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of Sterling Drug Inc – was granted
a licence to market Atebrin. The granting of the licence did not mean that Winthrop Laboratories had the right to manufacture the product. The German company that held the patent did not disclose the intermediates used to manufacture Atebrin. This simply meant that small quantities of Atebrin could be produced in a laboratory but production of commercial quantities on a large scale was impossible.
The Pacific war
When General Douglas MacArthur assumed command of allied military forces, he became aware that the health of his troops was of paramount importance. He knew that malaria was rife in the area. He is on record as saying that if Java fell to the Japanese and the supply of quinine was no longer available he could be placed in a situation that for every division of troops facing the Japanese, he could count on a second division in hospital with an acute attack of malaria,
and a third division in a rest camp recuperating. It became a top priority for medical scientists to come up with an alternative to quinine.
Atebrin’s
intermediates
As previously mentioned, the Winthrop Chemical Company marketed Atebrin in the USA but
its activities were fairly restricted, being dependent upon the import
of finished product from Germany. When Germany declared war in 1939 and the hostile attitude between Japan and the Allies indicating the Pacific area becoming a theatre of war, the Winthrop Company looked at the possibility of ‘cracking’ the Atebrin formula. A group of scientists located at the Winthrop Research Institute
set out to identify the intermediates. The task was long, tedious and at time disappointing but towards the end of 1941, success was achieved.
Atebrin tablets could now be manufactured by pharmaceutical companies in allied countries. A quote
in a medical publication read: ‘By the end of 1941, the little yellow tablet became the daily diet of troops serving in malarious areas of the world.’ Production of the tablet assumed colossal proportions – 200 tons per annum. Winthrop gave royalty-free licences to pharmaceutical companies to produce Atebrin for the war effort.
An authoritative report on the malaria problem stated: In the early stages
of the war in New Guinea casualties from malaria ran the rate of 740 per 1000. Mainly by the use of Atebrin, this was reduced in November 1944 to 26 per 1000. The evidence in favour of Atebrin became so strong that many considered it to be established that if a soldier suffered from malaria it was proof that he had not been taking his daily dose of Atebrin.
Conclusion
It is recognised that the events at Hiroshima and Nagasaki shortened the war. If it were possible it would be an interesting exercise to assess the effect that Atebrin had on the SWPA war. How many lives did it save? Did it shorten the war?
Investigations into antimalarial treatment at the Sterling Winthrop Institute continued. A stroke of good fortune occurred in 1943 when the British Eighth Army occupied Tunis. The medical section of the Afrika Corps left behind the details of an antimalarial agent called sontoquine (nivaquine C) which had been synthesised by I G Farbenindustrie. Derivatives of it were investigated
by Sterling Winthrop and clinical trials on one of them, chloroquine, indicated that it was superior to Atebrin in the treatment of malaria. The drug was adopted by the
American armed forces and had the war continued, it would have replaced Atebrin.
Postscript
Prior to chloroquine becoming available, extensive studies were carried out to assess its efficacy as an antimalarial. These studies indicated that the substance was an efficient treatment for malaria but it had
other indications. A number of volunteers who participated in the trial were suffering from rheumatoid arthritis. Clinicians who conducted the trial noted that, while the malarial condition was successfully treated, those with rheumatoid arthritis experienced remissions from their condition. This led investigators
to look at other indications for chloroquine. It was found that chloroquine was useful in treating acute and chronic rheumatoid arthritis; lupus erythrematosus; polymorphic light eruptions; malaria due to Plasmodium falciparum and Ps vivax; and giardiasis. A number of ocular adverse effects, both reversible and irreversible, were reported. Further work in the same laboratories produced hydroxychloroquine, known as Plaquenil, which was as effective as chloroquine but with less toxicity.
Frank Mercovich had been employed by Winthrop Laboratories and Sterling Pharmaceuticals for many years. He was made an Honorary Member of the Pharmaceutical Society of Australia in August 2007 for services to pharmacy. He died in April 2008.
volume 5 no 37 NOVEMBER 2009
Pharmacy History Australia 27
Atebrin parade