Custom antibody cracks cocaine molecule.

The behavior of a laboratory rat addicted to cocaine soon shrinks to a single action: pushing a metal lever to flood its central nervous, system with molecules of pleasure. But for all cocaine's initial narcotic fury, the pleasure soon trickles away, as natural enzymes begin to break down the drug. To compensate, the rat pushes the lever again and again. "The animal will neglect food and sex. It will perform the task necessary to get the cocaine--eve n if it triggers electric shocks," explains organic chemist Donald W. Landry. "The reinforcing tendency of the drug is almost overwhelming."

Now Landry and others at the Columbia University College of Physicians and Surgeons in New York City have created a unique catalytic antibody -- a kind of fast-acting, artificial enzyme - that may someday help humans beat cocaine addiction. The antibody rapidly cleaves cocaine molecules into two inert fragments, neither of which has any narcotic effect.

Unlike a natural antibody, a catalytic antibody can disarm more than one cocaine molecule, possibly offering a long-lasting immunity against the drug, researchers report in the March 26 SCIENCE. Scientists invented the burgeoning field of catalytic antibody synthesis in 1986 (SN: 9/2/89, p. 152).

Cocaine users often seek treatment voluntarily. After a few days, however, drug cravings can overwhelm their desire to abstain, Landry explains. A series of attempts at sobriety and subsequent relapses may follow, "One clear way to break this cycle is to ensure that using the drug either doesn't give any high, or gives such a blunted high that the sort of maniacal behavior to obtain more drugs is not reinforced," Landry says.

Indeed, a 1970s study of heroin addiction in rhesus monkeys, which used the animals' own antibodies to build immunity, indicates that cravings may subside when attempts at intoxication end in failure, Landry notes. In humans, immunization with fast, long-lived cocaine antibodies may keep users sober long enough for conventional forms of treatment, including psychotherapy and antidepressant drugs, to take effect.

But there's a catch, says neuroscientist and cocaine researcher Bertha K. Madras of Harvard Medical School in Boston: A person could simply take enough cocaine to overwhelm his or her immunity to the drug.

This is why any habit-breaking drug based on catalytic antibodies would have to defang cocaine molecules 1,000 times faster than the body's own enzymes can, a rate other catalytic anti-bodies already have far exceeded, says Landry. This level of immunity could shield the brain from even large doses of cocaine, making it prohibitively expensive for people in treatment to satisfy their craving for the drug.

Next, the researchers will begin animal studies to learn if the antibody can provide immunity against typical doses of cocaine without serious toxic effects. Success may clear the way for tests of the antibody in humans, Landry says.