Thursday, December 21, 2006

Lahn profile, part 2   posted by p-ter @ 12/21/2006 10:36:00 PM

Ah, what the hell, I'm putting the full text of the initial profile below the fold (the full sidebar on research into ASPM and microencephalin is here). If anyone is horribly offended by this, I'll take it down. But hey, if they remark that unnamed "bloggers" (well, John Derbyshire is mentioned by name) "jumped on" the race angle, they should be happy to let us jump on this as well:
CHICAGO--In 1993, not long after Bruce Lahn joined David Page's genetics lab at the Massachusetts Institute of Technology (MIT), Page invited all lab members on a 2-day hike in New Hampshire's rugged White Mountains. Page circulated a list of items to pack and stressed bringing enough food and water. Everyone showed up with stuffed backpacks--everyone, that is, except Lahn, who arrived toting only a small shoulder bag. When asked, Lahn pulled out the bag's sole contents: a gallon jar of Chinese pickled eggs.

"That was classic Bruce," Page recalls. "He didn't follow instructions." Lahn's insistence on doing things his way has made him one of the fastest rising stars in genetics and also one of the most controversial. His work with Page to decipher the evolutionary history of the human Y chromosome was a major landmark in genome research. It led directly to a position at the University of Chicago in Illinois, where Lahn achieved tenure in an unusually rapid 5 years, and to an investigator award from the Howard Hughes Medical Institute.

But Lahn's more recent work, seeking to identify the genes behind our species' superior cognition, has sparked skepticism (see sidebar, p. 1872) and plunged this Chinese-American scientist into contentious debates over genetics, race, and intelligence. Two Science papers concluding that purportedly beneficial brain mutations are common in Eurasia but rare in Africa have made Lahn a darling of right-wing commentators seeking evidence of racial differences in cognition. Some scientists say Lahn overinterpreted and sensationalized his findings, and one co-author has distanced herself from one of the paper's more speculative conclusions.

The papers have such serious social implications that they needed to meet a higher standard of proof, says David Altshuler of the Broad Institute in Cambridge, Massachusetts--and they didn't. The links to cognition in particular were "wild speculation," he says. "We have a powerful responsibility to think about how society will interpret [such work]."

Lahn finds the political fallout discomfiting, insisting that he is a staunch antiracist and "extremely liberal" in his personal politics. He says he is a lifetime member of the National Association for the Advancement of Colored People and gives money to Democratic candidates. Yet Lahn is fascinated by differences among people and says he has long wondered whether variations in social status have genetic underpinnings. "You can't deny that people are different at the level of their genes," Lahn says, citing the examples of skin color and physical appearance. "This is not to deny the role of culture, but there may be a biological basis [for differences] above and beyond culture."

Becoming Bruce
Lahn, 38, is slim and handsome, with expressive hands that gesture animatedly as he speaks. He was born in China to two physicists who both suffered from the country's political turmoil. His mother was branded a "rightist" by the Communist Party during the 1950s, leading his maternal grandmother to commit suicide out of shame. His paternal grandfather died in a Communist labor camp. "From early on, I had a sense of what had happened to my family, and that made me a bit of a rebel," Lahn says. "I was hyperactive and always in trouble at school."

Lahn's rebelliousness made him keenly interested in China's social inequalities. He was particularly struck by the privileges foreigners received when they visited China. "I was deeply traumatized by that," Lahn says. He wondered whether there might be a genetic basis for these class differences. "But I didn't know what genes were exactly."

In 1986, Lahn began studying genetics at Beijing University. He soon got caught up in the nascent democracy movement, putting up one of the first wall posters on campus. "We were very naive," he recalls. "We really thought that we had the power to change the government." When Lahn heard he was on a watch list, he decided to leave China and was accepted at Harvard University in 1988.

When he arrived in the United States, Lahn was still going by his Chinese name, Lan Tian. But one day, a McDonald's janitor told him he looked like the late martial arts actor Bruce Lee, and Lahn's friends started calling him "Bruce." Lahn soon adopted it as his legal first name and Anglicized the spelling of his last name.

Lahn thrived at Harvard. Geneticist James Birchler, now at the University of Missouri, Columbia, supervised Lahn's senior thesis. "He had golden hands" in the lab, Birchler recalls, "and he was intellectually fearless and adventuresome."

In 1991, after beginning Ph.D. studies at MIT, Lahn asked Page to take him on as a student. But Page says at first he was not keen to do so: "A number of people in the lab were unsure about whether it was wise. He seemed brash and cocky and too self-confident." Page put Lahn on a small project investigating a rare defect in the human Y chromosome. "But Bruce thought [the project's] range was too limited. He started conducting secret experiments in the lab that he thought I wasn't aware of." Finally, Lahn announced that he wanted to isolate all of the Y chromosome's genes. Page let him go ahead. Within 18 months, Lahn had cloned about half of the dozen genes then known on the male part of the chromosome. Page and Lahn went on to show that the human Y chromosome evolved from a series of rearrangements of the mammalian X chromosome (Science, 29 October 1999, p. 877).

"Bruce had a deadly killer instinct," Page says. "He kept his eye on the prize. And he was very charismatic. … After he left, some of us felt that we would never see the likes of him again."

Tackling the evolving brain
Soon after Lahn's move to the University of Chicago in 2000, he began looking for genes that might explain the evolution of the human brain, motivated in part by his long-standing interest in human differences. In 2004, his team reported that two genes thought to regulate brain growth, called microcephalin and ASPM, appeared to have undergone strong natural selection since the human and chimpanzee lineages split between 5 million and 7 million years ago. These genes are implicated in regulating cell division in developing neural cells, and some mutations in them result in a tiny brain, or microcephaly. But their function in normal humans is not clear, and they are expressed in non-neural tissues as well.

Then, in two papers in Science last year, Lahn reported that variants of the two genes appear to have been strongly favored by recent natural selection (Science, 9 September 2005, pp. 1717 and 1720). That implies that the variants conferred a survival or reproductive benefit, perhaps a cognitive one. In media interviews, Lahn conceded that there was no real evidence natural selection had acted on cognition or intelligence. But both papers pointed out that the mutations arose when key events in human cultural development occurred: The microcephalin variant was dated to about 37,000 years ago, when the first art and symbolism showed up in Europe, and the ASPM variant to 5800 years ago, when the first cities arose.

Lahn's papers also reported the skewed geographic distribution of the genetic variants. Variants in microcephalin turned up in 75% or more of some Europeans and Asians Lahn studied, but in less than 10% of some African groups. The ASPM variant was also much less frequent in Africa.

Bloggers jumped on the news, trumpeting the papers as support for the idea that African Americans have lower intelligence than whites. Two months later, in the conservative National Review Online, columnist John Derbyshire wrote that the research implied that "our cherished national dream of a well-mixed and harmonious meritocracy … may be unattainable."

Among some geneticists, there was consternation. "There was no evidence whatsoever that these [genetic variants] have any effect" on differences between people, Altshuler says, adding that the controversy over the work was "easily anticipated." Harvard geneticist Richard Lewontin goes further, criticizing both Lahn and Science for publishing such speculative links to cultural advances. "These two papers are particularly egregious examples of going well beyond the data to try to make a splash," he says. And archaeologist Scott MacEachern of Bowdoin College in Brunswick, Maine, says the archaeological links in the papers are simplistic and outdated. The symbolic revolution, agriculture, and urbanism developed "over many thousands of years, and none was restricted to Europe and the Middle East," he says.

Even one of the co-authors of the papers, Sarah Tishkoff of the University of Maryland, College Park, has now distanced herself from the attempt to link the ASPM variant to human advances, saying that she didn't see the wording until page proofs.

Lahn points out that the papers include disclaimers, stating, as one of them put it, that it was "formally possible" that natural selection had acted on the genes' roles outside the brain. And in media interviews he emphasized that a number of genes other than microcephalin and ASPM are probably involved in cognition. But he insists that the evidence points to some sort of brain function as the most likely target of selection.

Lahn asserts that some scientists "start with a political agenda and fit the evidence to that." This political bias, he argues, "takes credibility away from an antiracist program that I agree with. … If someday we discover that there are genetic differences in cognitive abilities, would that mean that racism is now justified?"

And some scientists believe that Lahn has shown courage in pursuing his research. "There is widespread fear of this [research] among scientists," says geneticist Henry Harpending of University of Utah in Salt Lake City, who has suggested evolutionary explanations for high IQ scores in Ashkenazi Jews. Even some researchers who scoff at racial differences in intelligence think the research should go on. Geneticist Michael Hammer of the University of Arizona in Tucson says he's not worried about the end result: "I have no serious concerns that Europeans or Asians are going to be proven to be more intelligent, so I say go at it, let the chips fall where they may."

Lahn says the controversy has made him back away "from going after these kinds of questions aggressively," although he continues to test whether the variants affect IQ. He has begun diverting his energies to another high-profile project: stem cells. He became interested in the topic after running into a Chinese colleague at a meeting and is collaborating with a center at Sun Yat-sen University in Guangzhou. He was motivated in part by China's relatively liberal attitude toward this research and also, he says, by his desire to help China modernize.

Time, and further research, will tell if Lahn was right about microcephalin and ASPM. But Page says that few other scientists would have been willing to get involved in such controversial questions in the first place: "That willingness to venture into this territory without his guard up is entirely in keeping with who Bruce is. Anybody who would have packed their bag as instructed for that White Mountain hike would have steered clear of all this."