The Dawn of Drug Safety

Abstract

Clinical pharmacologists have a great deal to learn from Myles Stephens's panoramic view of drug safety, even though he confines himself largely to events prior to McBride's Lancet letter of 16th December 1961 that described ‘multiple severe abnormalities in babies delivered of women who were given the drug thalidomide (Distival) during pregnancy’. The author protests that his is ‘not a history book.’ This is contradicted by the first eight chapters, which run in chronological order from 80 000 BC to 1961, listing a host of facts, and providing a rich store of quotations. There is Hippocrates's advice to ‘leave your drug in the chemist's pot if you can heal the patient with food’ (370 BC). We learn of the seven categories of potential drug–drug interaction listed in a Chinese herbal of the 2nd century AD, which also notes that with chronic mercury ingestion ‘you will become a celestial being.’ Sir Samuel Garth (1699) observes that ‘Death in ambush lay in ev'ry pill’ and Dr Frances Kelsey describes how, a week after beginning her career as a reviewing officer at the US Food & Drug Administration, she was assigned the task of considering the new drug application for thalidomide. The chronology is a tour de force, but it often wanders from drug safety. For example, a substantial section deals with the consequences of syphilis and the cures proposed for it. Dr Stephens points out that the first general account of adverse drug reactions, an obscure French thesis, was not published until 1862, and that the first major work was Louis Lewin's textbook from 1881. It could be argued that the reader might have been spared a great deal of herbal lore and a fairly extensive treatise on venereology, although I for one enjoyed learning that ‘pudendagra’ was a synonym for syphilis. Stephens dissects in a second section the adverse reactions to six marker drugs, Veratrum spp., Hyoscyamus niger, mercury compounds, opiates, aspirin and streptomycin. The most impressive finding for the first four of these is how many of the adverse effects recorded in the 2007 edition of Myler's Side Effects of Drugs had already been listed in Lewin's textbook. The well-referenced sections on aspirin and streptomycin are fascinating. There is a remarkable account by Geogre Orwell of his adverse reaction to streptomycin treatment for tuberculosis, affecting his skin, nails, hair and mucous membranes. Dr Stephens, author of the textbook on the detection of adverse drug reactions, allows his readers to make their own deductions about this (surely Stevens-Johnson syndrome) and much else. An anecdote of a painter with palsies and colic is said to represent mercury poisoning, although lead poisoning seems more probable. The carefully tabulated relationship between salicylate concentration and toxic effects is at best contestable. The book brings together much that must have taken a life-time in pharmacovigilance to learn. It will be a valuable reference source. The author apologizes for his ‘inept proof-reading’ and when it is reprinted there will be the opportunity to remove the ‘imminent physicians,’ to correct ‘schlerosing,’ and to decide which system of transliteration from Chinese will be best.