Researchers Link Gene to Aggression : Science: Controversial study supports relationship between biological factors and violence but experts say findings cannot be applied to general population.
More than three decades ago, a Dutch schoolteacher, troubled by a pattern of violence among his male relatives, traced the pattern’s origin to a couple who married in 1780. He concluded that his kin must be suffering from an inherited mental disability. Pretending to be a dispassionate outsider, he wrote up his notes under the title “A Curious Case.”
The teacher has long since died. But today, his “curious case” earns a page in the annals of science as a team of researchers from the Netherlands and the United States reports that some men in his family harbor a mutant gene that predisposes them to aggressive behavior.
The discovery of what has been dubbed the “aggression gene” marks the first time a specific genetic defect has ever been linked to violent tendencies in humans. It adds to a growing--and hotly debated--body of evidence that indicates biological factors, as well as social and environmental causes, contribute to violent behavior.
The researchers found that the overaggressive men had abnormal genes for a brain chemical that assists in coping with stress. But experts caution that their study, published in today’s issue of the journal Science, is limited and cannot be applied to the general population, or used to explain the high rate of violence in the United States.
The study could be as controversial as it is dramatic. Research into the link between biology and crime has come under fire in recent months from those who fear such studies could be used to discriminate against racial minorities. Last year, the National Institutes of Health canceled a conference on the topic, and last week black activists in Los Angeles protested a similar academic meeting.
Sensitive to these complaints, the Dutch and American scientists emphasized that the flawed gene, although important, is probably not the sole reason for the family’s history of what they call “aggressive outbursts”--which include a rape that occurred 50 years ago, two arsons and an incident in which one man tried to run over his boss with a car after receiving a negative performance evaluation.
“I think this is the most convincing evidence for a biological factor so far,” said Dr. Han G. Brunner, the Dutch geneticist who headed the study. “But our study does not give you an idea of how important biological factors are in aggression as a whole.”
He noted that while one man in the study continues to have repeated outbursts, his brother--who also has the genetic abnormality--has not had one for many years, which suggests social factors and environment also play a role. “There is not a very simple cause and effect relationship here.”
Other experts are equally reserved in their assessment of the work. “We’re still unsure as to what it all means,” said Gregory Carey, a University of Colorado psychologist who last year published a review of all scientific studies that have attempted to link crime to genetics. “We are not certain at all the extent of which this gene is present in the general population.”
The study also drew criticism from geneticist Jonathan Beckwith of Harvard University Medical School, who faulted the researchers for providing too little detail on the family’s behavior. Although Brunner said the scientists are being purposely vague to shield the family’s privacy, Beckwith said the study failed to prove a true pattern of violence.
“What stunned me about this article was that there were plenty of statistics and numbers about the mapping of the gene, but there was basically no information that one could evaluate about whether the people were truly aggressive,” Beckwith said. “A lot of it just seemed to be anecdotal stories told by the family.”
In the past, research on the link between biology and violence has relied primarily on twins or adoptees. For example, studies have shown that adopted children whose biological parents broke the law are more likely than other children to be lawbreakers themselves.
More recently, sophisticated technology has improved the ability of scientists to look for genetic and other biological clues to the root causes of violence. Researchers at the National Institute on Alcohol Abuse and Alcoholism, for instance, have shown that low levels of the brain chemical serotonin seem to be linked to impulsive, violent behavior.
The Dutch family first came to Brunner’s attention in 1978, when some women--the grandnieces of the schoolteacher--visited his office at University Hospital in Nijmegen and told him their male relatives seemed to be mentally handicapped. They shared their uncle’s written history and asked for his help in determining if they were carriers of the condition.
Because only men were affected, Brunner suspected the disorder was caused by a recessive gene on the female, or X chromosome. Men have only one X chromosome and therefore would show symptoms if they had a flawed gene; women, with two X chromosomes, would have a good gene to cancel out the bad one.
Still, there was no way for Brunner and his colleagues to prove this, or to pinpoint the gene. More than a decade would pass before technology permitted them to do so.
In 1988, with the advent of new techniques for identifying genes, the researchers embarked on a series of “genetic linkage” studies involving 24 members of the family. They determined that all the affected men were of low intelligence, with an average IQ of about 85--borderline retarded but within the normal range. They also determined that there was a common thread to the men’s behavior: a lack of ability to control their impulses.
This finding led the researchers to an enzyme called monoamine oxidase A. The enzyme is a brain chemical that helps break down several neurotransmitters that--if permitted to build up--might cause a person to overreact to stress. Urine samples taken from three affected men showed they lacked this crucial enzyme, Brunner said, but the enzyme was present in the urine of men who were not affected.
In June, the Dutch researchers published an article in the American Journal of Human Genetics in which they suggested that the gene was probably at fault. They enlisted the aid of Dr. Xandra Breakefield, a neurogeneticist at Massachusetts General Hospital who helped them locate the gene, and specify the mutation.
Through a recently developed technique called polymerase chain reaction, which allows scientists to scrutinize strands of DNA genetic material, they determined that out of more than 1,200 amino acids that make up the monoamine oxidase A gene, there was one crucial alteration in five men who exhibited aggressive tendencies.
Brunner said he is investigating whether it is possible to develop treatments for the men that would correct the enzyme deficiency. No therapy is currently available, and experts say the brain enzyme cannot be administered directly. He and Breakefield said further work is needed to determine how prevalent the flawed gene is in the general population.
They suspect the defect is rare. Breakefield, who has studied the enzyme for years, has long suspected that there are people who lack the enzyme. She hypothesized that it would create a nervous system imbalance that could cause mental retardation. She said she searched for 15 years for such people, without success, until finding the Dutch family.
“This is the end of a long quest,” she said, “and it didn’t turn out quite the way I predicted.”
