MRC National Institute for Medical Research, London
Science for Health
Neil Brown (1929-2012)
25 July 2012
Neil Brown died on 25 April 2012. He worked in NIMR's Division of Parasitology for 35 years, in malaria parasite biology and host immunity.
Kendrick (Neil) Brown attended Southgate County Grammar School then went on to do National Service in the Royal Army Veterinary Corps. In 1953 he completed an honours degree in Zoology at Imperial College, already specializing in parasitology - the subject that was to define the whole of his career in science. In 1955 he completed a two-year Animal Health Trust research studentship at the London School of Hygiene and Tropical Medicine.
From 1955-59 Neil worked in the Biological Research Division of the drug company May and Baker, investigating the chemotherapy of trypanosomiasis and specifically focusing on the development of Metamidium for use in the treatment of cattle trypanosomiasis. During this time he was seconded to East Africa to help with the first large-scale field trial of this compound. Related work on the interactions between host immunity and the chemotherapeutic action of Metamidium helped to focus his research efforts on parasite-encoded immunogenic proteins (antigens) and their interaction with host immunity.
In 1960 Neil moved to the Division of Chemotherapy at NIMR where initially he continued working (with James Williamson) on the chemotherapy of malaria and trypanosomiasis. He focused particularly on the characterization of trypanosome antigens, determining that these were both invariant and, when surface exposed, variant. This work led to the award of his PhD from the University of London in 1963. Neil developed the view that these highly immunogenic variable antigens played an important role in the way in which human trypanosome and malaria infections present with such a chronic relapsing course; that is to say that they aid in parasite persistence and must therefore be allowing the parasite to evade the host immune response.
Neil Brown
It was around this time that Neil came across the 1938 paper of Eaton and colleagues working on the monkey malaria Plasmodium knowlesi. These workers demonstrated the ability of serum (antibodies) from a P. knowlesi immune monkey to specifically recognize, bind to and then agglutinate and aggregate monkey erythrocytes infected with mature stages (schizonts) of the parasite. Neil refined Eaton’s schizont infected cell agglutination (SICA) test and looked at chronic P. knowlesi infections in monkeys rendered semi-immune in various ways. He demonstrated, along with IN Brown, LA Hills and other colleagues, that parasites isolated during the chronic phase were varying their surface antigens. Antibodies induced by previous SICA variants did not recognize each successive variant appearing in the blood. Importantly, Neil and colleagues were able to show that these antigens induced (variant specific) non-protective and protective immune responses, which associated with the induction of new (SICA) variants and parasite killing respectively.
Neil’s findings did not sit well with some members of the malaria research community at first. His hypothesis suggested that the development of an efficient malaria vaccine might well be compromised by the ability of the parasite to undergo antigenic variation and thus evade the induced immunity. In some quarters this hypothesis was ignored or dismissed out of hand as no such variable antigen(s) had been found in the major human malaria pathogen Plasmodium falciparum and it was not considered that antigenic variation occurred in this parasite. However, Neil’s work rejuvenated the search for these antigen(s) in P. falciparum. The discovery in the mid 1990s of both the antigens and the multi-gene family which encodes them, enabled studies providing important answers to questions of virulence, pathology, antigenic variation and evasion of the host immune response in P. falciparum infections. Neil’s vision and his tenacious adherence to his view of the importance of antigenic variation in immunity to malaria were acknowledged by his peers at a Festschrift held in his honour by the Wellcome Trust in 1994.
Neil retired from NIMR in 1995 but scientific publications bearing his name were published by his colleagues up until 2008.
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