Preface & Introduction
PREFACE (Written by Dr. E.D. Kilbourne)             

Over the years many people have made valuable contributions, directly or indirectly, to the research underlying the fabrication and accumulation of the viruses represented in the Kilbourne Flu Archive. Where appropriate, their contributions are acknowledged in the publications listed herein under "references".

None has contributed more, however, than Ms Barbara A. Pokorny, who has worked with Dr. Kilbourne for more than 4 decades in the laboratories of 3 different medical institutions, at Cornell, Mount Sinai, and New York Medical Colleges. Often, her contributions have been creative as well as technical. I know that she and I both have found special satisfaction in the knowledge that our high yielding reassortants have helped substantially in ensuring an adequate supply of influenza vaccine for the prevention of disease and death throughout the world.

INTRODUCTION (Written by Dr. E.D. Kilbourne)

Origin, Scope and Limitations of the Archive

Origin - A personal note

My interest in the genetics of influenza viruses began in the early 1950's when my study of the effects of corticosteroid hormones on viral replication and interference led to evidence of multiplicity reactivation when large amounts of non-infective (inactivated) influenza B virus appeared to be "reactivated" in chick embryos previously given small doses of cortisone. Multiplicity reactivation had been described earlier for bacteriophage and depended on the complementation of damaged genes by others damaged at different loci when a high multiplicity of virus particles/host cell was inoculated.

Fifty years later, the exact mechanism of the corticosteroid effect is not known. However, we have published evidence that the synthesis of interferon is inhibited by cortisone during influenza virus infection of the chick embryo as well as the damaging effects of influenza virus replication on the host cell. Therefore, it is not unreasonable to speculate that multiplicity reactivation and increased virus yields may depend on the demonstrable protection of the host cell from the effects of partially inactivated viral particles.

Somewhat earlier MacFarlane Burnet and later George Hirst had demonstrated high efficiency "recombination" of influenza viruses distinguishable by a limited number of phenotypic markers. Both concluded early on that in the case of these RNA viruses some sort of gene reassortment rather than the classical crossing over seen with DNA agents was occurring. Indeed, this has proved to be correct with the demonstration that genetic information in influenza viruses is carried by discrete and separable RNA molecules. Pragmatic applications were sought for the efficient reassortment of influenza virus genes in mixed infection with different strains. In 1957 and in subsequent years of this modern "Asian" pandemic attempts to enhance the poor yields of the H2N2 strains in vaccine production by recombination were unsuccessful, including efforts in my own laboratory.

However, in 1958-59, James Murphy and I, using viral morphology as a less ambiguous marker, were able to demonstrate: "rapid (in ovo) adaptation of early passage Asian strain isolates by combination with PR8" (A/PR/8/34), a standard laboratory strain which grew regularly to high titer in chick embryos. It was not until 1971 that the first practical application of this discovery was made just after the "Hong Kong" H3N2 pandemic. Since then, virtually all influenza vaccines have been high yield (hy) reassortants, including 29 from my laboratory, as is detailed elsewhere in these archives.

Much more important, in my view, than the obviously worth-while facilitation of vaccine production with the immediate goal of preventing illness and death, is the basic information that has often been revealed in the course of reassortment for this pragmatic purpose. This will become clear as details concerning these viruses are presented in their individual files and in their categorization summaries.