thalidomide

thalidomide and the thalidomide disaster are firmly riveted together in the minds of the population, and it is worth considering how such a tragedy could occur and whether a similar occurence might be repeated with another new and promising drug. Thalidomide was introduced around 1957 as a safe hypnotic and sedative. In an immediate sense it was safe, massive doses producing no acute toxicity in animals. It was considered that the drug was far safer than the barbiturates, which were at that time the commonly used hypnotic, and often used by people committing suicide. It was impossible to commit suicide using thalidomide.

The drug became popular in Germany and because of the lack of acute toxicity it became available over the counter without prescription. Around 1960 a number of cases of phocomelia (meaning ‘seal-like limbs’), in which long limb bones failed to develop, appeared in new-born babies both in Germany and Australia. It took a long time before the connection was made between thalidomide and birth defects. The reasons for this are clear in retrospect. First, only a small proportion of the population taking the drug were pregnant, and even women who were pregnant needed to take the drug between the thirty-seventh and fifty-fourth day following the last menstruation for the teratogenic effects (drug-induced fetal abnormalities) to be manifest. Finally, not all women who took the drug during the crucial period produced babies with teratogenic abnormalities. Other candidates considered to be responsible were radioactive fallout from atomic testing, X-rays, hormones, food additives, and contraceptive pills. The correlation between those taking thalidomide in the crucial period and the incidence of phocomelia became more evident, and the drug was withdrawn in 1961. It must be noted that correlation and causation are not the same, although there can now be no doubt that thalidomide was the cause.

At the time questions were asked why tests for teratogenic potential of the drug had not been made before it was released. First, the effects produced by thalidomide in pregnant women had not occurred before with other drugs and secondly, it was not easy to replicate the effects seen in humans in animal species. Altogether there were some 10 000 cases of babies with phocomelia, mostly in Europe, with some in Australia and a few in the US, of whom about 50% survived with deformed limbs, eyes, hearts, alimentary, and urinary tracts. All of these have required long term care and treatment, only partially ameliorated by the settlement made by the manufacturer. Another question asked was why there were so many cases before the cause of the teratogenic effects was identified. It was unlikely that any medical practitioner would have seen more than one case, and while the incidence of fetal abnormalities of the thalidomide type in normal pregnancy are very rare, the incidence is not zero. It was a German paediatrician who had encountered more than one case, and noted that thalidomide had been taken in all instances, who suggested the connection which was eventually verified.

While the human misery that resulted from the introduction of this seemingly harmless drug is incalculable, an important new development was introduced. To make it less likely that other, yet unknown, bizarre effects from the introduction of new drugs can ever occur on the same scale, most countries have introduced a monitoring system. In the UK, practitioners record any effect a patient reports, or signs which become obvious upon examination, together with the drugs prescribed. This data is entered immediately onto a national database. Of course, most of the reported effects will be nothing at all to do with drug treatment, but as the data will come from an entire country, or group of countries, correlations of effects with drug usage will be quickly spotted and sound the alarm before thousands of people are affected. The thalidomide story also illustrates another problem in regard to the introduction of new drugs: the public demand the unattainable — that all drugs should be perfectly safe under all conditions — but ultimate answers can be provided only by the consequences of general release.

Alan W. Cuthbert

See also congenital abnormalities; drug.