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David Tyrrell (physician)
David Tyrrell (physician)
David Arthur John Tyrrell CBE FRS (19 June 1925 – 2 May 2005) was a British virologist who was the director of the Common Cold Unit, which investigated viruses that caused common colds. He discovered the first human coronavirus (designated B814) in 1965. With June Almeida he made the first comparative study of human and chicken coronaviruses in 1967, and invented the name coronavirus in 1968.
Tyrrell was born on 19 June 1925 to Sidney Tyrrell and Agnes Kate Blewett. He had a younger brother Andrew.[2] He attended elementary schools at Ashford, Middlesex. His family moved to Sheffield in 1940, where he completed secondary education at King Edward VII School. While studying medicine at the University of Sheffield he suffered from a detached retina, which meant he was exempted from military conscription, and had a lifelong preference for monocular microscopes.[3] He graduated in 1948 and earned membership of the Royal College of Physicians in 1949.[4] During those years he worked as a house physician at the Professorial Medical Unit of Sheffield Royal Hospital and at the City General Hospital in Sheffield. He was appointed as the first Research Registrar post under the Hospital Endowment Fund of Sheffield in 1950.[2]
He moved to the Rockefeller Institute in New York to work under Frank Horsfall as an assistant from 1951 to 1954. He was briefly enrolled in the US Army during the Korean War (1950–1953).[citation needed] In 1954, he gained an appointment as External Scientific Staff of the Medical Research Council at the Virus Research Laboratory in Sheffield, where he worked until 1957.[3] Upon an invitation from Sir Harold Himsworth, Secretary of MRC, he moved to the MRC's Common Cold Unit on the outskirts of Salisbury on 1 April 1957,[4] becoming its head from 1962 succeeding Christopher Andrewes.[5] He was also appointed as head of the Division of Communicable Diseases in 1967 and then deputy director of the MRC's Clinical Research Centre at Northwick Park Hospital, Harrow, Middlesex, in 1970, while still attached to CCU.[3] The Clinical Research Centre was closed in 1984 following which Tyrrell returned full time at CCU in 1985, and remained there until its official closure in 1990.[4]
In the 1960s, after June Almeida produced the first images of the rubella virus using immune-electronmicroscopy,[6] Tyrrell and Almeida worked on characterising a new type of viruses, now called coronaviruses.[7]
He retired from the Common Cold Unit in 1990[8] and subsequently carried out research at the Centre for Applied Microbiology and Research at Porton Down, where he also worked on his scientific autobiography, Cold Wars: The Fight Against the Common Cold.[2] He died of prostate cancer on 2 May 2005 at Salisbury.[4]
Tyrrell married Moyra Wylie,[9] a general practitioner, in 1950.[3] They had one son and two daughters. He was a devoted Christian and served as an organist and choirmaster at his local church.[4]
Soon after he joined CCU, Tyrrell developed a system of categorising cold viruses. Some viruses could be maintained only in human-embryo-kidney cell culture and were designated H strain, and others could be maintained both in human-embryo-kidney cell culture and monkey-embryo-kidney cell culture and were labelled M strain.[10][11] One nasal swab sample collected on 17 February 1961 from a schoolboy in Epsom, Surrey, was different as it could not be maintained in any of the culture media. The specimen designated B814 when experimented on healthy volunteers was highly contagious and produced the symptoms of cold within a few days.[12] Due to its unusual nature, they were uncertain whether the pathogen was a virus or a bacterium. Without any other method to study, the specimen was preserved for four years. Returning from a visit to the Lund University in Sweden in 1965, Andrewes told Tyrrell that there was a young Swedish surgeon who was able to grow complex viruses. The Swede was Bertil Hoorn who had developed a culture method using human trachea tissue.[13] Tyrrell immediately invited Hoorn to visit CCU, and after which they were was able to grow different viruses which could not be cultured earlier.[14] Specimen B814 could the be confirmed as a virus, but was unique from all known cold viruses based on its antigenic property and symptoms it produced.
Tyrrell and Malcolm L. Bynoe reported the discovery in the 5 June 1965 issue of the British Medical Journal, concluding: "After considerable initial doubts we now believe that the B814 strain is a virus virtually unrelated to any other known virus of the human respiratory tract, although, since it is ether-labile, it may be a myxovirus."[15] This was the discovery of human coronavirus. But the virus was difficult to maintain in culture and the structure was difficult to study. In 1966, June Dalziel Almeida had just joined as an electron microscopist at the St Thomas's Hospital Medical School in London. She had earlier developed techniques for studying viruses under electron microscope,[16][17] and had also studied the first two coronaviruses discovered, infectious bronchitis virus (IBV) and mouse hepatitis virus (MHV). Tyrrell sent her the specimen, including one new human virus called 229E, which was recently discovered by Dorothy Hamre and John J. Procknow at the University of Chicago.[18] Almeida revealed that the two human viruses were identical to each other, and to IBV as well. Almeida and Tyrrell reported in the April 1967 issue of the Journal of General Virology, writing: "Probably the most interesting finding from these experiments was that two human respiratory viruses, 229 E and B814 are morphologically identical with avian infectious bronchitis."[19]
The new discovery was supported by independent discovery of new human viruses (OC43) by Kenneth McIntosh and co-workers at the National Institute of Health, Bethesda, almost at the same time.[20] It was becoming evident that all these viruses including MHV were of the same kind. Almeida and Tyrrell came up with the name "coronavirus". As Tyrrell recollected in Cold Wars: The Fight Against the Common Cold:
We looked more closely at the appearance of the new viruses and noticed that they had a kind of halo surrounding them. Recourse to a dictionary produced the Latin equivalent, corona, and so the name coronavirus was born.[21]
At the Rockefeller Institute, Tyrrell worked on the epidemiology on poliomyelitis. He presented his findings at the second International Congress on Poliomyelitis in Copenhagen on 3–7 September 1951,[2] and published in The Lancet at the end of the year.[22] At CCU, he developed techniques for culturing different cold viruses. He was the first to grow certain cold viruses (rhinoviruses) using nasal epithelial cells. He published a series of papers on his new technique in The Lancet in 1960.[23][24][25] With researchers from University College London, he also investigated the role of human parvovirus B19 during 1985–1987. They discovered that the virus is the causative agent of erythematous rash illness and temporary stoppage of blood formation in persons with chronic haemolytic anaemia.[26][27]
Tyrrell was elected a Fellow of the Royal Society in 1970, and was appointed Commander of the Order of British Empire (CBE) in 1980.[2] He held honorary degrees from the University of Sheffield (1979) and the University of Southampton (1990), and received the Stewart Prize (1977), the Ambuj Nath Bose prize (1983), and the Conway Evans Prize (1986).[2]
^ Barclay, Wendy S. (1988). The humoral immune response to rhinovirus infection. copac.jisc.ac.uk (PhD thesis). University of Reading. OCLC 499917328. EThOS uk.bl.ethos.383380.
^
a b c d e f Kerr, J. R.; Taylor-Robinson, D. (2007). "David Arthur John Tyrrell. 19 June 1925 – 2 May 2005: Elected FRS 1970". Biographical Memoirs of Fellows of the Royal Society. Royal Society. 53: 349–363. doi:10.1098/rsbm.2007.0014. PMID 18543468. S2CID 73300843.
^
a b c d Taylor-Robinson, David (30 May 2005). "Dr David Tyrrell". The Independent. Retrieved 29 August 2020.
^
a b c d e Richmond, Caroline (2005). "David Tyrrell". BMJ. 330 (7505): 1451. doi:10.1136/bmj.330.7505.1451. PMC 558394.
^ Lalchhandama K (2020). "The chronicles of coronaviruses: the bronchitis, the hepatitis and the common cold". Science Vision. 20 (1): 43–53. doi:10.33493/scivis.20.01.04.
^ Paterson, Andrew (2017). Brilliant! Scottish inventors, innovators, scientists and engineers who changed the world. London: Austin Macauley. p. 577. ISBN 9781786294357.
^ Booss, John; August, Marilyn J (2013). To catch a virus. Washington, DC: ASM Press. p. 217. ISBN 978-1-55581-507-3.
^ Tilli Tansey; Pippa Catterall; Sonia V Willhoft; Daphne Christie; Lois Reynolds, eds. (1997). Technology Transfer in Britain: The Case of Monoclonal Antibodies; Self and Non-Self: A History of Autoimmunity; Endogenous Opiates; The Committee on Safety of Drugs. Wellcome Witnesses to Contemporary Medicine. History of Modern Biomedicine Research Group. ISBN 978-1-869835-79-8. OL 9320034M. Wikidata Q29581528.
^ Oransky, Ivan (2005). "David Tyrrell" (PDF). The Lancet. 365 (9477): 2084. doi:10.1016/S0140-6736(05)66722-0. PMID 16121448. S2CID 43188254.
^ Tyrrell DA, Bynoe ML (February 1961). "Some further virus isolations from common colds". British Medical Journal. 1 (5223): 393–7. doi:10.1136/bmj.1.5223.393. PMC 1953283. PMID 13778900.
^ Tyrrell DA, Buckland FE, Bynoe ML, Hayflick L (August 1962). "The cultivation in human-embryo cells of a virus (D.C.) causing colds in man". Lancet. 2 (7251): 320–2. doi:10.1016/S0140-6736(62)90107-1. PMID 13923371.
^ Kendall EJ, Bynoe ML, Tyrrell DA (July 1962). "Virus isolations from common colds occurring in a residential school". British Medical Journal. 2(5297): 82–6. doi:10.1136/bmj.2.5297.82. PMC 1925312. PMID 14455113.
^ Hoorn, B. (1964). "Respiratory viruses in model experiments". Acta Oto-Laryngologica. 188 (Sup188): 138–144. doi:10.3109/00016486409134552. PMID 14146666.
^ Hoorn, B.; Tyrrell, D. A. (1965). "On the growth of certain "newer" respiratory viruses in organ cultures". British Journal of Experimental Pathology. 46 (2): 109–118. PMC 2095265. PMID 14286939.
^ Tyrrell DA, Bynoe ML (June 1965). "Cultivation of a Novel Type of Common-cold Virus in Organ Cultures". British Medical Journal. 1 (5448): 1467–70. doi:10.1136/bmj.1.5448.1467. PMC 2166670. PMID 14288084.
^ Almeida, J. D.; Howatson, A. F. (1963). "A negative staining method for cell-associated virus". The Journal of Cell Biology. 16 (3): 616–620. doi:10.1083/jcb.16.3.616. PMC 2106233. PMID 14012223.
^ Almeida, J.; Cinader, B.; Howatson, A. (1 September 1963). "The structure of antigen-antibody complexes. A study by electron microscopy". The Journal of Experimental Medicine. 118 (3): 327–340. doi:10.1084/jem.118.3.327. PMC 2137656. PMID 14077994.
^ Hamre, D.; Procknow, J. J. (1966). "A new virus isolated from the human respiratory tract". Experimental Biology and Medicine. 121 (1): 190–193. doi:10.3181/00379727-121-30734. PMID 4285768. S2CID 1314901.
^ Almeida, J. D.; Tyrrell, D. A. J. (1967). "The morphology of three previously uncharacterized human respiratory viruses that grow in organ culture". Journal of General Virology. 1 (2): 175–178. doi:10.1099/0022-1317-1-2-175. PMID 4293939.
^ McIntosh, K.; Dees, J. H.; Becker, W. B.; Kapikian, A. Z.; Chanock, R. M. (1967). "Recovery in tracheal organ cultures of novel viruses from patients with respiratory disease". Proceedings of the National Academy of Sciences of the United States of America. 57 (4): 933–940. Bibcode:1967PNAS...57..933M. doi:10.1073/pnas.57.4.933. PMC 224637. PMID 5231356.
^ Tyrrell DA, Fielder M (2002). Op. cit. p. 96. ISBN 978-0-19-263285-2.
^ Tyrrell, D. a. J. (1951). "Poliomyelitis in a rural area; report on a Lincolnshire outbreak". Lancet. 2 (6694): 1129–1133. doi:10.1016/s0140-6736(51)93040-1. PMID 14881586.
^ Tyrrell, D. A.; Bynoe, M. L.; Hitchcock, G.; Pereira, H. G.; Andrewes, C. H. (1960). "Some virus isolations from common colds. I. Experiments employing human volunteers". Lancet. 1 (7118): 235–237. doi:10.1016/s0140-6736(60)90166-5. PMID 13840112.
^ Hitchcock, G.; Tyrrell, D. A. (1960). "Some virus isolations from common colds. II. Virus interference in tissue cultures". Lancet. 1 (7118): 237–239. doi:10.1016/s0140-6736(60)90167-7. PMID 14402042.
^ Tyrrell, D. A.; Parsons, R. (1960). "Some virus isolations from common colds. III. Cytopathic effects in tissue cultures". Lancet. 1 (7118): 239–242. doi:10.1016/s0140-6736(60)90168-9. PMID 13840115.
^ Anderson, M. J.; Higgins, P. G.; Davis, L. R.; Willman, J. S.; Jones, S. E.; Kidd, I. M.; Pattison, J. R.; Tyrrell, D. A. (1985). "Experimental parvoviral infection in humans". The Journal of Infectious Diseases. 152 (2): 257–265. doi:10.1093/infdis/152.2.257. PMID 2993431.
^ Potter, C. G.; Potter, A. C.; Hatton, C. S.; Chapel, H. M.; Anderson, M. J.; Pattison, J. R.; Tyrrell, D. A.; Higgins, P. G.; Willman, J. S.; Parry, H. F. (1987). "Variation of erythroid and myeloid precursors in the marrow and peripheral blood of volunteer subjects infected with human parvovirus (B19)". The Journal of Clinical Investigation. 79 (5): 1486–1492. doi:10.1172/JCI112978. PMC 424424. PMID 3033026.
David Tyrrell
Born
David Arthur John Tyrrell
19 June 1925
Ashford, Middlesex, England
Died
2 May 2005 (aged 79)
Salisbury, England
Nationality
British
Alma mater
Known for
Discovery and naming of coronaviruses
Spouse
Moyra Wylie (m. 1950)
Children
3 (1 son and 2 daughters)
Scientific career
Institutions
Rockefeller Institute for Medical Research
Medical Research Council, Sheffield
Doctoral students
https://www.thelancet.com/journals/lancet/article/PIIS0140673605667220/fulltext
2005-06-18-the-lancet-obituary-david-tyrrell.pdf
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OBITUARY| VOLUME 365, ISSUE 9477, P2084, JUNE 18, 2005
David Tyrrell
David Tyrrell
David Tyrrell
Published:June 18, 2005DOI:https://doi.org/10.1016/S0140-6736(05)66722-0
Researcher who led efforts at the UK's Common Cold Unit from 1957 to 1990. Born on June 19, 1925, in Ashford, UK, he died in Salisbury, UK, on May 2, 2005, aged 79 years.
The UK's Common Cold Research Unit (later the Common Cold Unit), in Salisbury, came into being after World War II when Harvard University donated a wartime hospital it had set up for the British military. In 1957, David Tyrrell, who had worked at the Rockefeller Institute in New York, USA, and at the then-infant UK's Medical Research Council but was still a “reluctant young virologist”, as he would later describe himself, became head of the unit. He took over what was planned as a last-ditch effort to culture the virus responsible for the common cold to forestall the closure of the unit.
The assignment, scheduled to last 3 years, paid off in 1960 with the publication of three papers describing common cold virus isolates in The Lancet. The Common Cold Unit lasted until 1990, when it was shut down. In that time, Tyrrell became well known for isolating some of the early rhinoviruses, coronoviruses, and parainfluenza viruses, according to Ronald Eccles, who runs the Common Cold Centre in Cardiff, UK. Tyrrell studied treatment options, undertook studies of influenza and cold virus vaccines, and eventually studied the relation between stress and colds. “He saw the whole development of the common cold story from the discovery of the viruses right up to the treatments”, Eccles said, “which so far have not proven very effective”.
The Common Cold Unit produced 1006 papers from 1948 to 1989, according to Tom Jefferson, of the Cochrane Collaboration, who did a review of the unit's literature. Closing the unit, Jefferson said, was “scientific vandalism”. “It was very fashionable and very exciting in the 1960s when the rhinoviruses were discovered”, said Jack Gwaltney, a cold researcher at the University of Virginia, Charlottesville, USA. “Things change. Herpes virus came along, then AIDS. Colds are pretty much an area that doesn't get much attention right now.”
“Of course it is the failure to find a cure which has hit most strongly upon the public consciousness”, Tyrrell wrote in his memoir Cold Wars with co-author Michael Fielder in 2002. “Why, will people ask, in this age of advanced science, do we appear to have got nowhere in combating this age-old affliction? The truth is that we have made enormous progress, although it has needed detailed research in many centres. Knowing its causes, the mechanics of how it is caught and its variety of forms is a very significant advance. But it is this variety which is at the heart of the problem.” When the group found that there were about 100 different rhinovirus serotypes and that the body saw the “common cold virus” as 100 different viruses, they realised there was “no way you could start to discover a vaccine”, Eccles said. “Rhinoviruses are also rather unstable because they are RNA viruses—there's no spellchecker when it's produced.”
The Common Cold Unit was well-known for its uses of volunteers, some 20 000 of whom spent days or weeks taking part in trials after responding to advertisements such as “Free 10 Day Autumn or Winter Break: You May Not Win A Nobel Prize, But You Could Help Find a Cure for the Common Cold.” A character in Iris Murdoch's Under the Net met another character through volunteering there. Such volunteers “were often pleased to know that they would appear as a dot on a graph or a digit when the paper was published in The Lancet,” Tyrrell and Fielder wrote. In one experiment, colleague James Lovelock “built a rig that trickled a solution of a fluorescent dye out of the nose of one of the laboratory staff. They set it running and then played cards together. After that they turned out the lights and put on a fluorescent lamp. To their amazement they found that the dye had got onto the cards, tables, their fingers, and other parts of the room.”
“I suppose when everyone else was running around looking at impact factors and this sort of thing, David was thinking about what this meant for the patients”, said Jonathan Kerr, who worked with Tyrrell in the 1990s when his interests turned to chronic fatigue syndrome. “That's what motivated him and he was ultimately more successful for it.” He also had a wonderful sense of humour, Kerr told The Lancet. One of his favourite poems, by A P Herbert, spoke of physicians' knowledge of the common cold: “And I will eat my only hat; if they know anything of that!” Tyrrell is survived by his wife of 55 years, Moyra Wylie, and two daughters. A son predeceased him.
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Published: 18 June 2005
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DOI: https://doi.org/10.1016/S0140-6736(05)66722-0
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https://royalsocietypublishing.org/doi/pdf/10.1098/rsbm.2007.0014
doi:10.1098/rsbm.2007.0014351 © 2007 The Royal Society
DAVID ARTHUR JOHN TYRRELL CBE
19 June 1925 — 2 May 2005
Biogr. Mems Fell. R. Soc. 53, 349–363 (2007)
DAVID ARTHUR JOHN TYRRELL CBE
19 June 1925 — 2 May 2005
Elected FRS 1970
BY J. R. KERR1 & D. TAYLOR-ROBINSON2
1 Department of Cellular and Molecular Medicine,
St George’s University of London, London SW17 0RE, UK
2 Division of Medicine, Imperial College London, St Mary’s Campus,
London W2 1NY, UK
David Tyrrell is remembered by physicians and scientists principally for his discovery of the
common cold viruses and elucidation of their pathogenesis, but also for his work in various
other areas, including influenza, bovine spongiform encephalopathy (BSE) and chronic
fatigue syndrome (CFS). David possessed a deep humanity, honesty, perseverance and a vision
of collaboration as a means of making discoveries that would contribute meaningfully to the
alleviation of human suffering. He also had a warmth and a mischievous sense of humour that
was frequently directed at bureaucracy, which he thoroughly disliked.
INTRODUCTION
The name David Tyrrell will forever be linked with the discovery of the common cold viruses
and elucidation of their disease pathogenesis. He was a physician and virologist who directed
his medical and scientific training towards the benefit of his fellow man. The area he finally
chose was that of respiratory virus infection and in particular the common cold.
After his graduation from medical school in Sheffield, and a three-year research fellowship
at the Virology Laboratory of the Rockefeller Institute under the direction of Frank Horsfall,
he was invited in 1957 by Sir Harold Himsworth FRS, Secretary of the Medical Research
Council (MRC), to work at the Common Cold Unit (CCU) in Wiltshire with the aim of growing
the common cold virus. David’s unique approach of using well-oxygenated nasal epithelial
cells grown at 33 °C (the temperature of the nose) enabled him to grow rhinoviruses for the
first time, as described in a series of exciting papers in The Lancet in 1960. He gained a
worldwide reputation, as did the unusual volunteer-based CCU. It soon became clear that there
were more than 100 different types of rhinovirus, and also other viruses that could cause the
common cold, for example, the coronaviruses.
In 1967, David became Head of the Division of Communicable Diseases at the MRC’s
Clinical Research Centre, built in association with Northwick Park Hospital, Harrow,
Middlesex, and was Deputy Director of the Centre from 1970. During this time, he studied
gastrointestinal infections in children, febrile convulsions, encephalitis and schizophrenia
while maintaining control of research at the CCU, part of which involved determining the
effectiveness of antiviral drugs.
ASHFORD
David was born on 19 June 1925, the first child of Sidney Tyrrell and Agnes Kate Blewett, and
grew up in a small bungalow in Ashford, Middlesex (now Surrey), in a ‘protected environment’
with his mother, father and brother, Andrew, who was 18 months younger than himself.
His father had served in the infantry in World War I; he had risen through the ranks to become
a captain and had served for almost the entire war, mainly in France, despite wounds and ‘shell
shock’. Later, he became an accountant and joined Parke Davis & Co. Ltd. at Hounslow as a
cost accountant. He later discovered that his father would have liked to have studied medicine
if funds had permitted. Sidney Tyrrell talked frequently about the development and testing of
drugs and the animal experiments at Hounslow and had a considerable intellectual influence
on David. Sidney was restless and talkative and was a great reader of history and biography,
‘yet a great debunker and hostile to the abstract, the academic and the intellectual who was
detached from real life’. He was very much against dishonesty in business and refused lucrative
posts rather than be compromised. David’s mother trained as a teacher at Hereford
College and had a special interest in French and mathematics; she taught for 5 years but then
stopped to take care of her family. Interestingly, in later life, David spoke French fluently, and
German too. In his childhood, he played with his brother and other friends; garden cricket, fantasy
games involving exploration and the circus, riding bicycles, swimming and boxing.
Swimming, and also sailing, he very much enjoyed in later life, although he freely admitted
that he had no aptitude for games that involved eye–hand or foot coordination. As a child, he
enjoyed reading, particularly stories about the sea, travel and animals. He learned to play the
ukulele and piano and played piano duets with his mother. He continued playing the piano
throughout his life, being at one time part of a musical quartet, and extended his musical experience
by learning to play the organ. When young, David and the family would go to church
and he and his brother attended the Crusaders on Sundays; this encouraged his personal commitment
to the Christian faith, which was maintained throughout his life.
He loved adventure stories and wanted to go to sea but could not because of his eyesight
(see below), but did enthuse his brother, Andrew, to go to sea; Andrew became a navigating
officer and was eventually in the senior management of his shipping line. At primary school
David was noted for being ‘dreamy, forgetful and untidy’. However, at grammar school, first
at County School, Ashford, David ‘enjoyed being top of the class’ in his studies of French,
Latin, geography and science.
SHEFFIELD
When World War II broke out in 1939, the family was on holiday in Scotland, and David and
Andrew were at school for a term in Greenock. The family returned to London but in 1940
moved to Sheffield. David attended the King Edward VII School and studied physics, chemistry,
mathematics, German and music, but later had to drop the music lessons to provide time
for the other subjects.
The Tyrrell family had been friendly with the family of Dr A. Sutherland, a general practitioner
(GP) in Ashford; David had, through them, been to the Royal Institution Christmas lectures
on ‘Young chemists and great discoveries’ and recalled the excitement of witnessing at
first hand the actual performance of historic experiments. This brought to life books like
Simple science, which David had received as a form prize and which he had read more than
once.
As a career, he wished to do something that would help people and initially considered
school teaching; however, this idea faded because he did not like the atmosphere of his school
or the personality of most of the masters. However, in the second year of his sixth form he
finally settled on medicine. An interview was arranged for him with the Dean of the Medical
School in Sheffield, Professor G. A. Clark, who was very encouraging and offered him a place
in his Honours BSc year, assuming that his exam results would be good, as they later were.
He was excused most of first MB and read physiology, anatomy and zoology for the first year,
and was accepted to enrol for an Honours BSc in physiology, in which he received lectures
from Dr H. A. (later Sir Hans) Krebs (FRS 1947) on intermediary metabolism but ‘could find
no account in our books of the cycle he described’! He later concluded that these lectures must
have been the earliest presentations of the citric acid cycle.
At the end of the first term, David had to take several months off for surgical management
of a detached retina, which was the reason why he was not accepted for military service after
his graduation. He enjoyed all the clinical subjects except forensic medicine and gynaecology,
and entered twice for the undergraduate Woodcock Essay Prize. His first attempt, on endotoxins,
met with criticism for lack of original ideas and interpretation, but two years later he
was awarded the prize for an essay on ‘The role of the hypothalamus in the phenomenon of
sleep’. Because of the war, students were spread out thinly and were able to do active clinical
work. David enjoyed casualty and orthopaedics and for a while wanted to do surgery. In his
last year of university, the war was over, Charles H. Stuart-Harris was appointed Professor of
Medicine and David visited him to make some complaints on behalf of his fellow final-year
medical students. David remembered him as very charming. Stuart-Harris was to have a big
influence on David’s career.
In 1948, as a house physician at the Professorial Medical Unit of Sheffield Royal Hospital,
he became interested in internal medicine and, encouraged to do clinical research, undertook
a small project on changes in cerebrospinal fluid pressure after lumbar puncture (1)*. Later,
from 1948 to 1949 as a house physician at the City General Hospital in Sheffield, he was
involved in a systematic clinical and microbiological study of influenza pneumonia in which
he saw and recorded the patients and collected the specimens (3). Thus he became interested
in clinical virology. Later he worked at the infirmary and did some research in organizing a
hypertension clinic with A. W. P. Leishmann, while he studied for and obtained his
* Numbers in this form refer to the bibliography at the end of the text.
membership of the Royal College of Physicians. During this time, during discussions with
Alick Isaacs (FRS 1966), he learned about the basic behaviour of viruses and cells. Alick
would discuss with David what he was doing, and on one occasion he was surprised that David
could interpret the results of an experiment on virus–cell interactions.
There was little chance for David to continue his training in internal medicine because so
many ex-servicemen took priority. He was tempted for a while by general practice and had
been befriended by his family GP, Dr H. N. Skelton of Chapeltown. However, after a discussion
with his clinical tutor, H. R. Vickers, he decided to try to remain in academic work, at
least for a while. He was offered the first Research Registrar post financed by the Hospital
Endowment Fund and, in 1950, began some benchwork in influenza virology accompanied by
a few diabetic clinics each week. In the same year, he married Dr Moyra Wylie, a GP.
He wanted a period of study abroad, so he wrote to A. J. Rhodes in Toronto for a fellowship;
however, he was told that they could not offer a large enough salary for a married man
with a baby ‘to have a pleasant time’. Then, in the spring of 1951, Dr C. H. (later Sir
Christopher) Andrewes FRS passed on to Professor Stuart-Harris a letter he had received from
Frank L. Horsfall Jr, who wanted to appoint an assistant in the Rockefeller Institute and assistant
physician at the Rockefeller Hospital in New York. With the agreement of Moyra, David
applied and was appointed with a smaller salary than had been available in Toronto. David had
done some epidemiology on poliomyelitis (2) in response to a request from a GP in
Lincolnshire, Dr Smallhorn, to Stuart-Harris and presented this work at the second
International Congress on Poliomyelitis in Copenhagen, where he ‘met the virological literature,
eg. Stanley, Enders & Salk, and my new chief, Horsfall’. This work on poliomyelitis was
published in The Lancet and was the first of many such papers by David (2).
THE ROCKEFELLER INSTITUTE, NEW YORK
Within a month of the Copenhagen conference, the family arrived in New York, living in an
apartment across the street from the Rockefeller Institute. He had planned to be there for nine
months but ended up staying for three years. His work was initially directed and supervised
closely by Horsfall, but later he was given much more freedom and, by the end of three years,
he merely kept his boss informed of progress and occasionally asked his advice. David was
taught the need for systematic and rigorous proof and a well-controlled experimental protocol,
and received an excellent training in virology and in research methods. He was surrounded
with eminent and stimulating people, whom he met at lunch and heard talk at the Friday sessions.
Those who made a deep impression and provided an example to follow were Stanford
Moore and William Stein (amino acid chromatography), George Palade (ForMemRS 1984)
and Keith Porter (electron-microscopic structure of cells), René Dubos (biology of infection),
and Robert Shope and Max Theiler (vertebrate viruses). There was little clinical work to do
but he occasionally visited the New York Hospital, which was next door. It was during this
time that he learned to think about the basic nature of the interaction between viruses and cells
and between viruses and inhibitors, and also about the mechanisms of virus interference and
synthetic antiviral chemicals.
During the Korean War, he was formally enrolled in the US Army, but he returned to
Sheffield in the summer of 1954.
VIRUS RESEARCH LABORATORY, UNIVERSITY OF SHEFFIELD
In Sheffield, Stuart-Harris and C. P. Beattie had started a Virus Research Laboratory at
Lodgemoor Hospital, and David began work there, mainly in clinical virology, setting up
many techniques from scratch. He worked with adenoviruses, which had just been discovered
at that time (4); he did one of the first studies in the UK on inactivated poliovirus vaccine (5)
and described an epidemic of a new enterovirus (6, 7). During this time, he had his first experience
of training other scientists and running a small team.
THE MRC COMMON COLD UNIT
During part of his time in Sheffield, he was on the External Scientific Staff of the MRC, and
in 1957 he was casually told by Stuart-Harris that the Secretary of the MRC would like to see
him. Sitting before Sir Harold Himsworth, the ‘dynamic head of the MRC’, David was asked
‘would you like to work at the Common Cold Research Unit’ (CCRU; later shortened to CCU)
to attempt to cultivate ‘the common cold virus’? It is appropriate to mention at this point that
the American Red Cross–Harvard Hospital was brought across the Atlantic in prefabricated
units to Salisbury at the beginning of World War II. After assembly, the hospital opened in
1941 to deal with epidemics of infectious disease that might occur during the war. Thereafter,
in disuse, Christopher Andrewes saw it as being ideal for housing volunteers who could be isolated
from each other and so facilitate work on the common cold. Thus, the CCU was born and
the first volunteers arrived in July 1946. In considering the offer to work there, he felt that he
had been so fortunate that it would do him no harm to struggle with this problem for a few
years. He had two ideas: one was to grow the virus in human kidney cells, which seemed very
susceptible to other viruses, and the other was to use the temperature of the human nose, which
he had once measured in himself and found to be 33 °C. At the CCU (figure 1), arriving on
All Fools Day, 1957, he enjoyed the space and quiet, and quickly adapted to the philosophy
of experimenting on human volunteers. He
planned to make a systematic attempt to find out more about the basic properties of the virus by experiments
in volunteers, to put tested specimens into a variety of cultures, on the assumption that only one combination
of cells and conditions might work, and to do other more quickly moving studies with known viruses to get
results of some sort and to learn about possible methods of virus detection and other cell–virus interactions.
The CCU quickly built up a substantial reputation for common cold research, but its fame
spread even more widely through its use of human volunteers, who came willingly in large
numbers for a 10-day holiday in the Wiltshire countryside, paid for by the CCU, in compensation
for the possibility that they might receive a cold virus intranasally. They were in strict
quarantine and they recorded any symptoms and the number of tissues they required, and so
on. Many used this solitude as an opportunity to study for examinations. Journalists sometimes
came to visit the unit when trials were running, and they sometimes came as volunteers; one
pretended she was a teacher but was exposed on receiving a telephone call from her editor.
One man, who had come to the unit nine times, on one occasion developed a ‘romantic feeling’
for a woman volunteer, an oboist who played with a London orchestra. ‘I had brought my
guitar down with me’, he said, ‘and we played duets at 30 feet while the trial lasted, and closer
at the end.’
'
Figure 1. An aerial view of the Common Cold Unit, Salisbury, Wiltshire.
At first, David was under the direction of Christopher Andrewes, who was then Head of the
Virology Division of the National Institute for Medical Research, but Charles (later Sir
Charles) Harington FRS, the Director of the Institute, said that David was to have a free hand
in planning the experiments. Andrewes came down from London about every two weeks to
discuss progress and David found him very stimulating, Andrewes’s idea of studying viruses
from an ecological or natural history point of view being particularly appealing.
Within a year or so, it was clear that ‘something’ was growing—and so the family sold their
house in Sheffield and moved to Salisbury. Early in 1960, David and his team published their
results showing that rhinoviruses, as they became known (figure 2), could be grown and
detected in tissue cultures (8–10). The notion of ‘the common cold virus’ was dispelled, as
subsequently different types of rhinovirus, more than 100, were discovered. The work
increased in volume and speed, and the group became interested both in basic questions on the
nature of the viruses and also in applied questions such as the possibility of making vaccines,
and studying the mode of spread from person to person.
Andrewes was also very good on taxonomy and international relations, and the unit subsequently
became a WHO Reference Laboratory. Andrewes retired in 1962 and came to live in
the vicinity of the CCU; he would call in to talk and use the library. Alick Isaacs formally
became Head of the Division but was too ill to take an active role, and in due course the Unit
became a Division of NIMR with David as Head.
David Arthur John Tyrrell 357
Figure 2. Electron micrograph of particles of rhinovirus type 9 clumped together by specific antibody. Some particles
are empty; in these the medium has entered the interior, which is normally occupied by nucleic acid.
(Photograph by Barry Dowsett, CAMR.)
David described his work as strenuous but very satisfying, and he particularly enjoyed several
aspects of it. One of these was the number of visiting workers who came through the laboratory,
and another was the development of the local and unofficial scientific society, the South
Wiltshire Virological Society, which grew from a dozen people sitting around a coffee table to
regular meetings with attendances of 60 or more. There were also the increasing contacts with
the Virus Unit of the WHO, Geneva, the development of the Reference Centre system and the
numerous international contacts and occasional working meetings that emerged from all of this
in the 1960s. Through the WHO, he and his team developed a particular relationship with the
laboratory of Dr Robert M. Chanock at the National Institutes of Health (NIH), Bethesda, MD,
USA, and Dr David Taylor-Robinson worked there for some time. There was a mixture of
rivalry and cooperation between the two laboratories as well as good personal relationships,
which kept the work moving forward. David tried to steer the work of the CCU so that his team
did not get into competition with the Chanock laboratory on aspects such as large-scale epidemiology
and serology, for which the Americans had superior resources and organization.
After an enquiry from Sweden to Andrewes, David was put in touch with Bertil Hoorn, an
ear, nose and throat surgeon interested in the function of cilia. Bertil had developed a simplified
form of organ culture, which he later set up at the CCU. This was then used to grow many
of the known respiratory viruses, using human fetal ciliated trachea, and with them he eventually
propagated and recognized a new group of viruses of colds, the coronaviruses (14).
THE MRC CLINICAL RESEARCH CENTRE
During David’s time at the CCU, he had been interviewed by Sir Harold Himsworth, who
enthused him with his concept of a Clinical Research Centre (CRC) to be built in close association
with a district general hospital. David began working at intervals in Birmingham with
a small group under Professor John Squire, the Director Designate, on the planning of the
whole complex, which was to be at Northwick Park in northwest London. He was particularly
involved with the animal house and the infectious disease wards and found it stimulating to
imagine the integration of clinical work and laboratory work and research. In the meantime,
he kept in touch with clinical work mainly by doing a medical out-patient clinic at Salisbury
Hospital.
In 1967, the family moved to London in anticipation of the opening of the CRC and at a
convenient time to move schools. He was made a consultant physician and looked after infectious
disease beds at Neasden Hospital, although he still managed to spend about two days a
week in Salisbury. He turned his attention to the problem of acute diarrhoea in infants and
adults, in which the bacteriology of the day could not explain most cases. He took over the
adult side of a small infectious disease unit at West Hendon Hospital and noticed the frequency
of gastroenteritis as a cause of admission and how often it was not possible to find causative
bacteria. In the laboratory, using intestinal specimens, he tried to grow viruses from them in
organ cultures of intestinal epithelium, although by then others had detected the rotaviruses
and other viruses.
The untimely death of John Squire in 1966 was followed by the appointment of Graham
Bull, who patiently and carefully supervised the planning of one division after another, and
generated an atmosphere of amiability and goodwill. Graham was especially good at managing
the complex relationships between the hospital staff and the CRC. David was made
Deputy Director, ‘which entailed little extra work’. For the first few years at the CRC, from
1970, there were many teething problems, laboratory work was difficult and there was no
infectious disease service. However, there was steady progress, and the development of work
on infectious diseases was such that it merited and attained divisional status as the Division of
Communicable Diseases. Apart from David, this comprised David Taylor-Robinson and Ten
Feizi. David Taylor-Robinson worked first with rhinoviruses and other respiratory viruses at
Salisbury (11–13); later he worked with mycoplasmas, in which field he achieved international
recognition, building up a group working on sexually transmitted diseases (which later
became the Division of Sexually Transmitted Diseases). Ten Feizi, who had collaborated with
Taylor-Robinson at Salisbury, came back from the Rockefeller Institute to set up an immunochemical
group, particularly to study Ii antigens.
During this time there was much collaborative work between Divisions in the CRC and
with physicians in the district general hospital at Northwick Park. Indeed, the philosophy
behind the existence of the CRC was that emphasis should be on the study of common diseases.
David, of course, was no stranger to this, having studied in Salisbury perhaps the most
common of common diseases. Thus, studies on gastrointestinal and respiratory infections in
children, as well as those on febrile convulsions, encephalitis and schizophrenia, were set up.
The possibility of a viral cause of schizophrenia, suggested by both David and Tim Crowe,
was intriguing and supported by the fact that specimens of cerebrospinal fluid from patients
with the disease produced changes in cell cultures, whereas those from other patients did not
(15, 16). However, despite considerable effort a virus could not be found, in sharp contrast to
the success in Salisbury and in other projects. Also, during this time, David gave quite a lot of
time to the virus diagnostic laboratory and directed, in a general way, the work of A. S. Beare
and S. E. Reed, who had remained at Salisbury.
While at the CRC, he made regular visits to scientific meetings abroad, in the USA, South
Africa and Australia. He built up a regular relationship and personal friendship with Robert
Chanock and A. Z. Kapikian at the NIH, and retained a friendship with Igor Tamm, with
whom he had worked at the Rockefeller Institute. David always valued the occasional updating
and strategic discussions he had with Tamm when he passed through New York. He
attended WHO meetings as a Director of a Reference Laboratory and as an occasional consultant.
He wrote about the WHO:
I always felt that I received more than I gave, though I was often unhappy that we were doing little to further
the health of the world as a whole. However, such international collaboration facilitated the work of establishing
rhinovirus serotypes and reagents for them.
The impending closure of the CRC, regarded by many as a political decision by the MRC
rather than a sound scientific one, was a major reason for David’s return full time to the CCU
in 1985. The closure of the CCU a few years later on David’s retirement, largely as a result of
financial constraints, came at a time when good work was still being undertaken, particularly
on antiviral drugs. He held the view that both decisions were not in the interests of scientific
progress, but he nevertheless recognized that the MRC had given him unrivalled opportunities
for research. He once said, ‘people say that place never found the cold cure, did it?’ Of course,
the enlightened realized that the finding of a plethora of different responsible viruses made the
possibility of an effective vaccine more or less hopeless. It is safe to say that as far as he was
concerned there could be no self-recrimination, and right to the end of his time at the CCU,
David made significant discoveries that were to change and inform the course of future
research in various areas.
With Mary Anderson and John Pattison from University College London, in 1985, David
led the seminal studies of experimental parvovirus B19 infection in human volunteers at the
CCU (17, 18). Healthy adult volunteers were inoculated intranasally with human parvovirus
obtained from an asymptomatic blood donor. One week after inoculation, intense viraemia
was observed in seronegative volunteers; this was accompanied by a flu-like illness. In the following
week volunteers suffered reticulocytopenia with an associated slight drop in haemoglobin
concentration, lymphopenia, neutropenia, and a drop in platelet count. Rash and
arthralgia occurred 17–18 days after inoculation, coincident with the appearance of specific
IgG, suggesting that these symptoms were mediated by an immunological mechanism. This
study confirmed the aetiological role of human parvovirus B19 in erythematous rash illness
and in the temporary arrest of erythropoiesis that leads to aplastic crisis in persons with
chronic haemolytic anaemia.
At the CCU, he studied the effect of psychological stress on the incidence of symptoms during
experimental infections of human volunteers with cold virus. After completing questionnaires
assessing degrees of psychological stress, 394 healthy subjects were given nasal drops
containing one of five respiratory viruses (rhinovirus type 2, 9 or 14, respiratory syncytial
virus, or coronavirus type 229E), and an additional 26 were given saline nasal drops. The subjects
were then quarantined and monitored for the development of evidence of infection and
symptoms. The rates of both respiratory infection and clinical colds increased in a
dose–response manner with increases in the degree of psychological stress. These effects were
not altered after taking into account a range of factors that could diminish their significance.
Moreover, the associations observed were similar for all five challenge viruses, and several
potential stress–illness mediators, such as smoking or alcohol consumption, did not explain
the association between stress and illness (19). This work has subsequently been reproduced
by Sheldon Cohen and colleagues at Carnegie Mellon University, Pittsburgh, PA, USA.
Psychological stress is now known to alter the effectiveness of the immune response markedly,
but the precise mechanisms involved have yet to be elucidated.
David’s many achievements were recognized by the award of a CBE in 1980, honorary
degrees from the universities of Sheffield in 1979 and Southampton in 1990, the Stewart Prize
by the British Medical Association in 1977, the Ambuj Nath Bose prize in 1983, and the
Conway Evans Prize of the Royal College of Pathologists in 1986.
PORTON DOWN
After his retirement, David moved to the Centre for Applied Microbiology and Research
(CAMR), Porton Down, where he had an office in which to research and prepare the writing
of his book, Cold wars (25). This is his scientific autobiography and provides a detailed history
of the CCU and the research on the common cold. One reviewer stated (Treanor 2004):
The book is written in a friendly, conversational tone, and one could imagine that this is the story one might
have heard from Dr. Tyrrell himself during, say, a long train ride. There is a wealth of anecdote here that one
could never find elsewhere, and anyone with more than a passing interest in the common cold would be well
advised to spend an afternoon in front of the fireplace with this book and a warm drink. I know I did that, and
I was glad afterward.
Also at this time, David took part in several research projects on infections with respiratory
viruses and their influence on bronchial reactivity and the presentation of asthma (21, 22), on
bovine spongiform encephalopathy (BSE) (20), and on respiratory syncytial virus (RSV) vaccine.
THE CFS RESEARCH FOUNDATION
While he was at Northwick Park he had a few patients who apparently had infectious illnesses
that were then followed by what seemed to be chronic fatigue syndrome (CFS). He was familiar
with the dogma that this condition was psychogenic in origin, but in some of his patients
this seemed not to be true. He was asked by Dr R. Sykes, Director of the charity Westcare,
which provided counselling for CFS patients, to participate in a National Task Force to review
the evidence that CFS was a real disease. David chaired the Task Force, which produced a
report, published by Westcare. This presented the case that CFS is a significant health problem
and reviewed the possible causes and disease processes. Following this, the Royal Colleges
produced reports that agreed that CFS is a significant health problem with no radical treatment:
they emphasized the psychiatric approach and proposed that there should be studies of various
management approaches such as cognitive behavioural therapy. The Department of Health and
an MRC report took the same view and were against research on biological factors.
David was not happy with these opinions and recalled his experience with Sudden Infant
Death Syndrome. He had been on the first Research Committee of the Foundation for the
Study of Infant Deaths (FSID). At the time this was a mysterious condition, often regarded as
child murder (or overlaying) with a possible viral cause and other contributing factors. David
and his colleagues had been told at an informal meeting of the MRC that the MRC ‘does not
work on non-existent diseases’. He remembered that the FSID had, despite being a small charity,
supported research on aetiology and environmental factors that was later confirmed by
larger charities and nationwide studies, followed by national campaigns to increase awareness
about the harmful effects of maternal smoking and overlaying, among others, which markedly
decreased the incidence of sudden infant deaths.
At about this time, in 1992, the medical charity the Chronic Fatigue Syndrome Research
Foundation (CFSRF) was registered; it was launched in the following year. David was invited
by its Honorary Director, Mr Hugh Faulkner, to join the Research Committee, and he was glad
to be a part of this small charity because of its commitment to the specific purpose of supporting
high-quality basic research into the pathogenesis of CFS. In 1998, he was appointed
Vice-Chairman and in 2001 he was made Trustee and Chairman of the Research Committee.
He was involved in all aspects of the Foundation’s business: fundraising, management, chairing
the research committee, and even with the research when required.
He was particularly involved in two studies, both also involving Jonathan Kerr. The first
showed that parvovirus B19 had a role in the pathogenesis of CFS in that it could trigger the
development of CFS in some subjects, and that B19-associated CFS was indistinguishable from
idiopathic CFS and was associated with raised levels of interferon- and tumour necrosis factor-
(23, 24). The second study concerned the molecular pathogenesis of CFS, in which David
was instrumental in setting up collaborative work. This began with a simple pilot study with
microarrays, identifying 16 genes that were at significantly different levels in CFS subjects
from those in normal controls (26). When David received news of the confirmation of these 16
genes by polymerase chain reaction technology, he said that he celebrated by mowing the lawn
while singing ‘Praise, my soul, the King of Heaven’! While he was still Chairman of the
Research Committee, a larger study was approved for funding, led by Jonathan Kerr at St
George’s University of London. This confirmed the involvement of 15 of the original 16 genes,
and found a total of 89 genes that were differentially expressed in CFS, including the original
16. The top functions of these genes include immunity, infection, cancer, neurological disease
and apoptosis, processes that have been documented previously in patients with CFS and present
several opportunities for experimental therapy (J. R. Kerr, R. Petty, B. Burke, J. Gough, D.
Fear, L. I. Sinclair, D. L. Mattey, J. Montgomery, S. C. M. Richards, D. A. Baldwin, P. Kellam,
T. J. Harrison, G. E. Griffin, D. Emlander, D. J. Nutt and S. T. Holgate, unpublished work).
However, shortly after the approval of this study, David died on 2 May 2005 of a complication
of a terminal illness. Two weeks before, he had met to discuss research progress, and
on the morning of the day he died he had discussed by telephone the future of the CFSRF.
ACKNOWLEDGEMENTS
We thank the various people who have given advice and information in preparing this memoir. These include Anne
Faulkner (Honorary Director, CFS Research Foundation), Peter Hammond (Site Historian, Centre for Applied
Microbiology and Research (CAMR)), Barry Dowsett (Centre for Applied Microbiology and Research (CAMR)), and
David’s surviving daughters Frances and Sue.
The frontispiece photograph was taken in 1978 by Godfrey Argent, and is reproduced with permission.
REFERENCE TO OTHER AUTHOR
Treanor, J. J. 2004 Cold wars. N. Engl. J. Med. 350, 522.
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