It didn’t seem like a good thing when a precious shipment of human tumor samples headed from Kampala, Uganda, to Heathrow was diverted to Manchester. When the samples finally arrived at Middlesex Hospital in London, they were swimming in cloudy liquid in their vials as if contaminated with bacteria.
But when pathologist Anthony Epstein looked at the fluid under the microscope, he saw no bacteria, just individual cells that had shaken loose from the tumors. And that was exactly what he needed to search for elusive virus particles and test his suspicion that they caused cancer.
In the early 1960s, Epstein, who died at the age of 102, had heard a lecture by Dennis Burkittan Irish surgeon working in Kampala who described strange tumors (now known as Burkitt’s lymphoma) growing around the jaws of children in equatorial Africa.
Intriguingly, the geographical distribution of the condition appeared to depend on temperature and rainfall, suggesting a biological cause. Epstein, who had worked with viruses that cause cancer in chickens, immediately suspected that a virus might be involved, perhaps linked to another tropical disease such as malaria.
Epstein began working with Burkitt, who provided him with tumors from children he had treated. But Epstein’s attempts to grow pieces of tumor in the laboratory and isolate a virus had all been unsuccessful until the dissociated cells arrived.
Together with his graduate student Yvonne Barr, he then decided to view cultures of these cells in an electron microscope, a powerful instrument that had only recently become available in his laboratory.
The very first image showed a telltale outline that resembled a virus from the herpes virus family. It turned out to be a previously undescribed member of that family, and was named 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 – which was greeted by widespread skepticism, even though they went on to show that the EB virus caused tumors in monkeys .
Thanks to samples provided by Epstein, in 1970 Werner and Gertrude Henle of Children’s Hospital in Philadelphia discovered that the EB virus also caused glandular fever. That made it possible to design a test for antibodies against the virus to confirm a diagnosis. The EB virus was found to be very common, infecting most children early in life, although it usually causes glandular fever only in older teenagers and young adults. Not only does it cause Burkitt’s lymphoma in endemic areas of Africa and Papua New Guinea, but it is also associated with cancer of the nose and throat, the most common cancer in men in southern China, as well as cancer in people whose the immune system does not work properly. are compromised, such as those infected with HIV.
More recent research suggests that the EB virus may also be involved in some cases of multiple sclerosis, and that people who have previously had glandular fever may be more susceptible to severe Covid-19.
After the discovery, Epstein and others spent time and effort figuring out under what conditions the 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 confidently accept the EB virus as the cause.
It wasn’t until 1997 that the International Agency for Research on Cancer classified it as a Group 1 carcinogen, formally recognizing its role in a variety of cancers.
The discovery of the EB virus opened up a completely new field of research into cancer-causing viruses. It also raised the exciting possibility of preventing cancer through vaccination, an advance that has now been made in the cases of the human papilloma virus, which causes cervical cancer, and the hepatitis B virus, which causes liver cancer.
By the time he retired in 1985, Epstein’s research group at the University of Bristol had developed a vaccine candidate that protected monkeys infected with the EB virus from tumors, but neither this nor any other candidate has yet been successfully developed for human use.
Epstein was born in London, one of three children of Olga (née 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 in charity work in the Jewish community. Anthony attended St Paul’s school in west London, where biology teacher Sidney Pask encouraged boys to go far beyond the syllabus. Robert Winston and Jonathan Miller.
Epstein won a place to study medicine at Trinity College, Cambridge. He moved to the medical school at Middlesex Hospital in wartime London to complete his training, before serving his national service in India with the Royal Army Medical Corps. He returned to Middlesex Hospital as an assistant pathologist and carried out his own investigation. Thinking that electron microscopy might be useful in his research on 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 after, he attended Burkitt’s lecture and began the serendipitous path 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 in 1986 as a fellow of Wolfson College and became an honorary fellow in 2001.
An exemplary scientific citizen, he was Foreign Secretary and Vice-President of the Royal Society, and served on the boards and councils of numerous national and international research organizations, including as Special Representative of the Director-General of UNESCO; he was also a patron of Humanists UK. Among his many awards and honorary degrees, he received the International Gairdner Prize for Biomedical Research in 1988. He was appointed CBE in 1985 and knighted in 1991.
“It was actually a series of accidents,” he said of his discovery in a conversation with Burkitt that they recorded in 1991 for Oxford Brookes University’s oral history archive. “Happy Quirks.” Burkitt immediately responded with Louis Pasteur’s aphorism: “Chance favors the prepared mind.”
Epstein was a deeply cultured man who retained a keen interest in many subjects to the end of his life – especially oriental carpets, Tibet and amphibians.
He is survived by his partner Kate Ward, his children Susan, Simon and Michael, from his marriage to Lisbeth Knight, from whom he was divorced in 1965 and who died in 2015, and by two grandchildren and two great-grandchildren.