This story ran on page C1 of the Boston Globe on 4/23/2002.
© Copyright 2002 Globe Newspaper Company.

Fruit fly fight club Looking for the genetic roots of human aggression in insect combat By Gareth Cook , Globe Staff, 4/23/2002 Inside a clear box that offers no possibility of escape, a column of light shines down on the platform where the violent contests are decided. The ritual that follows is executed without deviation. At the center of the stage, a headless carcass is laid down by a worker who shows not the slightest hint of emotion. Nearby, the contestants - one representing Team White, the other Team Yellow - are readied. And then, before the cool eye of a digital video camera, the two competitors are ushered in with a single goal - total domination. These brutal contests take place regularly at a Harvard Medical School laboratory, where they have a nickname, the ''Fruit Fly Fight Club.'' By carefully observing the lunging, boxing and smack downs of fruit flies spurred on by the scent of food and a female, the researchers are searching for the deep genetic roots of aggression and violence in humans. ''Violence is a serious problem in society,'' said lead researcher Edward Kravitz, sitting in his office after the morning bouts had ended. ''And it is a problem with a biological basis.'' Eventually, scientists like Kravitz dream of creating a safer world, where its most pathologically violent members can be treated. But the very idea of studying the genetic links to violence is highly controversial because of its racist overtones: White racists have long championed the idea that some ethnic groups are biologically inferior, and thus more prone to violence or crime. And the concept of medically treating violence is equally explosive because, in the past, scientists have championed treatments for criminals or the mentally ill - such as removing parts of the brain - that are now considered brutal and ineffective. ''The treatment approaches of the past are a dark chapter in the history of biomedical research,'' said Klaus Miczek, a professor of psychology at Tufts University in Medford who is a leading researcher in the study of aggression. For example, Miczek said, in 1949 the Nobel Prize in Medicine was awarded to Antonia Egas Moniz, who pioneered a procedure for treating violent mental patients by removing sections of their brains. Despite a revolution of biological knowledge - and the most violent century in human history - very little is still known about the biological basis of human violence. There are a large number of studies that show that aggressiveness is a personality trait with a genetic component, according to Gregory Carey, a professor of psychology at the University of Colorado. Twins, for example, are more likely to have similar scores in measures of aggressiveness, even if they were raised apart. And in 1987, a team of researchers reported a landmark study of twins and crime in Denmark. In cases where one identical twin had committed a felony, the other twin was more likely to have committed a felony, according to Irving I. Gottesman, a professor at the University of Minnesota Medical School who was involved in the study. Fraternal twins, who share only half of their genetic material on average, were not as closely tied as identical twins, but more closely tied than would be expected by chance, Gottesman said. But other studies have contradicted the findings, Carey said, and the relationship between violence and genetics remains an open question. In the modern quest for the genetic basis of aggression, scientists are not looking for a single gene that rules. With the exception of extremely rare mutations that could cause sudden violent outbursts, the vast majority of human behavior - from road rage to war - is the product of complex interactions between large numbers of genes and the changing environment. ''We humans do not inherit behavior like we inherit eye color,'' Carey said. To begin to sort out the workings of human aggression, scientists have turned to animals. One major focus of the recent work has been the neurotransmitter serotonin, an important chemical messenger in the brain. In one set of experiments, scientists tracked the increase in violent fighting that occurs in laboratory animals after they are given alcohol to drink. They then showed that a drug that lowers the amount of serotonin in one part of the brain can moderate these violent bouts, Miczek said. In his own lab, Miczek of Tufts has done painstaking experiments on rats in which he can track the flow of serotonin during a bout of fighting. The rats have been given micro-thin implants that can measure the levels of chemicals in the brain. Miczek said he has found consistent patterns of spikes and drops in levels of serotonin and dopamine, another neurotransmitter, when the rats fight and finish fighting. If scientists could understand the genes that regulate how serotonin is produced, transmitted and detected by neurons in the brain, they would be closer to understanding how differences between people could increase their propensity towards violence. This is the lure of the fruit fly. The fruit fly is one of the most highly studied animals in all of biology, and its entire genetic blueprint has already been sequenced, providing Harvard's Kravitz with a range of tools he would not have in other animals. Fruit flies are also relatively easy to work with. ''Their lifetime is short, and the flies are cheap,'' said Kravitz, who has done extensive research on aggression in lobsters. To begin the work, Kravitz set out to establish the baseline fighting behavior of a creature that most people would not expect to fight at all. A food dish to attract the flies is placed inside a box that is clear so that the experiment can be videotaped. A female is also placed in the middle of the food dish to attract the males - decapitated so she won't fly away. Harvard student Ann Yeelin Lee then delicately places drops of colored paint on the flies, one yellow and one white, so she can tell them apart. When the flies are then placed in the box, they jockey for position on the food dish, using a series of fighting moves that Kravitz has carefully documented. Eventually, one of the flies will establish dominance, walking around near the center, while the other one cowers off in some corner. After each battle, Lee kills the flies and then places them in containers so their genetic material can be analyzed. Kravitz has created a system of scoring, from the most aggressive moves to the least, that allows the researcher to rate the flies. By studing the film, Kravitz cam determine how aggressive individual flies are, and also understand their fighting behavior in general. He has determined the precise amount of time, on average, that the flies spend doing various moves - ''boxing'' versus ''fencing,'' for example - and how likely each move is to lead to another move. These results were published this month in the Proceedings of the National Academy of Sciences. With this research done, he is now beginning two more ambitious experiments. In one, he will use flies that have been genetically modified so that the serotonin systems in some neurons will shut off when the temperature is raised slightly. He wants to see what will happen to the fly's fighting behavior when this is done mid-fight. And, in a second experiment, he is separating the flies that win their bouts from the flies that lose, and then sending them to collaborators at the University of Basel in Switzerland. At this lab, the scientists will look for subtle genetic variations between the more-violent winners and the more-submissive losers. Eventually, this could yield insights into the roots of human violence and, hopefully, make the world a slightly more peaceful place. The flies, Kravitz said, are fighting for a good cause. Gareth Cook can be reached at cook@globe.com.