Biology Reference
In-Depth Information
bark - capable of yielding 1.3 million kilograms of purified quinine. As late
as 1941, most malaria in the world was being treated with quinine from
those plantations. The earliest cinchona plantations were established on a
high plateau near Bandung, West Java (
Taylor, 1945
). In 1896, the Dutch
established a Pasteur Institute adjacent to a cinchona plantation at Band-
ung, largely aimed at improving the efficiency (and profitability) of quinine
extraction and purification. Bandung in contemporary Indonesia is the hub
of a vibrant pharmaceutical manufacturing industry derived from the tech-
nology of quinine production.
3.2. Modern Antimalarials
In 1856, the chemist Perkins attempted to synthesize quinine in a dye
works in Perth, Australia. That unsuccessful effort nonetheless resulted in
the discovery of coal tar dyes and gave birth to the aniline dye industry
(
Field, 1938
). In 1891, Erlich and Guttman, noting the affinity for parasites
shown by the aniline dye methylene blue in stained blood films, successfully
treated two malaria patients (
Schlitzer, 2007
). But methylene blue was never
licensed or marketed as a therapy for malaria because it was considered
inferior to quinine. Only the absence of quinine would inspire alternatives
to it, and the consolidation of production at a single location and the con-
sequences of war would provide such motivation.
According to
Greenwood (1995)
, quinine was widely used in troops in
many theatres of World War I (1914-1918). Governments having access to
Java's Quinine Bureau, a co-op of planters controlled by the Dutch govern-
ment with annual output of 102,000 kg quinine, seized available stocks for
prioritizing military use. Germany, at war with its European neighbours,
may have had limited access. This may have spurred the immediate efforts
by German industry to replace quinine with synthetic antimalarials, but no
documentation affirms this as a strategic imperative.
During the 1920s and 1930s, scientists at the Elberfeld laboratory of
Bayer (one of six firms in the I.G. Farbenindustrie chemical conglom-
erate) used methylene blue as the starting point for rational systematic
molecular assessments of the antimalarial activity of synthetic compounds.
They used bird malaria models, principally
Plasmodium relictum
in Javanese
finches, the export of which the Dutch authorities subsequently forbade
as a potential threat to their hard-earned monopoly (
Greenwood, 1995
).
The company strategized to break the Dutch commercial hold on treat-
ment of malaria by offering alternatives to quinine. Bayer brought three
important drugs to clinical trials and commercial distribution: pamaquine
