Monday, April 15

Dr. Anthony Epstein, Pathologist Who Discovered Epstein-Barr Virus, Dies at 102

In March 1961, Dr. Anthony Epstein, a pathologist at Middlesex Hospital in London, almost skipped a visiting physician’s afternoon lecture about children with exceptionally large facial tumors in Uganda.

The physician, Dr. Denis Burkitt, a native of Ireland who called himself a bush surgeon, showed slides of bulbous tumors that emerged along the jawline and occurred in tropical African regions where rainfall was high. During his lecture, Dr. Burkitt mapped a veritable pediatric cancer belt that extended across equatorial Africa.

Despite Dr. Epstein’s initial reluctance to attend the talk — he sat in the rear so he could make a quick escape — his excitement grew the longer Dr. Burkitt spoke. By the time the lecture was over, he knew that he would drop all of his ongoing projects to find the cause of that unusual malignancy. His doctoral student, Yvonne Barr, soon joined him and, by 1964, their groundbreaking research had uncovered the first virus capable of causing cancer in humans.

He rocked the scientific world with the announcement. Some physicians and scientists applauded the discovery; others refused to accept it.

Dr. Epstein died on Feb. 6 at his home in London. He was 102. His death was confirmed by the University of Bristol, where he was a professor of pathology from 1968 to 1985, and where he had served as the head of the department for 15 years.

The pathogen that came to bear his and Dr. Barr’s names — Epstein-Barr virus — belongs to the herpes family and is one of the most ubiquitous on the planet. An estimated 90 percent of the world’s adult population carries the virus, which is also known as E.B.V.

“To have the insight and to be able to follow his hypothesis, with a little acknowledged serendipity, and identify the novel virus was pioneering,” Dr. Darryl Hill, who heads the University of Bristol’s School of Cellular and Molecular Medicine in England, said in an email.

Studies since Dr. Epstein’s discovery have linked E.B.V., which is spread through close human contact, to many medical conditions, including multiple sclerosis and long Covid. As with other members of the herpes family, once infected with the virus, a person is infected for life.

“Most people never know they’re infected,” Jeffrey Cohen, the chief of the Laboratory of Infectious Diseases at the National Institute of Allergy and Infectious Diseases, told The New York Times in 2022.

E.B.V. is the cause of mononucleosis, the so-called kissing disease, which primarily afflicts teenagers and young adults with a fever and swollen lymph nodes. It is also associated with Hodgkin’s lymphoma and a nose-and-throat cancer common in China.

The tumor that affects children in Africa, known as Burkitt lymphoma, has also been diagnosed in other tropical regions, such as Brazil and New Guinea. Medical scientists theorize that E.B.V. causes pediatric lymphomas in tropical zones because children in such areas often have weakened immunity from exposure to malaria parasites. The World Health Organization estimates that there are three to six cases of Burkitt lymphoma per 100,000 children annually in endemic regions.

When the 50th anniversary of E.B.V.’s discovery was celebrated in 2014, Dr. Epstein told an interviewer with the BBC what he had been thinking as he listened to Dr. Burkitt speak in 1961.

“I thought there must be some biological agent involved,” Dr. Epstein said. “I was working on chicken viruses which cause cancer. I had virus-inducing tumors at the front of my head.”

The chicken virus he was referring to was Rous sarcoma virus, the first cancer-causing virus to be discovered, in 1911 by Dr. Francis Peyton Rous, a pathologist at Rockefeller University in New York. Dr. Rous won the 1966 Nobel Prize in Physiology or Medicine. Although a Nobel eluded Dr. Epstein and Dr. Barr, their discovery has had a lasting impact on science and medicine.

“We now know of several viruses and bacterial species that are able to cause certain types of cancer,” Dr. Hill said. “However, one could argue that the Epstein-Barr virus discovery paved the way for some cancers to be preventable by vaccination.”

Vaccines are available against human papillomavirus, or HPV, which causes cervical and other forms of cancer. The hepatitis B vaccine helps to thwart liver cancer. But there is no vaccine against Epstein-Barr, though two candidate vaccines are in early-phase clinical research.

The discovery of the virus was not quick. Dr. Burkitt sent tumor biopsies to London from Kampala, Uganda, but Dr. Epstein couldn’t find viruses in the early specimens, according to Dr. Hill, who wrote a remembrance of Dr. Epstein for the University of Bristol.

When another biopsy shipment was diverted from Heathrow Airport to another airport, in Manchester, England, because of fog, the sample seemed doomed, Dr. Hill said.

“By the time the sample reached Tony, it had gone cloudy — usually a sign of bacterial contamination that would consign it to the bin,” Dr. Hill wrote in his tribute. “Tony did not throw it away but examined it carefully,”

“He discovered, to his surprise, that the cloudiness was due to lymphoid tumor cells that had been shaken off the biopsy in transit and were now floating merrily in suspension.” He continued, “Tony exploited this chance finding to grow cell lines, derived from the tumor, in culture. He showed that these stayed alive indefinitely.”

Studying his new sample with a powerful electron microscope, Dr. Epstein was able to spot the distinct viral signature of a herpes virus. Dr. Hill called the discovery a eureka moment.

Dr. Epstein, Dr. Barr and Dr. Bert Achong, who prepared the specimens for electron microscopy, announced the discovery in a scientific paper published in the March 1964 issue of the scientific journal The Lancet.

Dr. Barr died at age 83 in 2016.

Michael Anthony Epstein was born on May 18, 1921, in London and was educated at Trinity College of the University of Cambridge. He was a graduate of Middlesex Hospital Medical School, according to Wolfson College at the University of Oxford.

After leaving the University of Bristol in 1985, Dr. Epstein became a fellow at Wolfson College and remained at the institution until he retired in 2001. He was knighted by Queen Elizabeth II in 1991.

His marriage to Lisbeth Knight ended in divorce in the 1960s. Survivors include his longtime partner, Dr. Katherine Ward, a virologist; two sons from his marriage, Michael and Simon; and a daughter, Susan Holmes.

Dr. Epstein told the BBC in 2014 that one of his most ardent wishes was the development of a vaccine against E.B.V. His wish may come true in the not-too-distant future if current research prevails.