SCIENTISTS, LIKE MOST MORtals, grow attached to which ever theory works. For geneticists, it's a model that one researcher calls OGOD. It stands for ""one gene, one disorder,'' and it means that a single gene causes, and is enough by itself to cause, a disease. Huntington's and cystic fibrosis are two single-gene diseases for which researchers have identified the culprit DNA; there are scores of others. But lately, the cries of ""OGOD'' from biology labs have not been whoops of victory in nabbing yet another disease gene. They have instead been cries of dismay as some researchers apply the OGOD model to traits and behaviors as complex as ""novelty seeking'' and schizophrenia. ""Looking for single genes for complex behaviors reminds me of the old story of losing your wallet in a dark alley but looking for it under the street lamp because the light is better there,'' says Robert Plomin, a behavioral geneticist at the Institute of Psychiatry in London. Critics outside the field are even harsher. ""Many of these "results' [in behavioral genetics] disappear when you do the statistics right,'' psychologist Helena Kraemer of Stanford University told a recent meeting at the Institute of Medicine in Washington. ""Fallacious methods are very common.''
The latest offering in ""the gene for...'' sweepstakes is ""happy DNA.'' In the current issue of the journal Nature Genetics, molecular biologist Dean Hamer of the National Cancer Institute reviews studies suggesting that one's baseline level of happiness--the very small range within which one's happiness level fluctuates--is ""largely a matter of heredity.'' Identical twins (who have exactly the same genes) are alike in their happiness level 44 percent of the time, according to studies at the University of Minnesota. Fraternal twins, who are no more genetically similar than other siblings, are alike only 8 percent of the time. ""These data show that the broad heritability of well being is 40 to 50%,'' Hamer writes. Moreover, people's happiness levels seem extraordinarily stable through the years (NEWSWEEK, July 29); they are affected neither by winning a lottery nor by becoming paralyzed. Studies of twins suggest that 80 percent of this stable component of happiness is heritable. ""How you feel right now is about equally genetic and circumstantial,'' says Hamer. ""But how you'll feel on average over the next ten years is fully 80% because of your genes.'' Though no one has identified genes wearing teeny smiles, Hamer suggests that a good place to look would be the DNA involved in the brain's ""pleasure chemical,'' dopamine. This molecule is released in the brain after good food or good sex, for instance. ""I don't think there will be a gene for happiness,'' Hamer says, ""but rather many genes, each explaining maybe 1 percent'' of someone's happiness level.
Critics argue that nongenetic reasons can explain why identical twins' happiness levels are more closely correlated than those of fraternal twins. Perhaps people who are treated better by society--by parents, teachers, store clerks, cops--are, all things being equal, happier than those treated shabbily, suggests Stanford's Kraemer. Perhaps, too, one is treated better if one is attractive, thin or even-tempered. Or if one is not a member of a minority group. All of these traits are partly or completely under genetic control. Then is it not possible, Kraemer asks, that this thing called ""happiness'' is not itself genetic but is instead a proxy for traits that are? ""Although a high heritability is being claimed,'' she says, ""in fact the whole explanation may be environmental.''
It would not be the first time that a genetic explanation collapsed. All sorts of complexities can trip up researchers. One of the biggest comes when scientists try, as Hamer does, to calculate ""heritability,'' which is supposed to be a measure of how much of the variation in a trait from one person to the next is explained by genes. (What's not explained by genes is accounted for by people's different ""environments,'' which include everything from obstetrical complications to education, relationships and wealth.) A heritability of 100 percent means a trait is fully and only determined by genes. Eye color is 100 percent heritable; using chopsticks is presumably zero percent heritable. A common way to calculate heritability is through studies of twins. If identical twins are more alike in some trait than fraternal twins, then the trait is thought to have a high heritability. ""But whenever you measure heritability this way, you are glossing over the fact that the similarity of environments for identical twins is much greater than it is for fraternal twins,'' says biologist Marcus Feldman of Stanford (whose own identical twins are now in medical school). Identicals often dress alike, are treated alike and create their own secluded, two-person world. But fraternal twins, according to years of psychological studies, are typically no closer than other siblings. By failing to take into account that identicals share more environmental influences, argues Feldman, geneticists risk ascribing twins' similarities in happiness levels and other traits more to their genes than is warranted.
Over the last decade geneticists have reported finding genes causing schizophrenia, bipolar disorder (manic-depression), alcoholism, novelty seeking and other complex traits. Few have held up (table). Some, such as the claim for a schizophrenia gene, have been withdrawn; others have simply not been replicated (yet) by other scientists. In the latest such attempt, researchers led by psychologist Michael Pogue-Geile of the University of Pittsburgh searched the DNA of 287 twins, hunting for the gene that two separate research groups recently linked to novelty seeking, the yen for new experiences. ""We didn't find anything,'' Pogue-Geile told NEWSWEEK; a paper describing the work is being submitted to a journal. Failure to replicate could mean that the effect of the novelty-seeking gene is too weak to be easily detected; it could also mean that the claim is wrong. Outright fraud seems to lie behind at least one claim of a gene for a complex trait.
Even the harshest critics do not deny that genes play some role in behaviors. Behavior, after all, comes from thought, which comes from the brain. The brain runs on neurotransmitters (chemicals that carry messages from one neuron to another) and receptors (sites on neurons at which neurotransmitters dock, like spacecraft on a space station). Both neurotransmitters and receptors are made according to instructions in genes. But it's a long way from these connections to ""genes determine behavior.'' For one thing, environment influences which of the body's 100,000 or so genes are turned on: like a computer hard drive loaded with programs, only the one opened by a click of the mouse runs. So it is with genes. Take schizophrenia. Someone growing up in bucolic environs may carry the exact same ""schizophrenia'' genes as a kid in South-Central. Since stress increases the risk of schizophrenia, the denizen of the inner city will develop the disease but his country cousin will not, explains psychologist Irving Gottesman of the University of Virginia. If one twin is schizophrenic, his identical twin is schizophrenic only about 48 percent of the time: the environment has not ""opened'' his disease genes.
Because of such complications, behavioral genetics is moving from OGOD to the idea that no single gene is sufficient for a complex trait. Genes are propensities and probabilities, not destiny. But science has not heard the end of these claims. In July, at Jackson Laboratory in Bar Harbor, Maine, NCI's Hamer described his research on genes linked to neuroticism, a trait he called ""much more heritable than [a susceptibility to] breast cancer.'' The gene is involved in the brain's serotonin system, he said. A paper on the ""neurotic gene'' will be published in the journal Science, according to one source, sometime in the next few months. The public, and the press, will likely eat it up, as they have earlier claims of behavioral geneticists. As philosopher Philip Kitcher of the University of California, San Diego, says, ""The seduction of a simple explanation for complicated problems is the strongest force driving this field.'' But keep your ears pricked. Cries of ""OGOD'' will continue to echo throughout the land.
Initial excitement over the "discovery" of a gene for a behavior or complex trait has often turned to disappointment as other researchers have been unable to confirm the claims.
IDENTIFCATION
GENE CLAIMED CURRENT STATUS
Manic-depression 1987 Claim retracted. Other hints of
links to a gene or genes persists.
Schizophrenia 1988 Numerous failures to replicate the
results; one claim has been retracted,
reports of seven other possible geenes
remain.
Alcoholism 1990 A 1993 review found no link between
alcoholism and the purported gene.
Happiness 1996 Unresolved.
Novelty seeking 1996 Reported by two research teams.
The only attempt at repication by
other scientists failed to find
the gene.
Neuroticism 1996 To be published later this year.