Gregory Cochran has always been drawn to puzzles. This one had been gnawing at him for several years: Why are European Jews prone to so many deadly genetic diseases?
Tay-Sachs disease. Canavan disease. More than a dozen more.
It offended Cochran's sense of logic. Natural selection, the self-taught genetics buff knew, should flush dangerous DNA from the gene pool. Perhaps the mutations causing these diseases had some other, beneficial purpose. But what?
At 3:17 one morning, after a long night searching a database of scientific journals from his disheveled home office in Albuquerque, Cochran fired off an e-mail to his collaborator Henry Harpending, a distinguished professor of anthropology at the University of Utah in Salt Lake City and a member of the National Academy of Sciences.
"I've figured it out, I think," Cochran typed. "Pardon my crazed excitement."
The "faulty" genes, Cochran concluded, make Jews smarter.
That provocative -- some would say inflammatory -- hypothesis has landed Cochran and Harpending in the middle of a charged debate about the link between IQ and DNA.
They have been sneered at by colleagues and excoriated on Internet forums. They have been welcomed to speak at a synagogue and a Jewish medical society. They were asked to write a book; that effort, "The 10,000 Year Explosion," was published early this year.
Scientists are increasingly finding that propensities for human behaviors -- for addiction, aggression, risk-taking and more -- are written in our genes. But the idea that some groups of people are inherently smarter is troubling to many. Some scientists say it has such racist implications it's unworthy of consideration.
"What are their theories about those on the opposite end of the spectrum?" asked Neil Risch, director of the Institute for Human Genetics at UC San Francisco, who finds the matter so offensive he can barely discuss it without raising his voice. "Do they have genetic theories about why Latinos and African Americans perform worse academically?"
The biological basis for intelligence can be a thankless arena of inquiry. The authors of "The Bell Curve" were vilified 15 years ago for suggesting genes played a role in IQ differences among racial groups.
But Cochran, 55, and Harpending, 65, say there's no question that as a whole, Ashkenazi Jews -- those of European descent -- have an abundance of brain power. (Neither man is Jewish.)
Psychologists and educational researchers have pegged their average IQ at 107.5 to 115. That's only modestly higher than the overall European average of 100, but the gap is large enough to produce a huge difference in the proportion of geniuses. When a group's average IQ is 100, the percentage of people above 140 is 0.4%; when the average is 110, the genius rate is 2.3%.
Though Jews make up less than 3% of the U.S. population, they have won more than 25% of the Nobel Prizes awarded to American scientists since 1950, account for 20% of this country's chief executives and make up 22% of Ivy League students, the pair write.
"People are perfectly willing to admit that some people are taller or some people are shorter," Cochran said. "But no one wants to say 'This group is smarter.' "
Once Cochran gets talking, it's hard to get him to stop. He jumps from idea to idea, beginning new sentences before finishing old ones. In e-mail discussion groups, where he befriended Harpending, he thrives on debating people and proving them wrong.
A PhD physicist, he started out in El Segundo, developing satellite imaging systems and other optics hardware for Hughes Aircraft in the 1980s. As the Cold War ended and defense budgets shrank, Cochran moved his family to Albuquerque and became an optics consultant while indulging his amateur interest in biology.
He worked for a while with evolutionary biologist Paul Ewald on theories that germs cause common disorders like heart disease and Alzheimer's. The pair courted controversy by postulating that some unidentified pathogen prompts a hormonal imbalance that makes babies more likely to become gay.
Cochran read more than 15 genetics textbooks and became intrigued by the deadly diseases that disproportionately afflict Ashkenazi Jews: Tay-Sachs, a neurological disorder that debilitates children before killing them, usually by age 4. Canavan disease, which turns the brain into spongy tissue and typically claims its victims before they can start kindergarten. Niemann-Pick disease Type A, in which babies accumulate dangerous amounts of fats in various organs and suffer profound brain damage and death before their second birthday.
He was struck by the fact that so many of the diseases involved problems with processing sphingolipids, the fat molecules that transmit nerve signals.
This seemed an unlikely coincidence. Genetically isolated groups often have higher rates of certain diseases. But of the more than 20,000 human genes, only 108 are known to be involved in sphingolipid metabolism. The odds of Ashkenazi Jews having four sphingolipid storage disorders by random chance are less than 1 in 100,000, he calculated.
He talked it over with Harpending, an expert in human population genetics. They came to believe this was an example of heterozygote advantage -- where having two copies of a mutated gene can mean disaster but one copy is helpful.
The most famous example of this is sickle cell anemia, which strikes people of African descent who have two defective copies of the hemoglobin B gene. As a result, they make red blood cells that are too curvy to carry oxygen to critical organs.
People who have only one bad copy make useful red blood cells that are deformed just enough to protect them from the malaria parasite, insulating them against the disease.
Instead of sickle cell anemia, Ashkenazi Jews had to contend with Tay-Sachs, Niemann-Pick and other diseases.
Instead of malaria resistance, Cochran and Harpending reasoned, Jews got an IQ boost.
The idea didn't come out of nowhere. Researchers have been drawn to the question of Jewish intelligence and genetic diseases at least since the 1920s, when some of the disorders were first being studied. Many physicians remarked on the unusual intelligence of their patients.
One of the first to conduct a systematic study was Dr. Roswell Eldridge, a neurogeneticist at the National Institutes of Health. He compared IQs of 14 children with torsion dystonia -- a neurological disorder afflicting Ashkenazi Jews that twists the body through uncontrollable muscle contractions -- against 10 of their healthy siblings and against unrelated Jewish students matched by age, sex and school.
The patients had an average IQ score of 121, compared with 111 for the control students, he found. Siblings had an average IQ of 119, compared with 112 for their matched controls. The results were published in 1970 in the medical journal Lancet.
Dr. Ari Zimran, director of Shaare Zedek Medical Center's Gaucher Clinic in Jerusalem, thought he would get similar results by studying the very bright patients he treated for Gaucher disease, another Ashkenazi genetic disorder in which excessive amounts of a fatty substance build up in certain organs, causing pain, fatigue and other symptoms.
His small study in the 1980s found no difference between IQs of patients and unaffected relatives. A larger study might have done so, Zimran said. But he decided not to pursue it.
"There is enough anti-Semitism," he said.
Cochran and Harpending are the first to make a broad case linking multiple Jewish genetic diseases to intelligence. Their theory draws on history, statistics, neurobiology and population genetics.
Jews first came to Europe in the 8th and 9th centuries, long before they were known for intellectual prowess, Cochran and Harpending say. They worked as traders before taking financial jobs made available by Christians who were forbidden by the Church from charging interest. By 1100, local registries listed most Ashkenazi Jews as lenders.
That set the stage for natural selection to do its work, Cochran and Harpending theorized. Jews didn't intermarry, keeping their gene pool closed. They were subjected to periodic persecution, which kept the population from outgrowing its professional niche.
According to the theory, the smartest individuals made the most money, and the wealthiest families had the most surviving children. The genes of the most intelligent Jews spread most, slowly raising the average IQ of the entire group.
Over 40 generations -- roughly 1,000 years -- an increase of just 0.3 points per generation would have added up to a cumulative advantage of 12 points, Cochran and Harpending theorized. Some of their other models projected a benefit of 16 to 20 IQ points.
They wrote up their theory and sent it off to a journal. It was rejected.
Harpending said he gave it to an anthropologist friend, editor of another journal, who asked to publish it there. That plan was called off. The friend, who asked not to be identified because of the sensitive nature of the topic, said the paper was clearly controversial and its extraordinary claims required extraordinary evidence -- which was lacking.
The paper found a home in a 2006 issue of the Journal of Biosocial Science, published by Cambridge University, after its release online in 2005.
The theory quickly spread among anthropologists and geneticists.
Within a few months, "every academic I came in contact with knew about this," said R. Brian Ferguson, an anthropologist at Rutgers University in Newark, N.J. Many found it irresistible. A young colleague told Ferguson that the paper convinced him of the power of using genetics to study behavioral differences among people.
To Ferguson, that was a dangerous idea. There may indeed be versions of genes that are unique to Ashkenazi Jews, but it would be impossible, he said, to prove that those genes are responsible for higher IQs.
"This is not a legitimate area of research," he said.
Others are more receptive to the theory, despite its thorny implications.
Dr. Melvin Konner, a biological anthropologist at Emory University in Atlanta, said he's impressed by the theory's ability to explain why all the Ashkenazi diseases are clustered "on about five pages of a biochemistry textbook." But, he added, Cochran and Harpending still have to show that the genes play a direct role in brain development.
"There's evidence that some of them do," he said. "It's not a crazy idea. It's just not nearly a proven idea."
It would be easy to test the theory, said Steven Pinker, a Harvard cognition researcher: "See if carriers of the Ashkenazi-typical genetic mutations score higher on IQ tests than their noncarrier siblings."
Cochran and Harpending readily acknowledge the need for such experiments. But they have no plans to do them. They say their role as theorists is to generate hypotheses that others can test.
"One criticism about our paper is 'It can't mean anything because they didn't do any new experiments,' " Cochran said. "OK, then I guess Einstein's papers didn't mean anything either."