`NOVELTY-SEEKING GENE' CAN'T BE REPRODUCED.

Byline: Natalie Angier The New York Times

For those hard-nosed people who were skeptical of a widely heralded finding earlier this year that linked a single gene to a personality trait called novelty-seeking, a group of scientists now says: ``You had reason to be.''

In January, two teams of scientists reported in separate studies that people with an unquenchable thirst for new sensations, who are impulsive, hot-blooded, fickle, excitable and extravagant, tend to have a distinctive variant of a gene that allows the brain to respond to dopamine, an essential chemical communication signal.

The work was said to be the first detection of a gene involved in a normal personality trait, and it received as much extravagant and breathless attention as the disposition it supposedly described, including an article on Page 1 of The New York Times.

Now researchers from the United States and Finland have announced that they tried to replicate the findings in two separate groups of Finnish men, but came up empty-beakered. They looked first at a group of 193 men who were deemed ``normal'' by psychiatric evaluation, and whose degree of novelty-seeking behavior had been determined through a personality questionnaire, as it had been in the previous studies.

They looked next at a group of 138 alcoholic criminal offenders who scored significantly higher in novelty-seeking behavior than did the men judged normal. In both cases, the scientists searched for an association between a taste for the novel and a particular variant in the so-called dopamine D4 receptor gene.

The gene exists in several lengths, the two most common being the 4-repeat form, in which a short section of the gene is repeated four times, and the 7-repeat form. The previous studies had detected a link between novelty-seeking behavior and the 7-repeat version of the receptor gene.

But neither in the normal Finnish men nor in the alcoholics could scientists in the latest study detect any connection between a taste for the novel and the slightly longer gene variant. In fact, among the alcoholics, the findings suggested the opposite. The men were less likely to be novelty-seekers if they had the 7-repeat version of the receptor.

The researchers conclude in their paper, which appears in this month's issue of the journal Molecular Psychiatry: ``These data suggest that D4DR may require re-evaluation as a candidate gene for personality variation.''

And while the scientists admitted that negative findings like theirs were less splashy than positive ones, and harder to publish in high-profile scientific journals, they said it was important to get the negative results publicized if the fledgling field of behavioral or psychiatric genetics is to gain acceptance, credibility and rigor. In the past, claims of an association between one or another gene and mental disorders like manic-depression have evaporated on closer inspection.

``When you see positive findings, a little healthy skepticism is in order,'' said Dr. Anil K. Malhotra of the National Institute of Mental Health, in Bethesda, Md., the first author on the new report. ``Our field is littered with failures to replicate.''

Malhotra, a nattily dressed, pixieish, and smoothly confident young man, described himself as a classic novelty-seeking type. He screened his own dopamine D4 receptor gene, he said, to see if he had the 7-repeat version of it, but found he did not.

``That clinched the case against it for me,'' he said.

His co-authors on the report include Dr. David Goldman of the National Institute on Alcohol Abuse and Alcoholism, and researchers at the University of Helsinki, in Finland.

The scientists who published the initial findings in the January issue of Nature Genetics expressed disappointment but not surprise that an effort to replicate their work had not succeeded.

In a telephone interview, Dr. Richard P. Ebstein of the Herzog Memorial Hospital, in Jerusalem, an author on one of the two papers, pointed out that the dopamine receptor gene was thought to be only one of maybe half a dozen genes that play a role in novelty-seeking behavior, and that one would not expect it to be a factor in all cases of the personality characteristic.