POLITICS OF BIOLOGY
How the nature vs. nurture debate shapes public policy and our view of ourselves

by Wray Herbert.

This article, in longer form, appeared in Newsweek

Nearly every week there is a report of a new gene for one trait or another. Novelty seeking, religiosity, shyness, the tendency to divorce, and even happiness (or the lack of it) are among the traits that may result in part from a gene, according to new research. This cultural shift has political and personal implications.

On the personal level, a belief in the power of genes necessarily diminishes the potency of such personal qualities as will, capacity to choose, and sense of responsibility for those choices --if it's in your genes, you're not accountable. It allows the alcoholic, for example, to treat himself as a helpless victim of his biology rather than as a willful agent with control of his own behavior. Genetic determinism can free victims and their families of guilt --or lock them in their suffering.

On the political level, biological determinism now colors all sorts of public policy debates on issues such as gay rights, health care, juvenile justice, and welfare reform. The effort to dismantle social programs is fueled by the belief that government interventions (the nurturing side in the nature-nurture debate) don't work very well --and the corollary idea that society can't make up for every unfortunate citizen's bad luck. It's probably no coincidence that the biologizing of culture has accompanied the country's shift to the political right, since conservatives traditionally are more dubious about human perfectability than are liberals.

A 1993 National Research Council study, for example, reported strong evidence of genetic influence on antisocial personality disorder, but it also noted that many genes are probably involved. Getting from those unknown genes to an actual act of vandalism or assault, or a life of barbaric violence, requires at this point a monstrous leap of faith.
Yet it's a leap that many are willing to make. When geneticist Xandra Breakefield reported a possible genetic link to violent crime a few years ago, she immediately started receiving phone inquiries from attorneys representing clients in prison; they were hoping that such genetic findings might absolve their clients of culpability for their acts.

Mutations and emotions. Just two decades ago, the National Institute of Mental Health was funding studies of economic recession, unemployment, and urban ills as possible contributors to serious emotional disturbance. A whole branch of psychiatry known as "social psychiatry" was dedicated to helping the mentally ill by rooting out such pathogens as poverty and racism. There is no longer much evidence of these sensibilities at work today. NIMH now focuses its studies almost exclusively on brain research and on the genetic underpinnings of emotional illnesses.

The decision to reorder the federal research portfolio was both scientific and political. Major advances in neuroscience methods opened up research that wasn't possible a generation ago, and that research has paid off in drugs that very effectively treat some disorders. But there was also a concerted political campaign to reinterpret mental illness. A generation ago, the leading theory about schizophrenia was that this devastating emotional and mental disorder was caused by cold and distant mothering, itself the result of the mother's unconscious wish that her child had never been born. A nationwide lobbying effort was launched to combat such unfounded mother blaming, and 20 years later that artifact of the Freudian era is entirely discredited. It's widely accepted today that psychotic disorders are brain disorders, probably with genetic roots.

But this neurogenetic victory may be double edged. For example, family and consumer groups have argued convincingly that schizophrenia is a brain disease like epilepsy, one piece of evidence being that it is treatable with powerful antipsychotic drugs. Managed-care companies, however, have seized upon the disease model, and now will rarely authorize anything but drug treatment: it's efficient, and justified by the arguments of biological psychiatry. The American Psychiatric Association just this month issued elaborate guidelines for treating schizophrenia, including not only drugs but an array of psychosocial services–services the insurance industry is highly unlikely to pay for.

The search for genes for severe mental disorders has been inconclusive. Years of studies of families, adoptees, and twins separated at birth suggest that both schizophrenia and manic-depressive illness run in families. But if that family pattern is the result of genes, it's clearly very complicated, because most of the siblings of schizophrenics (including half of identical twins, who have the same genes) don't develop the disorder. Behavioral geneticists suspect that several genes may underlie the illness, and that some environmental stress--perhaps a virus or birth complications--also might be required to trigger the disorder.

Synapses of desire. It would be a mistake to focus only on biological explanations of psychopathology; the cultural shift is much broader than that. A generation ago, the gay community was at war with organized psychiatry, arguing (successfully) that sexual orientation was a lifestyle choice and ought to be deleted from the manual of disorders. Recently the same community was celebrating new evidence that homosexuality is a biological (and perhaps genetic) trait, not a choice at all.

Whatever's going on, it's clear that this new mistrust of genetic power is consonant with what science is now beginning to show. Indeed, the very expression "gene for" is misleading, according to philosopher Philip Kitcher, author of The Lives to Come. Kitcher critiques what he calls "gene talk," a simplistic shorthand for talking about genetic advances that has led to the widespread misunderstanding of DNA's real powers. He suggests that public discourse may need to include more scientific jargon, not a lot, but some, so as not to oversimplify the complexity of the gene-environment interaction. For example, when geneticists say they've found a gene for a particular trait, what they mean is that people carrying a certain "allele,"a variation in a stretch of DNA that normally codes for a certain protein, will develop the given trait in a standard environment. The last few words, "in a standard environment," are very important, because what scientists are not saying is that a given allele will necessarily lead to that trait in every environment. Indeed, there is mounting evidence that a particular allele will not produce the same result if the environment changes significantly; that is to say, the environment has a strong influence on whether and how a gene gets "expressed."

The emerging view of nature-nurture is that many complicated behaviors probably have some measure of genetic loading that gives some people a susceptibility, for schizophrenia, for instance, or for aggression. But the development of the behavior or pathology requires more, what National Institute of Mental Health Director Stephen Hyman calls an environmental second hit." This second hit operates, counter-intuitively, through the genes themselves to "sculpt" the brain. So with depression, for example, it appears as though a bad experience in the world, for example, a devastating loss, can actually create chemical changes in the body that affect certain genes, which in turn affect certain brain proteins that make a person more susceptible to depression in the future. Nature or nurture? Similarly, Hyman's own work has shown that exposure to addictive substances can lead to biochemical changes at the genetic and molecular levels that commandeer brain circuits involving volition, and thus undermine the very motivation needed to take charge of one's destructive behavior. So the choice to experiment with drugs or alcohol may, in certain people, create the biological substrate of the addictive disorder. The distinction between biology and experience begins to lose its edge.

The proliferation of "official" psychiatric disturbances since 1952, when the first "Diagnostic and Statistical Manual of Mental Disorders'' (DSM) was published has increased from 60 to 145 (2nd edition, 1968) to 410 (4th edition, 1994). Cynics think therapists are spreading a wider net to90 catch more clients, but new brain imaging techniques and genetic studies have converged on the likelihood that these all may reflect variations in brain function. ``ultimately,'' says Dean Hamer, a leading behavioral geneticist at the National Cancer Institute. . .``it might mean that we're all a little bit crazy.''

The 1997 book ``Shadow Syndromes,'' by psychiatrist John Ratey of Harvard Medical School and Catherine Johnson of the National Alliance for Autism Research argues that all sorts of quirky behaviors are actually mild mental illnesses.
"The athletic megastar who is as cool as ice in the championship game but explodes at a bar is not just a spoiled brat; he is beset by intermittent rage disorder. Men who are unable to talk about their feelings suffer ``from an unrecognized adult form of attention deficit disorder'' (ADD). Mild ADD also marks the business titan who can't file his taxes on time. The deadbeat dad, who dotes on his children when they visit but who can't seem to remember to send the child-support checks, is neither a louse nor someone chafing at an unfair custody arrangement. He has mild ``environmental dependency syndrome'': he can't focus on his kids unless he's with them. And the woman who can't abide a husband who fails to help with the house and kids once the two of them return from their jobs may suffer from ``a very mild form of obsessive-compulsive disorder.'' Call it Mental Illness Lite."

"Since many people have occasional and temporary symptoms of mental illness--from sadness to exuberance bordering on mania--``it's very difficult to say where mental illness shades into normalcy,'' admits Dr. Mark Olfson of Columbia University. ``And that poses real questions for treatment: when should you prescribe antidepressants? In fact, they've exploded in use and are now prescribed for subclinical symptoms.''

"A new book, ``Making Us Crazy,'' by social scientists Herb Kutchins and Stuart Kirk, blasts the DSM for being scientifically unsound, swayed by politics (homosexuality is a mental illness; no, it isn't) and pathologizing everyday behaviors like holding a grudge or worrying about public speaking. ``The psychiatric bible has been making us crazy--when we are just human,'' they argue."

"It's absolutely going to be the case that geneticists will come to the aid of psychiatrists in this debate,'' says Stanford University neuroscientist Robert Sapolsky. "The idea of a continuum represents a major cognitive breakthrough for genetics. It suggests that a middling genetic load [of mental-illness genes] gives you a personality disorder, a lighter one gives you a personality quirk and a still lighter one gives you mainstream America.''

"Researchers found the first hints that mental illness comes in mild forms when they examined relatives of seriously ill people. "So-called schizoid personalities, who are extremely withdrawn, are commoner in families of schizophrenics,'' says Dr. Jonathan Benjamin of Ben Gurion University in Israel. ``And awkward social behavior is more frequent in the biological parents of autistic children.'' That suggests that while the patient has many mental-illness genes, the relatives have only a few, and thus have ``shadow syndromes.''

"Schizophrenia offers the classic illustration. Schizophrenics have less gray matter in the frontal cortex, the seat of higher thought, says psychiatrist Tyrone Cannon of the University of Pennsylvania. And in the hippocampus, which helps run memory and emotion, cells are out of place. People with mild schizophrenia, whose symptoms are not severe enough to keep them socially isolated, have mild versions of these brain abnormalities. People with severe schizophrenia, who are unable to distinguish fears and fantasies from reality, have severe versions. ``Our twins study suggests that people with two genes out of a hypothetical 10 might have only subtle changes in brain structure and function,'' says Cannon. ``But as you increase the number of genes you pass over the threshold to clinical significance.''
"LAST YEAR . . . Researchers discovered an abnormally long version, or allele, of a gene on chromosome 11 (humans have 23 pairs of rod-shaped chromosomes, along which genes are strung like pearls). The allele was found more often in heroin addicts than in nonaddicts. The job of this gene is to produce a receptor--a sort of molecular docking site--for the brain chemical dopamine. Here's where the continuum comes in: the long version of the gene is also common in mentally healthy people who exhibit ``novelty-seeking'' behavior, according to research groups in Israel and at the National Institutes of Health in 1996. Such people tend to be impulsive, fickle, excitable, quick-tempered and extravagant; they seek thrills and feel exhilarated in novel situations. They are the world's race-car drivers and its explorers. This gene is only one of an estimated 10 or so that determine novelty-seeking, explains Ben Gurion's Benjamin. Someone with 2 or 3 of the 10 might be a little impulsive. Someone with all 10 might be a risk freak--or a heroin addict."

"In just the last two years, researchers have discovered several genes that may account for personality quirks and, in combination with other genes, trigger mild or full-blown mental illness: In 1996 researchers led by NCI's Hamer identified a gene on chromosome 17 that contributes to neuroticism. This catchall term includes being anxious and sometimes depressed, hostile and impulsive. The gene comes in short and long forms, Hamer explains in ``Living With Our Genes,'' a book due in March. It makes what is called a transporter, a protein that sweeps away the brain chemical serotonin from between neurons. Serotonin, Hamer believes, causes anxiety and depression. The short form of the gene makes less transporter, which is less effective at removing serotonin. One would therefore expect a connection: short gene, more serotonin, more anxiety. That's what the researchers found--the short form of the gene is more common in people who are neurotic (as determined by questionnaires). But this gene accounts for only a tiny amount of the differences in people's genetically determined degree of neurotic behavior. Hamer estimates it at 7 to 9 percent. In other words, there are other neuroticism genes. Having few or many could mean the difference between glancing anxiously at the clock when your teenager is out past her curfew . . . and being Woody Allen.

OCD. In 1997 researchers linked a gene on chromosome 22 to obsessive-compulsive disorder. OCD is marked by intrusive, upsetting thoughts (the ``O''), like not being able to let go of the idea that you forgot to turn off the oven, and repetitive behaviors that interfere with daily life (the ``C''), like constant hand-washing. The purported OCD gene makes a sort of bio-vacuum cleaner--an enzyme that gets rid of brain chemicals after they have carried a signal between neurons. Everyone has this enzyme, but the OCD version makes such a wimpy version of it that the brain chemicals keep delivering the same infernal message over and over--a nagging ``did you turn off the oven?'' Again, several genes are thought to cause OCD. Someone with all of them might be so tied up in worries and obsessions as to be dysfunctional. Someone with one or two might keep a superneat desk.

New research suggests that milder forms of OCD arise from milder brain abnormalities, too. PET scans, which detect regions of high activity in the brain, have shown that a circuit running from the orbital frontal cortex--the bottom front of the brain, which acts as a sort of error-detection system--is hyperactive in OCD patients, finds Jeffrey Schwartz of UCLA. ``It gives you the feeling of being stuck in gear,'' he says. In people with depression but not OCD, just the outer rim of the orbital frontal cortex is running full tilt. ``These people have problems getting ruminations out of their mind,'' says Schwartz. ``It's not a true obsession, but a milder thing''--with a milder brain abnormality.

In December, researchers at Johns Hopkins University traced a gene for manic-depression to chromosome 18. That makes at least five genes associated with this disease. ``It may be that if you have only one gene,'' says Dr. Francis McMahon, who led the team, ``you might be more susceptible to mood elevations that let you meet deadlines through a burst of activity, or lead your business team across the finish line. The gene may be overrepresented among artists and creative types.'' Actor Robin Williams has described his deep depressions; any fan can see his mania. But someone with all five manic-depression genes might be too buffeted by mood swings to function. Says neuroscientist Dr. Samuel Barondes of UC, San Francisco, ``Maybe having one of these genes is really good for you, but having all of them makes you crazy.''

Genes associated with mental illness might, in fact, keep society supplied with the personality types it needs. People with schizotypal personality disorder, explains Stanford's Sapolsky, gravitate toward solitary lives. They are lighthouse keepers and fire-tower rangers. Those with a touch of OCD are the dogged employees who don't let go of a task until it is complete. Long ago, they may have been shamans and witch doctors and, perhaps, the men who established religious rituals. Who else could have thought up a Hindu ritual of washing the left hand 10 times, the right one 7 and both 5 more at the beginning of the day? The visions of Joan of Arc, the prophet Muhammad and Saint Paul are suggestive of hallucinations produced by temporal-lobe epilepsy. And in 1990 researchers in Minnesota, studying identical twins, calculated that religious belief is 50 percent genetic. Mercifully, they refrained from calling it the God Gene.

EVEN IF NEUROSCIENTISTS FIND brain lesions linked to holding grudges or spending too much time on the Internet, and even if geneticists find stretches of DNA linked to being aloof or persistent, that will not prove that biology is destiny. For one thing, the structure and activity patterns of the brain reflect experience, not just the biology one is born with. The 40-year-old who has no interest in his lover's feelings may indeed have ``bad brain chemistry.'' But that chemistry could be the product of a bad relationship with his father, social pressures to be emotionally distant--even a traumatic first date. And Schwartz's work with OCD patients has shown that they can overcome their ``brain lock'' by ``willfully activating healthy circuits to predominate over the unhealthy ones,'' he says. Even genes that affect behavior by acting on the brain may determine our fate only in part. In a recent study, biologists found that baby rats whose mothers lick them have physically different brain structures from those whose mothers don't. The differences lie in regions that respond to stress. Licked rats handle it better than deprived rats do, suggesting that life's experience shapes the brain even when it comes to a trait as basic as temperament.

The idea that eccentric behaviors may be mild forms of mental illness is so new that its implications for society are unclear. But some scientists already worry about stigmatizing people who carry even a few genes for serious mental illness. Will couples count their respective ``crazy genes'' before they have children--or abort fetuses with too many of them? Will prospective mates demand to look at each other's brain scans? What will that do to the world's supply of artists and dreamers, adventurers and inventors? ``If we discover that there are many genes associated with mental illness,'' says Hopkins's McMahon, ``and that at least some of them are pretty common, it could make us realize that we're all in the same boat.'' Which suggests that when everyone is crazy, no one will be. So pundits will still get to poke fun at the notion that road rage, gourmand syndrome and other nouveaux disorders are real mental illnesses. But as genetic and neuroscience discoveries add support to the idea that something real, something physical, underlies these and other seemingly trivial ills, it will be harder to laugh.