The history of coronaviruses is an account of the discovery of the diseases caused by coronaviruses and the diseases they cause. It starts with the first report of a new type of upper-respiratory tract disease among chickens in the U.S. state of North Dakota, in 1931. The causative agent was identified as a virus in 1933. By 1936, the disease and the virus were recognised as unique from other viral disease. They became known as infectious bronchitis virus (IBV), but later officially renamed as Avian coronavirus.
A new brain disease of mice (murine encephalomyelitis) was discovered in 1947 at Harvard Medical School in Boston. The virus causing the disease was called JHM (after Harvard pathologist John Howard Mueller). Three years later a new mouse hepatitis was reported from the National Institute for Medical Research in London. The causative virus was identified as mouse hepatitis virus (MHV), later renamed Murine coronavirus.
In 1961, a virus was obtained from a school boy in Epsom, England, who was suffering from common cold. The sample designated B814 was confirmed as novel virus in 1965. New common cold viruses (assigned 229E) collected from medical students at the University of Chicago were also reported in 1966. Structural analyses of IBV, MHV, B814 and 229E using transmission electron microscopy revealed that they all belong to the same group of viruses. Making a crucial comparison in 1967, June Almeida and David Tyrrell invented the collective name coronavirus, as all those viruses were characterised by solar corona-like projections (called spikes) on their surfaces.
Other coronaviruses have been discovered from pigs, dogs, cats, rodents, cows, horses, camels, Beluga whales, birds and bats. As of 2022, 52 species are described. Bats are found to be the richest source of different species of coronaviruses. All coronaviruses originated from a common ancestor about 293 million years ago. Zoonotic species such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV), Middle East respiratory syndrome-related coronavirus (MERS-CoV) and Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), a variant of SARS-CoV, emerged during the past two decades and caused the first pandemics of the 21st century.
Discovery of chicken coronavirus
Arthur Frederick Schalk and Merle C. Fawn at the North Dakota Agricultural College were the first to report what was later identified as coronavirus disease in chickens. Their publication in the Journal of the American Veterinary Medical Association in 1931 indicates that there was a new respiratory disease that mostly affected 2-day-old to 3-week-old chickens. They referred to the disease as "an apparently new respiratory disease of baby chicks." The symptoms included severe shortness of breath and physical weakness. The infection was contagious and virulent, easily transmitted through direct contact between chickens or experimental transfer of the bronchial exudates from infected to healthy chickens. The maximum mortality recorded was 90%.
The causative pathogen could not be identified. Charles D. Hudson and Fred Robert Beaudette at the New Jersey Agricultural Experiment Station in New Brunswick, New Jersey, put forth a hypothesis in 1932 that virus could be the cause and introduced the name as "virus of the infectious bronchitis." But this was a misattribution because at the time another related disease, known as infectious laryngotracheitis, was reported that exhibited almost similar symptoms but mostly affected adult chickens. As Beaudette later recalled in 1937, the disease he described was infectious layngotracheitis, saying: "Infectious laryngotracheitis is said to be the correct name for this disease rather than infectious bronchitis… Moreover, the gasping symptom ordinarily accepted as typical of the disease is also a prominent symptom in infectious bronchitis (gasping disease, chick bronchitis)." The names infectious bronchitis and infectious laryngotracheitis were till then used synonymously and interchangeably.
Unaware of the developments, Leland David Bushnell and Carl Alfred Brandly at the Kansas Agricultural Experiment Station studied a similar case which they called "gasping disease" due to the apparent symptom. They had known the disease since 1928. Their report in 1933 titled "Laryngotracheitis in chicks" published in the Poultry Science indicated a clear distinction of infectious bronchitis from infectious laryngotracheitis (cause by a herpes virus) as the main organ affected was the bronchi. The bronchi infection resulted in severe gasping and swift death due to inability to eat food. It was also found that the pathogens could not be bacteria or protozoans as they passed through membranes (Berkefield filter) that would block those pathogens. The isolation and identification of the pathogen as a virus was reported as:
In several experiments we have reproduced the disease in chicks by the intratracheal, subcutaneous and intraperitoneal injection of Berkefeld filtered material. The chicks developed typical gasping symptoms after various periods of incubation, different groups of chicks first showing symptoms in six, seventeen, nineteen, etc., days after receiving the filtrate... The disease may also be transferred by means of filtrates of spleen, liver, and kidney tissues and by the transfer of bacteriologically sterile blood.
This was the discovery of infectious bronchitis virus (IBV), the first coronavirus. But Bushnell and Brandy made an erroneous remark by saying, "The symptoms and lesions in the chicks [caused by IBV] are similar to those seen in so-called laryngotracheitis of adult birds and are probably due to the same agent."
In 1936, Jerry Raymond Beach and Oscar William Schalm at the University of California, Berkeley, reexamined Bushnell and Brady's experiment with a conclusion that infectious laryngotracheitis and infectious bronchitis with their causative viruses were different. (In 1931, Beach had discovered the virus of infectious laryngotracheitis, now called Gallid alphaherpesvirus 1.) They concluded that:
It was found that chickens that recovered from an infection with one of the two strains of virus were refractory to further infection with either strain. It was also found that the sera from chickens that have recovered from an infection with one strain of the virus would neutralize virus of either strain. These results show the identity of the two strains of virus. Chickens refractory to infection with this virus were shown to be susceptible to the virus of laryngotracheitis. Likewise, chickens refractory to the latter virus were susceptible to the former. These results demonstrate that the two viruses are distinct from one another.Hudson and Beaudette later in 1937 were able to culture IBV for the first time using chicken embryos. This specimen, known as the Beaudette strain, became the first coronavirus to have its genome completely sequenced in 1987.
Discovery of mouse coronaviruses In 1949, Francis Sargent Cheever, Joan B. Daniels, Alwin Max Pappenheimer Jr., and Orville T. Bailey investigated the case of brain disease (murine encephalitis) at the Department of Bacteriology and Immunology of Harvard Medical School in Boston. Two laboratory mice (Schwenktker strains) of 17 and 18 days old had flaccid paralysis and died. It was generally believed that the mice had murine encephalitis. By then it was known that murine encephalitis was caused by a picornavirus, called Theiler's virus, which was discovered by Max Theiler at the Rockefeller Foundation in New York in 1937. However, the Harvard scientists found that the two mice had unusual symptoms other than brain damage (demyelination). The mice had no visible illness or diarrhoea, which usually are associated with murine encephalitis. In addition, the causative virus was isolated from different organs including liver, spleen, lungs, and kidneys. This indicated that brain was not the primary target organ. Liver was particularly affected with severe tissue damage (necrosis), indicating hepatitis. The new virus was named JHM, after the initials of John Howard Mueller, a pioneer microbiologist at Harvard.
In the autumn of 1950 there was a sudden outbreak of fatal hepatitis among laboratory mice (Parkes or P strains) at the National Institute for Medical Research, Mill Hill, London. Alan Watson Gledhill and Christopher Howard Andrewes isolated the causative virus, which experimentally was highly infectious to healthy mice. They named the virus as "mouse hepatitis virus (MHV)." Gledhill called the experiments on the highly infectious nature of the virus as a "bizarre discovery".
In 1959, John A. Morris at the National Institutes of Health, Bethesda, discovered a new mouse virus, which he named H747, from samples in Japan. When he compared the virus with JHM and MHV using serological tests, he found that they were both antigenically related, for which he created a common name "hepatoencephalitis group of murine viruses." In 1961, Robert A. Manaker and his team at the National Cancer Institute, Bethesda, reported the discovery of a new virus (designated as MHV-A59) from murine leukemia virus-infected mice, remarking that it was a member of the hepatoencephalitis group. The virus primary cause fatal hepatitis and encephalitis. Pneumonia-causing rat coronavirus (RCV) discovered in 1970, and sialodacryoadenitis virus (SDAV), which infects nasal cavities, lungs, salivary glands and the Harderian gland in rats, discovered in 1972 were found to be the same kind of hepatoencephalitis viruses.
Discovery of human coronaviruses Human coronaviruses were discovered as one of the many causative viruses of common cold. Research on the study of common cold originated when the British Medical Research Council and the Ministry of Health established the Common Cold Research Unit (CCRU) at Salisbury in 1946. Directed by Andrewes, the research laboratory discovered several viruses such as influenza viruses, parainfluenza viruses and rhinoviruses that cause common cold.
David Arthur John Tyrrell joined CCRU in 1957 and succeeded Andrewes in 1962. He developed a technique for growing rhinoviruses using nasal epithelial cells for the first time in 1960. Based on the technique, his team soon after formulated a concept of broad categorisation of common cold viruses into two groups: one group, called H strain, could be maintained only in human-embryo-kidney cell culture, and another group, designated M strain, could be maintained both in human-embryo-kidney cell culture and monkey-embryo-kidney cell culture. By then many common cold viruses could be grown in either of these cell cultures and were accordingly classified as M or H strain.
During 1960–1961, Tyrrell's team collected throat swabs from 170 school boys having common cold at a boarding school in Epsom, Surrey. England. Among few samples that could not be cultured in any of the culture media, a specimen designated B814, collected on 17 February 1961, was particularly infectious among healthy volunteers. There was no evidence whether the pathogen in B814 was a bacterium or a virus as all bacterial and viral culture methods available showed negative results. In the early 1965, while visiting the University of Lund in Sweden to receive an honorary doctorate, Andrewes learned of Bertil Hoorn who had developed a culture method for viruses using human trachea tissue. Hoorn had successfully cultured influenza viruses. After learning about these developments from Andrewes, Tyrrell invited Hoorn to visit CCRU. Using the new culture method, they were able to grow many viruses which could not be maintained in other culture methods.