Epstein-Barr virus

Sir Anthony Epstein FRS

EpsteinClick on the image to open a larger version. Copyright: Anthony Epstein

In 1961 I chanced to hear, in London, an unknown surgeon from Uganda give the first description of a bizarre, new children’s cancer subsequently named after him, Burkitt’s lymphoma. I had worked on chicken cancer-causing viruses and when Burkitt mentioned the lymphoma’s temperature and rainfall geography I immediately postulated a climate-dependent arthropod vector carrying a human tumour virus and decided to seek it. Although an unorthodox idea, I was funded to visit Uganda to acquire lymphoma samples to be flown to my lab.

For two years standard biological virus isolations were negative; electron microscopy, rare then, was also negative, disappointing since I had worked with G.E.Palade (Nobel Prize 1974; ForMemRS) during his seminal contributions to biological electron microscopy.

I wondered next if lymphoma cells cultured away from host defences might activate a latent cancer virus like some chicken tumours. However, no human lymphoid cells had ever grown in vitro and unsurprisingly, my fragment cultures proved unsuccessful. These failures were alarming for an insecure career.

On 5 December 1963 a diverted Uganda flight delayed the sample; on arrival, cloudy transit fluid suggested bacterial contamination but microscopy showed nothing but suspended floating tumour cells shaken free on the overlong journey. This reminded me that mouse lymphomas would only grow from cell suspensions so the sample was initiated as a suspension culture and the first ever human lymphoid cells proliferated in vitro. Publication proved difficult because referees doubted such cells had grown, yet today suspension culture is routine for human lymphoid cells worldwide.

The cultures gave negative biological virus isolation tests, but the first electron microscopy grid held a cell infected with an unequivocal herpesvirus. Contemporaneously, virus identification required biological or immunological evidence, but Palade’s influence convinced me morphology allowed recognition of virus families as had been done for decades with bacteria. Furthermore, biological inertness suggested a new herpesvirus and immunology and biochemistry soon confirmed this. The source and later associations with cancer made this the first human tumour virus. It was named by others for me and a research assistant who cultured the cells.

These electronmicrographs, taken in 1964 when Epstein-Barr virus was discovered, are of ultra-thin sections cut through virus particles in various planes (1) inset a single mature enveloped particle x170,000 and (2) numerous immature particles (as yet without their envelopes) lying in the cytoplasm of an infected cell x160,000.

Sir Anthony Epstein was Foreign Secretary of the Royal Society from 1986-1991.