Introduction - Uppsala Monitoring Centre

Intravenous Veratrum viride was found to be a potent vasodepressor
lowering the blood pressure and slowing the pulse. The side effects
were: tingling, a coolness or numbness of the lips, face, tongue and
trunk... sensation of warmth usually about the mouth, forehead and
chest…perspiration…slight nausea, vomiting, hiccough… sensation
of substernal pressure’. (Elek, 1953).
1954 ‘Stalinon’ An organic compound of tin, diethyltin di-iodide + vitamin K,
in a 15 mg/capsule, linoleic acid (100 mg/capsule), which went on
the market in 1953 and was used in the treatment of anthrax,
furunculosis, osteomyelitis and acne had impurities, ethyl triiodide,
triethyltin iodide and tetraethyltin. Of the (estimated) 1000 persons
that had taken the drug, there were 102 deaths of a total of about
210 cases of cerebral oedema. Of all the affected people only 10
completely recovered. Triethyltin iodide is believed to be the primary
cause of this poisoning The formation of a cerebral oedema after
organotin intoxication had already been seen with mice and monkeys
(BMJ, 1958; WHO, 1980)
The Stalinon case, resulted in new legislation governing marketing
licences and the issue of quality control of medicines in France in
1958-59: the judicial enquiry and subsequent court case in 1958
concluded that the manufacturers (Février) were liable for having put
on the market a product of insufficient quality. The Chief Executive,
Ms Feuillet, was sent to prison for two years and fined. Apart from
the legal penalties, the French State also amended the legislation
governing the issuance of marketing licences, enacting the
Ordinance of 4th February 1959, which set new requirements for
marketing licences, which included the duty to provide details of all
clinical trial reports (Bonah, 2007).
Chemie Grünenthal synthesized thalidomide (alpha-[N-phthalimido]
glutarimide) and tested it in mice, dogs, rats, guinea pigs and rabbits
(Mellin & Katzenstein, 1962). It had not been tested in pregnant
animals, but the same effect was found in mice, rats, hamsters,
rabbits, macaques, marmosets, baboons and rhesus monkeys. An
LD 50 (median lethal dose) was never established since there was no
apparent toxicity even in high doses (Burley, 1988) (see under
regulatory responses).
A year after the ‘Maladies Médicamenteuses’ G. Duchesanay
produced ‘Le Risque Thérapeutique, prevention et traitment des
accidents’ (The therapeutic risk, prevention and treatment of adverse
reactions). This is again very clinical and covers contraindications