Frances Oldham Kelsey (b. 1914), Widukind Lenz (1919–1995), William McBride (b. 1927)
A MONUMENTAL MEDICAL TRAGEDY. When thalidomide was introduced in 1957 to promote sleep and treat morning sickness, it seemed remarkably safe. The following year, it was approved in the United Kingdom and, by 1961, was marketed in Canada and more than twenty countries in Europe and Africa. In 1960, Richardson Merrell aggressively sought approval to market thalidomide (Kevadon) in the United States and distributed 2.5 million tablets, which were received by 20,000 patients; by 1961, seventeen cases of birth defects were reported. Frances Kelsey, an FDA pharmacologist, reviewed the application. Her concerns about the drug’s safety led her to recommend its rejection, and in 1962, she received the President’s Award for Distinguished Federal Civilian Service from John F. Kennedy for “sparing the nation a human tragedy.”
Working independently in 1961, William McBride in Australia and Widukind Lenz in Germany established the linkage between thalidomide and the birth defects. By the time thalidomide was withdrawn that year, more than 10,000 babies worldwide were born with major birth defects. The most extreme were very rare malformations of the limbs—known as phocomelia—often characterized by flipper-like hands extending from the shoulder. These dramatic effects occurred after women took as little as one dose during the first three months of pregnancy.
The thalidomide tragedy focused attention on the effectiveness of the “placental barrier.” The placenta serves as a respiratory, circulatory, and excretory organ for the fetus, and we now know that this barrier is ineffective in protecting the fetus against most drugs taken by the mother. As a result of this disaster, an essential component of testing now includes an evaluation of drug effects on the developing fetus during pregnancy. Among the drugs known to be teratogenic (from Greek terat or monster, in reference to birth defects) are remedies for acne (Accutane), seizures (Dilantin and valproic acid), and cancer (methotrexate), with many others suspected of causing defects.
Thalidomide (Thalomid) returned in the late 1990s for the treatment of multiple myeloma (a blood cell cancer) and complications of leprosy.
SEE ALSO Dilantin (1938), Amethopterin and Methotrexate (1947), Kefauver-Harris Amendment (1962), Valproic Acid (1967), Accutane (1982).
Frances Oldham Kelsey was singularly responsible for averting a thalidomide birth-defect disaster in the United States. In recognition, John F. Kennedy presented her with the President’s Award for Distinguished Federal Civilian Service in 1962.