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1936

In countless laboratories around the world today, scientists are working with chicken eggs to research flu viruses using a technique pioneered by Sir Frank Macfarlane Burnet almost 70 years ago.

In countless laboratories around the world today, scientists are working with chicken eggs to research flu viruses using a technique pioneered by Sir Frank Macfarlane Burnet almost 70 years ago.

The technique, Burnet’s first major contribution to the field of virology, paved the way to mass-produce vaccine.

Burnet’s technique, improved but fundamentally the same, has allowed easier, cheaper and higher volume production of flu virus vaccine globally and remains the gold standard for this.

First attempts

Burnet first attempts to grow animal viruses in fertile hen’s eggs at the National Institute for Medical Research at Hampstead, London, where he is on leave from the Walter and Eliza Hall Institute on a two-year fellowship in 1932-3.

He uses a method developed by American scientist Ernest Goodpasture who had grown fowl pox and other viruses on the chorioallantoic (CAM) membrane of chick embryos. Burnet’s wife Linda has a favourite story of how Burnet borrowed an egg from her larder and a nail file one day to have a go at exposing the membrane – before enlisting the help of a dentist with a dental drill.

Improving infection growth

Once back at the Walter and Eliza Hall Institute in 1934, Burnet improved on the CAM method, ‘dropping’ the membrane to create an air space between it and the shell. The exposed membrane could then be inoculated with virus and the opening of the shell covered. The viruses produce a small white pock or clone of infected cells. Pocks could then be counted or ‘titrated’, allowing a valuable new way of measuring virus activity. It was cheap, robust and required little attention.

Burnet, who takes great pride in his expert handling of eggs, writes a monograph on the technique, published by the Medical Research Council of Great Britain in 1936. The Journal of the American Medical Association the following year accurately predicts that the method could have ‘great future importance’ in research work and, practically, in prevention and treatment.

Great future importance

At the time, the Walter and Eliza Hall Institute has the only virus research unit in Australia and a headstart on laboratories overseas in using the technique. To Burnet, “The world was our oyster.”

By 1940, Burnet can claim that the Walter and Eliza Hall Institute researchers have cultured more than 10 viruses for the first time (allowing for two viruses that had their preliminary tests at Hampstead) . These include several viruses that attacked animals, including myxomatosis, three strains of influenza and herpes simplex.

Drawing on the discovery by George Hirst in America in 1941 that the flu virus agglutinated – or clumped – chicken red blood cells, institute researchers find that large quantities of virus could be grown in, and easily collected from the allantoic fluid surrounding the chick embryo. Growing the virus allantoically later helps antigen studies and research into immunity.

Making flu viruses

Burnet’s technique, improved but fundamentally the same, has allowed easier, cheaper and higher volume production of viruses globally and remains the gold standard for the production of flu viruses.

Around 90 per cent of influenza vaccines are made using egg-based technology.

Melbourne-based biotechnology company CSL manufactures season flu vaccine in Australia. CSL sources more than one million eggs every week.

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