations is most likely wrong. For example, my laboratory discovered in 2016, based on our sequencing of ancient human genomes, that “whites” are not derived from a population that existed from time immemorial, as some people believe. Instead, “whites” represent a mixture of four ancient populations that lived 10,000 years ago and were each as different from one another as Europeans and East Asians are today.

So how should we prepare for the likelihood that in the coming years, genetic studies will show that many traits are influenced by genetic variations, and that these traits will differ on average across human populations? It will be impossible — indeed, anti-scientific, foolish and absurd — to deny those differences.

For me, a natural response to the challenge is to learn from the example of the biological differences that exist between males and females. The differences between the sexes are far more profound than those that exist among human populations, reflecting more than 100 million years of evolution and adaptation. Males and females differ by huge tracts of genetic material — a Y chromosome that males have and that females don’t, and a second X chromosome that females have and males don’t.

Most everyone accepts that the biological differences between males and females are profound. In addition to anatomical differences, men and women exhibit average differences in size and physical strength. (There are also average differences in temperament and behavior, though there are important unresolved questions about the extent to which these differences are influenced by social expectations and upbringing.)

How do we accommodate the biological differences between men and women? I think the answer is obvious: We should both recognize that genetic differences between males and females exist and we should accord each sex the same freedoms and opportunities regardless of those differences.

It is clear from the inequities that persist between women and men in our society that fulfilling these aspirations in practice is a challenge. Yet conceptually it is straightforward. And if this is the case with men and women, then it is surely the case with whatever differences we may find among human populations, the great majority of which will be far less profound.

An abiding challenge for our civilization is to treat each human being as an individual and to empower all people, regardless of what hand they are dealt from the deck of life. Compared with the enormous differences that exist among individuals, differences among populations are on average many times smaller, so it should be only a modest challenge to accommodate a reality in which the average genetic contributions to human traits differ.

It is important to face whatever science will reveal without prejudging the outcome and with the confidence that we can be mature enough to handle any findings. Arguing that no substantial differences among human populations are possible will only invite the racist misuse of genetics that we wish to avoid.

David Reich is a professor of genetics at Harvard and the author of the forthcoming book “Who We Are and How We Got Here: Ancient DNA and the New Science of the Human Past,” from which this article is adapted.

This is a recent Reich lecture with the same title as his forthcoming book.

Brains, genes, backlash

We posted before about Bruce Lahn's research. Lahn showed that two variants of a gene suspected to be related to brain function exhibit very different distributions in different ethnic groups, and show signs of having been subject to strong selection fairly recently in human history. Today the WSJ ran a front page article on Lahn and the backlash against his research (excerpts below). See also this interview with Lahn from Science.

Last September, Bruce Lahn, a professor of human genetics at the University of Chicago, stood before a packed lecture hall and reported the results of a new DNA analysis: He had found signs of recent evolution in the brains of some people, but not of others.

It was a triumphant moment for the young scientist. He was up for tenure and his research was being featured in back-to-back articles in the country's most prestigious science journal. Yet today, Dr. Lahn says he is moving away from the research. "It's getting too controversial," he says.

Dr. Lahn had touched a raw nerve in science: race and intelligence.

What Dr. Lahn told his audience was that genetic changes over the past several thousand years might be linked to brain size and intelligence. He flashed maps that showed the changes had taken hold and spread widely in Europe, Asia and the Americas, but weren't common in sub-Saharan Africa.

Web sites and magazines promoting white "racialism" quickly seized on Dr. Lahn's suggestive scientific snapshot. One magazine that blames black and Hispanic people for social ills hailed his discovery as "the moment the antiracists and egalitarians have dreaded."

Dr. Lahn has drawn sharp fire from other leading genetics researchers. They say the genetic differences he found may not signify any recent evolution -- and even if they do, it is too big a leap to suggest any link to intelligence. "This is not the place you want to report a weak association that might or might not stand up," says Francis Collins, director of the genome program at the National Institutes of Health.

Several scientific groups have set out to disprove or challenge Dr. Lahn's discoveries. His own university now says it is abandoning a patent application it filed to cover a DNA-based intelligence test that drew on his work.

As scientific tools for probing genes become increasingly powerful, research into human differences has exploded. Most of the time, scientists are looking for clues about the causes of disease. But some research is raising tensions as scientists such as Dr. Lahn venture into studies of genetic differences in behavior or intelligence.

Pilar Ossorio, a professor of law and medical ethics at the University of Wisconsin, criticizes Dr. Lahn for implying a conclusion similar to "The Bell Curve," a controversial 1994 bestseller by Richard J. Herrnstein and Charles Murray. The book argued that the lower average performance by African-Americans on IQ tests had a genetic component and wasn't solely the result of social factors. Referring to Dr. Lahn and his co-authors, Prof. Ossorio says: "It's exactly what they were getting at. There was a lot of hallway talk. People said he's doing damage to the whole field of genetics."

The 37-year-old Dr. Lahn says his research papers, published in Science last September, offered no view on race and intelligence. He personally believes it is possible that some populations will have more advantageous intelligence genes than others. And he thinks that "society will have to grapple with some very difficult facts" as scientific data accumulate. Yet Dr. Lahn, who left China after participating in prodemocracy protests, says intellectual "police" in the U.S. make such questions difficult to pursue.

Scientists believe that a small group of anatomically modern humans struck out from Africa probably less than 100,000 years ago. After arriving on the Eurasian land mass, they continued to split up and eventually humans populated nearly every corner of the globe. One use of genetic research is to probe how each group evolved differently after becoming isolated from the others. Recently created genetic maps of people of African, Asian and European ancestry make that research easier.

For instance, researchers have found that most Europeans have a genetic variant that lets them fully digest milk as adults. The variant is much less common in Africa and Asia, where lactose intolerance is widespread. Scientists theorize that it spread quickly among Europeans because drinking milk from domesticated dairy animals conferred a nutritional advantage. Similar evolutionary reasoning may explain why many people in malaria-prone parts of Africa carry gene variants linked to malaria resistance.

Other research is starting to explain variations in human skin color and hair texture. But scientists tense up when it comes to doing the same sort of research on the brain. Sociologist Troy Duster, who studies the use of racial categories by geneticists, worries that scientists will interpret data in ways that fit their prejudices. He cites the sorry history of phrenology, a study of skull shapes popular in the 19th century, and other pseudoscientific techniques used to categorize people as inferior. "Science doesn't transcend the social milieu," says Dr. Duster, of New York University.

Dr. Lahn traces his interest in human differences back to his youth in China. Foreigners there used to have a special currency that they could use at stores closed to ordinary Chinese. "I wondered why people were different, and why Chinese were at the bottom," he says.

By the time violence struck Tiananmen Square in 1989, Dr. Lahn, the son of two physicists, was an undergraduate at Harvard University. He channeled his curiosity into genetics and built his reputation with a groundbreaking study of the Y chromosome. After taking a post at the University of Chicago in 2000, Dr. Lahn won a prestigious fellowship from the Howard Hughes Medical Institute.

The fellowship pays most of his research bills and has allowed him to pursue creative projects, often on attention-grabbing subjects. One study looked at how promiscuity among female chimpanzees, gorillas and humans affected the evolution of a gene that makes sperm sticky. "Bruce is in a hurry to be famous," says Martin Kreitman, a Chicago colleague who is friendly with him.

Henry Harpending, a University of Utah anthropology professor who recently published a theory for why Ashkenazi Jews tend to have high IQ's, says Dr. Lahn once suggested they co-author an article for Scientific American about the genetics of behavior, in which they could explain why "Chinese are boring."

"I think that Bruce doesn't understand political correctness," Dr. Harpending says. Dr. Lahn says he only vaguely recalls the conversation but confirms that he wonders whether during China's imperial times there was "some selection" against rebellious individuals.

In recent years, Dr. Lahn has become interested in why the human brain is so large and complex. Although humans and chimpanzees share about 96% of their DNA, human brains are about four times larger. Even today, researchers can find a correlation, on average, between people's brain size and their IQ.

Dr. Lahn's group zeroed in on the role of two genes, called ASPM and microcephalin, that are known to have a role in brain size. Humans with defective copies of either gene are born with brains only about one-third the normal size.

Studying DNA from several species, the Chicago team found that, over millions of years, the genes had undergone more rapid change in monkeys, apes and humans than in other animals. Their next step was to determine if evolution had continued in modern humans. Dr. Lahn's graduate students began decoding DNA from 1,184 people belonging to 59 groups from around the world, including Bedouins, Pima Indians and French-speaking Basques.

The data showed that evolution had continued in recent millennia. A statistical analysis of DNA patterns suggested that new mutations in each of the two brain-related genes had spread quickly through some human populations. Evidently, these mutations were advantageous among those populations -- just as the genetic variant promoting milk digestion was advantageous to early Europeans. Dr. Lahn and his team further observed that the new mutations are found most frequently outside of Africa.

What the data didn't say was how the mutations were advantageous. Perhaps the genes play a role outside of the brain or affect a brain function that has nothing to do with intelligence.

While acknowledging that the evidence doesn't permit a firm conclusion, Dr. Lahn favors the idea that the advantage conferred by the mutations was a bigger and smarter brain. He found ways to suggest that in his papers. One mutation, which according to his estimates arose some 40,000 years ago, coincided with the first art found in caves, the paper observed. The other mutation, present mostly in people from the Middle East and Europe, and estimated to be 5,800 years old, coincided with the "development of cities and written language."

That suggested brain evolution might have occurred in tandem with important cultural changes. Yet because neither variant is common in sub-Saharan Africa, there was another potential implication: Some groups had been left out.

The dean of the University of Chicago's medical school, James L. Madara, says he approached Dr. Lahn before the papers were published. They discussed whether the report could be taken out of context. "Let the chips lie where they may," Dr. Madara says he told Dr. Lahn. As long as the ideas and data are clear, "don't worry about the implications," the dean said.

John Easton, head of media relations at the medical school, says his office was worried the work could be misinterpreted and abused by racist groups. Mr. Easton borrowed a copy of "The Mismeasure of Man," the famous attack on IQ tests and brain-volume measurements by the late paleontologist Stephen Jay Gould. Mr. Easton helped Dr. Lahn with talking points about his research. "We said, 'Don't be shy about telling people what it doesn't mean,' " Mr. Easton recalls.

Mr. Easton says Dr. Lahn "makes us nervous" but "with Bruce we know it's not driven by personal bias." That is because Asians "don't score at the top" in the frequency of the brain-gene mutations, Mr. Easton says.

Dr. Lahn's paper and talk at his university -- in which he also claimed the gene variants were probably linked to higher IQ -- provoked a strong reaction both on and off campus. Dr. Collins, head of the federal genome program, obtained advance copies of the papers and circulated them to top population geneticists. He wasn't persuaded by the statistical evidence for evolution and criticized Dr. Lahn's work in media interviews.

The papers won wide attention among researchers, and several responded by setting out to test Dr. Lahn's findings. Scientists at the Broad Institute, a top genetics center in Cambridge, Mass., have been reanalyzing some of the data and say they may challenge Dr. Lahn's finding that evolution acted on ASPM, one of the genes. Broad's influential chief, Eric Lander, says scientists probing recent evolution run the risk of "seeing a difference, and saying there is a story to fit it."

A team at the University of California, Los Angeles, recently tested whether the gene variants actually affect brain size. They studied DNA from 120 people whose brain volumes they had already measured using magnetic-resonance imaging. They didn't find any difference. "It certainly makes you want to look at other explanations" of what the variations mean, says Roger P. Woods, a UCLA brain-mapping expert who reported the results in May.

Some of Dr. Lahn's co-authors are also uncomfortable with the work. Sarah Tishkoff, a geneticist at the University of Maryland who provided DNA from remote African groups, says she is bothered how one paper drew a link between the genetic changes and the rise of civilization. She thinks it is too early to reach any conclusions about why the changes spread and says it is "very simplistic" to imagine that a single gene could have a major effect on complex cultural traits.

Several groups of scientists have sent letters to Science criticizing the papers. Dr. Lahn prepared responses, sending one earlier this month, but Dr. Tishkoff wasn't willing to add her name to them.

"You have to follow the data wherever it leads, but speculating in this field is dangerous," says Spencer Wells, head of the National Geographic Society's Genographic Project, a five-year, $40 million effort to collect DNA samples from 100,000 indigenous people. Dr. Wells says the project team might try to find evolutionary reasons for physical differences such as why Danes are taller than pygmies. But Dr. Wells says National Geographic won't study the brain. "I think there is very little evidence of IQ differences between races," he says.

The accuracy of Dr. Lahn's work and his views on race came up in his tenure review last fall, says a person familiar with it. After debate, his department voted unanimously in his favor, according to another faculty member. A more senior committee agreed and awarded Dr. Lahn the post of full professor, although it wasn't unanimous, this person says.

Dr. Lahn stands by his work but says that because of the controversy he is moving into other projects. Earlier this year, Mr. Easton of the university's media department forwarded Dr. Lahn a paper by two economists looking at the IQ of infants of different races. Dr. Lahn wasn't interested. "I'm surprised anyone studies this," he replied in an email.

Dr. Lahn says he isn't as eager as he once was to continue studying brain differences. P. Thomas Schoenemann, a professor of anthropology at the University of Michigan-Dearborn, says that at Dr. Lahn's request he collected DNA from 25 people whose brain sizes he had studied previously. But the two scientists haven't been in touch recently.

The university's patent office is also having second thoughts. Its director, Alan Thomas, says his office is dropping a patent application filed last year that would cover using Dr. Lahn's work as a DNA-based intelligence test. "We really don't want to end up on the front page...for doing eugenics," Mr. Thomas says.

More recently, Dr. Lahn says he was moved when a student asked him whether some knowledge might not be worth having. It is a notion to which he has been warming. Dr. Lahn says he once tried testing himself for which version of the brain genes he has. The experiment's outcome was blurry "but it wasn't looking good," he says. He hasn't tried testing himself again.

What's New Since Montagu?

I wrote this to help a journalist who is trying to understand the current controversy over A Troubled Inheritance, the new book by NYTimes genetics correspondent Nicholas Wade. (Link above goes to earlier discussion on this blog, with additional useful links and figures.)

The anthropologist Ashley Montagu advanced the idea that race is a social construct rather than a biological reality. For Wade, Montagu is a foil against which to benchmark recent advances in human genomics.

Wade: ... So I decided that I would write a book that explained what we know about race and what the consequences might be, and I think Montagu made a terrible mistake, though I share his motives.

Note the discussion below avoids using the term "race" and focuses instead on groups of humans that share ancestry. The degree of sharing can now be directly measured through genotypes.

What's New Since Montagu?

Two modern humans differ at about 1 in 1000 loci (out of ~ 3 billion in the human genome). There are a few million differences between any two individuals across their entire genome.

A common argument is that 99.9 percent genetic similarity cannot leave room for "consequential" differences. But modern humans and Neanderthals are almost as similar (~ 99.8 percent; we have high accuracy sequences now for Neanderthals), and there are significant differences between us and them: both physical and cognitive. However, because humans and Neanderthals are known to have interbred, we are still part of the same species. (Would it be fair to refer to them as a separate "race"? Is the modern-Neanderthal difference merely a social construct?) Furthermore, this 0.1 percent genetic variation accounts for human diversity encompassing Confucius, Einstein, Shaq and Shakespeare.

Genetic variation is patterned -- two individuals who trace their ancestry to the same geographical region (e.g., two Japanese) will have about 15 percent fewer total differences between them than if we were to compare individuals from widely separated ancestries (e.g., a Nigerian and a Japanese). This means hundreds of thousands of fewer differences between individuals from the same group than for two randomly selected people from different groups. 

Gene variants (alleles) which are common in one population (e.g., 90 percent of Japanese have version A) can be rare in another (e.g., only 20 percent of Nigerians have version A). Differences in allele frequencies are correlated across populations. From these correlations one can easily identify a genome (or even a small chunk of DNA as long as it includes many alleles) as belonging to a particular ancestral group. To oversimplify: just ask whether the DNA chunk in question has mostly the variants that are common in one group as opposed to another. Even if the differences in allele frequency are small -- e.g., allele X is 62 percent likely in Japanese, versus 57 percent likely in Nigerians -- once we consider thousands of such alleles the statistical signal becomes apparent. Each individual (or chunk of DNA) can be associated with a particular ancestral group.

Is this genetic difference consequential? Does it make two Nigerians more similar, on average, to each other than to a random European? Obviously, on some superficial phenotypes such as skin color or nose shape, the answer is yes.

But what about more complicated traits, such as height or cognitive ability or personality? All of these are known to be significantly heritable, through twin and adoption studies, as well as more modern methods.

We can't answer the question without understanding the specific genetic architecture of the trait. For example, are alleles that slightly increase height more common in one group than another? We need to know exactly which alleles affect height... But this is challenging as the traits I listed are almost certainly controlled by hundreds or thousands of genes. Could population averages on these traits differ between groups, due to differences in allele frequencies? I know of no argument, taking into account the information above, showing that they could not.

In fact, in the case of height we are close to answering the question. We have identified hundreds of loci correlated to height. Detailed analysis suggests that the difference in average height between N and S Europeans (about one population SD, or a couple of inches) is partially genetic (N Europeans, on average, have a larger number of height increasing alleles than S Europeans), due to different selection pressures that the populations experienced in the recent past (i.e., past 10k years).

Many who argue on Montagu's side hold the prior belief that the ~ 50k years of isolation between continental populations is not enough time for differential selection to produce group differences, particularly in complex traits governed by many loci. This is of course a quantitative question depending on strength of selection in different environments. The new results on height should cause them to reconsider their priors.

It is fair to say that results on height, as well as on simpler traits such as lactose or altitude tolerance, are consistent with Wade's theme that evolution has been recent, copious, and regional.

Further extrapolation to behavioral and cognitive traits will require more data, but:

1) The question is scientific -- it can be answered with known methods. (I estimate of order millions of genotype-phenotype pairs will allow us to extract the genetic architecture of complex traits like cognitive ability -- perhaps sometime in the coming decade.)

2) There is no a priori argument, given what we currently know, that such differences cannot exist. (Cf. Neanderthals!) Note this is NOT an argument that differences exist -- merely that they might, and that we cannot exclude the possibility.

An honest Ashley Montagu would have to concede points 1 and 2 above.

The second part of A Troublesome Inheritance covers controversial topics such as genetic group differences in behavioral and cognitive predispositions, and their societal implications. Wade is mostly careful to present these as speculative hypotheses, but nevertheless his advocacy leaves him vulnerable to easy attack. What I have summarized above are the incontestable (albeit, in some circles, perhaps still controversial and poorly understood) new results that have accumulated through the last decade of genomic research.

See also Recent human evolution: European height and The Neanderthal Problem.

Note Added: Distinguished evolutionary biologist H. Allen Orr has written a review in The New York Review of Books which I find quite similar to mine.

There was some back and forth between Razib Khan, Orr and Jerry Coyne. I added the comment below.

My take on the book is similar to that of Orr/Coyne: does a decent job of explaining population structure; too much speculation in the second part.

However, I think Orr/Coyne/Wade all miss the most interesting piece of science regarding strength of recent selection: evidence that the N-S height gradient (about 1 SD of difference between the two regions) in Europeans is due to selection pressure. That would constitute an example of fairly strong (in the context of the debate over group differences in humans) selection pressure acting over relatively short periods of time (~ 10 kya or less). I would think this result, if it holds up, might require significant updating of priors for certain people. It also provides a good example of how science in this area should be done: observed phenotype group difference, large data sets (GIANT) teasing out the genetic architecture, tests for selection on associated genetic variants.

http://infoproc.blogspot.com/2014/05/whats-new-since-montagu.html
http://infoproc.blogspot.com/2012/08/recent-human-evolution-european-height.html

Another point, for the cognoscenti: Wade does a good job explaining the difference between soft and hard sweeps. Orr notes that small adjustments of allele frequencies is one of the primary mechanisms for evolutionary change (so nothing new in Wade’s discussion; goes all the way back to Fisher), but many many readers, even biologists who aren’t in population genetics, don’t understand this point very well. So reading that section in the book would increase understanding for a large number of people.

Designer babies

Enhanced or unenhanced? You be the judge... From the episode Space Seed (trailer); full video.

McCoy: The Eugenics Wars of the 1990s.
Spock: Your attempt to improve the race by selective breeding.
McCoy: Oh no not our attempt, Mr. Spock. A group of ambitious scientists.





Soon to be outlawed? Probably not in Asia...

WSJ: Want a daughter with blond hair, green eyes and pale skin?

A Los Angeles clinic says it will soon help couples select both gender and physical traits in a baby when they undergo a form of fertility treatment. The clinic, Fertility Institutes, says it has received "half a dozen" requests for the service, which is based on a procedure called pre-implantation genetic diagnosis, or PGD.

While PGD has long been used for the medical purpose of averting life-threatening diseases in children, the science behind it has quietly progressed to the point that it could potentially be used to create designer babies. It isn't clear that Fertility Institutes can yet deliver on its claims of trait selection. But the growth of PGD, unfettered by any state or federal regulations in the U.S., has accelerated genetic knowledge swiftly enough that pre-selecting cosmetic traits in a baby is no longer the stuff of science fiction.

"It's technically feasible and it can be done," says Mark Hughes, a pioneer of the PGD process and director of Genesis Genetics Institute, a large fertility laboratory in Detroit. However, he adds that "no legitimate lab would get into it and, if they did, they'd be ostracized."

But Fertility Institutes disagrees. "This is cosmetic medicine," says Jeff Steinberg, director of the clinic that is advertising gender and physical trait selection on its Web site. "Others are frightened by the criticism but we have no problems with it."

PGD is a technique whereby a three-day-old embryo, consisting of about six cells, is tested in a lab to see if it carries a particular genetic disease. Embryos free of that disease are implanted in the mother's womb. Introduced in the 1990s, it has allowed thousands of parents to avoid passing on deadly disorders to their children.

...In a recent U.S. survey of 999 people who sought genetic counseling, a majority said they supported prenatal genetic tests for the elimination of certain serious diseases. The survey found that 56% supported using them to counter blindness and 75% for mental retardation.

More provocatively, about 10% of respondents said they would want genetic testing for athletic ability, while another 10% voted for improved height. Nearly 13% backed the approach to select for superior intelligence, according to the survey conducted by researchers at the New York University School of Medicine.

There are significant hurdles to any form of genetic enhancement. Most human traits are controlled by multiple genetic factors, and knowledge about their complex workings, though accelerating, is incomplete. And traits such as athleticism and intelligence are affected not just by DNA, but by environmental factors that cannot be controlled in a lab.

While many countries have banned the use of PGD for gender selection, it is permitted in the U.S. In 2006, a survey by the Genetics and Public Policy Center at Johns Hopkins University found that 42% of 137 PGD clinics offered a gender-selection service.

The science of PGD has steadily expanded its scope, often in contentious ways. Embryo screening, for example, is sometimes used to create a genetically matched "savior sibling" -- a younger sister or brother whose healthy cells can be harvested to treat an older sibling with a serious illness.

It also is increasingly used to weed out embryos at risk of genetic diseases -- such as breast cancer -- that could be treated, or that might not strike a person later in life. In 2007, the Bridge Centre fertility clinic in London screened embryos so that a baby wouldn't suffer from a serious squint that afflicted the father.

...For trait selection, a big hurdle is getting enough useful DNA material from the embryo. In a typical PGD procedure, a single cell is removed from a six-cell embryo and tested for the relevant genes or SNPs. It's relatively easy to check and eliminate diseases such as cystic fibrosis that are linked to a single malfunctioning gene. But to read the larger number of SNP markers associated with complex ailments such as diabetes, or traits like hair color, there often isn't enough high-quality genetic material.

William Kearns, a medical geneticist and director of the Shady Grove Center for Preimplantation Genetics in Rockville, Md., says he has made headway in cracking the problem. In a presentation made at a November meeting of the American Society of Human Genetics in Philadelphia, he described how he had managed to amplify the DNA available from a single embryonic cell to identify complex diseases and also certain physical traits.

Of 42 embryos tested, Dr. Kearns said he had enough data to identify SNPs that relate to northern European skin, hair and eye pigmentation in 80% of the samples. (A patent for Dr. Kearn's technique is pending; the test data are unpublished and have yet to be reviewed by other scientists.)

Dr. Kearns' talk attracted the attention of Dr. Steinberg, the head of Fertility Institutes, which already offers PGD for gender selection. The clinic had hoped to collaborate with Dr. Kearns to offer trait selection as well. In December, the clinic's Web site announced that couples who signed up for embryo screening would soon be able to make "a pre-selected choice of gender, eye color, hair color and complexion, along with screening for potentially lethal diseases."

Nicholas Wade interview: A Troublesome Inheritance

Leonard Lopate interviews Nicholas Wade (veteran genetics correspondent for the NYTimes) about his new book A Troublesome Inheritance: Genes, Race and Human History. The interview is slow at first but the second half is good.



Update: Another interview (May 9), with CBC, that gets right to the point regarding "social construction" -- the convenient but incorrect legacy of anthropologist Ashley Montagu (Israel Ehrenberg). The second guest, Stanford anthropologist Duana Fullwiley, foreshadows the counterattack on Wade.

See also this well-written essay in Time, adapted from the book.


I received a copy of A Troublesome Inheritance from the publisher. My initial impressions:

(1) The first part of the book covers well-established science concerning the genetic clustering of human populations. Some of the results will be surprising to those who have not followed the last 10 years of progress in genomics. See, e.g., here and here for my thoughts on this subject.

(2) The second part of the book covers controversial topics such as genetic group differences in behavioral and cognitive predispositions. Wade is mostly careful to present these as speculative hypotheses, but nevertheless his advocacy leaves him vulnerable to easy attack.

It will be interesting to see how this book, by a prominent science writer (indeed, the chief genetics correspondent for the paper of record), is received by the intelligentsia, the punditocracy, and actual scientists.

Additional remarks:

 

Below I have excerpted from the first link in (1) above, a post I originally wrote in 2007. I think these remarks are quite relevant to Wade's new book; note specific comments in brackets [ ... ].

... Two groups that form distinct [ genetic ] clusters are likely to exhibit different frequency distributions over various genes, leading to group differences. [ One does not require a more precise definition of "races" to get immediately to the thorny questions: two groups that differ in allele frequencies may differ statistically in phenotype! ]

This leads us to two very different possibilities in human genetic variation:

Hypothesis 1: (the PC mantra) The only group differences that exist between the clusters (races) are innocuous and superficial, for example related to skin color, hair color, body type, etc.

Hypothesis 2: (the dangerous one) Group differences exist which might affect important (let us say, deep rather than superficial) and measurable characteristics, such as cognitive abilities, personality, athletic prowess, etc.

... As scientists, we don't know whether H1 or H2 is correct, but given the revolution in biotechnology, we will eventually. Let me reiterate, before someone labels me a racist: we don't know with high confidence whether H1 or H2 is correct.

... it is important to note that group differences are statistical in nature and do not imply anything definitive about a particular individual. Rather than rely on the scientifically unsupported claim that we are all equal, it would be better to emphasize that we all have inalienable human rights regardless of our abilities or genetic makeup. [ Consider individuals, who are clearly unequal in their gifts: greater abilities should not confer greater rights! ]

... Clustering makes it possible that H2 is correct, because the alleles (genetic variants) affecting a particular phenotype will tend to have different frequencies in different groups. The average value of the trait might or might not be the same in different groups. In the case of height, enough is known to suggest that variants which lead to increased height are more frequent in northern Europe than in the south, and there is evidence that this is due to selection, not drift. [ i.e., this is evidence of recent selection driving group differences in a complex trait, controlled by thousands of loci. Wade: “Human evolution has been recent, copious, and regional.” ]

... I think it's especially important to be epistemologically careful in thinking about these matters, because of our difficult history with race. [ By articulating so many speculative theories in the second part of his book, Wade risks being perceived as not careful. ]

... I would much rather live in a world where H1 is true and H2 false. But my preference alone does not make it so. (I would also much rather live in a universe created by a loving God, and in which I and my children have eternal souls; not a cruel Darwinian universe in which our species arose merely by chance. But my preference does not make it so.)

Maxwell's Demon and genetic engineering

Ronald Fisher on positive alleles for intelligence, in Mendelism and Biometry (1911).

Suppose we knew, for example, 20 pairs of mental characters [loci in the genome]. These would combine in over a million pure mental types; each of these would naturally occur rather less frequently than once in a billion; or in a country like England about once in 20,000 generations; it will give some idea as to the excellence of the best of these types when we consider that the Englishmen from Shakespeare to Darwin have occurred within 10 generations; the thought of a race of men combining the illustrious qualities of these giants, and breeding true to them, is almost too overwhelming, but such a race will inevitably arise in whatever country first sees the inheritance of mental characters elucidated.

The amount of variation in intelligence within a particular family is almost as large as in the population as a whole, mainly due to the diploid nature of our genomes (half of the genes come randomly from each parent). Thus, as Fisher noted, superior characteristics do not "breed true" (see earlier discussion of regression and the residual SD of about 12 even after parental midpoint is fixed; note what is commonly referred to as regression to the mean has a large environmental component, which is distinct from what is discussed here). It is unlikely for a particular descendant to inherit most of the positive variants from both the mother and the father. If loci with positive effect on intelligence were identified, and selection performed on gametes (or zygotes), one could ensure offspring with many more advantageous alleles than normally obtained by chance. We would obtain the best from the set of possible offspring of a given mother and father. A process of this type can be thought of as a Maxwell's Demon of reproduction -- it suppresses fluctuations of the wrong sign.

The mathematical theory of additive (linear) genetics was elucidated by Fisher -- he even gave estimates for the non-additive part of heritability (CP9 and CP24 here). It seems likely to me that the first applications on humans (as opposed to selective breeding of plants and animals, which has already taken place) of Fisher's insights will come just over a hundred years later! Technology may finally allow us to explore the most interesting regions of the space of genetic variation :-)

PS I thought about titling this post They Might Be Giants, but the statistical mechanic in me won out :-) Fisher was well aware of the parallels between his use of multivariate statistics in genetics and the corresponding application in the theory of gases.

Twitter Attacks, and a Defense of Scientific Inquiry

I have not responded to these nasty Twitter attacks, but unfortunately they have gotten enough traction that I feel I need to respond now. [ Note: I have been informed that some of the signatures on their petition are fake, including one purported to be from my colleague Corey Washington! See counter petition and support letters on my behalf. ]

The attacks attempt to depict me as a racist and sexist, using short video clips out of context, and also by misrepresenting the content of some of my blog posts. A cursory inspection reveals bad faith in their presentation.

The accusations are entirely false -- I am neither racist nor sexist.

The Twitter mobs want to suppress scientific work that they find objectionable. What is really at stake: academic freedom, open discussion of important ideas, scientific inquiry. All are imperiled and all must be defended.


One of the video clips is taken from an interview I did with YouTuber Stefan Molyneux in 2017. Molyneux was not a controversial figure in 2017, although he has since become one. Prominent scientists working on human intelligence who were interviewed on his show around the same time include James Flynn and Eric Turkheimer. (Noam Chomsky was also a guest some time after I was.) Here is what I said to Molyneux about genetic group differences in intelligence:



Here is a similar interview I did with Cambridge University PhD student Daphne Martschenko:



As you can see, contrary to the Twitter accusations (lies), I do not endorse claims of genetic group differences. In fact I urge great caution in this area.


The tweets also criticize two podcasts I recorded with my co-host Corey Washington: a discussion with a prominent MSU Psychology professor who studies police shootings (this discussion has elicited a strong response due to the tragic death of George Floyd), and with Claude Steele, a renowned African American researcher who discovered Stereotype Threat and has been Provost at Columbia and Berkeley. The conversation with Steele is a nuanced discussion of race, discrimination, and education in America.






The blog posts under attack, dating back over a decade, are almost all discussions of published scientific papers by leading scholars in Psychology, Neuroscience, Genomics, Machine Learning, and other fields. The papers are published in journals like Nature and the Proceedings of the National Academy of Sciences. However, a detailed reading is required to judge the research and related inferences. I maintain that all the work described is well-motivated and potentially important. Certainly worthy of a blog post. (I have written several thousand blog posts; apparently these are the most objectionable out of those thousands!)

In several of the blog posts I explicitly denounce racism and discrimination based on identity.


This paper, from 2008, discusses early capability to ascertain ancestry from gene sequence. The topic was highly controversial in 2008 (subject to political attack, because it suggested there could be a genetic basis for “race”), but the science is correct. It is now common for people to investigate their heritage using DNA samples (23andMe, Ancestry) using exactly these methods. This case provides a perfect example of science that faced suppression for political reasons, but has since been developed for many useful applications.

https://infoproc.blogspot.com/2008/01/no-scientific-basis-for-race.html


This 2016 paper is by the UCSD Pediatric Imaging, Neurocognition, and Genetics collaboration. They claim that fMRI features of brain morphology can be predicted by genetic ancestry via machine learning.

https://infoproc.blogspot.com/2016/03/genetic-ancestry-and-brain-morphology.html


These blog posts discuss the firing of software engineer James Damore by Google over a memo on diversity practices. The first post describes the legal situation and quotes a professor of labor law at Notre Dame. The second compares the claims made in Damore’s memo to an article in the Stanford Medical School magazine, which covers similar material and was (by coincidence) published around the same time.

https://infoproc.blogspot.com/2017/08/damore-vs-google-trial-of-century.html
https://infoproc.blogspot.com/2017/08/meanwhile-down-on-farm.html


These papers discuss evidence from large DNA datasets for recent natural selection in human evolution. This research has been attacked for political reasons, but should be defended since it addresses fundamental questions in deep human history and evolution.

https://infoproc.blogspot.com/2018/10/the-truth-shall-make-you-free.html


Regarding my work as Vice President for Research, the numbers speak for themselves. MSU went from roughly $500M in annual research expenditures to about $700M during my tenure. We have often been ranked #1 in the Big Ten for research growth. I participated in the recruitment of numerous prominent female and minority professors, in fields like Precision Medicine, Genomics, Chemistry, and many others. Until this Twitter attack there has been not even a single allegation (over 8 years) of bias or discrimination on my part in promotion and tenure or faculty recruitment. These are two activities at the heart of the modern research university, involving hundreds of individuals each year.

Academics and scientists must not submit to mob rule.


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Media coverage:

A Twitter Mob Takes Down an Administrator at Michigan State (Wall Street Journal June 25)

Scholar forced to resign over study that found police shootings not biased against blacks (The College Fix)

On Steve Hsu and the Campaign to Thwart Free Inquiry (Quillette)

Michigan State University VP of Research Ousted (Reason Magazine, Eugene Volokh, UCLA)

Research isn’t advocacy (NY Post Editorial Board)

Podcast interview on Tom Woods show (July 2)

College professor forced to resign for citing study that found police shootings not biased against blacks (Law Enforcement Today, July 5)

"Racist" College Researcher Ousted After Sharing Study Showing No Racial Bias In Police Shootings (ZeroHedge, July 6)

Twitter mob: College researcher forced to resign after study finding no racial bias in police shootings (Reclaim the Net, July 8)

Horowitz: Asian-American researcher fired from Michigan State administration for advancing facts about police shootings (The Blaze, July 8)

I Cited Their Study, So They Disavowed It: If scientists retract research that challenges reigning orthodoxies, politics will drive scholarship (Wall Street Journal July 8)

Conservative author cites research on police shootings and race. Researchers ask for its retraction in response (The College Fix, July 8)

Academics Seek to Retract Study Disproving Racist Police Shootings After Conservative Cites It (Hans Bader, CNSNews, July 9)

The Ideological Corruption of Science (theoretical physicist Lawrence Krauss in the Wall Street Journal, July 12)

Foundation for Individual Rights in Education: "chilling academic freedom" (Peter Bonilla, July 22)

The Ideological Corruption of Science (Lawrence Krauss in the Wall Street Journal)

Theoretical Physicist Lawrence Krauss writes in the Wall Street Journal.

WSJ: In the 1980s, when I was a young professor of physics and astronomy at Yale, deconstructionism was in vogue in the English Department. We in the science departments would scoff at the lack of objective intellectual standards in the humanities, epitomized by a movement that argued against the existence of objective truth itself, arguing that all such claims to knowledge were tainted by ideological biases due to race, sex or economic dominance.

It could never happen in the hard sciences, except perhaps under dictatorships, such as the Nazi condemnation of “Jewish” science, or the Stalinist campaign against genetics led by Trofim Lysenko, in which literally thousands of mainstream geneticists were dismissed in the effort to suppress any opposition to the prevailing political view of the state.

Or so we thought. In recent years, and especially since the police killing of George Floyd in Minneapolis, academic science leaders have adopted wholesale the language of dominance and oppression previously restricted to “cultural studies” journals to guide their disciplines, to censor dissenting views, to remove faculty from leadership positions if their research is claimed by opponents to support systemic oppression.

... At Michigan State University, one group used the strike to organize and coordinate a protest campaign against the vice president for research, physicist Stephen Hsu, whose crimes included doing research on computational genomics to study how human genetics might be related to cognitive ability—something that to the protesters smacked of eugenics. He was also accused of supporting psychology research at MSU on the statistics of police shootings that didn’t clearly support claims of racial bias. Within a week, the university president forced Mr. Hsu to resign.

... Shortly after Mr. Hsu resigned, the authors of the psychology study asked the Proceedings of the National Academy of Science to retract their paper—not because of flaws in their statistical analysis, but because of what they called the “misuse” of their article by journalists who argued that it countered the prevailing view that police forces are racist. They later amended the retraction request to claim, conveniently, that it “had nothing to do with political considerations, ‘mob’ pressure, threats to the authors, or distaste for the political views of people citing the work approvingly.” As a cosmologist, I can say that if we retracted all the papers in cosmology that we felt were misrepresented by journalists, there would hardly be any papers left.

Actual censorship is also occurring. A distinguished chemist in Canada argued in favor of merit-based science and against hiring practices that aim at equality of outcome if they result “in discrimination against the most meritorious candidates.” For that he was censured by his university provost, his published review article on research and education in organic synthesis was removed from the journal website, and two editors involved in accepting it were suspended.

An Italian scientist at the international laboratory CERN, home to the Large Hadron Collider, had his scheduled seminar on statistical imbalances between the sexes in physics canceled and his position at the laboratory revoked because he suggested that apparent inequities might not be directly due to sexism. A group of linguistics students initiated a public petition asking that the psychologist Steven Pinker be stripped of his position as a Linguistics Society of America Fellow for such offenses as tweeting a New York Times article they disapproved of.

Whenever science has been corrupted by falling prey to ideology, scientific progress suffers. This was the case in Nazi Germany, the Soviet Union—and in the U.S. in the 19th century when racist views dominated biology, and during the McCarthy era, when prominent scientists like Robert Oppenheimer were ostracized for their political views. To stem the slide, scientific leaders, scientific societies and senior academic administrators must publicly stand up not only for free speech in science, but for quality, independent of political doctrine and divorced from the demands of political factions.

Mr. Krauss a theoretical physicist, is president of the Origins Project Foundation and author of “The Physics of Climate Change,” forthcoming in January.

Media coverage:

A Twitter Mob Takes Down an Administrator at Michigan State (Wall Street Journal June 25)

Scholar forced to resign over study that found police shootings not biased against blacks (The College Fix)

On Steve Hsu and the Campaign to Thwart Free Inquiry (Quillette)

Michigan State University VP of Research Ousted (Reason Magazine, Eugene Volokh, UCLA)

Research isn’t advocacy (NY Post Editorial Board)

Podcast interview on Tom Woods show (July 2)

College professor forced to resign for citing study that found police shootings not biased against blacks (Law Enforcement Today, July 5)

"Racist" College Researcher Ousted After Sharing Study Showing No Racial Bias In Police Shootings (ZeroHedge, July 6)

Twitter mob: College researcher forced to resign after study finding no racial bias in police shootings (Reclaim the Net, July 8)

Horowitz: Asian-American researcher fired from Michigan State administration for advancing facts about police shootings (The Blaze, July 8)

I Cited Their Study, So They Disavowed It: If scientists retract research that challenges reigning orthodoxies, politics will drive scholarship (Wall Street Journal July 8)

Conservative author cites research on police shootings and race. Researchers ask for its retraction in response (The College Fix, July 8)

Academics Seek to Retract Study Disproving Racist Police Shootings After Conservative Cites It (Hans Bader, CNSNews, July 9)

The Ideological Corruption of Science (theoretical physicist Lawrence Krauss in the Wall Street Journal, July 12)

Foundation for Individual Rights in Education: "chilling academic freedom" (Peter Bonilla, July 22)

Metric on the space of genomes and the scientific basis for race

[Note: the science has advanced considerably since I wrote this post. See here for a nice picture of clustering by ethnicity. I've added some comments at the bottom.]

Suppose that the human genome has 30,000 distinct genes, which we will label as i = 1,2, ... N, where N = 30k. Next, suppose that there are n_i variants or alleles (mutations) of the i-th gene. Then, each human's genetic information can be described as a point on a lattice of size n_1 x n_2 x n_3 ... n_N, or equivalently an N-tuple of integers, each of whose values range from 1 to n_i. For the simplified case where there are exactly 10 variants of each gene, the number of points in this N dimensional space is 10^N or 10^{30k}, one for each distinct 30k digit number. It's a space of very high dimension, but this doesn't stop us from defining a metric, or measure of distance between any two points in the space. (For simplicity we ignore restrictions on this space which might result from incompatibility of certain combinations, etc.)

Note that the genomes of all of the humans who have ever lived occupy only a small subset of this space -- most possible variations have never been realized. For this reason, the surprise expressed by biologists that humans have so few genes (not many more than a worm, and far less than the 100k of earlier estimates) is no cause for concern -- the number of possible organisms that might result from 30k genes is enormous -- far more than the number of molecules in the visible universe.

To define a metric, we need a notion of how far apart two different alleles are. We can do this by counting base pair differences -- most mutations only alter a few base pairs in the genetic code. We can define the distance between two alleles in terms of the number of base pair changes between them (this is always a positive number). Then, we can define the distance between two genomes as the sum of each of the i=1,2,..,N individual gene distances. It is natural, although perhaps not always possible, to choose the n_i labeling of alleles to reflect relative distances, so variants n_1 and n_2 are close together, and both very far from n_10.

The exact definition of the metric and the allele labeling are somewhat arbitrary, but you can see it is easy to define a meaningful measure of how far apart any two individuals are in genome space.

Now plot the genome of each human as a point on our lattice. Not surprisingly, there are readily identifiable clusters of points, corresponding to traditional continental ethnic groups: Europeans, Africans, Asians, Native Americans, etc. (See, for example, Risch et al., Am. J. Hum. Genet. 76:268–275, 2005.) Of course, we can get into endless arguments about how we define European or Asian, and of course there is substructure within the clusters, but it is rather obvious that there are identifiable groupings, and as the Risch study shows, they correspond very well to self-identified notions of race.

From the conclusions of the Risch paper (Am. J. Hum. Genet. 76:268–275, 2005):

Attention has recently focused on genetic structure in the human population. Some have argued that the amount of genetic variation within populations dwarfs the variation between populations, suggesting that discrete genetic categories are not useful (Lewontin 1972; Cooper et al. 2003; Haga and Venter 2003). On the other hand, several studies have shown that individuals tend to cluster genetically with others of the same ancestral geographic origins (Mountain and Cavalli-Sforza 1997; Stephens et al. 2001; Bamshad et al. 2003). Prior studies have generally been performed on a relatively small number of individuals and/or markers. A recent study (Rosenberg et al. 2002) examined 377 autosomal micro-satellite markers in 1,056 individuals from a global sample of 52 populations and found significant evidence of genetic clustering, largely along geographic (continental) lines. Consistent with prior studies, the major genetic clusters consisted of Europeans/West Asians (whites), sub-Saharan Africans, East Asians, Pacific Islanders, and Native Americans. ... We have shown a nearly perfect correspondence between genetic cluster and SIRE [self-reported ethnicity] for major ethnic groups living in the United States, with a discrepancy rate of only 0.14%.

This clustering is a natural consequence of geographical isolation, inheritance and natural selection operating over the last 50k years since humans left Africa.

Every allele probably occurs in each ethnic group, but with varying frequency. Suppose that for a particular gene there are 3 common variants (v1, v2, v3) all the rest being very rare. Then, for example, one might find that in ethnic group A the distribution is v1 75%, v2 15%, v3 10%, while for ethnic group B the distribution is v1 2% v2 6% v3 92%. Suppose this pattern is repeated for several genes, with the common variants in population A being rare in population B, and vice versa. Then, one might find a very dramatic difference in expressed phenotype between the two populations. For example, if skin color is determined by (say) 10 genes, and those genes have the distribution pattern given above, nearly all of population A might be fair skinned while all of population B is dark, even though there is complete overlap in the set of common alleles. Perhaps having the third type of variant v3 in 7 out of 10 pigmentation genes makes you dark. This is highly likely for an individual in population B with the given probabilities, but highly unlikely in population A.

We see that there can be dramatic group differences in phenotypes even if there is complete allele overlap between two groups - as long as the frequency or probability distributions are distinct. But it is these distributions that are measured by the metric we defined earlier. Two groups that form distinct clusters are likely to exhibit different frequency distributions over various genes, leading to group differences.

This leads us to two very different possibilities in human genetic variation:

Hypothesis 1: (the PC mantra) The only group differences that exist between the clusters (races) are innocuous and superficial, for example related to skin color, hair color, body type, etc.

Hypothesis 2: (the dangerous one) Group differences exist which might affect important (let us say, deep rather than superficial) and measurable characteristics, such as cognitive abilities, personality, athletic prowess, etc.

Note H1 is under constant revision, as new genetically driven group differences (e.g., particularly in disease resistance) are being discovered. According to the mantra of H1 these must all (by definition) be superficial differences.

A standard argument against H2 is that the 50k years during which groups have been separated is not long enough for differential natural selection to cause any group differences in deep characteristics. I find this argument quite naive, given what we know about animal breeding and how evolution has affected the (ever expanding list of) "superficial" characteristics. Many genes are now suspected of having been subject to strong selection over timescales of order 5k years or less. For further discussion of H2 by Steve Pinker, see here.

The predominant view among social scientists is that H1 is obviously correct and H2 obviously false. However, this is mainly wishful thinking. Official statements by the American Sociological Association and the American Anthropological Association even endorse the view that race is not a valid biological concept, which is clearly incorrect.

As scientists, we don't know whether H1 or H2 is correct, but given the revolution in biotechnology, we will eventually. Let me reiterate, before someone labels me a racist: we don't know with high confidence whether H1 or H2 is correct.

Finally, it is important to note that group differences are statistical in nature and do not imply anything definitive about a particular individual. Rather than rely on the scientifically unsupported claim that we are all equal, it would be better to emphasize that we all have inalienable human rights regardless of our abilities or genetic makeup.

[See here (Economist's View blog) for more comments.]

[See Gene Expression for more discussion and references.]

Note added: See related Risch article which discusses H1 and H2: Assessing genetic contributions to phenotypic differences among 'racial' and 'ethnic' groups (Nature 2004), and also these 2013 comments in an interview with Ta-Nehisi Coates for The Atlantic:

Q: One last question. Your paper on assessing genetic contributions to phenotype, seemed skeptical that we would ever tease out a group-wide genetic component when looking at things like cognitive skills or personality disposition. Am I reading that right? Are "intelligence" and "disposition" just too complicated?

A: (Risch) Joanna Mountain and I tried to explain this in our Nature Genetics paper on group differences. It is very challenging to assign causes to group differences. As far as genetics goes, if you have identified a particular gene which clearly influences a trait, and the frequency of that gene differs between populations, that would be pretty good evidence. But traits like "intelligence" or other behaviors (at least in the normal range), to the extent they are genetic, are "polygenic." That means no single genes have large effects -- there are many genes involved, each with a very small effect. Such gene effects are difficult if not impossible to find. The problem in assessing group differences is the confounding between genetic and social/cultural factors. If you had individuals who are genetically one thing but socially another, you might be able to tease it apart, but that is generally not the case.

In our paper, we tried to show that a trait can appear to have high "genetic heritability" in any particular population, but the explanation for a group difference for that trait could be either entirely genetic or entirely environmental or some combination in between.

So, in my view, at this point, any comment about the etiology of group differences, for "intelligence" or anything else, in the absence of specific identified genes (or environmental factors, for that matter), is speculation.

To repeat, I think it is fair to say that we don't know*** whether H1 or H2 is correct, even though we do know that populations cluster (genetically) by ancestry. Clustering makes it possible that H2 is correct, because the alleles (genetic variants) affecting a particular phenotype will tend to have different frequencies in different groups. The average value of the trait might or might not be the same in different groups. In the case of height, enough is known to suggest that variants which lead to increased height are more frequent in northern Europe than in the south, and there is evidence that this is due to selection, not drift.

*** I think it's especially important to be epistemologically careful in thinking about these matters, because of our difficult history with race. I would much rather live in a world where H1 is true and H2 false. But my preference alone does not make it so. (I would also much rather live in a universe created by a loving God, and in which I and my children have eternal souls; not a cruel Darwinian universe in which our species arose merely by chance. But my preference does not make it so.)