Introduction - Uppsala Monitoring Centre

scurvy in 12 patients, i.e. two patients per treatment and in 1760 twelve patients
using mercurial ointment were compared with twelve taking Keyser pills. In 1768
Watson gave pre-treatment before innoculation with three alternatives: mercury,
senna plus rose syrup and no pre-treatment, the first use of ‘no treatment’ as a
control. The first use of a placebo control group was in 1801 when Haygarth
compared ‘Perkin’s metallic rods’ against imitation wooden rods. The first doubleblind
placebo controlled trial was probably in 1835 (the Nuremburg salt test). The
first randomised controlled trial was in 1898 when patients were randomised
according to their date of hospital admission for a study of diphtheria. In 1948 a
randomised (based on random sampling numbers) trial of streptomycin and placebo
was started by the MRC (see streptomycin). A subsequent MRC study in 1950
comparing streptomycin, PAS and a combination of both, used a form which
included ‘observation of toxic reactions’. In neither of these studies did the patients
know that they were in a clinical trial. Otherwise, I have not found any studies where
one of the stated aims was related to drug safety.
The terminology used in these communications evolved over time: before the
birth of Christ I have the impression that they recorded only the most severe
adverse effect, e.g. death and then later gradually more specific symptoms and
signs are mentioned in lay terms. By the 18 th century we see more frequently the
emergence of specific medical terms and syndromes, e.g. ‘iliac passion’, tenesmus
and hemicrania. It is only after 1850 that the terms used reflect the increasing
knowledge of physiology and pathology. The use of Greek, Latin and Arabic meant
that translators played an important part in spreading information on adverse drug
effects (The Nestorians, Mesue, Gerard of Cremona and Constantine (Wakim,
1944; Van Hoof, 2001). Medical and herbal books were written in Latin and it wasn’t
until 1392 that we have the first surgical text in English (Ellerbeck, 2005). Probably
the last book written in Latin was Heberden’s ‘Commentarii’ in 1802 (Wulff, 2004). In
some countries Latin survived in this context up to the end of the 19 th century
(Dzuganova, 2002). This meant that the mass of uneducated public were denied
access to information on drug safety.
Part 2: Analysis of the Marker Drugs
Chapter 9: Hellebore
Chapter 10: Henbane
Chapter 11: Mercury
Chapter 12: Opium
Chapter 13: Aspirin
Chapter 14: Streptomycin