BIOLOGY AND RACE: A CLEARER LINK

NEW GENETIC RESEARCH ESTABLISHES FIRMER BASIS FOR CONNECTION

(First part of fourth-page feature on the human genome)

Thursday, May 8, 2003

A torrent of information is pouring out of genetics, eroding many assumptions made by scientists and non-scientists alike about human biology and behavior.

At its annual convention, held in Denver, the American Association for the Advancement of Science examined the new genetics and its impact on other fields. One panel titled "Ethical, social and policy implications of studies of human genetic variation" drew a surprisingly large and lively crowd. Why? I suspect it's because they expected some of the panelists would break one of the strictest taboos in science: mentioning "race" and "biology" in the same sentence.

In 1998, the American Anthropological Association issued a "statement on 'race' " that said the facts "render any attempt to establish lines of division among biological populations both arbitrary and subjective," and that "physical variations in the human species have no meaning except the social ones that humans put on them."

The complete statement, which is more subtle than that (available at www.aaanet.org/stmts/racepp.htm on the Web), also gives a capsule summary of the historical reasons why scientists today are so skittish about anything that might link them to the discredited racist views of the past. It's worth reading. But as a statement about biology it is wrong.

Statistically significant differences in susceptibility to a wide range of diseases, in response to treatments, and in sensitivity to environmental contamination are "physical variations" meaningful indeed to the people who get sick. The claim that these differences "have no meaning" except the social one is akin to the equally untenable claim that differences between men and women have nothing to do with biology but are "socially constructed." Of course culture and society have a great deal to do with what kind of differences are observed, but the underlying biology shapes what societies construct.

Mildred Cho, co-director of the Stanford Center for Biomedical Ethics, organized the panel. Last year she and Pamela Sankar, who is at the Center for Bioethics at the University of Pennsylvania, published an article for Science magazine about the need for an acceptable vocabulary for discussing population-based genetic diversity.

"Rejecting race as genetic hierarchy is not tantamount to rejecting the idea that human populations differ genetically," the authors said. "The debate is over the scientific, clinical and social significance of labeling genetic differences as race, as something else, or not at all."

David Altshuler, a geneticist and endocrinologist who does research into diabetes at Massachusetts General Hospital, led off the panel with a discussion of why genetic research is important in medicine.

Given two Americans, one of whom has been diagnosed with diabetes, he said, you can ask whether the other will be also. If the two are unrelated, the risk is 5 percent to 10 percent. If they're siblings, it rises to 40 percent, and if they're identical twins it reaches an 80 percent lifetime risk.

Genetics isn't everything, because it never exists separate from the environment, but it is an important clue.

The question of how similar or different people are has been around a long time. For example, Altshuler said, around the time of the Civil War the celebrated American naturalist Louis Agassiz argued vigorously that groups from different parts of the world might be considered different species.

The genetic answer is clear, however. We're all one species, and in fact surprisingly alike at the level of the genes.

How alike? We each have two copies of the human genome in each of our cells. "If we took one copy of my genome," Altshuler said, "and one from anybody else in the room, or one from anywhere on earth, it turns out the answer is the same. How many letters among the 3 billion in the genome would vary? One in a thousand or less."

And when there is a difference how likely is it to be private to you, or to your near relatives over the last several hundred years? Not very. About 90 percent of the variation that does exist is very old, tracing back on average about 400,000 years. At some point in the species' history there was only one small population living in one place.

"So 99.99 percent of your genome is either exactly the same as everyone's, or if it varies it varies in a way that wherever you went on earth you'd find the same variants," Altshuler said.

Typically there are four or five variations in a particular spot on the genome -- though sometimes there's an extra one in Africa because the human race started in Africa and not all the variations at all the spots were present in the small groups that migrated out. But because there are so many spots where variation occurs, and the frequencies of the variants are different, information from enough spots across the whole genome is enough to identify a unique copy (except for identical twins).

Altshuler was followed by Noah Rosenberg from the University of Southern California, who discussed his research using a computer algorithm to identify genetic clusters in the human population structure.

Rosenberg and his colleagues used what are called "microsatellite markers," a particular spot on the genome where a tiny fragment of DNA -- "GATA," for example, using letters from the genetic code -- is repeated a number of times. The number of repetitions varies because copies tend to be added or lost by mutation. For individuals from Africa the number of copies of this fragment ranges from 16 to 22. Each different type is called an allele. They typically have no effect on anything that could be called a genetic trait because they are from the part of the genome that doesn't code for any genes.

The researchers picked 377 different markers and on average each of them existed in 12 alleles, a few common and several rare. Take two people at random and the chances are three out of four that they will have different alleles at any given marker.

Nearly half of all the possible alleles are found everywhere in the world. Only about 7.4 percent are found in only one region -- and most of those in Africa. But for most of the 377 different markers the frequencies are different in different regions. Given enough people and enough computer time you can pretty well sort them into regions without telling the computer ahead of time what the regions ought to be.

The project used information from 377 marker sites for 1,056 people from 52 fairly distinct populations (you wouldn't learn much by sampling people in New York). When the algorithm separated them into five clusters, the clusters were populations from Africa, three regions together including Europe, the Middle East and Central and South Asia, East Asia, Oceania and the Americas.

That might be what you'd expect. However, the important thing to understand is that the computation isn't influenced by what you expected because it doesn't use information about the sampling location. If there were a more plausible way to separate people into clusters the algorithm would find it.

You will have noticed that these divisions roughly correspond to what have traditionally been called "races," although the U.S. Census Bureau puts South Asians in with East Asians, a decision that makes no biological sense.

But does clustering matter? As Altshuler noted, the information you get from the algorithm is pretty much what people will tell you about their ancestry. And neither his work nor Rosenberg's deals with observable genetic traits, or with the potentially problematic question of whether there might exist genetic traits that are culturally or socially important.

The reason research of this kind is threatening is that it unequivocally demolishes the claim that racial categories have no support from biology, as the anthropologists' statement claimed -- a claim that, as Altshuler pointed out, is itself political.

So it's not surprising that the panelists sounded more than a little uneasy. I mentioned this to someone after the panel concluded and he said, "Of course. You have to understand that being misquoted on this topic can mean the end of your career."

Actually, I do understand that. I just think it's unfortunate and I'm encouraged that the discussion is at least beginning.