Adverse drug reactions through the ages....

At present the timeline runs until the early 1970s

1780 BC The Babylonian Code of Hammurabi details the punishments of medical harm.

"If a physician make a large incision with the operating knife, and kill him, or open a tumor with the operating knife, and cut out the eye, his hands shall be cut off."

950 BC Homer's Odyssey:

"Such useful medicines, only borne in grace
Of what was good, would Helen ever have.
And this juice to her Polydamna gave
The wife of Thoon, all Ægyptian born,
Whose rich earth herbs of medicine do adorn
In great abundance. Many healthful are,
And many baneful. Every man is there
A good physician out of Nature's grace,
For all the nation sprung of Paeon's race.

460-377 BC Hippocrates' Primum non nocere, "First do no harm"

131-201 The Greek physician Galen “warned against badly written and obscure prescriptions” . Galen paid careful attention to the precise quantities of the various ingredients used in his remedies, and to the doses which had to be given. Galen argued that all medicines were capable of mild, strong, harmful or even fatal effects on the patient, based on the dose given.

10 th century Salerno medical school was empowered to inspect drugs for adulteration, with dire penalties for transgressors: “whosoever shall have or sell any poison or noxious drug not useful or necessary to his art, let him be hanged”

1224 The Hohenstaufen Emperor Frederick II, ordered the regular inspection of the drugs and mixtures prepared by apocatharies, and ruled that the life of the seller of a poison, magic elixir, or love potion would be forfeit if the consumer died.

13 th century Oath for apothecaries in Basle Switzerland published; it included the line that drugs should be “of such good quality and of such usefulness that he knows, upon his oath, that it will be good and useful for the confection what the physician is making"

Mez-Mangold, L. (1971). A history of Drugs, p'83 F Hoffman-La Roche and Co., Basle .

1509-1547 The reign of King Henry VIII led to controls on the quality of medicines. He empowered The Royal College of Physicians of London to appoint four fellows of the College as inspectors of apothecaries' wares. These inspectors had the power to destroy defective stock within the London area. In the early seventeenth century the Society of Apothecaries also supplied inspectors.

1599 King James VI of Scotland issued a charter making provisions for the supervision of the sales of drug and poisons. The first inspector appointed was William Spang , who was responsible for approving "droggis" (drugs) offered for sale in the city of Glasgow .

1618 The London Pharmacopoeia's preface discussed "the very noxious fraud and deceit of those people who are allowed to sell the most filthy concoctions… under the name and title of medicaments"

17 th century The Paris Faculty of Physicians forbid antimony use by physicians.

1785 William Withering sets out his classical description of the toxicity of digoxin.

“The foxglove, when given in very large and quickly repeated doses, occasions sickness, vomiting, purging, giddiness, confused vision, objects appearing green or yellow, increased secretion of urine with frequent motions to part with it, and sometimes inability to retain; slow pulse, even as low as 35 in a minute, cold sweats, convulsions, syncope, and death” .

18 th century Calomel (mercurous chloride) was used widely in American states suffering outbreaks of yellow fever.   Clinical mercurialism including intense salivation, loosening of the teeth, ulceration, gangrene of the mouth and cheeks, osteomyelitis of the mandible became common.   Despite this calomel became a cure-all for many physicians, but laymen had a more sceptical view of the medicine:  

Since calomel's become their boast,
How many patients have they lost,  
How many thousands they make ill,  
Of poison with their calomel.

It remained in fashion for many years.

1848 America passed the first statue to control the quality of drugs, after quinine imported for the US army was found adulterated.

1861 Oliver Wendall Holmes, with calomel in mind, “if the whole material medica, as it is used now, could be sunk to the bottom of the sea, it would be all the better for mankind - and all the worse for the fishes”

1880   The Glasgow Commission Inquiry into the deaths due to chloroform anaesthesia was appointed by the British Medical Association. The British Medical Association appointed the Glasgow committee in 1880 which concluded that "Chloroform was injurious to the heart and in comparison more dangerous than ether". In 1888 Edward Lawrie in Hyderabad claimed that he had administered chloroform anaesthesia to 40,000 people without a single fatality and formed the "First Hyderabad Chloroform Commission". 141 animal experiments were done and it was concluded "Chloroform may be given with perfect safety and without any fear of accidental death, if only respiration is carefully attended to". This was not accepted in England and so the "Second Hyderabad Chloroform Commission" was formed to which a representative from Lancet was sent. The Nizam of Hyderabad offered £ 1000 for a commission consisting of Lauder Bruntor, F.R.S. U.K. , Surgeons Lawrie and Rustomji. Experiments were carried out on 430 animals (dogs, monkeys, horses, goats, rats, rabbits and cats) and a clinical study on 54 humans. They concluded that the Edinburgh School was right.
Divekar VM, Naik LD. Evolution of anaesthesia in India . J Postgrad Med 2001; 47 :149-52

1881 The first book on Adverse Drug Reactions published.

Lewin L: Die nebenwirkungen der arzneimittel . Published: Berlin A. Hirschwald 1881.

Translated as The untoward effects of drugs. A pharmacological and clinical manual. By Mulheron JJ. Geo S Davis, Medical Publishers, Detroit , 1883.

1899 First bottle of aspirin sold.

1922 Inquiry into arsenical treatment of syphilis causing jaundice.

1929 Formation of the Food, Drug and Insecticide Administration (later the Food and Drug Administration).

1929 : Leake ”many drug firms make the mistake of believing that their chemists can furnish trustworthy pharmacological opinion, Indeed some eminent chemists impatient with careful pharmacological technic have ventured to estimate for themselves the clinical possibilities of their own synthetics… There is no short cut from the chemical laboratory to the clinic except one that passes too close to the morgue.”

1937 107 people die as a result of poisoning with an elixir of sulphanilamide containing as a solvent diethylene glycol.

1938 Aspirin noted to be a cause of gastric haemorrhage,39 years after its first use.

1952 First edition of Meyler's Side Effects of Drugs published.

1954 One hundred deaths in France caused by poisoning with Stalinon, an inorganic compound of tin, in a treatment for boils.

1958 Knowledge of aspirin's gastric side effects becomes widely known.

1960 FDA begin to collect reports of adverse reactions and sponsor hospital drug monitoring.

1961 Thalidomide disaster.

McBride's famous letter to The Lancet.
McBride WG. Thalidomide and Congenital Abnormalities Lancet December 16th 1961

Dr. Widukind Lenz also played an important part in the recognition of thalidomide's adverse effects, and gives a brief history of his experiences in a lecture he delivered in 1992.

1960s Oral contraceptives linked to thromboembolism in young women.

1964 Yellow Card Scheme started in the UK .

1966 Adverse Drug Reaction Bulletin published.

1968 Medicines Act passed by UK Parliament, bringing in new and comprehensive safeguards covering most aspects of drug development.

1970s Practolol linked to syndrome involving the skin and eyes.

1972 Thirty-six French infants are killed by a manufacturing error.

"in 1972, 204 children in Paris, aged 3 months to 3 years, developed severe diaper rash and neurologic abnormalities after use of an infant powder that accidentally contained 6.3% HCP when there was supposed to be none. Thirty-six children died. The talc was prepared in the same area that HCP was kept, and 38 kg of HCP contaminated 600 kg of infant powder that went into 2898 cans."

RW Miller. How Environmental Hazards in Childhood Have Been Discovered: Carcinogens, Teratogens, Neurotoxicants, and Others. Pediatrics 2004; 113(4) :945-951