Biology Reference
In-Depth Information
of quinacrine in their colonies (
Field, 1938
). Atabrine, however, also did
not seriously challenge the quinine monopoly because it caused the skin
and eyes of patients to turn distinctly yellow. Most practitioners of that era
typically considered atabrine an option only in the absence of quinine. The
onset of war in Germany in 1939 interrupted the development of sonto-
chin but it had already been evaluated successfully in over 1000 malaria
patients in Germany and elsewhere. The onset of war in the Pacific in late
1941 also forced the Allies to turn to both atabrine and pamaquine as their
primary chemotherapeutics against malaria.
The occupation of the Netherlands by the Nazis and of Netherlands
East Indies by the Imperial Japanese denied the Allies access to quinine.
This prompted an urgent scale-up of the production of atabrine in the
USA, and seizure of available pamaquine and quinine stocks by the authori-
ties (
Shannon, 1946
). During mid- to late 1942, the Allies conducted their
first offensive actions against the Japanese at Guadalcanal in the Solomon
Islands and experienced the grave challenge of malaria (
Downs et al., 1947
).
The inadequacy of atabrine for treatment and prophylaxis became apparent
with attack rates of 1.7/person-year. The poor performance of atabrine was
later found to be a consequence of variable and poor prescribing practice,
in addition to poor adherence spurred by gastric upset and skin discolor-
ation (
Shannon, 1946
). Divisions of soldiers evacuated from Guadalcanal for
recuperation in non-malarious Fiji suffered relapse of vivax malaria at rates
reaching 3.7 per person-year (
Downs et al., 1947
). The Allies faced a very
serious threat with very poor chemotherapeutic options.
Even as war loomed in mid-1941, the US government organized the
Conference on Chemotherapy of Malaria, which became the Board for the
Coordination of Malaria Studies (BMCS) under the aegis of the National
Research Council in November 1943 (
Coatney, 1963
). The vast network
of laboratories and clinics it oversaw (including work with allied labora-
tories in the UK and Australia) managed the evaluation and progress of
over 14,000 compounds from drug discovery to clinical trials (
Clark, 1946
).
However, it would be the I.G. Farbenindustrie patents held in the USA by
their cartel partner, Winthrop Chemical Company of NewYork that would
yield the greatest chemotherapeutics prize - chloroquine.
Coatney (1963)
, a former BMCS board member, gives a detailed account
of the discovery and development of chloroquine, the synthetic antimalarial
that demolished quinine's centuries-long hold as the front line for treatment of
the acute attack of malaria. In 1934, Andersag at Elberfeld synthesized a drug
he named resochin. Kikuth evaluated the drug in birds with passing marks,
