Thalidomide was first introduced as a sedative by the German drug company Chemie Grünenthal in 1957, and by the Distillers company in Britain a year later. Although animals could tolerate massive doses without ill-effect,1 thalidomide was soon found to cause peripheral neuritis in human patients: feelings of numbness were followed by severe muscular cramps, weakness of the limbs and a lack of coordination.
The Australian obstetrician William McBride was first alerted to thalidomide's most notorious side-effect after seeing 3 babies born with very unusual birth defects. Unfortunately, his warnings to the medical profession were delayed because he tried to "confirm" his observations by testing the drug in mice and guinea pigs, both of whom proved resistant to the drug.2 Only after seeing further human cases did McBride publish his findings.
Although not specifically tested for birth defects prior to marketing, subsequent experiments revealed "extreme variability in species susceptibility to thalidomide.”3 For instance, mice could safely tolerate 8000 times the dose found harmful to human babies.4 In his book Drugs as Teratogens, Schardein writes, “in approximately 10 strains of rats, 15 strains of mice, eleven breeds of rabbit, two breeds of dogs, three strains of hamsters, eight species of primates and in other such varied species as cats, armadillos, guinea pigs, swine and ferrets in which thalidomide has been tested,teratogenic effects (birth defects) have been induced only occasionally". Scientists eventually discovered that birth defects similar to those found in people could be induced in certain types of rabbit and primate. Nevertheless, New Zealand white rabbits had to be dosed with 300 times the amount dangerous to humans.5
The thalidomide disaster prompted additional,extensive testing of drugs and chemicals in pregnant animals,but some scientists believe that “animal malformations seldom correlate with those of humans.”6 Furthermore, "..no animal model has been found which responds satisfactorily to all known teratologic agents in humans to permit reliable screening of substances for their teratologic potential. Careful surveillance, reporting and prospective study ...remain the mainstays for detection of adverse effects following foetal drug exposure."
1) R.D.Mann, Modern Drug Use, an Enquiry on Historical Principles (MTP Press, 1984).
2) The Sunday Times “Insight” Team, Suffer the Children - The Story of Thalidomide (Andre Deutsche, 1979).
3) T.H.Shepard, Catalogue of Teratogenic Agents (Johns Hopkins Press, 1976).
4) S.K.Keller & M.K.Smith, Teratogenesis, Carcinogenesis & Mutagenesis, 1982, vol.2, 361-374.
5) New Zealand White rabbits were sensitive to doses of 1 50mg/Kg of thalidomide (ref.6) whilst the dangerous human dose was O.5mg/Kg (ref.4).
6) R.M.Ward & T.P.Green, Pharmacology & Therapeutics, 1988, vol.36, 326.
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