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Introductory Remarks

Richard M. Krause

National Institute of Allergy and Infectious Diseases
National Institutes of Health
Bethesda, Maryland

It is a special pleasure for me to participate in this Workshop on the Origins of Inbred Mice, and the National Institute of Allergy and Infectious Diseases is proud to take part in this program. I congratulate, also, the awardees who will be honored later this morning.

I welcome you all to the NIH. But apart from my official greeting, I welcome you from a very personal point of view. My research career began at the Rockefeller University, then the Rockefeller Institute for Medical Research. During the course of nearly a quarter century, I came to know Clara Lynch and to admire her contributions to the development and use of inbred mice in probing the genetic determinants of resistance and susceptibility to infections and tumors.

Clara Lynch joined Murphy's laboratory in 1920. She inbred her mice so that the strains became progressively more uniform. During the inbreeding, she noted that two strains of separate origin showed a significant difference in incidence of lung tumors. Subsequent breeding studies demonstrated that susceptibility to these tumors is genetically controlled.

But all was not tumor biology for Clara Lynch. Infection was then, and still is today, modulated by genetic forces. Lynch used her Swiss mice as one of the strains to show that susceptibility to yellow fever virus was influenced by hereditary factors. This work on yellow fever had practical consequences in the development of mouse susceptibility tests for use in epidemiological surveys. In later years, Lynch also examined the genetic susceptibility to tuberculosis.

Perhaps not all of you participating in this workshop know the origin of the Swiss mice. Lynch introduced them to this country from a laboratory in Lausanne. The original population was two males and seven females which Dr. Lynch brought into this country in a shoebox, kept in her stateroom on board ship. Science was lived at a more leisurely pace in those days. Incidentally, she arrived and proceeded through customs with no permit from the Department of Agriculture! Lynch, of course, exploited this strain and derivatives of these Swiss mice have been used throughout the world.

There was in the early years, I am sure, more than one shoebox in the origins of inbred mice -- a legacy of those honored and assembled here. And from those simple origins sprung an intricate genealogy. But how you do complicate matters with a whole new lexicon which rhymes in no one's ear except your own! You go on and on with BALB/c, MOPC, A/J, SWR -- sort of a New Deal bureaucracy for a latter day Orwellian animal farm.

I am most familiar with what is done in immunology with inbred mice. But the matter is not yet all of a piece. What exactly are the determinants of immunity? There is a subtlety here that still escapes us. It is as if nature were deliberately evasive. But it will come. Spring is in the air -- even on a late winter day like this. "In March -- the lawn is full of south," said Emily Dickinson, the Belle of Amherst -- "the lawn is full of south."

My own work has taken me far afield and into immunogenetic studies with rabbits. Indeed, in May we will be sponsoring here at the NIH a conference on rabbit genetics. When I mentioned this to my good friend, Wally Rowe, he chortled with some amusement and said, "Just like rabbit geneticists, still running behind the mouse geneticists." But my students have moved with the times -- if that is what it is -- and they are mouse immunologists.

I have talked too long, but when asked to greet you at this Workshop on the Origins of Inbred Mice, it occurred to me that, in a manner of speaking, I was present at the beginning through my association with Clara Lynch.

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