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Atavism: Embryology, Development and Evolution

Thalidomide (α-(N-phthalimido)glutarimide) — a synthetic glutamic-acid derivative — was manufactured and marketed by the German pharmaceutical company Chemie Grunenthal during the mid-1950s (BOX 1; TIMELINE). It is a non-barbiturate drug with sedative and antiemetic activity and was found to be useful because of an apparent lack of toxicity in human volunteers. These properties led to it being marketed as the safest available sedative of its time. It rapidly became popular as a drug to counter the effects of morning sickness in Europe, Australia, Asia and South America, although it did not receive Food and Drug Administration (FDA) approval in the United States because of concerns about neuropathy — tingling hands and feet after long-term administration — that were associated with its use. It was withdrawn from the other markets in early 1961 after two clinicians — William McBride in Australia and Widukind Lenz in Germany — reported independently that thalidomide use was associated with birth defects1,2.Areport associating thalidomide use with neuropathies was also reported at around this time3 . Unfortunately, this withdrawal was too late to prevent the birth of between 8,000 and 12,000 babies with severe developmental deformities, which include the stuntedlimb development that is characteristic of ‘thalidomide babies’. In 1965, following a serendipitous discovery by Israeli dermatologist Jacob Sheskin, it was reported that thalidomide was remarkably effective at improving lesions, fever and night sweats in patients with erythema nodosum leprosum (ENL) — a potentially life-threatening inflammatory complication of lepromatous leprosy4 . After finding thalidomide in the clinic and remembering that it was a sedative, Sheskin administered it to a patient who was having trouble sleeping and — remarkably — the next morning the patient’s inflammation was significantly reduced. This discovery was investigated in a study that was coordinated by the World Health Organization in thousands of men who had ENL and showed that a vast majority had complete remission within a couple of weeks of starting thalidomide treatment5 .