1979-04-02

Although drugs have been used for decades to fight mental illness, scientists have not really understood how they worked. Now all that is changing. A miraculous pharmacopoeia is being explored to deal with every kind of ailment in the mind and body. Not too far off may be tailor-made drugs that will lull insomniacs into peaceful sleep, dull the throbbing of pain, organize a schizophrenic's thoughts and perhaps even simulate the pleasures of sex.

This revolution has been gradually brewing. Until they discovered in the 1930s that the disease pellagra was caused simply by a deficiency of B-complex vitamins, doctors thought that it was a form of psychosis. But proof that body and psyche are really part and parcel of the same physiological system did not come until the discovery of the first tranquilizers in the early 1950s. It was drugs like Thorazine that rapidly emptied mental hospitals, reducing a population of 560,000 to fewer than 200,000 in barely a generation.

Still, discoveries almost amounted to biochemical wizardry. Why, for instance, did drugs control disordered thought and hallucinations in some schizophrenics, yet fail abysmally in others? To unravel such puzzles, researchers turned increasingly to the brain, composed of tens of billions of nerve cells called neurons. Passing electrical impulses from one part of the brain to another, these elongated, finger-like cells communicate with one another across junctions or gaps—synapses—by the release of chemicals called neurotransmitters. As these chemical broad jumpers leap across a synapse, carrying their message, they attach themselves to the neighboring cell, triggering a fresh electrical charge in the adjoining neuron.

So far, scientists, have found at least 20 neurotransmitters. Each of these chemicals has a unique molecular configuration. As a result, neurotransmitters and any of the chemicals that mimic them—work like keys in a lock. They can only fit into those sites, or receptors, on the nerves that are specifically designed to accept them.

The intricacies of this system are just beginning to be unraveled. Scientists speculate that when the body produces too few or too many such chemicals, behavioral problems ensue. Severe depression, for instance, could be linked to abnormally low levels of a family of neurotransmitters called monoamines (serotonin, noradrenaline and dopamine), which can be destroyed by an enzyme called monoamine oxidase (MAO). To keep the enzyme from doing its work, chemists have developed drugs called MAO inhibitors. Other antidepressants, the tricyclics, increase the life of monoamines in the synapse.

Similarly, scientists have found that a low level of the neurotransmitter serotonin may be linked to insomnia. Researchers have been experimenting with tryptophan, the chemical from which the body makes serotonin. Only a small dose of tryptophan—which is found in many foods, notably milk—seems to ease the insomniac to sleep.

As promising as this research has been, Government agencies did not open the funding spigot for it until the 1970s, when the return of many drug-addicted veterans of Viet Nam prompted concern about just how such opiates as heroin and morphine work. The payoff came quickly. In 1973 three groups of researchers, Solomon Snyder and Candace Pert of Johns Hopkins University, Eric Simon of New York University and Lars Terenius of Uppsala, Sweden, announced almost simultaneously the discovery of specific receptors for such opiates in the brain. Snyder's lab located a high density of receptors in the medial thalamus, an area of the brain responsible for registering deep sustained pain; in the amygdala, a region of the brain's limbic system that plays a role in controlling emotion; and in the spinal cord.

But scientists wondered why the body developed opiate receptors in the first place, unless it somehow produces its own internal narcotics. Acting on just such a premise, Pharmacologists John Hughes and Hans Kosterlitz at Scotland's University of Aberdeen in 1975 isolated two peptides from the brains of pigs. Remarkably, the peptides seemed to be natural opiates. Hormonologist Choh Hao Li of the University of California in San Francisco had already discovered similar molecules in the pituitary glands of camels, animals whose insensitivity to pain had long intrigued scientists. Hughes and Kosterlitz dubbed the molecules enkephalins (from the Greek word for head). Subsequently, scientists identified kindred painkilling molecules that they called endorphins (meaning "the morphine within").

Researchers are convinced that such chemicals may explain many behavioral mysteries. During World War II, Army medics were astonished by some soldiers who had lost limbs yet did not complain of pain; scientists now believe that these wounded men produced extra endorphins to dull the agony. Similar chemical magic may explain how Indian fakirs walk over hot coals and how acupuncture and placebos work.

The mind chemicals also hold promise for controlling emotional pain. Because the emotion-controlling amygdala region of the brain is rich in enkephalin receptors, scientists speculate that the molecules may act as a defense against disappointments and trauma. At the Salk Institute, Floyd Bloom is studying the possibility that endorphins may be involved in the pleasure received from alcohol and opiates. Once a person begins taking heroin, say, the natural production of endorphins may decrease. Thus, if addicts try to go cold turkey, the agony of withdrawal is severe. If scientists can create nonaddictive chemicals that bind, like the opiates—and work at Yale with clonidine suggests that they can—to the appropriate receptors, they may be able to ease pain of all kinds, including that connected with stopping a heroin habit.

Once able to locate the brain's opiate receptors, scientists can use their new strategies to draw a biochemical map of all the other neurotransmitters and to learn how chemicals plug into the brain. At Northwestern University, Aryeh Routtenberg is studying the chemical pathways of the brain's reward system, which when stimulated produces sensations of pleasure. If schizophrenics are indeed on a dopamine "high."; their internal reward systems may be constantly turned on. His University of Chicago colleague Richard J. Miller is tracing the link between dopamine and endorphins. At M.I.T., Richard Wurtman, who is studying various neurotransmitters, notably acetylcholine, has found that their production can be increased by diet. Indeed, by upping a patient's intake of foods rich in lecithin—a precursor of acetylcholine —especially egg yolks, meat and fish, such disorders as senility, manic-depression and the loss of motor control associated with the degenerative disease Huntington's chorea, or tardive dyskinesia, can be substantially alleviated.

Some neuroscientists even foresee the day when these new biochemical tools may be used analytically. Thus it would become possible to diagnose mental illness from a simple blood, urine or spinal fluid sample. Once imbalances in body chemistry are determined, doctors would be able to adjust them by administering the appropriate drugs. Harvard's Dr. Seymour Kety insists that such tactics are far from mind control: "You can't manipulate an individual's behavior in the way the popular mind would like to think." But Northwestern's Routtenberg is not so sure. Says he: "These techniques are extremely powerful. Some day we're going to have to have a mind SALT talk."

http://www.time.com/time/magazine/article/0,9171,916741,00.html