In Memoriam Marian Koshland 1921−1997 Jim Allison J Immunol 1998; 161:545-546; ; This information is current as http://www.jimmunol.org/content/161/2/545 of September 25, 2021. Downloaded from

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The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 1998 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. In Memoriam Marian Koshland 1921–1997

It would not be at all an exaggeration to say that Marian Koshland’s career was spectacular. She made very important con- tributions to our field in each and every decade for the past half century. As a graduate student at the in the 1940s Bunny, as she was known, worked on a vaccine for Asiatic cholera. This work not only demonstrated the importance of mu- cosal in immunity but also led to her lifelong interest in the structure and origin of antibodies. By the early 1950s and before the formal definition of classes, Bunny had shown that secreted and serum-borne forms of Downloaded from antibodies were discrete molecules. By the 1960s, she began to address one of the central problems in immunology—the origin of antibody specificity. There was a raging debate between instructive models, which held that antibody proteins were all the same and just folded around their target antigens, and selective models, which argued that they were the products of different cells. Bunny http://www.jimmunol.org/ analyzed polyclonal antibodies directed against two different hap- tens, and on the basis of exquisitely careful amino acid composi- tion analyses, convincingly showed that these antibodies had dif- ferent amino acid compositions and therefore must differ in their amino acid sequence. These data had a profound effect on theories of antibody formation and how antibody specificity was generated. Legend has it that at the annual meeting of the American Associ-

ation of Immunology where she first presented her data, her talk by guest on September 25, 2021 was received by a standing ovation—quite high praise indeed. By the end of the 1960s, Bunny’s work had become part of the main- stream of an emerging idea that is now one of the cornerstones of immunology, that is, that antigen receptors, both of T cells and B cells, are encoded by multiple rearranging gene segments. Her work in this area was seminal. Charlie Janeway, who is currently the president of the American Association of Immunologists, re- of the American Association of Immunologists in 1997, she pre- cently commented that he had a clear memory of the time in med- sented a wonderful description of recent work from her lab dem- ical school when he first read Marian’s papers in this area, and that onstrating that the action of a transcription factor, BSAP, was very it was for him a defining moment that motivated him to embark on complex and dynamic, and that it could have both positive and a career in immunology. negative effects: extinguishing some genes whose products were By the 1970s, Marian had returned to her studies of secreted no longer needed, while turning on new genes with roles important versus serum-borne antibodies. She identified a novel antibody to the emerging antibody-producing arm of the immune system. subunit called the J chain, characterized it, and showed that it This talk was a marvel, and put together complex biochemical played a central role in antibody assembly and secretion and that phenomena in an understandable context of biological function. It the beginning of its expression marked a clear, discrete step in the was a testament not only to the quality and timeliness of her own maturation of B cells. This work led to the central theme of the work, but also to how far the field has come in a detailed under- remainder of her scientific career: understanding the way in which standing of the workings of the immune system in the half century a B cell becomes an active player in the immune response. since Marian entered it. In the late 1970s, Bunny did a sabbatical stay in David Balti- In honor of all of her accomplishments, Marian received awards more’s lab at MIT to learn molecular biology, as she felt that the that are much too numerous to completely list here. She was future of the field lay in this area. While at MIT she collaborated elected to the National Academy of Sciences, the American As- in cloning the gene encoding the J chain and brought the gene and sociation of Arts and Sciences, and to the Council of the American her knowledge of the emerging technology of molecular biology Association of Immunologists, which she served as President in back to the immunology group at Berkeley. In the 1980s Bunny 1982–1983. She received the FASEB Excellence in Science turned her attention to regulation of transcription of the J chain Award. She served on many committees of the National Institutes gene by B cell growth factors. By 1990s her work had extended to of Health and the National Science Foundation involved in setting the more general area of events that accompany and direct B cell national scientific policy, including the NIAID Advisory Council activation and maturation. In an invited talk at the national meeting and the National Science Board. She was noted for her courage and

Copyright © 1998 by The American Association of Immunologists 0022-1767/98/$02.00 546 IN MEMORIAM straightforwardness in speaking her mind, and for her honorable during the early stages of her career, she demonstrated that a positions on emerging issues. woman could have a spectacular career while successfully man- If there is any single feature that marked Bunny’s work, it aging to raise a family. It is in part for this that she was honored was her ability to reduce complex phenomena to experimentally by the AAI Committee for the Status of Women in Science at a addressable components. She did this by putting a very high special symposium held at the annual Meeting of the American emphasis on experimental rigor and absolute scientific integrity. Association of Immunologists this year. She was not affected by fads in science, but only by the bottom Reading back over some of Marian’s works recently, I noted line—how well hypotheses hold up to hard experimental scru- that in a memoir she wrote for the Annual Reviews of Immunology tiny. Bunny was well known for her impatience for and will- she said that she chose science as a career in part because of her ingness to challenge half-baked ideas. I am sure that there are conviction that science is a way of making lasting, if not immortal, many immunologists who, like me, can recall times when we contributions to mankind. The legacy that Marian has left us, in her were forced to defend our hypotheses to this formidable devil’s own scientific achievements as well as those of the students and advocate. Bunny was not at all shy in attacking and probing the fellows that she has trained and those of her colleagues like every assumption, every finding, every control. Merely surviv- myself on whom she had a strong influence, will indeed be very ing an encounter with Bunny always gave me confidence that I long lasting. She is, and will be, missed for a very long time by all could defend my ideas to anyone. who knew her and learned from her. Marian served as an inspirational role model for women pursu- ing careers in science. In a field that was clearly dominated by men Jim Allison Downloaded from http://www.jimmunol.org/ by guest on September 25, 2021