Those Risky Side Effects

Carney Love was 42, a slight and pretty woman, with two grown children and a record of generally good health; it was nothing more than bleeding gums from a recent tooth extraction that led her doctor, John Wolf of Redding, Calif., to give her the potent antibiotic Chloromycetin. She got the drug again six weeks later for bronchitis--eight prescriptions in all, counting renewals.

Now Mrs. Love's face is beet-red and scarred with acne, and she has to shave daily. She has muscles like a male athlete's. Doctors warn that because Mrs. Love has a tendency to bleed heavily, she cannot risk a cut or undergo ordinary surgery. A fortnight ago. a jury awarded her $334,046 in damages from Dr. Wolf and Parke. Davis & Co., the drug's manufacturers. Her case, the first of its type to go to a jury, dramatized what are laconically called the "side effects" of many valuable drugs, and the problems of balancing a drug's usefulness against its dangers.

A few months after she took Chloromycetin late in 1958, Mrs. Love felt weak and went to another doctor, who diagnosed aplastic anemia, in which the bone marrow fails to make enough blood cells. Her husband sold his business, the Beer Barrel Tavern outside Redding, to pay for her care, including 60 transfusions. At Palo Alto-Stanford Hospital Center, the transfusions and vigorous treatment with cortisone and testosterone kept Mrs. Love among the 25% of patients who get aplastic anemia and survive, but the hormones produced their own side effects. Though Chloromycetin causes these severe reactions in only one of an estimated 10,000 patients, Mrs. Love's attorney charged that Dr. Wolf had been negligent in prescribing it for such minor ailments. Dr. Wolf replied that many physicians were using it at the time for a wide range of infections, and he had not been sufficiently warned about its dangers.

Pros over Cons. The governmental bulwark against dangerous drugs is the Food & Drug Administration, part of the Department of Health, Education and Welfare. It is a relatively small bureau (2,423 employees, current budget $21.854.000), and two-thirds of its inspectors police purity of food products; the rest work on drugs and cosmetics. Its main power over drugs comes from a 1938 law (passed after an early version of sulfanilamide in a poisonous solvent killed 107 people) that authorizes FDA to require satisfactory prelicensing proof that a drug is safe.

Chloromycetin. which is Parke. Davis' trade name for the potent antibiotic chloramphenicol. got FDA approval in 1949. It attacked many bacteria against which penicillin was useless, notably the typhoid bacillus; equally important, it was the first effective drug against psittacosis (caused by an unusually large virus) and against such diseases as typhus, scrub typhus and spotted fever (caused by related microbes called rickettsiae ). Not until 1952, when hundreds of thousands of patients had had the drug--often for viral respiratory infections against which neither it nor any other antibiotic is effective--did evidence arise that it had caused a dozen or more cases, several fatal, of aplastic anemia.

The FDA got the National Academy of Sciences to set up a committee of topflight experts to study Chloromycetin.

Their conclusion was that its pros outweighed its cons: it should be left on the market, but with a warning to doctors not to use it unless the illness was so severe as to justify the risk. Sales of Chloromycetin slumped, then gradually picked up until 1960, when a new flurry of alarm set off a second reevaluation. Once more, the FDA's expert advisers concluded that to take the drug off the market would bring death to more people than to leave it-- on.

But they called for still stronger warnings, which Parke, Davis put out a year ago. The chief recommendation is that doctors using Chloromycetin for long-term or repeated treatment should keep close check on their patients' blood-cell counts.

Investigational Testing. The hard fact is that any potent drug is almost certain to have some dangerous incidental effects in some proportion of patients after it is widely used. To keep these backfires to a minimum. FDA first provisionally licenses a new drug"for investigational use only" (after testing in animals), whereupon most manufacturers get research physicians to try their product on 1,000 to 3,000 patients. It was this step-by-step procedure that fortuitously kept thalidomide. the sleeping pill now suspected of causing many malformations in babies in Europe and elsewhere (TIME, Feb. 23), off the U.S. markets. A sharp-eyed woman doctor on the FDA staff was not satisfied with a detail in the evidence submitted by the manufacturers with their application for a license. FDA asked for more information. While it was being gathered, the epidemic of malformations was reported in Europe, and the application died aborning.

Once a drug is licensed, if doubts about its safety arise the FDA must go through a complex, time-consuming procedure to get it off the market. Usually, in such cases, the drugmakers cooperate more or less voluntarily, since they have as much stake as anyone in weighing a drug's side effects against its advantages. Last week the Upjohn Co. withdrew Monase. a "psychic energizer,"after reporting to FDA that widespread use since June 1961 had produced seven cases of aplastic anemia, four of them fatal--though the drug was tested in 3,500 patients, with no sign of damage to their blood-cell mechanisms, before it was marketed.

And 48 Other Drugs. With the aim of getting maximum benefits for patients at a minimum cost in illness and death from side effects, the American Medical Association's Council on Drugs keeps a running score of aplastic-anemia cases and related blood disorders attributed to drugs.

Its latest compilation, just issued, shows that in the first half of 1961 there were 138 such cases reported and probably more unreported. By far the biggest offender was Chloromycetin, with 56 cases charged against it.

But the impossibility of achieving 100% freedom from side effects is shown in the council's listing of 48 other drugs that have, in at least a few patients, caused blood-cell damage. They include many of the most widely used sulfas and invaluable drugs universally prescribed for diabetes, arthritis, heart failure, epileptic seizures, tuberculosis, thyroid disease and emotional disorders. Even such old reliables as quinine and the painkillers phenacetin and aminopyrine are on the list.

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