~This Week’s Citation Classicz_______ Isaacs A & Lindenmann J. Virus interference. I. The interferon, Proc. Roy. Soc. London Set. B 147:258-73, 1957. [National Institute for Medical Research. London. England] Heat-inactivated influenza virus, added to tor seemed highly interested: How did I know fragments of chick chorioallantoic mem- the virus was truly inactivated? How did I branes, induced the formation of a sub- know it would not elute from red cells? This, stance, interferon, which, when added to I replied, was all to be read in an obscure pa- fresh membranes, inhibited the growth of per by some Australians I had come across. This paper, in fact, had2 been written by lsaacs live influenza virus. [the SCI~indicates and Margaret Edney. But when reading it, I that this paper has been cited in over had, in my mind, pronounced the name in 1,040 publications.] mid-European fashion as something like “Ee- zak,” whereas the man I had been introduced to was called “(ye-sacks.” It was only under his intense prodding that it suddenly dawned upon me that I was speaking to the very man whose work I was quoting, and never have I The First Stirrings of Interferon had to congratulate myself more for having read a paper carefully. Jean Lindenmann We immediately started a collaboration. Institute for Immunology and Virology What a relief from my frustrations with the University of Zurich polio work, which ofcourse went on for sev- CH-8028 Zurich eral months—disproving something is so much Switzerland more difficult and brings such trifling rewards compared with showing something3 new! We June 21, 1989 repeated the work with red cells but very soon realized that, of the three elements that I arrived at the National Institute for Medical entered into our experiments (inactivated vi- Research as a postdoc with a Swiss fellowship rus, red cells as carriers of the inactivated vi- in July 1956. I wanted to work in virology with rus, and hosttissue), the red cells were an un- Sir Christopher Andrewes. Somebody had necessary complication and that it was the in- claimed that poliovirus (at that time the real teraction of the inactivated virus with the host star among model viruses) could be cultivated cells that resulted in the release of a substance, in rabbit kidney cells, and I was assigned the called in laboratory slang “interferon,” that task of confirming this rather important find- inhibited viral growth when applied to fresh ing. This proved a disappointing experience, tissue. I have attempted to give a more scien4 - because poliovirus just does not grow in rabbit tific account of these early events elsewhere. cells. The idea that a substance, independent of Probably early in August I was introduced, the virus used to induce interference, was re- at teatime, to the worker next door, who sponsible for inhibition of the challenge virus, seemed to enjoy considerable prestige. “This met with the usual amount of healthy skepti- is Alick lsaacs,” I was told. He asked me what cism, but eventually prevailed, fortunately I had done before coming to England, and I early enough for lsaacs to reap some recogn.- replied that I had been interested in the phe- tion (he was elected a Fellow of the Royal So- nomenon of viral interference; I had even done ciety, an honor that he greatly appreciated, some as yet unpublished work on this, show- one year before his untimely death in 1967). ing that inactivated influenza virus was capa- But even in his moments of elation he cannot ble of interfering with the growth of live in- have visualized that interferons would be har- fluenza virus even when stuck to the surface bingers of the large and still growing family of red cells, from where the inactivated virus of regulatory5 peptides, as witnessed by a re- presumably could not escape.’ My interlocu- cent book. I. Mooser H & Lindenmann j. Homolone lnterferenz durth httzeinaktivierles, an Er throevien adsorbiertes Influenza-B-virus (Homologous interference by he t-in~ctjvatedinfluenza-B virus adsort,ed on ervthrocvtes), Experientia 13:147-8. 957. (cited 5 0mev.) 2. tsaacs A & Ednev hi. Interference hvween inactive and active influenza viruses in the chick embryo, I. Quantitative aspects of interference.,4ust. I Enp. Btttl. Med. Sd. 28:219-30. 950. Cited 40 lines.) 3. Ijndenmann J & lsaacs A. Versuche dber Virus-lnterlercnz Studies on virus interference). Schwe,z. Z.411g. Paled). Bakterto!. 20:640-6. 957, Cited times.) 4. Lindenmann J. From interference to interferon: a brief htsiorical introduction, Phil. T,anv Soc. Sov. London B 2993-6. 1982. cited 5 times.) 5. On Maever E & Dc Maever-Cuignard J. (ntert’erons and other regulawrs i’irokjnev, New York: Wiley. 988. 448 p. CURRENT CONTENTS® ©1989 by SI® LS, V. 32, #46. Nov. 13, 1989 19 /4-.--/~ C.