Frank W. Fitch, M.D., Ph.D.

 Brief Bio

Frank W. Fitch (1929–2021) was professor emeritus of the Department of Pathology and former director of the Ben May Institute (currently the Ben May Department of Cancer Research) at the University of Chicago. Dr. Fitch was president of The American Association of Immunologists from 1992 to 1993 and served on the AAI Council from 1987 to 1994. He also served as editor-in-chief of The Journal of Immunology from 1997 to 2002. From 1993 to 1994, Dr. Fitch was president of the Federation of American Societies for Experimental Biology. He was awarded the AAI Excellence in Mentoring Award in 2004, the AAI Distinguished Service Award in 2002, and the AAI Lifetime Achievement Award in 1996. Dr. Fitch was elected a Distinguished Fellow of AAI in 2019.

 Oral History - Full Interview

Interview Date: Wednesday, July 18, 2012
Location: Chicago, IL

Click here to see other interviews from the Oral History Project

 Oral History - Transcript

Click here to download the transcript of this interview

 Oral History - Clips

 AAI Service History

 President's Address

"The Good Old Days—Past, Present, and Future"

The Journal of Immunology 151, no. 4 (1993): 1747–56.

 Awards and Honors

• Lifetime Achievement Award, AAI, 1996
• Distinguished Service Award, AAI, 2002
• Distinguished Service Award, University of Chicago Medical and Biological Sciences Alumni Association, 2003
• Excellence in Mentoring Award, AAI, 2004
• Norman Maclean Faculty Award, University of Chicago, 2008
• Distinguished Fellow, AAI, 2019

 Institutional/Biographical Links

• Ben May Department for Cancer Research, University of Chicago, emeritus faculty page
• The Frank W. Fitch Monoclonal Antibody Facility

 AAI In Memoriam

Frank W. Fitch

AAI extends sincere condolences to the family, friends, and colleagues of Frank W. Fitch, M.D., Ph.D., DFAAI (AAI ’61), who died peacefully on April 2 at the age of 91. The following remembrance was authored by Jeffrey A. Bluestone, Ph.D. (AAI ’82), Arthur Weiss, M.D., Ph.D. (AAI ’81), Department of Medicine, University of California, San Francisco. It appeared in The Journal of Immunology June 15, 2021, 206 (12). AAI gratefully acknowledges the submission.

“When I say ‘I,’ I mean ‘we’; when I say ‘we,’ I mean ‘they.’” This quote, often said by Frank W. Fitch at the beginning of one of his talks, was just one of many Fitchisms about research, science, and life that all of us who knew him remember and cherish. Frank W. Fitch died peacefully in his home near the University of Chicago campus on April 2, 2021. When we lost Frank this year, we also lost a great scientist, mentor, colleague, educator, devoted husband, father, and friend. This celebratory essay by his former student, Art Weiss (AAI ’81); former AAI President 2008—2009, and his long-time colleague, Jeff Bluestone (AAI ’82), reflects on Frank’s many research and leadership accomplishments, but simply said, Frank was a true mensch. He will be missed. Frank was raised in the small town of Bushnell, IL (population ~2900), where he met his future wife and lifelong partner, Shirley Dobbins. He took an interest in science from an early age. His father, an osteopath, convinced Frank to go to medical school, hoping that Frank would return to Bushnell so that they could practice medicine together. Despite Frank’s decision to pursue pathology at the University of Chicago (M.D. ’53), he quickly realized the descriptive nature of pathology and medicine was not enough to satisfy him.

Inspired by Robert Wissler, M.D., Ph.D., the chair of pathology at the University of Chicago and a renowned scientist in the study of atherosclerosis, Frank trained for a research career, completing a Ph.D. in 1960. The University of Chicago was the home of the Manhattan Project, the code name for the federally funded research program to develop the atomic bomb. Thus, much of the university’s basic research was focused on understanding the consequences of the radiation released by the bombs. This spurred Frank’s interest in hematopoiesis and his thesis studies focused on the consequences of lethal X-irradiation on the immune system¹. This was his first foray into a lifelong passion for immunology research.

Upon completion of his training, Frank was immediately invited to join the faculty of the Pathology Department at the University of Chicago. He and Shirley had fallen in love with Hyde Park and the community of vibrant and exciting colleagues and friends. They decided to plant their roots, raise their family, and build a life. This decision would impact generations of scientists and colleagues. They never left Hyde Park, where Frank’s spectacular career, spanning more than 40 years on the faculty, was characterized by exciting cutting-edge research in immunology, inspirational teaching, unselfish mentoring, and most importantly, local and national leadership roles.

Frank’s long and productive career was at the forefront of cellular immunology. In some of his earliest studies in the 1960s, he collaborated with Don Rowley, a long-time colleague and friend, to show that antiserum from sheep RBC (SRBC_s)—immunized rats administered prior to i.v. challenge of a rat with SRBCs could suppress the subsequent host Ab response to SRBC_s^{2, 3}. This was one of the earliest examples of active immune regulation, which inspired the clinical use of passive Ab treatment to prevent erythroblastosis fetalis in newborns. Passive Ab treatment suppressed maternal Ab-mediated hemolysis of fetal cells during subsequent pregnancies of mothers carrying Rh⁺ fetuses. With the arrival of Frank Stuart, a transplant surgeon, Frank and Don discovered that passive alloantibodies could delay renal allograft survival in a rat transplant model. In fact, when combined with donor semiallogeneic (F1) spleen cells, alloantibodies against the donor graft Ags induced long-term Ag-specific renal allograft survival, a phenomenon termed “graft enhancement”^{4, 5}.

It was at this time (~1974) that Arthur Weiss, a first-year medical student, entered the Fitch laboratory for a research elective rotation. The model of renal allograft enhancement—a mechanism of specific tolerance that could potentially be applied to transplantation—excited Art, as did the extraordi- nary enthusiasm, comradery, and scientific spirit that pervaded the Fitch laboratory. When National Institutes of Health funding for the Medical Scientist Training program became available during that first year, Dr. Fitch (all his students called him Dr. Fitch) encouraged Art to apply and make the commitment to the combined degree program. As Art remembers, “It was a wonderful experience in the Fitch lab. With Frank’s guidance, I developed functional studies of rat T and B cells in vitro that enabled a greater understanding of the rat renal enhancement model ⁶. Unlike the unresponsive T cells of rats that were made tolerant via neonatal bone marrow chimerism, the T cells of long-term renal transplant-enhanced rats could mount primary responses but not memory responses⁷. The mechanism underlying long-term renal allograft enhancement has remained elusive to this day.”

Dr. Fitch enjoyed doing bench work and was a role model for us all. His trainees learned a great deal about repeating results, scientific rigor, and meticulous attention to detail. Most of all, they learned about the joy and satisfaction of just doing an experiment well. But, also, Dr. Fitch liked to dabble, so they also learned a lot about “gadgets” and bringing new technolo- gies into the laboratory. Dr. Fitch was always the first to sort out how to get a new instrument to work and to use the rather crude computers (at the time) to either drive the instrument or to analyze the data output. Bluestone helped Frank set up the first intranet in the department, running a primitive 10BASE-T ethernet line between Frank’s 28-pound “portable” Compaq computer and Jeff’s first-generation PC (Frank would not let us get Macs or use Microsoft products, period).

Frank’s interest in gadgets and his hands-on approach applied to his hobbies as well. He made his own down mittens for the brutal Chicago winters (think Bernie Sanders at Presi- dent Joe Biden’s inauguration), restored his own leaded glass china cabinet, and was an avid square-foot gardener. His boundless energy and enthusiasm for taking on new challenges in the laboratory and at home simply amazed all.

Frank was the kind of adventurous scientist we aspire to be. He actually took time off to study asteroids, hoping to find evidence of life by looking for microbe fossils embedded in the rocks but, instead, provided evidence that biogenic material in Orgueil meteorites was due to contamination⁸. On another occasion, he spent 2 years trying to understand why his T cell clone cultures were crashing. This led to the discovery of an orphan parvovirus that infected T cells, which he found to be endemic in many animal vendors’ facilities⁹. In fact, The Jackson Laboratory in Bar Harbor, ME, started screening for and eliminated the virus from their colony, which turned out to be key for anyone growing mouse T cell clones. This adventuresome and inquisitive spirit, combined with a dedication to using the best technologies to study basic immunology problems, led Frank to two sabbaticals at the Swiss Institute for Experimental Cancer Research in Switzerland where Theodore Brunner and Jean-Charles Cerrotini were developing novel technologies to isolate and clone cytolytic T cells.

During his second stint in Lausanne, and then back in the Chicago laboratory, Frank studied mechanisms involved in the development and differentiation of cytolytic T cells, using new techniques to reliably grow Ag-specific T cell clones¹⁰. Being able to consistently produce T cell clones led to studies of the regulation and interactions between T helper and killer cell clones in vitro¹¹. Moreover, Frank’s development of the techniques for making T cell growth factor (TCGF) to efficiently expand T cell clones was important in understanding the regulatory role of IL-2 as well as deepening our understanding of the various subsets of T cells.

In this regard, Dr. Fitch was the first to show the antiproliferative effects of IFN-γ on Th2 clones¹² and defined many of the biochemical and functional pathways that determined T cell anergy as well as the progression of T cells to functional subsets including Th1 and Th2^{13, 14}. He also became an early leader in the field of mAb development, generating the first anti-mouse CD4 mAb (GK1.5) in 1983¹⁵, one of the first mAbs made from rats immunized with mouse T cells. Frank was generous with his technological achievements. Like many in the field, Bluestone wrote to Dr. Fitch requesting the mAb for his own T cell studies. Within a week, Dr. Fitch sent the hybridoma, with no strings attached; he did this with many others as we recently learned from Bill Seaman at the University of California, San Francisco. His generosity had such a big impact on Bluestone as a young and aspiring scientist that when his laboratory made the first anti-mouse CD3 mAb¹⁶, he sent it to over 200 people before publishing the paper—another of Frank’s legacies.

Bluestone arrived at the University of Chicago in 1987 as a new faculty member when Dr. Fitch was at the peak of his career. Dr. Fitch was the Albert D. Lasker Professor of Medical Science, Director of the Ben May Institute, and a respected scientist and administrative leader on a national level. He had a reputation as a trustworthy colleague and superb mentor. Bluestone said, “Frank’s greatest attributes taught me the importance of honesty and integrity in science as well as having humility and passion, and most importantly, fun. Frank had a wry sense of humor accompanied by a twinkle in his eye, something we will all miss. He would critique my talks saying, ‘if it ain’t working for you, it’s working against you.’ He participated on many of my students’ committees with pithy comments like the student ‘had all the answers but just did not know what the questions were.’ Together, we taught an undergraduate course in immunology for nonscience majors. We discussed with the students why HIV was more dangerous than herpes, why we shouldn’t be teaching if we were infected with chicken pox, and what was ‘pus’ anyway? Frank was as entertaining as any teacher I knew, an important attribute when teaching science to humanities students.”

When Fitch took over as editor-in-chief of The Journal of Immunology in 1997, he made Bluestone deputy editor, and they focused on the “Cutting Edge” section for which Bluestone was responsible. To improve the citation rate for this section, Fitch and Bluestone included “Cutting Edge” in the manuscript titles so they would be included in PubMed citations.

Bluestone said, “Working with Frank, I felt that sense of support that one can only hope for in a boss and friend, and most importantly, we worked side-by-side on the science. We talked almost every day, and although I was concerned at first when I moved to Chicago that Frank and I might get into each other’s spaces, it was just the opposite. Frank was generous and supportive as we went about our research. When we both took an interest in CD28 and T cell anergy, we published separately¹³ as well as together¹⁷. When I got interested in CTLA-4, Frank stepped aside and gave me the space to pursue this area. We comentored students and sat on each other’s student committees. We worked on γδ T cells together, identifying the ways this novel cell subset recognized herpesvirus antigens¹⁸. Frank, and his students’ many discoveries, changed our thinking about T cell activation and inactivation. “When I say ‘I,’ I mean ‘we.’”

It is impossible to talk about Frank without acknowledging his impact outside the laboratory. “Committees” are a big deal at the University of Chicago, as interdisciplinary groups that weave the campus together. Frank was one of the founders and the first director of the Committee on Immunology in the Basic Science Division at the University of Chicago. He was an ever-present member of the leadership teams of the Basic Science Division, becoming the director of the Ben May Institute, which had been started by Charlie Huggins, the 1966 Nobel Laureate in Physiology and Medicine. During his tenure as third director, Frank grew the Institute from Huggins’ one laboratory to a collection of laboratories working in various areas of cancer research and immunology, thereby positioning it as a leader in cancer and immunology, which it remains today. He was President of the AAI from 1992 to 1993 and President of the Federation of the American Societies of Experimental Biology from 1993 to 1994. Toward the end of his career, he served as the editor-in-chief of The Journal of Immunology. He was a fair, objective, and deeply committed editor who read a large percentage of the 4000 submitted manuscripts, setting a lofty and challenging standard for future editors.

Of course, we cannot write a piece about Frank without highlighting his life partner, Shirley Dobbins Fitch. Shirley was Frank’s muse. She was the matriarch of the family, and by “family,” we mean the students and colleagues as well as their own children, Peggy and Mark. Shirley traveled everywhere with Frank, even when her health deteriorated. Together, they were fixtures at AAI annual meetings, as well as the Midwinter Conference of Immunologists held in beautiful Asilomar, CA. In fact, Shirley would tell Frank he was not allowed to travel over any large body of water without her (and that included Lake Michigan). In the last couple of decades, as Shirley’s health declined, Frank became the cook, house cleaner, financier, and quilt facilitator and would still go to the laboratory every day. They were a team, and everyone knew it.

So, what were Frank’s greatest achievements? Frank’s career has been well celebrated by AAI. He was awarded the AAI Lifetime Achievement Award in 1996, the AAI Distinguished Service Award in 2002, and the AAI Excellence in Mentoring Award in 2004. In 2019, he was elected a Distinguished Fellow of the AAI as part of the inaugural class. Frank is featured in the AAI Oral History project¹⁹, and his early years as a physician and scientist were highlighted in an article about him in the AAI Newsletter²⁰. This article was based on his memoirs as well as personal interviews²⁰. Furthermore, he received the Norman McLean Faculty Award from the University of Chicago, was named a John Simon Guggenheim fellow, and received the Borden Research and Lederle Medical Faculty Awards.

But Frank’s greatest accomplishments were as a teacher and role model for many generations of medical and graduate students. He directly trained 35 graduate students and seven postdoctoral fellows and influenced untold numbers of trainees with whom he interacted at the University of Chicago and beyond. Frank promoted independent thinking and discovery at every level. When you asked Frank a question related to the background of a project, he provided only so much information, so that you would have to discover the answer on your own... in the library!

Frank encouraged original thinking and discovery. To some extent you were on your own to pose questions and test hypotheses in the Fitch laboratory. When it was warranted, however, Frank stepped in at just the right moment to help you appropriately interpret, and most certainly not overinterpret, your experimental data. He taught his trainees to ask important questions and not fret over the competition because no scientist thinks exactly the same way and is unlikely to do exactly the same experiments. Frank taught the value of confirming other studies, although a more-important lesson he emphasized was that it was usually better to have others confirm your studies.

His generosity and interest in promoting the achievements of his students and trainees were unparalleled. When Art Weiss was in the laboratory, as a rule, each graduate student published his or her first paper completely independently. Fitch received acknowledgment in the paper, but he did not appear as a coauthor. He adopted this practice in response to his impression that some investigators took too much credit for the accomplishments of their trainees. Unfortunately, emerging pressures from the diminishing National Institutes of Health pay line and promotion committees prevented this precedent from surviving.

As we have been reading through the many e-mails referencing his passing, many words jumped off the page: integrity, generosity, honorable, principled, creative, socially conscious, courageous, and resilient. It is clear that Frank took enormous pride in his past students’ and postdoctoral fellows’ accomplishments. But this was also the case for all the colleagues he worked with, both scientifically and organizationally. Frank did everything he could to promote their achievements, mentoring them even after his retirement, providing career advice and encouragement long after their day-to-day interactions ended. His eyes would light up to hear about a promotion or award won, a great paper published, or a new discovery by one of his former students. And, of course, he was always pleased to learn of the continued success of his beloved AAI and The Journal of Immunology. His loyalty to the AAI was evidenced by his publication of some 90 papers in The Journal of Immunology over his career (out of a total of 246).

Frank W. Fitch made a difference in this world, a difference in peoples’ lives, and a difference in our understanding of immunology. He left a legacy of profound gentility and grace. As Bob Rich, former editor-in-chief of The Journal of Immunology, said after learning about Frank’s passing, “Every discipline has but a few GIANTS. Frank was one of ours!”
 

Jeffrey Bluestone
Arthur Weiss
Department of Medicine
University of California, San Francisco

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References

1. Fitch, F. W., R. W. Wissler, M. Lavia, and P. Barker. 1956. The timing of antigen injection relative to whole body x-irradiation and the development of circulating antibody and the splenic histologic reaction in the rat. J. Immunol. 76: 151—160.
2. Rowley, D. A., and F. W. Fitch. 1965. The mechanism of tolerance produced in rats to sheep erythrocytes. I. Plaque-forming cell and antibody response to single and multiple injections of antigen. J. Exp. Med. 121: 671—681.
3. Rowley, D. A., and F. W. Fitch. 1965. The mechanism of tolerance produced in rats to sheep erythrocytes. II. The plaque-forming cell and antibody response to multiple injections of antigen begun at birth. J. Exp. Med. 121: 683—695.
4. Stuart, F. P., T. Saitoh, and F. W. Fitch. 1968. Rejection of renal allografts: specific immunologic suppression. Science 160: 1463—1465.
5. Rowley, D. A., F. P. Stuart, and F. W. Fitch. 2011. Prevention of renal allograft rejection without immune suppression: a model to revisit. Clin. Transplant. 25: 104—110.
6. Weiss, A., and F. W. Fitch. 1977. Macrophages suppress CTL generation in rat mixed leukocyte cultures. J. Immunol. 119: 510—516.
7. Weiss, A., F. W. Fitch, T. J. McKearn, and F. P. Stuart. 1978. Immunological memory is regulated in the enhanced rat renal allograft recipient. Nature 273: 662—664.
8. Anders, E., E. R. Dufresne, R. Hayatsu, A. Cavaille, A. Dufresne, and F. W. Fitch. 1964. Contaminated meteorite. Science 146: 1157—1161.
9. McKisic, M. D., D. W. Lancki, G. Otto, P. Padrid, S. Snook, D. C. Cronin II, P. D. Lohmar, T. Wong, and F. W. Fitch. 1993. Identification and propagation of a putative immunosuppressive orphan parvovirus in cloned T cells. J. Immunol. 150: 419—428.
10. Glasebrook, A. L., M. Sarmiento, M. R. Loken, D. P. Dialynas, J. Quintans, L. Eisenberg, C. T. Lutz, D. Wilde, and F. W. Fitch. 1981. Murine T lymphocyte clones with distinct immunological functions. Immunol. Rev. 54: 225—266.
11. Glasebrook, A. L., and F. W. Fitch. 1980. Alloreactive cloned T cell lines. I. Interactions between cloned amplifier and cytolytic T cell lines. J. Exp. Med. 151: 876—895.
12. Gajewski, T. F., and F. W. Fitch. 1988. Anti-proliferative effect of IFN-gamma in immune regulation. I. IFN-gamma inhibits the proliferation of Th2 but not Th1 murine helper T lymphocyte clones. J. Immunol. 140: 4245—4252.
13. Fields, P. E., T. F. Gajewski, and F. W. Fitch. 1996. Blocked Ras activation in anergic CD41 T cells. Science 271: 1276—1278.
14. Gajewski, T. F., D. W. Lancki, R. Stack, and F. W. Fitch. 1994. “Anergy” of TH0 helper T lymphocytes induces downregulation of TH1 characteristics and a transition to a TH2-like phenotype. J. Exp. Med. 179: 481—491.
15. Dialynas, D. P., Z. S. Quan, K. A. Wall, A. Pierres, J. Quintans, M. R. Loken, M. Pierres, and F. W. Fitch. 1983. Characterization of the murine T cell surface molecule, designated L3T4, identified by monoclonal antibody GK1.5: similarity of L3T4 to the human Leu-3/T4 molecule. J. Immunol. 131: 2445—2451.
16. Leo, O., M. Foo, D. H. Sachs, L. E. Samelson, and J. A. Bluestone. 1987. Identification of a monoclonal antibody specific for a murine T3 polypeptide. Proc. Natl. Acad. Sci. USA 84: 1374—1378.
17. Rulifson, I. C., A. I. Sperling, P. E. Fields, F. W. Fitch, and J. A. Bluestone. 1997. CD28 costimulation promotes the production of Th2 cytokines. J. Immunol. 158: 658—665.
18. Johnson, R. M., D. W. Lancki, A. I. Sperling, R. F. Dick, P. G. Spear, F. W. Fitch, and J. A. Bluestone. 1992. A murine CD4-, CD8- T cell receptor-gamma delta T lymphocyte clone specific for herpes simplex virus glycoprotein I. J. Immunol. 148: 983—988.
19. Williams, B. The American Association of Immunologists Oral History Project. Interview with Frank W. Fitch, M.D., Ph.D. (AAI ’61, president 1992—1993). History of The JI. July 2012. https://www.aai.org/About/History/Past- Presidents-and-Officers/FrankWFitch.
20. Emrich, J. S., and C. Richter. 2018. Frank Fitch—The Air Force Years. AAI Newsletter (January/February):30—32.

Memorial donations may be made to:

The Frank W. and Shirley D. Fitch Lectureship
c/o University of Chicago Gift Administration and Business Data
Frank Fitch Memorial
5235 S. Harper Court, 4th Floor
Chicago, IL 60615
Check payable to: “The University of Chicago,” and write “Fitch Lectureship” in the memo line
Donate online at https://bit.ly/3dzyKWd.