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The Genetic Archaeology of Race - Page 2
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Decoding Human History

he best way to determine the genetic relationships among people is to compare the sequences of the nucleotides in their DNA. But in the early 1960s those sequences were inaccessible. Manipulating DNA in the laboratory at that time was like playing the piano with a baseball bat—existing tools were far too awkward to examine individual nucleotides. Cavalli-Sforza therefore turned to the next best thing: the many thousands of proteins in the human body. The sequence of nucleotides in DNA dictates the sequence of the amino acids that constitute proteins, though the translation between the two is a convoluted process that partially obscures the underlying DNA sequence. Still, by studying proteins Cavalli-Sforza could learn at least a little about the DNA differences among people.

The result was a decades-long string of remarkable, though in some cases still hotly contested, discoveries. In the early 1970s, for example, Cavalli-Sforza and the archaeologist Albert Ammerman proposed a radical new hypothesis for the peopling of Europe. At that time most anthropologists believed that modern Europeans were descended largely from the continent's Stone Age inhabitants, who replaced the Neanderthal people starting about 40,000 years ago. By analyzing the genetic variation of modern Europeans, Cavalli-Sforza and Ammerman came to a different conclusion. They decided that Europeans are descended largely from populations of farmers who started migrating out of the Middle East 9,000 years ago. As the sons and daughters of farming families left their parents' farms and moved into new territory, they interbred with the existing hunter-gatherer populations, which produced gradients of genetic change radiating from the Middle East. Only in mountainous areas unattractive to farmers—the Pyrenees homelands of the Basques, for example—were the genes of the indigenous peoples comparatively intact.

Other historical events, too, appeared to have influenced the European gene pool. For example, a genetic trail leads from the area north of the Black and Caspian Seas into the rest of Europe. Cavalli-Sforza linked this trail to the spread of the descendants of nomadic warriors and herders who first domesticated the horse, about 4,000 B.C.

Similar traces of historical events showed up on every other continent. The genetic history of China is dominated by a split between northern and southern people, despite the official position that all ethnic Chinese are descended from common ancestors. Native American proteins point to three major waves of migration, suggesting connections among groups that had never considered themselves related. And wherever Cavalli-Sforza looked, the fragmentary protein evidence hinted at much-greater detail to come.

Cavalli-Sforza didn't know it when he moved to Stanford in 1971, but a series of experiments then going on at the university and elsewhere were about to transform anthropological genetics—and much of the rest of biology. The Stanford biochemist Stanley Cohen and the University of California at San Francisco biochemist Herbert Boyer were figuring out how to cut DNA in precise locations, combine DNA from different organisms, and grow the resulting hybrid DNA in bacteria. For the first time, human beings could control DNA nucleotide by nucleotide. The age of genetic engineering had begun.

Elsewhere on the Web
Links to related material on other Web sites.

Automated DNA Sequencing
A description of automated DNA sequencing methods—including fluorescent sequencing—in use at the Joslin Diabetes Center facility in Boston.

"Polymerase Chain Reaction-Xeroxing DNA" (1999)
An explanation for laypeople of how polymerase chain reaction works. Posted by the National Health Museum, "the site for health and bioscience teachers and learners."
New tools followed rapidly, with names like fluorescent DNA sequencing and polymerase chain reaction. By the mid-1980s biologists had realized that they had the means to pursue a goal that would have been unthinkable just a decade earlier: with sufficient effort they could read the entire multibillion-nucleotide sequence of human DNA. In 1990 an international consortium of governments launched the Human Genome Project to determine the sequence. Spurred by competition from the private sector, the project is today more or less finished (some cleanup work is still needed to complete the sequence).

As far as Cavalli-Sforza was concerned, the Human Genome Project was a good idea but didn't go far enough. The DNA that was sequenced is a pastiche of chromosomal fragments from various unidentified donors, and the project has produced just a single generic sequence to represent all of humanity. To trace human history Cavalli-Sforza needed to know how DNA sequences vary among people from different parts of the world. He began to think about the best way to gather such data, and he traded ideas with friends and colleagues. The result was the Human Genome Diversity Project, which was proposed in 1991 and fleshed out over the next two years. According to the planning document for the project, the goal would be to collect DNA from several hundred distinct groups, including many indigenous groups. Immortalized in cell lines, this DNA would be used primarily to study human history, but it would also have more-practical applications. Medical researchers could use it to investigate the connections between genetics and disease. And according to the planning document, by demonstrating the nature of the genetic differences among people, research on genetic variation would "help to combat the widespread popular fear and ignorance of human genetics and will make a significant contribution to the elimination of racism." Who could be opposed to that?

Bioethics and Biopiracy

n 1993 an odd-looking document appeared on the desks of the Human Genome Diversity Project's organizers. Under the heading "RAFI communiqué" it was titled "Patents, Indigenous Peoples, and Human Genetic Diversity." An artful combination of analysis and innuendo, the document was unambiguous in its conclusion: "The Human Genome Diversity Project should immediately halt any collection efforts."

The campaign against the HGDP marked the first foray into human genetics for RAFI—the Rural Advancement Foundation International. A small organization based in Canada, RAFI had previously targeted corporations that removed indigenous plants from developing countries, repackaged their genetic material in hybrid seeds, and then offered the seeds to Third World farmers for exorbitant prices. Now it accused the HGDP of a similar form of "biopiracy." The DNA of indigenous people would be mined for valuable information. Pharmaceutical companies would then use this information to make drugs far too expensive for Third World people to buy.

The actions of the U.S. government seemed to bear out RAFI's claims. Federal agencies had applied for patents on cell lines containing DNAfrom several Third World groups. The patent applications, which were all aimed at medical uses, had nothing to do with the HGDP, and the project repeatedly dissociated itself from them. But opponents eagerly conflated the uproar over the patents with what they called the "vampire project."

Many Native Americans were especially critical of the HGDP. "The benefits for Native people are elusive or nonexistent, and the risks are tremendous," says Debra Harry, a member of the Northern Paiute Nation and the director of an organization called the Indigenous Peoples Council on Biocolonialism. Native American creation stories say that Native Americans have always lived in the Americas, Harry observes, not that their ancestors migrated across the Bering land bridge sometime before the arrival of Europeans. Furthermore, many Native American cultures hold that biological materials are sacred. "DNA is not ours to manipulate, alter, own, or sell," Harry says. "It was passed on from our ancestors and should be passed on to our children and future generations with its full integrity."

Native Americans and many other groups were also quick to raise the specter of biological warfare. What would stop a government from developing lethal microbes tailored to particular groups? This criticism especially galls geneticists, who say that it is too far-fetched to take seriously. Even if it were possible someday to devise a genetically based weapon, it would simply kill varying percentages of the people in different groups.

The tendency of critics to mix fact and fancy led to dark mutterings among the project's organizers. "These groups have to support themselves somehow," Cavalli-Sforza says, "and they've decided to use us." But the critics were much more skilled than the geneticists at ad hominem attacks. "Nice, smart, liberal—but naive and a bit arrogant—white guys firmly ensconced at reputable universities" is how a RAFI organizer once described Cavalli-Sforza and his colleagues to me.

Cavalli-Sforza quickly proved to be a liability as spokesman for the project. He is not one to weigh the effect of his words before speaking. With European frankness he simply says what he thinks. "He's never been very politically astute," one colleague says. "Sometimes we can't help cringing, because we know [what he says is] going to come out condescending or arrogant."

Realizing that his lifelong ambition was slipping from his grasp, in the fall of 1993 Cavalli-Sforza turned to a colleague to help represent the project: a Stanford law professor named Hank Greely. With a background in bioethics, Greely spearheaded the creation of a "Model Ethical Protocol" to govern the collection and use of DNA samples. He also reminded geneticists of the sensitivity of their work. But the controversy was spiraling out of control. Dozens of organizations representing indigenous peoples were protesting the project. They decried spending millions of dollars to collect the blood of groups that were disappearing because of poverty, disease, and official neglect. Project organizers responded by suggesting that they could provide medical assistance to participating groups. Then a new objection arose: indigenous peoples were being bribed for their DNA.

For Greely, the low point came in December of that year, when he traveled to Quetzaltenango, Guatemala, to represent the project at a meeting of the World Council of Indigenous Peoples. Scheduled to speak twice at the meeting, Greely spent most of his second session listening to angry speeches from the audience. By the end of the conference he was standing at the podium being accused of being a CIA agent. "I had the opportunity to respond after each comment and almost always did so," he later recounted in a report about the meeting.
I noted that this was not a project about indigenous peoples, but about all the world's peoples ... I stressed that populations would not be involved in the project unless they wanted to be. I agreed that the West and western science had done terrible things to indigenous peoples, but said that science could also do some good things. I urged that our project was different—that we were trying to do things right.
His protestations were to no avail. "My statements were uniformly either ignored or dismissed as lies," he recalls. "The only faintly positive feedback from the crowd was that two speakers complimented me for my courage."

Opponents of the HGDP have succeeded in linking the project with existing qualms about genetic testing. Say that a group has an unusually high frequency of a genetic variant associated with a disease. Would every member of that group be stigmatized, whether or not he or she had the variant? Or what if genetic studies conflict with a group's belief about its origins?

The traditional way of dealing with such qualms has been through informed consent. People must be fully informed about what a test can reveal and must be given the choice of whether or not to be tested. But the HGDP adds a twist to the idea of consent. Studies of genetic variation usually focus on groups—Han Chinese, New Guinea highlanders, Hopis—rather than on individuals (in fact, individual DNA donors are usually anonymous). By the logic of informed consent, groups ought to have some say over whether their members participate in the research. Some bioethicists argue strongly against this position, saying that it denies individual autonomy, but the committee set up to oversee the HGDP in North America agrees with it. Before the project collects any DNA in North America, the groups being studied must understand and okay their involvement. It's not always obvious who speaks for a group, Greely admits, but when a representative body can be identified, it should be consulted.

Of course, giving groups the right to consent means that some will decline. "That's fine," Greely says. "We're under no illusion that we're going to get samples of every human population. Our goal is to get just five percent—so nineteen of twenty could not participate."

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Copyright © 2001 by The Atlantic Monthly Group. All rights reserved.
The Atlantic Monthly; April 2001; The Genetic Archaeology of Race - 01.04; Volume 287, No. 4; page 69-80.