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Professor Fred Brown

Expert on foot-and-mouth disease

06 March 2004

Fred Brown, virologist: born Clayton-le-Moors, Lancashire 31 January 1925; Assistant Lecturer, Manchester University 1946-48; Lecturer, Bristol University Food Preservation Research Station 1948-50; Senior Scientific Officer, Hannah Diary Research Institute, Ayr 1950-53; Senior Scientific Officer, Christie Hospital and Holt Radium Institute, Manchester 1953-55; Head, Biochemistry Department, Animal Virus Research Institute, Pirbright 1955-83, Deputy Director 1980-83; FRS 1981; Head of Virology Division, Wellcome Research Laboratories, Beckenham 1983-90; Professorial Fellow, Queen's University, Belfast 1986-2004; Professor of Microbiology, Surrey University 1989-90; Adjunct Professor, School of Epidemiology and Public Health, Yale University 1990-2004; OBE 1999; married 1948 Audrey Doherty (two sons); died Normandy, Surrey 20 February 2004.

Fred Brown was a distinguished virologist known to the wider public as an expert on the control of foot-and-mouth disease.

He was not afraid to argue persuasively in favour of policies against the official line. I was told once that he was recruited on to the staff of the Animal Virus Research Institute, Pirbright, as their tame biochemist. What a mistake! Brown was never tame; he was a dedicated experimental scientist who followed where the science led regardless of orthodox opinion. He believed in telling it straight as it was, regardless of what authority thought to the contrary.

Fred Brown was born in 1925 and brought up in Burnley, where he was educated at the Grammar School. He went on to Manchester University, graduating in 1944 and going on to get his PhD in 1948. After that he held several increasingly senior posts, including spells at the Hannah Dairy Research Institute in Ayr and the Christie Hospital and Holt Radium Institute, Manchester, before in 1955 joining the laboratories at Pirbright in Surrey.

He worked there for nearly 30 years and built up a world-class unit applying biochemical methods and expertise to the study of foot-and-mouth disease and other viruses notably including rabies virus. His team was pre-eminent in the study of the structure and function of foot-and-mouth disease virus. He was an inspiring leader keen to give credit to his juniors and on the lookout for emerging talent.

Amongst the discoveries of his group, with biophysicists from Oxford, was the fine structure of the virus by X-ray crystallography at the Daresbury facility in Lancashire. This needed special clearance to allow Brown to drive the crystals of virus from Pirbright for examination. When the paper describing this work appeared in Nature, it was accompanied by a picture of the virus on the cover of the magazine; but unfortunately it was a mirror image. Brown and his colleagues joyfully pointed out that it was appropriate because Lewis Carroll (C.L. Dodgson) was born in Daresbury. Nature shortly afterwards printed a picture of the stained-glass window in the church recording the association.

Brown was always trying to apply the fundamental knowledge about the structure and function of the virus and its components to the control of the disease. A major contribution to the control of foot-and-mouth disease was his advocacy of the use of chemicals that selectively react with the nucleic acid of the virus leaving the protein coat of the virus in its native state. The chemical he chose was acetylethyleneimine (AEI) and it was adopted by the UK manufacturer, the Wellcome Foundation.

The conventional agent for killing microrganisms in the preparation of killed vaccines is formalin. It is well known that organisms escape killing by formalin in the presence of extraneous proteins, notoriously in the Cutter incident when cases of poliomyelitis were caused by residual living virus in the killed Salk-type poliovaccine. Similarly there have been many examples of vaccine-induced foot-and-mouth disease outbreaks associated with failure of complete killing of the virus in the formalin-treated vaccine. No such incidents have been reported when AEI-treated vaccine has been used.

Another problem that intrigued Brown and his colleagues was antigenic variation, the mechanism by which some viruses, notably foot-and-mouth, influenza and Aids, evade the protective immune response whereas others, such as poliovirus, measles and rabies, don't. He tried to understand the process and devise ways to thwart its consequences.

One clue was that some strains stimulate a broader protective immune response than others. He became enthusiastic about the possibility of using small peptides, strings of amino acids with such broad specificity as vaccines. These could be chemically synthesised to meet a new threat. Results were promising in tests on lab animals but failed in target species.

After he retired formally there was no question that he wouldn't remain active in science. He found a congenial niche as Visiting Scientist at the US Department of Agriculture Plum Island Animal Disease Center, off Long Island, New York. In these times of threat from terrorists the US authorities take the threat from bioterrorism very seriously, especially the deliberate introduction of foot-and-mouth disease.

Brown was the ideal man to push forward defensive measures starting with means of rapid virus diagnosis capable of being carried out on the farm. He helped to develop such a method and do preliminary tests of a user-friendly kit. The method had the additional advantage of distinguishing vaccinated animals from infected ones. This kit was offered by Usda to the British authorities in the 2001 outbreak and the help was declined, much to Brown's disappointment.

During that outbreak his opinion about the control measures used in England was often invoked in the press. He would have liked there to have been an evaluation of the diagnostic kit developed by Usda under field conditions but, more important, he advocated less reliance on slaughter and an earlier use of ring vaccination around infected premises. "Why destroy innocent animals?" he asked. He was disheartened that his unique experience and knowledge was not used in any advisory capacity during the epidemic, although he was a member of one of the Royal Society inquiries set up to learn lessons from the outbreak.

Brown wrote many scientific papers and was also an editor for example of the Journal for General Virology and for the International Association for Biological Standardization. He was a member of the Spongiform Encephalopathy Advisory Committee from 1990 to 1998, strongly advocating research in the field well before BSE raised its alarming head. He was interested and active in all aspects of virology from nomenclature and classification to the history of the science.

He listed among his recreations watching cricket and football. He should have said playing cricket - he brought all his enthusiasm and competitive spirit so clear in his work to his recreation. Cricket was a serious game - after all he had been offered a trial with Lancashire in his youth - so even when he played against visiting American virologists from Wellcome he would bowl straight and too fast for unaccustomed eyes so that sweet revenge would be had for humiliation at baseball.

Fred Brown was a great scientist, ever optimistic and ready to embrace new techniques and persistent in worrying at a problem; and he was a good friend and stalwart colleague.

John Beale