Correcting Brain Chemistry

Although medical researchers still do not agree on the origin of Parkinson's disease, there is no doubt that the immediate cause is damage to cells in a little-known part of the brain. Because of this damage, the victims of parkinsonism suffer from many symptoms that become progressively more severe and disabling: an involuntary tremor or pill-rolling movement of the fingers, rigidity of major limb muscles, hasty gait, slurred speech and difficulty in moving and turning. A parkinsonian patient falls frequently, and he develops a forward-leaning posture to protect him against toppling over backward.

Metals in the Body. Superficially, there would seem to be little relationship between parkinsonism and the plight of some Chilean miners who have suffered massive manganese poisoning. But an imaginative, Greek-born investigator now working at the Brookhaven National Laboratory noted that some of the symptoms are similar and that the same part of the brain is involved in both conditions. Thanks to his astute observation and his persistence in trying a "discarded treatment, 2,000 or more parkinsonism patients in the U.S. are now enjoying the first effective drug treatment for the disorder. There is hope that after the research phase is finished, the benefits can be extended to hundreds of thousands more. (The number of victims of parkinsonism in the U.S. alone is estimated at 300,000 to 1,500,000.) The drug is usually called L-dopa, or simply dopa, short for Levo-dihydroxyphenylalanine.

George Constantin Cotzias fled from his Nazi-occupied homeland in 1941 and resolved to get a medical education in the U.S. Turned down by seven schools, he took the advice of his father, a former mayor of Athens: "If you don't get what you want at first, try for something better." So young Cotzias went after the best, was accepted at Harvard Medical School--probably, Cotzias suggests, because no one there minded his fractured English--and was graduated cum laude. After training in neurology at the top places, Massachusetts General and Rockefeller University hospitals, Dr. Cotzias became a full-time researcher at the Brookhaven lab on Long Island, specializing in the movement and effects of trace metals in the body.

On a World Health Organization assignment in Chile, Cotzias suspected that the brains of manganese-poisoned miners had suffered chemical changes. He tried a chemical treatment. "It proved to be wrong," says the ebullient and totally unabashed Cotzias. Working on the analogous symptoms in parkinsonism at Brookhaven, he tried another drug treatment. This involved efforts to raise the brain's content of melanin, the pigment in suntanned skin. "Wrong again!" declares Cotzias, with the energy of a small volcano. "The patient's skin got darker, but the tremor got worse."

Ignorance Was Bliss. Research at Brookhaven and other centers indicated that L-dopa might correct the parkinsonian brain's defective chemistry. "We hadn't done our homework, hadn't read the journals and didn't know that it had already been rejected as useless," Cotzias booms. "Ignorance was bliss." Even so, Cotzias and his colleagues got no immediate improvement in his patients. If they had stopped the L-dopa treatment as early as other researchers had, they would have accomplished nothing. But they persisted, giving the drug month after month in gradually increasing doses, eventually far greater than any that had ever been tried in human patients before.

It worked with dramatic benefit in 75% or more of Brookhaven's patients (TIME, Oct. 4, 1968). A major pharmaceutical company agreed to mass-produce dopa for wider testing and, eventually, for general prescription use. Cotzias has already shown that L-dopa is also effective in relieving the worst symptoms of a crippling (and, until now, eventually fatal) childhood muscle disorder called dystonia musculorum deformans. He is working on its application for certain selected groups of patients with cerebral palsy.

From his Olympian view of neurology, Cotzias sees far wider use of chemistry in the correction of disorders of the brain and nervous system. For his contributions to date, Dr. Cotzias, 51, has just received the Clinical Medical Research Award of the Albert and Mary Lasker Foundation--$10,000, plus a replica of another Greek's masterpiece, the Victory of Samothrace.

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