It didn’t look like a good thing when a precious shipment of human tumor samples en route from Kampala, Uganda, to Heathrow was diverted to Manchester. When the samples finally arrived at the Middlesex Hospital in London, they were swimming in cloudy liquid in their vials as if infected with bacteria.
But when pathologist Anthony Epstein looked at the fluid under the microscope, he saw no bacteria, only individual cells shaken loose from the tumors. And it was just what he needed to search for elusive virus particles and test his suspicion that they cause cancer.
In the early 1960s, Epstein, who has died aged 102, heard a lecture by Dennis BurkittAn Irish surgeon working in Kampala who described strange tumors (now known as Burkitt lymphoma) growing around the jaws of children in equatorial Africa.
Interestingly, the geographic distribution of the condition appears to depend on temperature and rainfall, suggesting a biological cause. Epstein, who worked with viruses that cause cancer in chickens, immediately suspected that a virus might be involved, perhaps related to another tropical disease such as malaria.
Epstein began working with Burkitt, who provided him with tumors from children he treated. But Epstein’s attempts to grow pieces of tumor in the laboratory and isolate a virus were all 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 tool that had only recently become available in his laboratory.
The very first image showed a clear 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 met with widespread skepticism, although they went on to demonstrate that EB virus tumors caused in monkeys.
Thanks to samples provided by Epstein, in 1970 Werner and Gertrude Henle at the Children’s Hospital in Philadelphia discovered that EB virus also causes glandular fever. This made it possible to design a test for antibodies against the virus to confirm a diagnosis. EB virus appears to be very common, infecting most children in early life, although it usually only causes glandular fever 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 which is the most common male cancer in southern China, as well as cancers in people who have compromised immune systems, such as those infected with HIV.
More recent research suggests that EB virus may 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 conditions 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 a cause.
It was not until 1997 that the International Agency for Research left Cancer classifies it as a Group 1 carcinogen, formally recognizing 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 now achieved in the case of human papillomavirus, which causes cervical cancer, and hepatitis B virus, which causes liver cancer.
By his retirement in 1985, Epstein’s research group at the University of Bristol developed a candidate vaccine that protects monkeys infected with EB virus against 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 well beyond the syllabus and whose pupils included Robert Winston and Jonathan Miller.
Epstein won a place to study medicine at Trinity College, Cambridge. He moved to the 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 as an assistant pathologist to work at Middlesex Hospital and conduct his own research. Thinking that electron microscopy might be useful in his studies of cancer-causing viruses in chickens, he spent 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 funny 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 and became 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 organizations, including as a special representative of the director-general of Unesco; he was also a patron of Humanists UK. Among his many prizes and honours, he received the international Gairdner Award for biomedical research in 1988. He was appointed CBE in 1985 and knighted in 1991.
“It was really a series of accidents,” he said of his discovery in a conversation with Burkitt they recorded in 1991 for Oxford Brookes University’s oral history archive. “Happy Oddities.” Burkitt immediately responded with Louis Pasteur’s aphorism: “Chance favors the prepared mind.”
Epstein was a deeply cultured man who maintained a lively interest in many subjects – especially 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 divorced in 1965, and who died in 2015, and by two grandchildren and two great-grandchildren.
