Angier, Natalie. "Maybe It's Not a Gene Behind a Person's Thrill-Seeking Ways," New York

 

Angier, Natalie. "Maybe It's Not a Gene Behind a Person's Thrill-Seeking Ways," New York
Times, 1 November 1996, p. A22.

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 unslakeable
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 concluded in their paper, which appears in the November 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 was 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."

Dr. 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 that 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 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.

"It's like a Chinese menu, where you choose one from column A, one from column B," Dr.
Epstein said. "If you have six genes contributing to novelty-seeking, you're going to find that
some people have all six genes in common, some have only three, some have even fewer. We're
not going to be able to sort this out until we've identified all the genes involved."

Dr. Dean H. Hamer of the National Cancer Institute in Bethesda, an author on the second report,
said he would not expect his results to necessarily apply to Finnish men.

"The Finns are a very unusual genetic isolate that have been separated from the rest of the
population for a long time, since 1400 or thereabouts," Dr. Hamer said. "As a result, they show
many differences from other populations in their frequency of specific genes."

In the original reports, the Epstein researchers had studied a group of Israelis, the Hamer team a
group of Americans; both populations are thought to be more ethnically heterogeneous than are
the Finns. But Dr. Malhotra declared that the cleanness of the Finnish genetic palette is usually
considered an advantage for genetic studies, not a drawback.

"You're likelier to come up with a positive association by chance alone when you're looking at
an ethnically varied population" than when you're studying a genetically isolated group, he said.

Dr. Epstein expressed his faith that the initial findings eventually would be born out by other
scientists. He said there was ancillary support for the association between the dopamine receptor
and novelty-seeking behavior.

For example, Dr. James L. Kennedy, head of neurogenetics at the Clarke Institute of Psychiatry at
the University of Toronto, and his colleagues have found a strong link between the 7-repeat form
and a childhood condition, attention-deficit-hyperactivity disorder. Children with the disorder
were twice as likely to have the 7-repeat receptor than those without the condition.

Although hyperactivity in children and novelty-seeking behavior in adults are not, strictly
speaking, the same beast, Dr. Kennedy pointed out that the impulsiveness and desire for new
thrills seen in adult novelty-seekers is similar to the impulsive, restless, can't-do-my-homework
behavior typical of children with attention-deficit-hyperactivity disorder.

Despite their null finding, Dr. Malhotra and Dr. Goldman emphasized that, far from being social
constructionists who question the ability of genetics to explain the tangles and contingencies of
human nature, they considered psychiatric genetics to be their particular bridge to the 21st
century.

"It's the future," said Dr. Malhotra. "It leads to everything else. Our DNA is us." And that's the
long or short of it.