Denis Burkitt
Epstein-Barr virus (EBV) causes glandular fever, or the ‘kissing disease’. However, it was also the first virus to be implicated in a human cancer. Our awareness of EBV was triggered some fifty years ago, when Scottish surgeon, Denis Burkitt (1911-1993), then working at Mulago Hospital in Kampala, Uganda examined a five-year-old boy who had four large jaw tumours. Some weeks later, at another hospital, he saw a young girl whose mouth had similar tumours.
Burkitt’s Lymphoma
In 1958 he reported that the jaw tumours affected children between the ages of two and fourteen years, with a peak incidence occurring at five years. His next step was to take a ‘geographical biopsy’, and in 1961 Burkitt, accompanied by two medical missionaries, set off to gather more data by undertaking a 10,000-mile tour of East Africa. What became known as Burkitt’s lymphoma (BL) was found to occur in a band across tropical Africa, tailing partly down the east coast, and showing a similar distribution to holoendemic malaria.
Epstein and Barr
However, before setting off on his ‘long safari’, Burkitt had given a lecture in London on 22 March 1961. It was entitled: ‘The Commonest Children’s Cancer in Tropical Africa — a hitherto unrecognised syndrome’. Dr Anthony Epstein of the Middlesex Hospital was in the audience and suspected that BL had a viral association. He arranged with Burkitt for samples to be sent from Africa to his London laboratory.
Tumour material
The tumour lumps were transported in a sterile liquid culture medium, and on arrival, Epstein and co-workers attempted virus detection by inoculating the tumour material into newborn mice, embryonated hen eggs and a range of cell culture systems. However, for two years Epstein and his research assistant, Yvonne Barr, not only failed to detect a virus, but also failed to stimulate the tumour cells to grow.
Breakthrough
But in 1964 EBV was discovered by a chance breakthrough. When a tumour sample that had been delayed en route from Africa was delivered to the laboratory, its culture medium was cloudy, suggesting bacterial contamination. But when Epstein examined it under a light microscope, he found tumour cells, not bacteria, growing in what was effectively a suspension culture. And when Epstein examined the material by electron microscopy, he saw the viruses to which he and Yvonne Barr would give their name.
Glandular Fever
Meanwhile in Philadelphia, Werner and Gertrude Henle decided to look for EBV antibodies in the blood of children with BL, finding that every child with BL had EBV antibodies, often at high concentrations. However, they did not expect to discover that up to 95% of healthy children and adults throughout the world have EBV antibodies too. The Henles were convinced that EBV caused a common ailment. So they bled everyone in their lab. They all had antibodies to EBV — all except 19-year-old Elaine Hutkin. Time passed until 1967, when Elaine succumbed to glandular fever. When a sample of her blood was tested, it was found to contain EBV antibodies. The Henles had found EBV to be the cause of glandular fever.
