1960: Thalidomide Tragedy and Teratogenicity (1960)

Thalidomide was synthesised by West German company Chemie Grünenthal in 1954 and marketed in West
Germany from 1957 as a sedative and antiemetic under the trade name Contergan. It was aggressively
marketed as safe—"completely non-toxic"—partly because it showed very low acute toxicity in
standard animal tests, and rapidly became one of the most widely used sedatives in Europe, Canada,
and Australia. Physicians prescribed it extensively to pregnant women for morning sickness.

Between 1959 and 1961, paediatric reports described a sharp increase in phocomelia (limb
malformations—characteristically shortened or absent limbs) and other severe birth defects in
West Germany and other countries where thalidomide was sold. Hamburg paediatrician Widukind Lenz
and Australian obstetrician William McBride independently identified the association between
maternal thalidomide use in the first trimester and foetal malformations in 1961. Grünenthal
withdrew thalidomide from European markets in November 1961.

Estimated worldwide cases of thalidomide-related birth defects number between 10,000 and 20,000
infants, with about half surviving to adulthood. In the United States, the drug had not been
approved: FDA medical reviewer Frances Oldham Kelsey rejected the application in 1960, citing
inadequate safety data and noting peripheral neuropathy as a potential signal. Her refusal
shielded Americans from the epidemic and made her a public hero. President Kennedy awarded her
the President's Award for Distinguished Federal Civilian Service in 1962.

The thalidomide tragedy directly precipitated the 1962 Kefauver-Harris Drug Amendment to the
FD&C Act, which added requirements for proof of efficacy and mandated testing of new drugs in
pregnant animals before human trials.