Page 26 - Pharmacy History 37 Nov 2009

Atebrin: a brief history and its role during the Second World War
Frank Mercovich MPS (Hon)
This is an account of how a group of scientists made available a medication – Atebrin – which was able to control the incidence of malaria in the South West Pacific Area (SWPA) during the Second World War.
Atebrin – the
treatment
Atebrin is an acridine derivative formerly widely used as an antimalarial but superseded by chloroquine in recent years. It has also been used as an anthelmintic and in the treatment of giardiasis and malignant effusions. It is used in cell biological experiments as an inhibitor of phospholipase A2.
Malaria - the disease
Malaria is an infectious disease which is transmitted to mankind from
the bite of the anopheles mosquito. The mosquito is infected by biting a person who is infected with malaria, hence it is a disease that can quickly become endemic even if only a small percentage of the population is infected.
periods which are followed by further acute attacks which will eventually be fatal.
Islands in the SWPA filled the criteria for the spread of the disease.
Treatment
The first record of successful treatment of malaria appears to be by Juan Lopes, a Jesuit missionary who was living in Malacortes, Peru in 1600.
It was reported that Lopes was cured of the fever after an Indian chief
had Lopes suck the bark of a tree known locally as the fever tree. This tree is now known as the cinchona tree (Cinchona spp (rubiacae)) and commercial quantities of quinine are obtained from the bark.
Quinine was the recognised treatment for malaria until the middle of the 20th century. It has now been replaced by more sophisticated drugs.
Quinine – early source
of supply
The Jesuit missionaries carried out extensive investigation of the bark and its substance and reported their findings to colleagues in Europe. At that time, the substance was known as ‘Jesuit bark’ and was used extensively in Europe. The only drawback was that the bark had to be transported from Peru. Seeds were sent to Europe from Peru but efforts to grow the tree were unsuccessful. Various areas in Africa also failed to grow the tree.
The Dutch influence
Due to the problems with supply of cinchona bark the Dutch authorities, in 1852, sent Justus Charles Hasskarl, a botanist, to Bolivia and Peru on a cinchona seed collecting expedition.
He was successful, and from his seed collection he commenced cultivation in Java in 1854. This cultivation was highly successful and became the major centre for the supply of quinine worldwide.
At the outbreak of the Second
World War, the Dutch in Java had 37,500 acres of cinchona trees which produced 9,000 tons of bark annually. The Dutch quinine combine had created what amounted to the most effective crop monopoly of any kind in history - a dangerous situation when one considers that the soul source of an important medication was located on one island with distribution being in the hands of one distributor.
German antimalarials
Despite the fact that Germany lost its overseas territories after the First World War, some of which were in malarious areas, German medical scientists continued research into
the treatment of malaria. In 1930, two German scientists, Kiruth and Schulemann, isolated an antimalarial substance that was given the generic name, mepacrine.
Clinical trials indicated that mepacrine suppressed malaria with little or no side-effects with the exception that
the skin in Caucasians turned yellow. When the drug was ceased, the skin resumed its normal colour. Mepacrine was not a cure for malaria but a suppressant. A person who contracted malaria while taking mepacrine
did not suffer an acute attack and therefore could carry on day to day activities. Following the clinical trials of mepacrine, approval was given to market it under the trade name of Atebrin. In the USA, the Winthrop Chemical Company – a subsidiary
Anopheles mosquito
Its effect on the person who contracts the disease is characterised by fever, anaemia, chills, profuse sweating and a feeling of lethargy. If untreated one could obtain remissions for short
26 Pharmacy History Australia
volume 5 no 37 NOVEMBER 2009