Missed Chances on a Hopeful Road

Looking back, my scientific career seems to have been liberally strewn with missed opportunities. In fact, right at its outset I missed an opportunity by force of circumstance. After a six-year break in my studies occasioned by service with the Jewish Brigade in the 8th Army during World War II, I began work on my Ph.D. thesis at the Hebrew University in Jerusalem in 1947. The subject was a search for soil bacteria that would produce an antibiotic against typhoid and dysentery bacteria. At that time the only two known antibiotics were penicillin and streptomycin. I got off to a rather successful start by isolating a Bacillus whose colonies had the peculiar property of rotating synchronously on agar plates. An extract of the broth in which these bacteria grew inhibited the growth of typhoid bacteria. This microorganism was indeed later found to produce polymyxin, but I had to give up my project when hostilities broke out after the U.N. declaration creating the State of Israel. One day in January 1948 I was ambushed while driving with two students from Kibbutz Kiryat Anavini, where I was living, to the university. When bullets hit the car, I escaped along a gully, but one student was killed. Shortly after that the university was evacuated and all my cultures perished. Again my services were needed here. In 1951 I resumed my scientific career, this time on a new Ph.D. thesis on aerosol immunization of chickens against the dreaded Newcastle disease, which periodically decimated poultry flocks. This viral disease paralyzed and killed the afflicted birds. It was therefore important to protect flocks by vaccination, at that time done by intramuscular inoculation with an attenuated strain of the virus. Of the several strains available in the ‘50s, the so-called or Komarov strain developed by the director of the Israel Veterinary Institute caused about 1 percent mortality in vaccinated chicks. Having gained technical experience in producing aerosols at Harvard University Medical School, I returned to Israel after a year and embarked on the vaccination of young chicks with a device called the Chicago atomizer. Using the Komarov strain, I showed the efficacy of an aerosolized vaccine when administered in proper doses under controlled conditions. Chickens vaccinated in this way become completely resistant to a challenge with a lethal dose of virus. Komarov learned of my results and accepted my proposal to try the aerosol vaccine in the field. We selected a suitable flock of a few hundred two-week-old chickens at Kibbutz Maabarot. It was the end of December 1952, a very cold winter. We drove to the kibbutz, atomized the Komarov’s vaccine in the chicken pen and waited for the results. Rains set in and continued for a week, the kibbutz was isolated by floods and we could not reach it to see what was happening. When we finally got there the picture was of calamity. More than half of the birds were dead or paralyzed. It turned out that under conditions of cold and humidity the Komarov’s strain was lethal when the birds inhaled it rather than receiving it by intramuscular injection. These discouraging results very much dampened Komarov’s enthusiasm for further field experimentation and the project languished. But concomitantly, as I learned later, Ray Bankowski in California was getting good results with’ aerosolized vaccine using the much more attenuated B-1 strain of the Newcastle virus (NDV). Today aerosol vaccination is a widely accepted practice worldwide. In my youthful optimism I had hoped that a mesogenic strain of virus such as Komarov’s would do the trick. It did so in a controlled laboratory environment, but not, alas, under harsh field conditions. As a freshly baked Ph.D. my attention turned to studying the pathogenesis of the NDV infection. During the next six years I unraveled the sequence of events leading from infection by various routes (inhalation, feeding, injection) through the spread of the virus to various organs to its excretion in the feces of infected birds. With this expertise I went on sabbatical in 1958 to Robert Huebner at the Institute of Infectious and Allergic Diseases at NIH, where I intended to study the pathogenesis of avian leucosis (ALV), known at that time as visceral lymphomatosis. This disease had been studied extensively for more than a decade by Ben Burmester at East Lansing, Michigan. I thought the experience I had gained from my NDV studies would be useful in my proposed study of ALV. Until 1957 the only test for the presence of a virus in the environment or many bio logical material was to inject a sample into chickens and then wait six to nine month for the results, namely development of lymphomatous tumors in the visceral organs Using this procedure, Burmester was able to elucidate the pathway of transmission of this virus in nature from the hen through the egg to the hatched chick, as well as by air fron one chick to another. The procedure, how ever, was cumbersome and required maintenance of specially isolated, genetically Selected flocks. There was a rather urgent need for a more rapid test. To develop such a test—one that would take a few days instead of the better part of a year—I combined in my thinking two tests. It was known then that there was some serological connection between the Rous sarcoma virus (RSV) and the visceral lymphomatosis virus. In 1956, Vincent Groupé at Rutgers and Harry Rubin in California independently discovered that infection of chick embryo cultures (monosayers) with RSV produced characteristic foci (pocks) in the infected cultures. I also knew of the finding that rubella virus infection, normally not detectable in infected cultures, could be demonstrated by the so-called heterologous interference test, namely by superinfection of the rubella-infected cells with an enterovirus ECHO II. Normal, uninfected cells would be destroyed by ECHO H virus, while rubella-infected ones would survive. I therefore wrote to Rubin seeking his advice and cooperation in developing such an interference test for ALVs. His answer was disappointing. He did not believe there was much chance of success for such a test. About two years later Howard Temin and Rubin developed an interference test for ALV. Their work was based on a chance observation that not all cultures of chick embryos responded equally well to an infection with RSV; cloning experiments with chick embryos clearly demonstrated that only embryos hatched from eggs laid by lymphomatous hens were resistant to RSV infection. Nine years later, when I spent a sabbatical in Rubin’s lab at Berkeley, I asked him about his dismissal of my original proposal. Harry, the most honest and straightforward scientist I ever met, had no recollection of my letter to him and his response. This list of my missed opportunities is by no means complete. It all sounds very frustrating, yet I wouldn't have changed my career as a scientist for any other profession. There must be truth in the old adage, “It is better to travel hopefully than to arrive”—at any rate when applied to scientific research. Kohn read microbiology and biochemistry at the Hebrew University in Jerusalem, interrupting his studies to fight in North Africa and Europe during World War II and in the Israeli War of Independence. He later joined the Israel Institute for Biological Research, Ness Ziona, in 1952 and has served as both head of the Department of Biophysics and Virology and director of the institute. Now semi-retired, he remains professor of virology at Tel Aviv Medical SchooL Since 1956 Kohn has combined a prolific research career with editorship of the quirky Journal of Irreproducible Results.

Missed Chances on a Hopeful Road

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