Angier, Natalie. "Study Finds a Genetic Flaw That May Explain Some Male Violence," New

 

Angier, Natalie. "Study Finds a Genetic Flaw That May Explain Some Male Violence," New
York Times, 22 October 1993, p. A14.

Washington, Oct. 21 - Scientists have identified a tiny genetic defect that appears to predispose
some men toward aggression, impulsiveness and violence, a discovery that is likely to rekindle
the harsh debate over the causes of criminal and abnormal behavior.

Researchers emphasized, however, that the finding was thus far limited to a single large family,
and that the inherited illness was likely to be quite rare in the general population.

Nevertheless, scientists said the discovery counts as a persuasive advance for human behavioral
genetics, a field that has lately been in disarray as previous announcements of genes for
manic-depression, schizophrenia and alcoholism have either been disproved or come under
withering criticism.

In the new worm, researchers from the Netherlands and the United States studied a large Dutch
family with a history of erratic and often hostile behavior among some, but not all, males in the
group. Those afflicted often react to the most mildly stressful occasions with aggressive
outbursts, shouting at, cursing or assaulting the person they deem a threat.

At other times, the men have committed arson, attempted rape and exposed themselves in public.
In addition, their intelligence is on the low end of normal, with an average I.Q. of around 85 to
90.

The researchers have linked the abnormal behaviors to mutations in the gene responsible for the
body's production of monoamine oxidase-am a enzyme critical for breaking down chemicals that
allow brain cells to communicate. The scientists do not yet know the exact mechanism of the
disorder, but they propose that lacking the metabolic enzyme, the brains of afflicted men end up
with excess deposits of potent signaling molecules like serotonin, dopamine and noradrenaline.
These surplus neurotransmitters in turn stimulate erratic, often hostile conduct.

"A human behavior like aggression is very complex," said Dr. Han G. Brunner, a geneticist at
University Hospital in Nigmengen, the Netherlands. "But our study shows that in certain
instances a biological factor clearly influences the behavior." Dr. Brunner is the lead author of
the new report, which is appearing Friday in the journal Science.

Comparing the monamine oxidase-a genes in 5 afflicted and 12 nonafflicted males of the family,
the scientists found a difference in only a single biochemical building block among the thousands
that make up the gene, a type of defect called a point mutation. In each case, those who showed a
predisposition to aggressive, impulsive behavior had the mutation, and those who did not show
such symptoms lacked it.

Biochemical analysis of the men's skin's cells also showed a severe deficiency in the essential
enzyme.

"Other studies have implicated biological and inherited factors" in aggression, Dr. Brunner said.
"This is the first that actually pinpoints a specific gene and a specific mutation within that gene."

The gene is located on the X chromosome, which explains why only males with the single copy
of the X chromosome, can suffer from the enzyme deficiency. Women can serve as carriers of the
genetic defect, but are themselves protected from its symptoms by their possession of a second,
good copy of the gene, sitting on their second X chromosome.

The researchers do not yet know how many people worldwide may suffer from the enzyme
deficiency, but based on other types of hereditary disorders, they estimate that defects in
monoamine oxidase-a are likely to afflict no more than 1 in 100,000 people.

"What this paper does is give harder data to aggressive behavior in some people," said Dr. Emil
F. Coccaro, director of clinical neuroscience research at the Medical College of Pennsylvania in
Philadelphia. "Bug this is a rate disorder. It ain't the gene for all those people who are
committing murder left and right."

Dr. Markku Linnoila, the scientific director of the National Institute on Alcohol Abuse and
Alcoholism in Bethesda, Md., said: "This is an important step in understanding the biological
determinants of human behavior. We learn by looking at extremes - that's where the pay dirt is.
Once you're able to make these kinds of findings, you look to see how it generalizes to the wider
population.

Dr. Xandra O. Breakfield, an associate neurogeneticist at Massachusetts General Hospital in
Charlestown and an author of the new report, cautions that even in a seemingly straightforward
case like an enzyme disorder, the spectrum of the afflicted men's behaviors cannot be explained
by a single genetic defect alone.

"Different members of the family behavior differently," she said. "Some are functioning quite
well, and one is married, has children and a job. Obviously how this syndrome is manifested as a
behavior depends on many factors." She suggested that the finding could result in new therapies
for the disorder, either drugs to help metabolize neurotransmitters, or a change in diet to prevent
buildup of the chemicals.

Studies of the genetics of aggression and violence have fomented much acrimony among
researchers and academics, some of whom see the research as disguised racism or attempts to
reduce complex social and economic problems to a measurable blot on a laboratory X-ray. Last
year a political uproar prompted the National Institutes of Health to cancel a conference
scheduled to be held at the University of Maryland on the genetics of violence and criminal
behavior.

Even Dr. Brunner emphasized that he and his colleagues had not set out to seek the genetic
causes of aggression, but rather were responding to a request from a member of the Dutch family
who already had done enough investigations on his own to conclude that there was some
hereditary abnormality at work in his bloodline.

Dr. Jonathan Beckworth, professor of microbiology and molecular genetics at Harvard Medical
School in Boston and a critic of much research in behavioral genetics, complained that the latest
study, like others before it, failed to define aggressive behavior in sufficient detail.

"It's been a long-term problem in this area, an insufficient characterization of the behavior you're
looking at," he said. "That's one reason why there have been so many announcements of genes
that have later been retracted. There's often a lot less here than meets the eye."