It did not seem like a good thing when a precious consignment of human tumour samples on its way from Kampala, Uganda, to Heathrow was diverted to Manchester. When the samples finally arrived at the Middlesex hospital in London, they were swimming in murky fluid in their vials as though they had been infected with bacteria.
But when the pathologist Anthony Epstein looked at the fluid under the microscope he saw no bacteria, just individual cells that had been shaken loose from the tumours. And that was just what he needed in order to search for elusive virus particles and test his hunch that they were causing cancer.
In the early 1960s Epstein, who has died aged 102, had heard a lecture by Denis Burkitt, an Irish surgeon working in Kampala, that described strange tumours (now known as Burkitt lymphoma) growing around the jaws of children in equatorial Africa.
Intriguingly, the geographical distribution of the condition seemed to depend on temperature and rainfall, suggesting a biological cause. Epstein, who had been working with viruses that cause cancer in chickens, immediately suspected a virus might be involved, perhaps in association with another tropical disease such as malaria.
Epstein began to collaborate with Burkitt, who supplied him with tumours from children he had treated. But Epstein’s efforts to grow pieces of tumour in the laboratory and isolate a virus had all been unsuccessful until the dissociated cells arrived.
With his graduate student Yvonne Barr, he then decided to look at cultures of these cells in an electron microscope, a powerful instrument that had only recently become available in his lab.
The very first image showed a tell-tale outline that looked like one of the family of herpes viruses. It turned out to be a previously undescribed member of that family, and was given the name Epstein-Barr virus. In 1964, Epstein, Barr and Epstein’s research assistant, Bert Achong, published the first evidence that cancer in humans could be caused by a virus – to be greeted by widespread scepticism even though they went on to demonstrate that EB virus caused tumours in monkeys.
Thanks to samples supplied by Epstein, in 1970 Werner and Gertrude Henle at the Children’s hospital in Philadelphia discovered that EB virus also caused glandular fever. That made it possible to design a test for antibodies to the virus in order to confirm a diagnosis. EB virus turned out to be very common, infecting most children in early life, though it usually causes glandular fever only in older teenagers and young adults. As well as causing Burkitt lymphoma in endemic areas in Africa and Papua New Guinea, it is also associated with a cancer of the nose and throat that is the most common cancer of men in south China, as well as cancers in people whose immune systems have been compromised, such as those infected with HIV.
More recent research suggests that EB virus might also be involved in some cases of multiple sclerosis, and that people who have previously had glandular fever are more susceptible to severe Covid-19.
After the discovery, Epstein and others devoted time and effort to trying to find out under what circumstances EB virus causes cancer. The relationship between the virus, other diseases, human genetics and cancer is complex, and it took decades before the medical community could accept the EB virus as a cause with confidence.
Not until 1997 did the International Agency for Research on Cancer class it as a Group 1 carcinogen, formally acknowledging its role in a variety of cancers.
The discovery of EB virus opened up a whole new field of research into cancer-causing viruses. It also raised the exciting possibility of preventing cancers through vaccination, an advance that has now been achieved in the case of human papilloma virus, which causes cervical cancer, and hepatitis B virus, which causes liver cancer.
By the time of his retirement in 1985, Epstein’s research group at the University of Bristol had developed a candidate vaccine that protected monkeys infected with EB virus against tumours, but neither it nor any other candidate has yet been successfully developed for human use.
Epstein was born in London, one of three children of Olga (nee Oppenheimer) and Mortimer Epstein. Mortimer was a writer and translator who edited The Statesman’s Yearbook for Macmillan from 1924 until his death in 1946. Olga was involved with charitable work in the Jewish community. Anthony attended St Paul’s school in west London, where the biology teacher Sidney Pask encouraged boys to go far beyond the syllabus and whose pupils also included Robert Winston and Jonathan Miller.
Epstein won a place to study medicine at Trinity College, Cambridge. He moved to Middlesex hospital medical school in wartime London to complete his training, before doing his national service in India with the Royal Army Medical Corps. He returned to work at the Middlesex hospital as assistant pathologist, conducting his own research. Thinking electron microscopy might be useful in his studies of cancer-causing viruses in chickens, he spent some time learning the new technique at the Rockefeller Institute in New York (now Rockefeller University). Not long afterwards he attended Burkitt’s lecture and began the serendipitous route to his discovery.
In 1968 he was appointed professor and head of the department of pathology at the University of Bristol, where he remained until his retirement. He moved to Oxford as a fellow of Wolfson College in 1986, becoming an honorary fellow in 2001.
An exemplary scientific good citizen, he served as foreign secretary and vice-president of the Royal Society, and sat on boards and councils for numerous national and international research organisations, including as a special representative of the director general of Unesco; he was also a patron of Humanists UK. Among his many prizes and honorary degrees, he received the international Gairdner award for biomedical research in 1988. He was appointed CBE in 1985 and knighted in 1991.
“It was a series of accidents, really,” he said of his discovery in a conversation with Burkitt they recorded for Oxford Brookes University’s oral history archive in 1991. “Lucky quirks.” Burkitt immediately responded with Louis Pasteur’s aphorism: “Chance favours the prepared mind.”
Epstein was a deeply cultured man who retained a lively interest in many subjects – particularly oriental rugs, Tibet and amphibians – until the end of his life.
He is survived by his partner, Kate Ward, by his children Susan, Simon and Michael, from his marriage to Lisbeth Knight, from whom he was separated in 1965, and who died in 2015, and by two grandchildren and two great-grandchildren.
• Michael Anthony Epstein, pathologist, born 18 May 1921; died 6 February 2024
