Psychogeriatrics

of N-phthalyl glutamic acid imide (KI7). Br Med J 1958; I: 84-85. 4. Nulsen RO. Trial of thalidomide associated with the third trimester. Am J Obstet Gynecol 1961; 81: 245-248. 5. Berger FM, Lynes TE. Analeptic action of l-n-butylamino-3-p-toluidino-2-propanol (WI81) in sleep or paralysis produced by certain central nervous system depressants. J Pharm Exp Ther 1954; 112: 399-403. 6. Hunter v. State of Victoria [1960] VR 349. 7. McBride WG, Thalidomide and congenital abnormalities. Lancet 1961; 2: 1358. 8. Lenz W. Thalidomide and congenital abnormalities. Lancet 1962; I: 45. 9. Stevenson JSK. Neuropathy after thalidomide ("Distava1"). Br Med J 1961; 2: 1223. 10. Meade BW, Rosalki SB. Neuropathy after thalidomide ("Distaval"). Br Med J 1961; 2: 1223. II. Cahill PK. Neuropathy after thalidomide ("Distaval"). Br Med J 1961; 2: 1223. 12. Klinger MA, Weatherall JAC, eds. Epidemiologic methods for detection of teratogens. Basel: Karger, 1979. To the Editor: I concur with Professor Danks on all the main points of his leading article: the compulsion to find a scapegoat to sue over the 4070 or 5% of all babies who have birth defects; the perniciousness of the contingency fee system for lawyers in the USA; the probable efficacy and innocence of Debendox in the wake of over-reaction to the thalidomide tragedy, although I feel the compulsory warning in every piece of product literature today about "the safety of this product in pregnancy has not been established" may be counter-productive; and the detrimental effects of judgments against drug companies, which inhibit research and the marketing of safe drugs for use during pregnancy. Children with defects, and the community, do end up losers because of the sum cost of litigation and compensation. But the professor is wrong in both his references to thalidomide. It was not "a very good sedative and antiemetic drug for use in early pregnancy", as claimed in the 'Distaval promotion featuring a toddler climbing on a stool to the medicine cupboard. The manufacturers did not test it adequately, even by 1950 standards. The truth is horrifyingly revealed in Suffer the children by the Insight Team of The Sunday Times.' No sedative effect could be demonstrated by Chemie Griinenthal, the originators of thalidomide, in rats tested by the accepted "righting reflex" and "holding reflex" tests. They invented the complicated "jiggle cage" to produce spurious results which no other investigators could duplicate but which fooled licencing authorities except the US Food and Drug Administration. Smith, Kline & French rejected the Griinenthal offer for US marketing rights for thalidomide after a two-year investigation, finding it "to be without interesting pharmacological activity"; in particular, it had no sign of inducing sleep in mice in the light box test at 50 times Griinenthal's fanciful "hypnotic dose", and it demonstrated no antiemetic activity. Reports in Germany of side-effects, especially peripheral neuritis and paradoxical wakefulness, as early as 1955, were suppressed by the company. Yet Danks claims "the manufacturers ... had tried hard to check the safety of their drug in pregnant animals harder than had other manufacturers who were marketing drugs for similar purposes at the same time". This is simply incorrect. Pregnant rats were an unsuitable test species, responding not with fetal deformities but by ceasing fetal development and subsequent "resorption" . Thalidomide invariably reduced litter size, up to 50% at "moderate dosage". Before thalidomide was discovered, it had been established that fetal resorption indicated teratogenic potential. Such was also suggested by thalidomide's low molecular weight (enabling it easily to cross the placenta) and possible anti-thyroid activity. Distillers and Richardson-Merrell, the British and (eventual) US licencees, respectively, relied on the false reassurances of Grtinenthal. After the tragedy, Distillers used New Zealand white rabbits and obtained deformed offspring. "Since 1944 it had been routine procedure in Roche Laboratories to make reproductive studies in animals with any substance intended to be sold as a drug for human use", says the Insight team. ' Yet the marketers of thalidomide denied in these legal battles that 15 years later these standards should have been applied. As Knightly et al. conclude "it could happen again", in spite of the curbs now in effect in developed countries, which include voluntary post-marketing surveillance in Britain and Australia. Even long-established Europeanand US-based drug companies offend. Aggressivemarketing of clioquinol continued in other countries after Japan banned it in 1970. Chloramphenicol is still available without prescription in India and South America. The Dalkon Shield legal battle continues. Suffer the children should' be compulsory reading for every medical and pharmacy student and drug company executive. Lloyd K. Morgan, FRACGP Mcivor Road Bendigo, VIC 3550 I. Knightly P, Evans H, Potter E, Wallace M. Suffer the children; the story of thalidomide by The Sunday Times insight team. London: Andre Deutsch. 1979.