Thomas Henry Flewett

Dr Thomas Henry Flewett, MD, FRCPath, FRCP (June 29, 1922 - Dec 12, 2006) , received his medical education at Queen's University, Belfast, where he graduated with honours at the end of the World War II in 1945. He was a founder member (and subsequently Fellow) of the Royal College of Pathologists and was elected (by distinction) a Fellow of the Royal College of Physicians of London in 1978. He was chairman of the World Health Organisation(WHO) Steering Committee on Viral Diarrhoeal Diseases, 1990-3, and a member until 1996. His laboratory in Birmingham was a World Health Organisation Reference and Research Centre for Rotavirus Infections from 1980 until his retirement in 1987. He was an external examiner, visiting lecturer, and scientific journal editor. He was a member of the board of the Public Health Laboratory Service (now The Health Protection Agency [1] from 1977 to 1983 and was Chairman of the Public Health Laboratory Service, Committee on Electron Microscopy from 1977 to 1987.

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Childhood

Flewett was born in India, where his father, a graduate of Oxford University was a member of the Indian Forestry Service which, in 1966, became the Indian Forest Service of the Indian Civil Service. His mother wrote in a birthday card to him "I was so pleased when the servants told me that I had given birth to a boy".^[1]. He once described to Professor Margaret Thouless, (virologist and wife of the physicist David Thouless) "a joyous childhood", often spent "riding on the backs of elephants" ^[2]. He attended Campbell College, Belfast.

Early years 1948 - 1956

Flewett's scientific interest was in viruses, the diseases they cause, and the techniques used to diagnose virus infections. This began with membership of the scientific staff of the National Institute for Medical Research at Mill Hill, where he spent three years between 1948 and 1951 researching common cold viruses and exploring the effect of influenza viruses on cells in culture. This led to his first use of electron microscopy, in which he became a leading authority. In 1951 he moved as lecturer in bacteriology to Leeds University, where he was involved in the 1953 smallpox outbreak.^[3] This experience proved invaluable twenty-five years later when a laboratory-associated case of smallpox at the Medical School of the University of Birmingham, UK, lead to the death of Janet Parker.

Regional Virus Laboratory, Birmingham, England 1956 -1987

In 1956 Flewett was appointed consultant virologist to East Birmingham Hospital, where he established and became Director of one of the first regional virus laboratories in England, serving a population of more than five million. The proximity of the laboratory to the regional infectious diseases unit enabled him to provide confirmation of the clinical diagnosis ranging from poliomyelitis and childhood diarrhoea to smallpox and AIDS. He was active in the medical administration of East Birmingham (now Heartlands) Hospital and was instrumental in establishing the regional immunology laboratory in the hospital. 

At East Birmingham Hospital Flewett's interests covered further aspects of influenza, Coxsackie A and Coxsackie B viruses, major and minor variants of smallpox virus, and Hepatitis B virus. He was the first to describe "Hand, foot and mouth disease" as a clinical entity ^[4], but the work which gave him an international reputation began in the early 1970s with the discovery of viruses causing diarrhoea, particularly in infants and young children. Flewett was the first to name one of the most frequent causes of death in infants in tropical countries, rotaviruses, during the course of this research into the causes of gastroenteritis.

Norwalk virus had been discovered by Albert Kapikian using immune electron microscopy^[5] and Ruth Bishop and colleagues had seen different virus-like particles in gut biopsies by thin section electron microscopy.^[6] This was too cumbersome for routine use, and Flewett and his co-workers showed that these viruses could be seen directly in stool extracts.^[7] Flewett and his colleagues in his Birmingham laboratory had observed these viruses in the faeces of sick children before the publication of Ruth Bishop's paper but they failed to realise that they were the cause of the infection. The virus particles have a wheel-shaped appearance by electron microscopy, and it was Flewett who gave them the name "rotavirus," by which they have been known since.^[8] Flewett wrote: ‘At the South Wiltshire Virology Society I met Gerald Woode, then at Compton, in late 1973. He described a virus causing diarrhoea in calves. I realized we had much the same in children. We found his virus and ours were related – something new. We called them rotaviruses' ^{[9] [10]}

His original idea was to suggest the name “urbivirus” because of the structural similarity of rotavirus to orbivirus^[11]. Ruth Bishop, who was the first to describe rotaviruses as a cause of gastroenteritis had suggested “duovirus” because these viruses replicate in the duodenum and, at the time, were thought to have a double protein outer coat. The early research papers from the 1970s use both names.^[12]

Flewett did much collaborative work on rotaviruses with others to establish the varieties of rotavirus which infect the young of virtually every species of animal.^[13] His research group were the first to describe the different serotypes of rotavirus.^[14] This work was important to the development of a rotavirus vaccine. He also identified two new species of adenoviruses (later called types 40 and 41), as well as confirming the presence of caliciviruses, astroviruses, and faecal coronaviruses. He, along with H.G. Pereira also discovered Picobirnavirus ^{[15] [16]},[2] and with other colleagues first described human Torovirus. ^[17]

Birmingham smallpox tragedy

An account of the death from smallpox of Janet Parker in 1978 has been written ^[18]. The diagnosis was made by Professor A. Geddes and the virus was identified by Flewett in his laboratory, at East Birmingham Hospital where she had been admitted. Before the diagnosis had been confirmed, a member of Flewett’s laboratory had collected lymph from Janet Parker’s vesicles and taken it across the grounds of the hospital for examination in the virus laboratory. Flewett recognised the danger of an outbreak occurring and immediately ordered his staff to fumigate the laboratory with formaldehyde. The ward in which Janet Parker had been initially cared for was also fumigated. The building housing wards 33 and 34 were later demolished. Two members of Flewett’s team were subsequently quarantined but apart from Janet Parker’s mother, no further cases of smallpox occurred. This tragedy lead to the suicide of Professor Henry Bedson a friend and colleague of Flewett. Later, Flewett, with the contributions of other medical consultants established a trust fund for Bedson’s children.

WHO Reference and Research Laboratory 1980 -1987

Flewett's work on rotaviruses brought him international recognition both as a virologist and an electron microscopist. He was one of the first western virologists to be invited to the Peoples' Republic of China (in 1983) to lecture. He was a judge for the King Faisal International Prize in 1983, which was awarded to Professor John S. Fordtran, Dr William B. Greenough III and Professor Michael Field, for their work on oral rehydration therapy in reducing mortality and morbidity due to cholera and other acute infectious diarrhoeal diseases ^[19]. During these years he travelled widely as a World Health Organization consultant to most countries in which childhood diarrhoea is a major problem. He established The WHO Collaborating Centre for Reference and Research on Rotaviruses, (known as The WHO Lab), at his laboratory which was supported by The World Health Organisation from 1980 until his retirement in 1987. This laboratory was formerly a small tuberculosis bacteriology laboratory and the building was old and badly and in need of repair. ^[20] As well continuing with basic research on the viruses that cause gastroenteritis, this laboratory produced reagents for the laboratory diagnosis of rotavirus infections based on monoclonal antibodies developed by his research team ^[21]. These reagents were sent regularly to numerous hospital laboratories throughout the developing world. The WHO laboratory attracted many visiting scientists from many countries and his team of research scientists contributed to the development of a vaccine against rotavirus infections. ^[22] His laboratory was active in the search for other, novel causes of viral infections which Flewett called 'the diagnostic gap' because to this day many causes of gastroenteritis are still unknown. ^[23]

Unfulfilled ambition - FRS

Shortly before his retirement Flewett wrote a private letter to Dr David Tyrell FRS, former director of the Common Cold Unit, requesting support for admission to The Royal Society. Flewett had known David Tyrell for many years, (since his time at Mill Hill)[3] and he hoped that the support of this prestigious Fellow would help him get elected. Tyrell replied saying that Flewett should make his own case for election which he, Tyrell, would read. Flewett was a modest man and only sent Tyrell a list of publications. Tyrell's response was not encouraging and Flewett, (a man not used to failure), withdrew his request ^[24].

Hands on leader

There was little that was being done on the benches that he could not have done or had done himself. He was a hands-on leader of his laboratory. He could use and, in the case of the electron microscope, maintain, all the equipment. (He was a collector and restorer of antique clocks and kept one in his office along with an antique watch the hands of which were so radioactive, that he was forced to keep it in a lead-lined box). During the constant care and attention required by the Phillips electron microscope dating from the 1960s and with which he first observed rotaviruses, he accidentally showered himself with concentrated nitric acid whilst cleaning the vacuum pump ^[25]. He was later seen with a yellow streak on his face and hair and was heard complaining that he had "ruined a perfectly good necktie^[26]. In an earlier accident, a decade or so before, he breathed in fumes of osmium tetroxide, (used in electron microscopy) that left his sense of smell permanently impaired. Those colleagues who were ignorant of this were often amazed by Flewett’s tolerance of the bad odours associated with samples of faeces. Similarly, he was allergic to glutaraldehyde and banned its use in any room which he often frequented.

His character

Flewett was small of stature (5' 5"), silver-haired and quick of thought and action, He was very short-sighted and throughout his adult life he wore thick-rimmed glasses and when asked to examine something small, he shifted these down his nose and peered over the lenses. He spoke in a crisp incisive manner using concise and rather staccato phrases and an habitual cough - but he delivered his lectures and scientific presentations entirely from memory never using notes. This gave his public speaking a relaxed informality which he reinforced with numerous anecdotes about his famous and not so famous contemporaries. He rarely incorporated much raw scientific data into his lectures because he felt the spoken word to be an inappropriate forum for scientific discourse and much preferred the peer-reviewed scientific paper.
He spoke fluent French but his accent lacked the nasal vowels of the language. Politics did not seem to interest him much but he was a supporter of Margaret Thatcher and once, one the eve of the British General Election of 1983 said that he would retire if "Mrs. Thatcher did not get back in."^[27]. He spoke even less about the politics of his native Northern Ireland, but on the morning following the Brighton hotel bombing of 1984 advocated the return of Capital Punishment^[28]. He was, however, enraged by the portraits of Bonaparte in the Louvre proclaiming that "that man has so much blood on his hands" ^[29].
He was often a difficult man to work with and to work for^[30]. He was often rude, insensitive and distant. Having said that, he ordered the removal of a book about Japanese war atrocities from the WHO laboratory library when a visiting scientist from Japan joined his team. His reasons being that "all this happened before he, (the visitor), was born".^[31] He enjoyed watching The Six Million Dollar Man and Doctor Who. He often read science fiction. He played golf for most of his adult life and won many trophies. For many years he drove an old Rover P car that rivalled the comfort luxury car manufacturers such as Rolls Royce produced. He sold it in the early 1980s because " it drank too much petrol". Flewett suffered a severe stroke in November 2006 and he died one month later. His body was cremated at Robin Hood Crematorium in Birmingham, England.

His legacy

Flewett was educated at a time when very little was known about viruses and viral illness and when there were no laboratory tests to aid or confirm a diagnosis. Flewett was a pioneer - today diagnostic virology laboratories, like the one he established in 1956, can be found throughout the world. It is impossible to estimate how many lives he helped to save. During his lifetime, Thomas Henry Flewett published over 130 scientific and medical articles and papers. He was a scientist, a doctor, a father and a grandfather. He left estate valued at £815,846 net mostly to his daughters and grandchildren.[4]  

References, notes and sources

Obituary by Dick Madeley and Alasdair Geddes [5]

1. ^ Card found during the demolition of the W.H.O. Laboratory for Reference and Research on Rotaviruses, 1996
2. ^ Personal communication Margaret Thouless to G. M. Beards, 1981
3. ^ Flewett TH. The clinical and laboratory diagnosis of variola minor (alastrim). Br J Clin Pract. 1970 Sep;24(9):397-402.
4. ^ Flewett TH, Warin RP, Clarke SK. 'Hand, foot, and mouth disease' associated with Coxsackie A5 virus. J Clin Pathol. 1963 Jan;16:53-5.
5. ^ Kapikian AZ, Wyatt RG, Dolin R, Thornhill TS, Kalica AR, Chanock RM. Visualization by immune electron microscopy of a 27-nm particle associated with acute infectious nonbacterial gastroenteritis. J Virol. 1972 Nov;10(5):1075-81.
6. ^ Bishop RF, Davidson GP, Holmes IH, Ruck BJ. Virus particles in epithelial cells of duodenal mucosa from children with acute non-bacterial gastroenteritis. Lancet. 1973 Dec 8;2(7841):1281-3.
7. ^ Flewett TH, Bryden AS, Davies H. Letter: Virus particles in gastroenteritis. Lancet. 1973 Dec 29;2(7844):1497
8. ^ Flewett TH, Woode GN. The rotaviruses. Arch Virol. 1978;57(1):1-23.
9. ^ Letter to Dr Tilli Tansey, 8 February 1998. Woode was at the Institute for Research on Animal Diseases, Compton, Newbury, Berks. See Flewett T H, Bryden A S, Davies H, Woode G N, Bridger J C, Derrick J M. (1974) Relation between viruses from acute gastroenteritis of children and newborn calves. Lancet ii: 61–63.
10. ^ Flewett TH, Woode GN. The rotaviruses. Arch Virol. 1978;57(1):1-23.
11. ^ T.H. Flewett personal communication to G. M. Beards
12. ^ Wyatt GB, Hocking B, Bishop R, Wyatt JL. Duovirus infection as a cause of infantile gastro-enteritis in Port Moresby. P N G Med J. 1976 Sep;19(3):134-6.
13. ^ Flewett, T H., Bryden, A S., and Davies, H A. (1975) Virus diarrhoea in foals and other animals. Vet. Rec. 96, 477.
14. ^ Beards GM, Pilfold JN, Thouless ME, Flewett TH. Rotavirus serotypes by serum neutralisation. J Med Virol. 1980;5(3):231-7.
15. ^ Treanor, J. J., R. Dolin. 2005. Astroviruses and picobirnaviruses. 2201-2203, in: Mandell, Douglas and Bennett’s Principles and practice of infectious diseases (6th Ed.). Mandell G. L., Bennett J. E., Dolin R. (Editors). Elsevier Churchill Livingstone.
16. ^ Pereira, H. G., Flewett, T. H., Candeias, J. A. & Barth, O. M. (1988). A virus with a bisegmented double-stranded RNA genome in rat (Oryzomys nigripes) intestines. Journal of General Virology 69 ( Pt 11), 2749-2754.
17. ^ G. M. Beards, D.W.G., Brown, J. Green, T. H. Flewett: Preliminary Characterisation of Torovirus-Like Particles of Humans: Comparison With Berne Virus of Horses and Breda Virus of CalvesJournal of Medical Virology,20,1,67-78,1986
18. ^ Janet Parker
19. ^ Dialogue on Diarrhoea Online, Issue no.16 - February 1984
20. ^ The building was demolished in 1996.
21. ^ Beards GM, Campbell AD, Cottrell NR, Peiris JS, Rees N, Sanders RC, Shirley JA, Wood HC, Flewett TH. Enzyme-linked immunosorbent assays based on polyclonal and monoclonal antibodies for rotavirus detection. J Clin Microbiol. 1984 Feb;19(2):248-54.
22. ^ Vesikari T, Isolauri E, Delem A, d'Hondt E, Andre FE, Beards GM, Flewett TH. Clinical efficacy of the RIT 4237 live attenuated bovine rotavirus vaccine in infants vaccinated before a rotavirus epidemic. J Pediatr. 1985 Aug;107(2):189-94.
23. ^ J Med Virol. 2003 Jun;70(2):258-62.Infantile viral gastroenteritis: on the way to closing the diagnostic gap. Simpson R, Aliyu S, Iturriza-Gomara M, Desselberger U, Gray J.Clinical Microbiology and Public Health Laboratory, Addenbrooke's Hospital, Cambridge, United Kingdom.
24. ^ Copies of correspondence left with G. M. Beards
25. ^ G.M Beards, J.R. Foster personal observation
26. ^ Ibid
27. ^ G.M. Beards
28. ^ Conversation with G. M.Beards, October 12 1984
29. ^ R. C. Sanders and G. M. Beards, personal observations, 1984
30. ^ Staff of the Regional Virus Laboratory 1956-1987, personal communication to G.M beards
31. ^ A.D.Campbell and G. M. Beards, personal observation