Secret from the Guinea Pigs

A birthday party for a nonagenarian Texas oil millionaire is an unlikely occasion for the announcement of a new treatment that may be effective against some forms of cancer. No less unlikely, as a source of the promising substance, are common colon bacteria that multi ply in sewage and often result in the contamination and closing of beaches. Yet both these elements were present last week in the excitement over a procedure that has given signs of success in the case of just one cancer parent.

Arkansas-born John Keener Wadley, who lost his only grandson to leukemia in 1943, has since given more than $2,000,000 to the J. K. and Susie L. Wadley Research Institute in Dallas. When he turned 90, Wadley was confident that the Institute had now struck it rich in cancer research. At his party, he told how nine-year-old Frank Hayes Jr. had been in the last stages of acute leukemia when Dr. Joseph M. Hill began giving him injections of the bacterial extract, L-asparaginase. Within a month, the boy's grotesquely swollen glands had shrunk, and analysis of his blood cells showed no active cancer. Dr. Hill warned Wadley that this was technically a "remission," and no one could yet claim a cure. But the old man insisted:

"I don't know what could be called a cure if this isn't one."

L-Asparaginase. The story of L-asparaginase traces back to a 1953 observation by Cornell University's Dr. John G. Kidd that serum from normal, healthy guinea pigs killed some--but by no means all--types of cancer in mice, without harming the animals' other tissues. It took Cornell's Dr. John D.

Broome eight years to ferret out the guinea pigs' secret. These animals, and a few closely related species such as the agouti, have in their blood the enzyme L-asparaginase, so called because it effects a chemical breakdown of the amino acid L-asparagine.*Many of the body's cells need asparagine as a source of nourishment, and normal cells manufacture it within themselves. But some types of cancer cells, which also need it, cannot make it. So they steal it from healthy cells.

Several chemicals have been used for almost 20 years to starve cancer cells of necessary nutrients, but all, until now, have also had an adverse effect on healthy cells that need the same substances. L-asparaginase, says Dr. Lloyd J. Old of Manhattan's Sloan-Kettering Institute, is unique because it selectively deprives the cancer cells without harming the normal. But dependence upon asparagine does not extend to all types of cancer; it appears to be limited to some forms of leukemia and disease of the lymphatic system.

One great drawback in the use of L-asparaginase is its scarcity. If all Texas were turned into a giant guinea-pig farm, the yield would suffice for only a few patients. The break came in 1963, when researchers at the University of Delaware described an immensely complicated process for extracting the enzyme from colon bacilli, Escherichia coli. These bacteria were already being grown in vats to provide other substances used by biochemists, and New Jersey's Worthington Biochemical Corp, set about extracting L-asparaginase from them. It takes pounds of the microscopic bacteria, and would cost close to $15,000, to produce enough L-asparaginase for a month's treatment for one adult.

Allergic Reaction. Probably the first human being to receive the enzyme was a boy in Chicago who was dying of leukemia. After infusions of partially purified enzyme from guniea-pig serum, his white-cell count decreased, and so did the swelling of some of his organs. But his red-blood cells were being destroyed as an apparent side effect and treatment had to be stopped. The boy died of his leukemia. The problem of purification remains. Even the presumably safer material extracted from bacteria, in its currently purest form, causes allergic reactions in mice--as it did to some extent in the case of young Frank Hayes.

The boy's illness was diagnosed last September as acute lymphatic leukemia. Besides the usual abnormalities of white cells and bone marrow, he had a tendency to form tumor masses in the neck and armpits. He was given standard treatment with drugs that produced remission. But then came relapse. Dr. Hill finally decided to use his scant supply of L-asparaginase. In daily injections beginning Feb. 13, Frank Hayes received 213,000 units. On March 16, he developed hives and a lump in his throat, indicating an allergic reaction and suggesting to Dr. Hill that it may be best to give the drug in large doses over short periods. The boy improved, and has now gone back to school.

Comparable remissions have resulted from all the anti-leukemia drugs now in use. It will take hundreds of treated patients to show whether L-asparaginase can fulfill this one-shot promise. Of the Hayes case, Dr. Hill says: "It will take 63 more years for the boy to live out his normal life expectancy, so we'll consider it a remission until then." In all the world, there is not enough L-asparaginase to treat more than a dozen sufferers. Dr. Hill says that he is making it in Wadley's own labs, besides buying it from Washington. And Dr. Old's colleagues at the Memorial Sloan-Kettering Center have just begun treating three patients with it.

*Though its name comes from asparagus, it is found in many plants and animals. Both asparagine and asparaginase come in two forms, which are distinguished by whether their crystals make a beam of light rotate to the right (dextro, abbreviated to the letter D) or the left (levo, or L). The levo forms are by far the more abundant.

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