Friday, Jul. 08, 1966

The Ethics of Human Experiments

I will follow that system which . . . I consider for the benefit of my patients, and abstain from whatever is deleterious and mischievous.

—From the Hippocratic oath

The ethic of that ancient oath "by Apollo the Physician" is one that all doctors have sworn to and still swear by. Do they live up to it? Not always, is the grim conclusion of Harvard's Dr. Henry K. Beecher after a ten-year study of medical experiments recently performed on human subjects. Dr. Beecher has no quarrel with the physician who tries a new drug or a new operation for the benefit of a patient; he is concerned about experiments that are designed for the ultimate good of society in general but may well do harm to the subject involved.

Unsuspecting Hundreds. "Since World War II," says Dr. Beecher in the prestigious New England Journal of Medicine, there has been "increasing employment of patients as experimental subjects when it must be apparent that they would not have been available if they had been truly aware of the uses that would be made of them. It seems obvious that further hundreds have not known that they were the subjects of an experiment." Dr. Beecher charges that "grave consequences" have been suffered as the result of such work. In no case does he name the hospital or doctors involved; in no case does he give dates. But before they published his paper, the Journal's editors satisfied themselves about the authenticity of all his examples. Among them:

> Although, says Beecher, "it is known that rheumatic fever can usually be prevented" by giving penicillin to treat the recurrent "strep throats" that can cause rheumatic fever and heart disease, 109 sick U.S. servicemen were denied penicillin; two developed acute rheumatic fever, and one acute nephritis. In a related study, 500 U.S. servicemen were denied penicillin and given either sulfadiazine or no drug at all in order to compare the effects. The comparison, Beecher suggests, was distressingly clear: at least 25 of the 500 developed rheumatic fever, and one medical officer put the number as high as 70.

> Chloramphenicol (Chloromycetin), though one of the most dangerous drugs in wide use, is by far the best for typhoid fever. In the Philippines, among 408 charity patients suffering from typhoid, chloramphenicol was deliberately withheld from 157, of whom 36 died. Only 20 died among the 251 who got the standard treatment. By statistical deduction, 23 patients died needlessly for the sake of the study.

> In an experiment designed for studying the effects of the thymus gland on immune mechanisms and the "take" of grafts, eleven of 18 U.S. children, aged 31 months to 18 years, had their thymuses cut out while they were undergoing heart surgery. For comparison, the seven others were spared the thymus operation. Only occasionally is thymectomy done in connection with heart surgery, and in any case, "its eventual effects in children are not known." The experiment yielded only a negative result: there was no difference between the groups in the take of skin grafts.

> A piece of a melanoma (a highly malignant cancer) was transplanted from a desperately ill young woman to her mother "in the hope of gaining a little better understanding of cancer immunity, and in the hope that the mother's production of tumor antibodies might be helpful in the treatment of the cancer patient." The patient died the day after the transplant, the mother died of melanoma 15 months later.

What Is Innocent? "I am aware," says Dr. Beecher, a crusading professor of research in anesthesia, "that these are troubling charges. They have grown out of troubling practices." Other medical investigators, while agreeing with his basic tenets, are equally troubled by the way he used his data. The servicemen who did not get penicillin for strep throats, for example, were at Francis E. Warren Air Force Base in Wyoming. When Western Reserve University's Dr. Charles H. Rammelkamp Jr. began studying them in early 1949, no one knew whether penicillin was indeed the indispensable or even the best treatment. Rammelkamp had to continue his tests through 1953 to disprove another investigators claim that penicillin was not the answer. Dr. Rammelkamp's team published its definitive results in 1954. Only then, and not before, could Dr. Beecher have said "it is known" that penicillin is unquestionably the drug to use.

Other investigators who recognize their work in Dr. Beecher's study may also supply convincing rebuttals. The New England Journal itself offers a restrained and judicial editorial opinion: "In research conducted on such an expanding scale in the last two decades, the desire for results seems too often to have outweighed the means of arriving at them." As a guideline for researchers, the Journal quotes the great French physiologist-researcher Claude Bernard (1813-78) on human experiments: "Those that can only harm are forbidden." Those that involve no foreseeable harm to the patient are "innocent" and therefore permissible. "Those that may do good are obligatory." The problem in 1966 is to define "those that are innocent."