BehindTheMedspeak: Why doesn't DNA profiling work?

Sharon Begley, the superb Wall Street Journal science columnist, addressed the question in her July 7 column.

Long answer short: Because the future remains — at least as yet — unknowable.

Since genes must act in the real world — not in a laboratory vacuum with variables held to a minimum — unpredictable life events and circumstances govern the expression, or lack thereof, of our encoded genetic messages.

Commenting on why some individuals who have a gene associated with violence and aggression show no heightened aggression, Dr. Stephen Suomi of the National Institutes of Health, whose research centers on this subject, said, "If you have a good mother, it doesn't make a damn bit of difference which gene you have. Good mothering acts as a buffer."

Here's the column.

Life Events Thwart Scientists' Attempts To Draw DNA Profiles

Genetics might not seem to have a lot in common with birding, but the fields share one pesky little problem.

Birders are wont to fight over whether someone saw what he claimed. ("It's an ivory-billed woodpecker!" "No, you fool, it's a pileated!") Geneticists on the trail of genes for human behavior have a 15-year record of finding DNA that increases the likelihood that a person will be neurotic, depressed, schizophrenic, a thrill seeker ... only to see other scientists claim their research shows that the gene is no more common in people with that trait than in anyone else.

Now there is a glimmer of an explanation for why such "failures to replicate" are common in behavioral genetics: The same gene produces different traits in different people.

Contrary to traditional understanding, genes don't lead inevitably to traits. Instead, says Darlene Francis of the University of California, Berkeley, scientists are discovering that "there is this intervening variable called life," as she told the International Congress of Neuroendocrinology last month in Pittsburgh.

Life definitely intervenes between a gene called MAOA and the extreme aggression that researchers claimed it causes. In the late 1980s, a number of men in several generations of a large Dutch family were found to carry a mutation in the MAOA gene that made it inactive. They all had a long rap sheet of rape, attempted murder and arson. MAOA became known as the "violence gene," headlines warned of "a violence in the blood," and there was talk of screening everyone to identify carriers.

The link between MAOA and aggression made biological sense. MAOA breaks down brain chemicals, including serotonin. It comes in two forms, short and long. The short form, which about one-third of people have, can't do the breaking down as efficiently as the long form, disrupting the balance of neurotransmitters in the brain. The result was thought to be higher levels of aggression, as measured by a surge in activity in the brain's fear region -- the amygdala -- at the sight of an angry face. That might explain the hair-trigger tempers in that Dutch family.

In a study of 531 U.S. men, however, the violence gene didn't live up to its billing. When psychologist Stephen Manuck of the University of Pittsburgh analyzed men carrying the short form of the MAOA gene, he told the ICN meeting, only those who held antisocial attitudes, who received little parental affection as kids and whose fathers had low levels of education also had a history of aggression. Presumably, dad's low education is a marker for other traits, perhaps how he treats his kids.

"Men with none of these risk factors for aggression had the same low level of lifetime aggression even if they had the short form of the MAOA gene," says Prof. Manuck. That suggests the gene isn't associated with aggression per se, he says, but instead is tied to putting the brakes on tendencies that already are present for other, often environmental, reasons.

Another gene follows the same pattern. It makes a serotonin receptor in the brain and also comes in two forms. One form, which creates a slightly different version of the serotonin receptor, is associated with antisocial behavior and aggression, but only in men whose fathers never finished high school, Prof. Manuck finds. Again, dad's education is undoubtedly a proxy for something that acts directly on his children.

It should have been clear that the short form of the serotonin-receptor gene is no Jack-the-Ripper DNA. Some two-thirds of Japanese carry the short form, but that population isn't known for violence. That suggests something in Japanese culture or child-rearing practices defuses the gene's supposed effects, Prof. Francis speculates.

Snatching children from their parents so scientists can raise some one way and some another way is generally frowned upon, so researchers study the next best thing: monkeys. In research using rhesus monkeys, Stephen Suomi of the National Institutes of Health leaves some newborns with their mothers but moves others to be reared by other young monkeys. Like people, rhesus monkeys have either a long or short serotonin-transporter gene.

"Rhesus monkeys with the short form and who are reared by their mother show no heightened aggression," Dr. Suomi says. "The gene is associated with aggression only if they have a history of childhood abuse or neglect," just as in the humans Dr. Manuck studied. "If you have a good mother, it doesn't make a damn bit of difference which gene you have. Good mothering acts as a buffer."

There is a strange aspect to behavioral genetics. Both researchers and laypeople are smitten by the notion of genetic determinism, despite the drumbeat of discoveries like these. Why the DNA worship?

"Even for scientists, it's much easier to say this gene is related to this behavior," says Prof. Francis. "People have a hard time understanding that experience and social factors are transduced into biology. ... It's a radical idea." Figuring out how experiences reach down into the double helix is this field's next big challenge.

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Just as scientists are now learning, via functional MRI studies, that psychotherapy causes observable structural changes in the brain, so with behavioral genetics.

Once upon a time molecular biologists would have laughed at you if you'd suggested that nurture could alter the functional expression of your DNA.

They aren't laughing any more.

Could Lysenko have been right?