Introduction - Uppsala Monitoring Centre

The growth of pharmacological knowledge, after the realisation that there were
dose related effects, proceeded slowly. Tolerance was first described by
Theophrastus of Eresos in 320 BC. Idiosyncratic responses were first mentioned by
Titus Lucretius Carus in 49 BC and then in 78 AD Dioscorides mentions that
certain types of people are more sensitive to herbs than others. In 1025 Avicenna’s
contributions included seven conditions for testing new drugs. In 1624 Hildanus
recognised that death could occur a long time after drug administration. The first
intravenous injection for the study of opium took place in 1663. Although knowledge
of interactions is implicit in the theory of traditional Chinese medicine in 220AD
other than Gelen’s mention of ‘cooling drugs’ interacting the first mention in the
Western World of interactions was in 1667. The next big step forward was the
isolation of the active principles of known effective drugs in 1805 when Sertürner
isolated morphine. The beginning of synthetic drugs was in 1828 with synthesis of
urea and gathered pace during the rest of the century. In the same year Louis
advocated large randomised group comparisons. Francois Magendie, often called
the father of experimental pharmacology, published ‘Formulaire’ and he was
followed by his pupil Claude Bernard who published his experiments in 1857. From
thence forward pharmacology progressed rapidly.
Our only knowledge of drug safety was via the various methods of
communication: The Sumerian clay tablets and the Chinese oracle bones had
information on the current drugs, but probably nothing on the adverse effects of
drugs. Papyrus and parchment would have allowed larger documents to have been
made but required considerable skill and time and would have been available only
to scholars and the rich. Reproducing them required as much effort as the originals
and they would have been scarce, but they did allow the passage of drug
information to later generations. Once printing in 1452 AD became established there
was a vast outpouring of books, pamphlets, etc. The epidemic of syphilis in 1493
meant that there were hundreds of publication dealing with the subject from thence
forth. As most of the population was not literate the spread of information concerning
medicines would have only been via an educated healer. The next leap forward
was with the advent of the medical journal in 1670 when the publication of small
articles and letters on adverse drug reactions began to appear.
Most of the adverse effects mentioned in this book were found by either
individual cases or by case-series, that is without specific controls. However, they
were probably reported because they were outside the author’s previous
experience, i.e. historical controls. The use of comparisons, i.e. controls, in 1573 by
Fioravanti suggested comparing one physician’s results with those of the
physicians from Milan and then Helmont in 1662 suggested randomisation ‘let us
cast lots’ when comparing blood-letting and purging with not doing so. This would
have been the first controlled clinical trial, but the study never took place. In 1722
Nettleton suggested large cohort studies. Lind compared in 1753 six treatments for