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THALIDOMIDE: GLOBAL TRAGEDY

Unexpected Benefits

Thalidomide was developed in the United States as a possible antiseizure drug, but when it was found to have no antiseizure properties, rights were sold to a West German drug company (Chemie Gruenenthal) that continued testing. Chemie Gruenenthal found that thalidomide was a reasonably effective sedative with an unusual property: there was no fatal dosage. As a sedative, the drug could be prescribed to potentially suicidal patients without risk of overdose. After testing with what seems to have been rigged results, thalidomide was approved for distribution in West Germany. Subsequently, it became apparent that it relieved nausea, or morning sickness, in many women during early pregnancy. This discovery led to a tragedy affecting thousands of lives.

Side Effects

Chemie Gruenenthal marketed thalidomide successfully, both in its pure form and in multiple-drug combinations, for a wide variety of ailments. As thalidomide use spread quickly throughout Europe, physicians began noting an increase in a rare type of birth defect called phocomelia (literally, "seal limbs"), in which a baby's limbs do not fully form; the baby might be born without an arm, for instance, its hand coming directly out of its shoulder. Heart defects, kidney problems, and deafness also increased in newborns. Some obstetricians wrote to Chemie Gruenenthal to ask if thalidomide could be associated with the explosion of birth defects. The company insisted that there was no noticeable association with thalidomide.

An American Opponent

The William S. Merrell Company of Cincinnati bought the American license for the drug, but it needed FDA approval before it could distribute. Dr. Frances Oldham Kelsey stood in the way. Kelsey taught pharmacology at the University of South Dakota School of Medicine and had her own medical practice before she transferred to the FDA. One month after starting her new job, the Merrell application reached her desk. In accordance with agency policy, Kelsey insisted on proof of safety before approving the drug. Merrell responded with political pressure. Articles were written about Kelsey's bad judgment in keeping this inexpensive, lifesaving drug off the market.

A British Report

In February 1961 a report in the British Medical Journal caught Kelsey's eye. It described peripheral neuritis, nerve damage resulting in tingling and numbness of the arms and legs, which was sometimes permanent in long-term users of thalidomide. The report estimated this effect once in every 300,000 users. It was later learned that the incidence was 1 in 250. This report reinforced Kelsey's resolve to get adequate answers to her safety questions before approving the drug.

Disaster Averted. On

20 November 1961 West German pediatrician Dr. Widukind Lenz presented his findings that thalidomide caused phocomelia to a meeting of German pediatricians. By 29 November the drug was banned in West Germany. Chemie Gruenenthal cabled Merrell that day noting that thalidomide caused birth defects. The next day Merrelfs drug application to the FDA was withdrawn. A few days before, Kelsey was about to be fired for her opposition to the thalidomide approval. Now she was a heroine.

Merrell's Persistence

The nightmare was not over in the United States. Kevadon, the name for thalidomide marketed in Canada, was distributed by Merrell for testing in the United States. FDA regulations at the time allowed physicians free distribution of a drug under consideration for approval. Twelve hundred physicians received free samples of Kevadon, and many gave it to patients, some of whom could not be traced. At least three U.S. babies were affected by the testing samples. Other deformed babies were born to mothers who were given the drug in Canada or overseas. Through Kelsey's diligence, however, the United States was spared the thousands of severe birth defects caused by thalidomide in Europe, Australia, Japan, and Canada.