Several prestigious New York City medical centers have been experimenting on 6- to 11-year-old boys in an effort to prove that violence, aggression and even criminal behavior are caused by biological factors. One of these studies, first launched in 1992, was still underway in April when patient advocacy groups charged the researchers with violating federal ethics rules, unleashing a torrent of media scrutiny and outrage.Critics are asking why peer review panels at the New York State Psychiatric Institute (NYSPI), Mount Sinai Medical Center and the National Institute of Mental Health (NIMH), approved the experiments. Serious ethical considerations are raised by the age of the boys, the fact that many were poor minorities, and that the experiments were not designed to provide treatment for an existing illness. Investigators are looking at the researchers' use of fenfluramine, a drug banned last fall by the Food and Drug Administration (FDA) when the agency discovered that it had caused heart damage as part of the popular diet drug fen-phen. And legal advocates are examining the role of New York City's chief juvenile justice prosecutor in helping one team of researchers gather young subjects. Responding to the outcry, Congress held hearings in April on the FDA's role in approving the drug for experiments on children.But the studies also raise larger questions about the social and political implications of research into the roots of violence that focuses on disenfranchised, inner-city communities. NIMH, the federal agency that funded much of the research, has granted millions of dollars to studies investigating serotonin, the chemical that transmits signals between cells in the brain, and how it is connected to violent behavior. If they discover biological factors that lead to violence in minority boys, the research could inaugurate wholesale drug intervention for youngsters identified as "at-risk" for anti-social behavior. In an era when the government trades its previous commitment to battling poverty for a strategy of battling the impoverished, research that seeks the causes of violence in individuals and their body chemistry has an obvious appeal. If biology, not sociology, can be the predictor of crime, then that could justify clamping down on suspect populations.The New York City experiments involved one team of psychiatric researchers at NYSPI, part of Columbia University, and another team doing similar research at Queens College and Mount Sinai Medical Center in Manhattan. Several of the researchers had been laboring since 1990 to find a link between behavior and genetics in their sample of urban youth. "The proliferation of violence by youth in our society is reaching epidemic proportions," the NYSPI researchers told reporters in a prepared statement. "Each day we see instances of children committing violent acts against other children and adults, most recently [the schoolyard murders in] Jonesboro, [Ark.]. ... The correlation between serotonin and aggression in children needs to be studied in order to identify children at highest risk for impulsive, aggressive behavior."The NYSPI researchers, led by Daniel Pine and Gail Wasserman, were trying to prove that their subjects-young brothers of jailed delinquents-were predisposed to criminal behavior because of familial histories of aggressive behavior. In an article published last September in the Archives of General Psychiatry, Pine and Wasserman conclude: "In young boys, aggressive behavior and social circumstances that are conducive to the development of aggressive behavior are positively correlated with a marker of central serotonergic activity." In other words, kids who grow up around aggression are likely to be aggressive and have low levels of serotonin.The Queens College/Mount Sinai team was led by Jeffrey Halperin, whose findings were published last October in the Journal of the American Academy of Child Adolescent Psychiatry. Halperin's study also sought to correlate behaviors with serotonin levels in children. Based on a study of boys with aggressive pasts and Attention Deficit Hyperactivity Disorder (ADHD), he points to a correlation in his data between aggressive behavior in parents and lower serotonin levels in aggressive boys with ADHD, a psychiatric diagnosis that some researchers believe is a predictor of aggressive behavior in adults. But Halperin says he couldn't determine "the extent to which this association is environmentally and/or genetically transmitted."In both studies, researchers gave boys one-time doses of fenfluramine to help measure the amount of serotonin in their brains. All the boys had restricted diets for a month and were required to fast for 12 hours prior to the test. They were attached to IVs for up to six hours as blood samples were taken and only allowed to drink water. Halperin's group consisted of 41 boys with ADHD. Twelve of Halperin's subjects on medication for ADHD were required to stop taking it for a month before the test-a procedure known as "a wash-out." Pine and Wasserman followed virtually the same protocols in their two studies, which involved 34 boys in one and 100 in the other.Many aspects of these experiments raise red flags for those who monitor the ethical implications of medical research on human subjects, but it was the use of fenfluramine that captured media attention. Though one dose of fenfluramine is unlikely to cause permanent heart damage, there is no research on the drug's effects in children. One study on adults showed that 90 percent of healthy subjects who were given doses of the drug experienced fatigue, headaches, lightheadedness and lack of concentration.The FDA's director, Dr. Michael Friedman, acknowledges that his agency approved researchers' continued use of fenfluramine on the boys even after the drug had been pulled from the market because it caused heart valve damage in some dieters. But he defended that decision at hearings before the House Committee on Government Reform and Oversight in April, saying that in February NYSPI revised the parental consent form to provide warnings about possible harmful side effects. But that was five months after fenfluramine was pulled from the market, and the FDA allowed NYSPI to enroll two more youths in the study before publicity halted it in April.Researchers at NYSPI also received cooperation from other governmental agencies. Wasserman began assembling subjects in 1991, at first using the New York City Department of Probation to find 6- to 10-year-old boys whose older brothers were incarcerated delinquents. After one month, probation officials balked, deciding that families of the youth might feel coerced into participating.Wasserman and her colleagues ultimately were aided by Peter Reinharz, head of the family court unit of the city's law department. Reinharz reportedly gave the researchers access to family court records, which are supposed to be confidential. His actions are being investigated by the Legal Aid Society. "We've filed a Freedom of Information request to find out which youth were identified," says Jane Spinak, the head of Legal Aid's juvenile rights division. "We think many of them were our clients. We believe their civil rights may have been violated."Attorneys at Disability Advocates and New York Lawyers in the Public Interest get credit for exposing the experiments. They came across the two studies while doing their own research for an ongoing case against the state Office of Mental Health. That suit challenges the state's practice of permitting research on incapacitated patients-children and adults-at psychiatric facilities, arguing that it violates the patient's right to informed consent. "There are so many angles that are problematic," says Ruth Lowenkron of New York Lawyers in the Public Interest. "To see this kind of non-therapeutic research raises questions about what was told to the parents. How was consent obtained? In the Mount Sinai experiments, kids were taken off their medication. What happened to them?"When the lawyers found out about the violence research studies in December, they filed a complaint with the Office of Protection from Research Risks (OPRR) at the Department of Health and Human Services. OPRR is the government agency charged with monitoring all medical research involving human and animal subjects to insure that it conforms with federal guidelines on informed consent and safety. Gary Ellis, OPRR head, says his office is investigating four complaints related to the studies, the most recent of which was filed in April. The complaints question whether the children in the studies and their families were adequately informed of the risks of the experiments and were therefore able to give real informed consent to participate. Ellis says his office will also investigate whether the studies violated government rules against exposing healthy children to potential harm in experiments that offer no therapeutic benefit. For its part, NYSPI asserts that the children in one group were at risk for suicide, so the experiments did offer some promise of helping them. Ellis says his investigation will take up to six months to complete.A racial component of the research also raises disturbing questions. In one of Pine and Wasserman's experiments, 60 percent of the 34 boys who participated were black, and the other 40 percent Latino. NYSPI insists that the racial/ethnic mix of the boys Pine and Wasserman studied simply reflects the population living around the institute. But for Ronald Walters, a political scientist at the University of Maryland, the New York studies are just a continuation of what started at NIMH in the early '90s.Walters served on a panel appointed by then Health and Human Services secretary Louis Sullivan in 1992 that reviewed government-funded research into violence for potential race bias. Then, as now, Walters and other critics believed such research reflects a widespread view among many whites that black and Latino people are predisposed by biology to commit crimes and violent acts. "Why haven't members of the Black and Hispanic Congressional Caucuses been more concerned with this?" asks Walters. "Black and brown children will be the obvious target in the inner city. This research is a shortcut way to deal with violence."The experiments in New York were conducted in the shadow of a long-running controversy over the very nature of the research: looking for biological causes for violence in individuals instead of examining social and economic factors. Six years ago, the federal National Institutes of Health was embroiled in a debate over the legitimacy of a five-year plan to study the causes of violence that including looking at genetic and biological factors. Dubbed "the violence initiative," the plan was scuttled after Dr. Frederick Goodwin, then head of the Alcohol, Drug Abuse and Mental Health Administration of NIMH, gave a speech in 1992 in which he compared inner-city males to Rhesus monkeys. A coalition of psychologists and sociologists from predominantly African-American organizations attacked Goodwin's pronouncements and his research agenda. Plans for a national conference on genetics and crime were jettisoned, discussions of the violence initiative became muted and Goodwin was forced to resign his post.Although Goodwin no longer heads the NIMH agency, research into the genetic and biological roots of aggression has continued. According to a 1993 article in Science magazine, NIMH was then funding close to 300 research projects into aggression and violence, many with multiyear grants. Since 1990, Pine, Wasserman and their colleagues have received three grants from NIMH totaling more than $7 million. Wasserman launched her initial work with a $1.25 million grant from the private Leon Lowenstein Foundation.Halperin has received nearly $1 million from NIMH since 1990 for his research. None of the researchers responded to interview requests, but senior researchers at NYSPI defended the studies in an interview published in the April 23 issue of Nature. Pine told Nature that his studies obeyed all federal ethics rules. He called violence "a major public health problem" and criticized his critics for opposing any study of "the relationship between aggression and biology."The search for a link between ethnicity and violence is not new. The phrenology movement of the late 1800s claimed criminal behavior could be predicted by examining the contours of the human head. Early criminologists and psychologists studied the skulls of juvenile delinquents-mostly Irish immigrant youth back then-in their search for the causes of aggression and anti-social behaviors.So how real is the link between serotonin levels in the brain and aggressive or violent behavior? In the past decade, psychiatric researchers have developed a fascination with serotonin. Serotonin deficits have been linked to depression and alcoholism, and drugs such as Prozac are designed to raise serotonin levels to inhibit depression. Today, some researchers believe that low levels of serotonin also are responsible for impulsive, even violent behavior. But there is no proof that genetics determine serotonin levels or even that serotonin levels alone are the cause of anything.Neurobiologist Evan Balaban of the Neurosciences Institute in San Diego is critical of serotonin research like that conducted in New York. He and two colleagues published an article in the October 1996 Journal of Neurogenetics that reviewed the findings in 100 studies claiming violent people have very low serotonin levels. They found the studies methodologically suspect and the results inconclusive. While they concurred that biology is important, it is not the sole causative factor. They concluded: "Geneticists and other biologists who are interested in understanding aggressive behavior should take a second look at whether the human and animal literature justifies linking the words 'serotonin' and 'aggression' with the words 'specific relationship.' "Dr. David Shore, director for clinical research at NIMH, says research into the biological causes of violence and aggression represents a small slice of the work funded by his agency. But Shore says that this kind of research is legitimate. "I don't think data linking violence and serotonin are strange," he says. "There have been studies that have shown all sorts of behavioral problems." Shore defends NIMH's funding of both studies: The researchers not only had to pass the peer review process at their own institutions but survive scrutiny of a panel of NIMH experts. He noted that the panel met in May and that the controversial New York studies were part of its agenda. Halperin's grant, now in its seventh year, is up for renewal, but Shore would not comment on whether the council voted to continue his funding.Sadly, it has become easier and easier to convince a frightened public that the goal of combating youth crime justifies any means. It has come to the point where NYSPI can boldly declare that the Jonesboro shootings in Arkansas are a justification for violating the integrity of six-year-old boys from Harlem and the Bronx.Annette Fuentes is a 1997-98 Prudential Fellow at Columbia Graduate School of Journalism, researching issues on children and the news.