The Friend leukaemia virus and Etienne de Harven - EPE

In 1957 Charlotte Friend was able to transmit, in mice, “a disease having the characteristics of leukaemia” by using cell-free filtrates obtained from the spleen of leukaemic mice. (Friend, J. Exp. Med. 1957; 105:307). In 1958 de Harven and Friend reported the finding in the filtrates of “virus-like” particles. “Particles were found in about one-quarter of the examined specimens from leukaemic mice, and were never observed in non-leukaemic mice of the same strain.” Among the electron micrographs, one (Fig. 5) shows a cell with what appears to be a bud, which they called “pseudopod” (de Harven et al 1958, J. Biophys. Biochem. Cytol., Vol. 4). Since the injected filtrates transmitted “a disease having the character of a leukaemia” (because the filtrates were transmitting the disease especially a malignancy, it does not mean that the filtrates contained a virus, Rous pointed this out in 1911) and the particles were not seen in the nonleukaemic mice, in a paper published in 1960 de Harven and Friend arbitrarily decided to call the particle “virus” particles instead of “virus-like”. “The particles, however, will be referred to as “viruses” and no longer as “virus-like” since all specimens were checked for infectivity and proved capable of transmitting the disease” (“providing that they have been inoculated into highly susceptible inbred mice”). The only evidence that they had for “infectivity” was the transmission of the disease to “highly susceptible inbred mice” by the filtrate. “The virus observed in the leukaemic material under study is considered to be the etiological factor responsible for the induction of the leukaemia in the mice” (emphasis ours). Describing their electron microscopy finding they wrote: “In many cases the viruses are in intimate contact with cell membranes of leukemic cells, suggesting that the virus particle is formed at the level of the cell membranes by a budding process...The virus of Gross’s leukemia appears to be morphologically similar to the one described in the present paper. The budding phenomenon of viruses along cell membranes has also been described for several other viruses”. (de Harven et al, J. Biophys. Biochem. Cytol. 1960, Vol. 7; 747).