Promote & Retard

One of the many mysteries about muscles is the fact that they rarely develop cancer. So, by the arcane logic of scientific research, what appears to be a hopeful line of cancer research is being conducted by one of the world's greatest authorities on muscle. He is Albert Szent-Gyorgyi, 69, the Hungarian-born Nobel prizewinner* who is head of the Institute for Muscle Research in Woods Hole, Mass.

Clue in the Neck. Dr. Szent-Gyorgyi (pronounced St. Georgie) entered the cancer field almost by chance. After he fled Hungary's Communist control in 1947, he was able to resume at Woods Hole his long work on muscle. Concentrating on one of the commonest of muscular diseases, myasthenia gravis, he had a clue. Sometimes a victim of "MG" does better after his thymus gland is removed. Searching for the explanation, Szent-Gyorgyi, who has a Cambridge Ph.D. in biochemistry besides his M.D., spent years doing delicate chemical dissections of the thymus glands of calves, supplied by Chicago's Armour & Co. The trail ran out. Szent-Gyorgyi had found nothing of value to MG patients. But by scientific serendipity he had found something that he hopes will prove to be even better: two substances, apparently hormones. One of them promotes the growth of cancer in mice, so Szent-Gyorgyi named it "promine," while the other retards such growth, and is called "retine."

Armour regularly shipped barrels of calf thymuses ("neck sweetbreads") to Szent-Gyorgyi in Woods Hole. His rooms atop the Marine Biological Laboratory building on Main Street began to overflow with centrifuges used to extract submicroscopic quantities of promine and retine. More recently, Dr. Szent-Gyorgyi and his colleagues, Dr. Andrew Hegyeli and Jane A. McLaughlin, have found a cheaper and more abundant source: human urine. So, at nearby Otis Air Force Base, six latrines have special urinals, which yield from 60 to 100 liters a day for Dr. Szent-Gyorgyi's research.

Mouse House. In a little frame build ing around the corner from his labs, one of his assistants pipes the urine into a heat exchanger to remove most of the water. Then other assistants subject the concentrate to a tedious series of steps, dissolving and redissolving, to get out the promine and retine. The two substances are maddeningly similar. To get them apart, the technicians rely on the fact that promine separates out more readily in an acid solution, and retine in one that is alkaline. What they have left after days of work is admittedly still impure. Dr. Szent-Gyorgyi hopes other scientists will find ways to improve it.

Dissolved in peanut oil, the promine and retine preparations are injected into mice to observe the effect on the animals' cancers. Dr. Szent-Gyorgyi's mouse house is across the yard from the lab building. There he has tested promine and retine on hundreds of tumors. Two of the three types of tumor he works with are favorites of researchers: transplanted from one animal to another, they grow fast, and give a quick indication of a drug's effects. Promine speeds the growth of these cancers; retine makes them grow more slowly and actually causes some tumors, already well grown, to shrink. Perhaps most important, retine also works in cancers that certain mice develop naturally, which makes them more nearly comparable to the human disease. And neither pro-mine nor retine seems to have any harmful incidental effects--in sharp contrast with virtually all anticancer drugs now in use.

Double the Retine? Nothing quite like promine and retine has been discovered before, although sex hormones and chemically related compounds are used in treating some forms of cancer. The commonest of the many kinds of cancer, Szent-Gyorgyi notes, are the types that usually develop in middle life. "We have some evidence from ani mals," he says, "that the body's output of both promine and retine may decline with advancing age. But what seems to be more important is that the ratio of the two substances changes. Later in life, the body makes proportionately less of the retarding retine. From our experiments so far, it looks as though changing the ratio back, by doubling the amount of retine, is necessary to make cancer regress."

Cancer researchers have had their hopes raised and then dashed so many times that they are jumping to no optimistic conclusions about Szent-Gyorgyi's latest work. Neither is he. "We have made only a preliminary report," he says. "We hope other laboratories will test our theory and help to prove or disprove it. I am already getting letters from all over, asking me to send 'the cancer cure.' There is no such thing, and I have not enough material even for other laboratories. The urgent thing is for other researchers to make and test these substances.

"Cancer is such a cruel disease," says Dr. Szent-Gyorgyi. He knows. Fortnight ago, his wife died of cancer, after a lingering, painful illness that began when he was in the midst of his retine research.

* In 1937, for demonstrating that the anti-scurvy vitamin is ascorbic acid, which he extracted by the pound from peppers.

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