Thalidomide

Thalidomide was sold during the 1950s and 1960s as a sleeping aid and to pregnant women as an antiemetic to combat morning sickness and other symptoms. The drug was synthesized in West Germany in 1953. It was marketed from October 1, 1957 mainly in Germany and Britain and was available in around fifty countries, although not in the USA, under at least forty different names (such as Talimol, Kevadon, Nibrol, Sedimide, Quietoplex, Contergan, Neurosedyn, etc.).

It was later 1960-61 found to be teratogenesis|teratogenic in fetal development, most visibly as a cause of amelia or phocomelia as the drug is an angiogenesis inhibitor - interfering with blood vessel development, especially if taken during the first 25 to 50 days of pregnancy. Around 15,000 fetuses were damaged by Thalidomide. Some 12,000 children in 46 countries were born with birth defects caused by Thalidomide, with only 8,000 of them surviving past the first year of life, and most of them are still alive, nearly all with disabilities caused by the drug.

Thalidomide was banned for its intended use but it has been found to be effective elsewhere and is currently (2001) undergoing clinical trials: as an antineoplastic agent, in the treatment of leprosy symtoms (ENL, erythema nodosum leprosum), in HIV related symptoms by reducing inflammation (blocking Tumor Necrosis Factor (TNF)), for advanced multiple myeloma, prostate cancer, and glioblastoma, and Crohn's disease.

The Thalidomide Tragedy

Thalidomide had passed safety tests performed on animals, primarily because the proper tests - particulary those involving pregnant animals - had not been correctly administered. These tests were either conducted inadequately, or the results were faked. In fact, later tests demonstrated that administering thalidomide to pregnant rats reduces the number in the litter by 50%, and giving it to rabbits produces characteristic deformities in the offspring. If such basic testing had ever been done, thalidomide would never have been approved to be sold anywhere. Some opponents of animal testing still incorrectly cite thalidomide as an example of the ineffectiveness of such testing.

In 1960, Chemie Grünenthal decided to expand into the United States, and applied to the Food and Drug Administration for approval to sell the drug. This approval was not expected to be controversial, and the case was given to the agency's newest reviewer, Frances Oldham Kelsey. Kelsey had previously done animal toxicity research (including effects in pregnancy), and refused to clear thalidomide for sale until she obtained better documentation of its effects, especially in light of some unusual neurolical side effects being reported in Britain. In fact, the testing had not been done adequately, and satisfactory documentation was not forthcoming.

Though the US marketer [William S. Merrell Company was increasing pressure to have it cleared for sale, Kelsey held out for more toxicity data before coming to a decision. The decision was pre-empted by births throughout the world giving evidence of thalidomide's effect on the embryo, and the manufacturers quickly withdrew their application. Kelsey's delay probably prevented thousands of deformities in the US, and made her a national hero. In August 1962, Frances Kelsey was awarded the President's award for distinguished Federal Civilian Service (the highest civilian award in the US) by President John F. Kennedy.