Ferrets, fever and flu
It’s 80 years today since the identification of the flu virus by researchers at the MRC National Institute for Medical Research was published in The Lancet. John McCauley, Director of the World Health Organization Influenza Centre based at NIMR, looks back on the discovery, how it led to the vaccination programmes we see today, and the role played by ferrets.
The devastating flu pandemic of 1918 killed more than 50 million people worldwide, highlighting the urgent need for research into the disease. But it was not until 1933 that scientists at the MRC NIMR (then based at Hampstead) identified and managed to grow the virus in the lab.
It was during a large flu epidemic in the winter of 1932 to 1933 that scientists at the NIMR’s animal research outpost at Mill Hill noticed that ferrets, being used to develop a vaccine against the disease canine distemper, were suffering from the same symptoms as people with flu.
This prompted the research team of Wilson Smith, Christopher Andrewes and Patrick Laidlaw to inoculate the ferrets with washings from the nose and throat of one of the team who had succumbed to flu. The ferrets went on to develop a fever.
The team determined that the infectious agent was a virus because it was small enough to pass through specially designed membranes, was transmissible between ferrets, and was neutralised by the sera of people who had recovered from flu (serum is the protein-rich part of blood which contains antibodies).
This discovery in 1933 led to a diverse programme of flu research at the institute, and on viruses in general (see timeline).
The first flu vaccines were licensed by the mid-1940s, after experimental vaccines were developed at NIMR. Researchers had noticed in the 1930s that flu viruses vary in their external proteins (which are recognised by the immune system) but it was not until after the Second World War, when vaccination during the 1947 flu epidemic failed, that researchers recognised the importance of this variation.
As a result an initiative was proposed to monitor the variation in flu viruses worldwide and the World Health Organization (WHO) asked Christopher Andrewes to establish the World Influenza Centre to collaborate with influenza centres around the world to monitor flu strains and recommend which viruses should be included in the vaccine.
The network has since developed into the WHO Global Influenza Surveillance and Response System, which is currently made up of 140 National Influenza Centres in 110 WHO member states and six WHO Collaborating Centres for Influenza. Together the centres carry out detailed analysis of flu viruses to detect emerging flu variants to which populations won’t be immune and so warrant an update to the influenza vaccine. They also monitor the emergence of viruses that can’t be treated with antiviral medicines such as Tamiflu, and assess the risk of humans becoming infected with emerging flu viruses from animals that could become pandemic.
Despite the advances that have occurred in molecular biology, many of these studies still use ferrets. We use sera from ferrets which have recovered from flu to monitor the protein variation of circulating and emerging flu viruses, and the ferret is used as the gold-standard animal in experiments to understand not only the ability of emerging strains to cause disease and how lethal they are, but also the potential for strains to be transmissible between infected and susceptible humans.
See below for a timeline of events in flu research at the MRC NIMR since the first isolation of the virus.