22 Jun 2020
Common colds and the hopefully uncommon Covid-19
Written by Nobel Laureate Professor Peter Doherty
The advertisement reads: “How would you like a cheap and comfortable holiday, everything free and no expense, and even 35p a day pocket money?” The munificent 35p dates it back to the 1946 beginnings of Britain’s Common Cold Unit (CCU). Set up as a branch of the National Institute of Medical Research, Mill Hill, London, the CCU was located in the long, single-storey army huts of the former Harvard Hospital located at Harnham Down near Salisbury, Wiltshire. Volunteers were told they had a one-in-three chance of catching a cold, which was spot on because one third of them had material thought to contain a virus that causes colds blown up their nose.
The idea was to identify the virus, or viruses, that cause the common cold so that preventive vaccines could be made. By the time the CCU closed in 1989, they knew that a vaccine strategy was impossible because colds can be caused by too many different viruses. But it was fun while it lasted! Two or three volunteers were housed together but subjected to strict social distancing from other groups. Apart from taking temperatures, swabs and blood samples for laboratory analysis, the basic measurement of disease severity was the single-use, paper handkerchief. Additional to recording the numbers used by each individual, these had to be spread out flat by the test subject so that the researcher could assess the quality and quantity of snot.
At least in the early days of post World War 2 Britain, times were tough and food was rationed. The 20,000 or so volunteers (often vacationing university students) who participated over the decades were well fed, provided with a radio (later a TV) and plenty of reading material. They could use the telephone and go for rural walks, but not to the local town. Requirements could include, for example, spending time outside in a deck chair and/or, being damped down a bit on a cold and windy day, or with a fan blowing to simulate sitting in a draft.
Rhinoviruses are the ‘usual suspects’ (30-80 per cent) for the 200 or so of common cold viruses, with the common cold coronaviruses (CoVs) being responsible for say 15 per cent and maybe five per cent caused by adenoviruses (Ads). The years the CCU operated spanned the era that saw virus isolation and growth in cultured mammalian cell lines emerge as a primary research and diagnostic tool. This began in 1941 when Harvard University medical researchers John Enders, Tom Weller and Fred Robbins successfully grew poliomyelitis virus in cultured human muscle cells, an achievement that was recognised by the 1954 Nobel Prize for Physiology or Medicine. With the availability (post World War 2) of antibiotics to limit bacterial contamination, tissue culture became a lot easier and a number of ‘immortalised’ cell lines were passaged indefinitely in glass, then plastic vessels. The SARS-CoV-2 virus replicates optimally in (and kills) monolayers of VERO cells which, in 1962, were grown-out from the kidney of an African Green Monkey.
That same year (1962), Medical Doctor and respiratory infection specialist David Tyrell became Director of the CCU. In 1965, Tyrrell and Bynoe isolated the first human CoV and, in 1967, St Thomas’ Hospital Medical School electron microscopist, June Almeida, took the first photographs that showed the characteristic corona (crown) of ‘spike’ proteins. Almeida had earlier seen similar structures in samples of avian infectious bronchitis virus and mouse hepatitis virus, so they named this new group the coronaviruses. The common cold adenoviruses were also isolated in the 1950s and 1960s, with much of that work being done at the US National Institutes of Health in Bethesda, Maryland. But, though the first rhinovirus was cultured in 1956 by Dr Winston Price at Johns Hopkins University, Baltimore, they proved notoriously difficult to grow.
The CCU group had been studying the rhinoviruses by infecting humans, and even chimpanzees, but that was clearly very limiting when it came to serious research. Then, reasoning that the temperature of the nose could be colder, especially in winter, they started growing their cell cultures at 33oC rather than 37oC. That worked and, by also tweaking the conditions a bit to use slightly acidic growth medium and bottles that turn on a mechanical roller to allow the attached cells to be alternately immersed and exposed, they got to be very good at growing rhinoviruses. Good cooks and gardeners often have ‘green hands’ in the lab!
Testing extensively in Victoria prior to switching to contact tracing from known cases, 0.2 per cent or less of those who came in with respiratory symptoms were positive for SARS-CoV-2. Apart from flu, most were likely infected with one or other of the common cold viruses. Still, as we try to establish whether COVID-19 remains active in the community, the more people who have cold or flu-like symptoms that are checked out, the better. So get yourself tested if you are sneezing or coughing. And, if you’re not showing any respiratory signs but suddenly lose your sense of smell, behave as though you have COVID-19 and don’t risk passing it to others. Surprised that you can’t smell Stilton cheese or the bouquet of a good Shiraz? Make being tested your top priority!