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Covid-19: First coronavirus was described in The BMJ in 1965

BMJ 2020; 369 doi: https://doi.org/10.1136/bmj.m1547 (Published 16 April 2020) Cite this as: BMJ 2020;369:m1547

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The history of coronaviruses since 1931

Dear Editor

It is certainly a great tribute to the memory of Hugh Clegg, quondam editor of the British Medical Journal, as it was then known, to record that he recognized the value of high-quality basic science with clinical relevance, when he published a paper by the virologist David Tyrrell, the then Director of the Medical Research Council's Common Cold Research Unit at Harnham Down near Salisbury in Wiltshire, and his colleague Mark Bynoe on 5 June 1965 [1], in which they described B814, later recognized as one of the group of viruses that we now call coronaviruses, and identified it as a cause of the common cold.

However, the history of these viruses goes back to at least the 1930s.

Avian infectious bronchitis in newborn chicks, an infection distinct from laryngotracheitis, was first described in 1931 by Schalk & Hawn [2] and by Bushnell & Brandly in 1933 [3]; both were quoted by Beach & Schalm, 1936 [4], who confirmed that it was due to a filterable virus and identified two strains, with cross-immunity. The virus was cultivated in 1937 by Fred Beaudette and Charles Hudson, from the New Jersey Agricultural Experiment Station [5] (cited by Marks [6]), and later by Cunningham & Stuart in 1947 [7].

In 1951 Gledhill & Andrewes isolated a hepatitis virus from mice [8], now also known to be a coronavirus.

In their 1965 paper [1], David Tyrrell and Mark Bynoe not only described B814 but also tried to characterize other viruses responsible for the common cold, although without much success, and thought that they were rhinoviruses.

On 1 April 1967 Tyrell, this time with his colleague June Almeida, from the Department of Medical Microbiology in London’s St Thomas's Hospital Medical School, identified three uncharacterized respiratory viruses, of which two had not previously been associated with human diseases [9]. They reported that two of the viruses, 229E and B814, of which they published electron micrographs, were indistinguishable from the particles of avian infectious bronchitis.

Then Almeida and Tyrell, with six other colleagues, described a group of viruses that caused not only avian bronchitis but also murine hepatitis and upper respiratory tract diseases in humans. Their findings were noted in Nature, whose Editor at the time was John Maddox, under the general heading “News and Views” [10]. This is the first recorded instance of the term “coronaviruses”.

The virus of avian infectious bronchitis is now classified as a gammacoronavirus, while most of the coronaviruses that infect humans are betacoronaviruses. The human coronavirus HCoV-229E that Almeida and Tyrrell described on 1 April 1967 is an alphacoronavirus. The viruses that they described were the first coronaviruses to be identified as ones that infect humans, as Elisabeth Mahase says in her first sentence. However, the headline to her article is inaccurate; other coronaviruses had been observed before.

References
1. Tyrrell DA, Bynoe ML. Cultivation of a novel type of common-cold virus in organ cultures. Br Med J 1965; 1(5448): 1467-70.
2. Schalk AF, Hawn MC. An apparently new respiratory disease of baby chicks. J Am Vet Med Assoc 1931; 78: 413-23.
3. Bushnell LD, Brandly CA. Laryngotracheitis in chicks. Poultry Science 1933; 12(1): 55-60.
4. Beach JR, Schalm OW. A filterable virus, distinct from that of laryngotracheitis, the cause of a respiratory disease of chicks. Poultry Sci 1936; 15(3): 199-206.
5. Beaudette FR, Hudson CB. Cultivation of the virus of infectious bronchitis. J Am Vet Med Assoc 1937; 90: 51–8.
6. Marks L. The history of Covid-19 within context of coronaviruses. https://www.whatisbiotechnology.org/index.php/covid/index/covid-19_history. (Accessed 6 May 2020).
7. Cunningham CH, Stuart HO. Cultivation of the virus of infectious bronchitis of chickens in embryonated chicken eggs. Am J Vet Res 1947; 8(27): 209-12.
8. Gledhill AW, Andrewes CH. A hepatitis virus of mice. Br J Exp Pathol 1951; 32(6): 559-68.
9. Almeida JD, Tyrrell DA. The morphology of three previously uncharacterized human respiratory viruses that grow in organ culture. J Gen Virol 1967; 1(2): 175-8.
10. Almeida JD, Berry DM, Cunningham CH, Hamre D, Hofstad MS, Mallucci L, McIntosh K, Tyrrell DAJ. Virology: Coronaviruses. Nature 1968; 220(5168): 650.

Competing interests: No competing interests

19 July 2020
Jeffrey K Aronson
Consultant Physician and Clinical Pharmacologist
Centre for Evidence Based Medicine, University of Oxford
Nuffield Department of Primary Care Health Sciences, Radcliffe Observatory Quarter, Woodstock Road, Oxford OX2 6GG