Introduction - Uppsala Monitoring Centre

the responsible organism, Treponema pallidum, was made by Fritz Schaudinn and
Eric Hoffman. Cure involved the conversion of a positive Wasserman to a negative
response. In view of the high spontaneous cure rate the efficacy of mercury could
only have been found by a controlled clinical trial against placebo and monitored by
following the Wassermann conversion rates. Many would have considered this to be
unethical as equipoise would not have been present. Arsphenamine had appeared
in 1910 and was believed to be the answer to syphilis, but no controlled clinical trials
were performed comparing it with mercury.
Hyman in 1941 evaluated the routine conservative treatment of syphilis, which
included mercury, bismuth and arsenic. He concluded: Paragraph 5: The
‘spontaneous’ course of early syphilis tends to “cure” in approximately 43 per cent of
all patients, and an additional 22 per cent will remain clinically well with positive
serology. Thus, two patients in three, afflicted with early syphilis, may be expected to
live their lives and eventually succumb without clinical manifestation of the infection.
Paragraph 17: The great triumph of specific chemotherapy in syphilis seems sharply
limited to those patients with early syphilis (constituting perhaps 16 per cent of
Wassermann-positive individuals) who have persisted through continuous and
continued forms of therapy (5% of those who initiate therapy) (Hyman, 1941).
I can find no evidence that there were any clinical trials comparing mercury with
Arsphenamine, again because of lack of equipoise; Arsphenamine was believed to
be very superior to mercury treatments. I conclude that mercury may have been
better than placebo, if given correctly for a long period, but only if given early in
primary syphilis and then only in a few patients.
Fernel comments in 1579 that all the late symptoms of syphilis were really due to
mercurial poisoning (Abraham, 1948) were probably an exaggeration and the
converse might have been true. Dr Swediaur said ‘To distinguish complaints arising
from mercury from real venereal ones great judgement is required.’ (Swediaur,
1788).
Mercury was used for other diseases, e.g. skin diseases, and examination of the
adverse events reported in these circumstances might clarify the situation as to
which ADRs could be attributable to mercury, but unfortunately there are not many
studies. A study of mercury ointment in psoriasis in 24 patients over 6 weeks
showed no symptoms of toxicity despite 13 patients having toxic mercury levels
(Inman et al., 1956).
The ADRs reported in books and articles on toxicology might be thought to be
relevant, but on the whole these tend to be those symptoms produced by vapour
from mercury used in industry (Buckell et al., 1946) or from suicide attempts where
the patients have taken corrosive sublimate (HgCl 2 ) in such large doses that the
initial symptoms progress rapidly to renal failure. These reports of suicide cases
might not contain the more subtle symptoms (Johnstone, 1931).
Mercury caused tremendous suffering over 450 years without the recompense of