Remarks by Jeffrey V. Ravetch

June 9, 2016

I am both honored and delighted to offer tonight’s tribute to my colleague and friend Max Cooper on receiving an honorary degree from The Rockefeller University.

Max Cooper is one of the towering figures of modern immunology, responsible for ground breaking observations on the development of the immune system that form the foundation of our understanding of this complex network of organs, cells and molecules responsible for insuring our survival in a hostile microbial world. Over a period of more than 50 years he has made remarkable contributions to the study of adaptive immunity, that arm of the immune system that responds with exquisite specificity to foreign threats and retains a memory of such encounters.  Max is rightly credited with having set that field in the mid-sixties to mid-seventies on the course it has followed ever since, paving the way for some of the greatest discoveries in the science of immunology with far-reaching implications for human medicine.

The outlines of Max’s scientific career are the kind of stuff we expect from the imaginations of Hollywood producers. Max Cooper was born in rural Mississippi, the son of schoolteachers, more interested in hunting, fishing and athletics than scholarship. This Tom Sawyer childhood was brutally interrupted by the tragic death of his beloved older brother in an automobile accident. Out of this grievous tragedy, however, came an unexpected gift. Max’s brother had named him the beneficiary of his service insurance policy, giving Max the financial means to attend medical school and setting him on the course that brought him here today, celebrated for the most profound scientific accomplishments. He attended medical school at Tulane University, receiving his doctoral degree in 1957. Max and his wife Rosalie moved to London where Max began his scientific career began in earnest in 1961 as a Research Assistant at the Hospital for Sick Children in London, followed by a year and at the University of San Francisco. While most of us might bring home a souvenir from our travels, a keepsake to remember a pleasant trip, Max and Rosalie had a different idea of how to remember a city – they had a child in each, Melinda in London and Bo in San Francisco.  In 1962, Max and Rosalie, now with Melinda and Bo in tow, moved to the University of Minnesota to continue his training, first as a postdoctoral fellow and then as an Assistant Professor at the University of Minnesota. And, as you probably guessed, Michael was born in Minneapolis (it was another city, after all).  What was to happen next was nothing less than extraordinary. In the movie version we’d see the clouds part and a beam of sunlight burst through to illuminate Max as he stood at his bench in the lab. We’d cue the chorus from the final scene of Turandot. For during the next five years Max was to accomplish nothing less than to revolutionize our understanding of the immune system, demonstrating that the adaptive immune response developed from two separate compartments of lymphocytes, and in the process discover the B cell, the source of antibody production. More on this shortly. He was then appointed Associate Professor at the University of Alabama, Birmingham, where he remained for more than 40 years, rising through the academic hierarchy to become a Professor and Division Director and, of course, a father for the fourth time; Chris was born in Birmingham. Max continued his remarkable career in Birmingham, discovering not only the diversification of antibody effector functions, a topic dear to my heart, and the cellular hierarchy of B cell development, but uncovering the evolutionary roots of the adaptive immune system in the earliest vertebrates. Max moved from Birmingham to Atlanta eight years ago where he is presently a Professor in the Department of Pathology at the Emory University School of Medicine in Atlanta, Georgia, and an Eminent Scholar of the Georgia Research Alliance. And while Atlanta is a new city for Max in his scientific march, and should have meant yet another child, apparently he and Rosalie have moved on from the production of children to the acquisition of grandchildren.

Allow me to take a minute or two to put Max’s accomplishments in perspective.  In 1964, when Max discovered that two distinct lineages of lymphocytes were responsible for the two arms of the adaptive immune response, the cellular and humoral, the field was in ferment.  Conflicting models were proposed for how the immune system recognized foreign matter and which organs, cells and molecules were responsible. Few tools existed to dissect the complexity of the immune response – gene cloning and sequencing were a decade or two away, the tricks of the cell biologists were still in their infancy.  Whole animal studies were the preferred route of experimentation, with all their inherent ambiguities and pitfalls. It took extraordinary skill and insight to design experiments that would yield clear results and truly illuminate a problem as complex as the immune response.  I’d like to think that Max came to the solution of this problem by virtue of his unique history, his boyhood roaming the woods in rural Mississippi, his familiarity and comfort with the diversity of natural forms.  For Max took an evolutionary approach to solving the problem of how the adaptive immune system works, turning to chickens to solve the problem.  You don’t hear much these days about chicken immunology and I’d be hard pressed to name anyone who would consider chickens as a model organism.  But to Max, they were the perfect species to address this thorny question.  In a series of tour de force experiments Max removed the specific organs from newly hatched chicks that were implicated in immunity, the thymus or the bursa of Fabricius, and then irradiated the surgically treated animals to remove all residual lymphocytes. Not only were these technically challenging studies, they were viewed with suspicion, and, I suspect, a fair bit of derision.  More than one colleague in the lab wondered what Max was up to with his sick chickens and whether he knew what he was doing.  But the results couldn’t have been any clearer.  Max demonstrated a complete absence of antibodies in every bursectomized and irradiated bird even though they had normal thymus development and an abundance of lymphocytes elsewhere in the body. Conversely, the thymectomized and irradiated chickens were grossly deficient in lymphocytes, yet retained the ability to make immunoglobulins. Follow-up studies indicated that the thymus was essential for development of the lymphocytes that mediate cellular immunity such as graft rejection or delayed type hypersensitivity. These results revealed an unmistakably clear view of two lymphocyte lineages, one thymus-dependent, hence the name T cells, and the other bursa-dependent, the eponymous B cells. In Max’s 1965 model of the immune system, the T cells were not only responsible for cellular immunity but also physically and functionally integrated with the immunoglobulin-producing lineage of B cells in peripheral tissues. The model has not only stood the test of time, but forms the foundation for all contemporaneous studies on the immune response and the revolution in vaccine development and immunotherapy that have improved the lives of millions.

The papers Max wrote on these experiments are classics, required reading for every immunology graduate student and, if it was up to me, should be required of every college student as well.  They are paradigms of scholarship, brilliantly illustrating how to approach a complex problem with clarity and to execute and then interpret the results in a way that every educated person should be able to understand and appreciate.  Reading these papers today still sends a chill up my spine.  If there’s a poetry to science, it is to be found in Max’s publications.

For most of us the studies that led to the discovery of the B cell would have been more than enough to define a career and cement a reputation.  Not for Max.  I’d love to go on to describe in detail the beauty of the experiments that followed (and unless I’m stopped I probably will), experiments that demonstrated that antibodies can switch from one isotype to another, explaining how different biological responses can be coupled to the same recognition function.  While always the quintessential scientist, Max was also a devoted clinician, dividing his efforts between patient care and laboratory research. His clinical activities centered on immune system disorders, including immunodeficiency diseases and lymphoid malignancies, defining many of the defects in the immune system that result in these clinical syndromes. And finally, as you’ve heard, throughout his career Max has maintained a keen interest in the evolution of the immune system. Typically for Max, he singled out and recently solved the most fundamental question of all, of how and when the adaptive immune system evolved.  It had been a matter of dogma that adaptive immunity with its remarkable ability for diversification through somatic recombination, mutation and selection arose only in the cartilaginous, jawed fishes, such as sharks. More primitive species were thought to lack such diversity. With uncanny perspicacity, Max turned his attention to a primitive jawless vertebrate, the lamprey, to make a mind-boggling observation.  Adaptive immunity arose in those organisms 500 million years ago in a tantalizingly different form, retaining features of diversification and compartmentalization familiar to us in mammalian evolution, but in a novel and equally effective way.  Max thus discovered that two adaptive immune systems arose independently, each built upon the principle of genetic recombination within somatic cells, but utilizing different molecular building blocks. It sometimes seems incomprehensible to me how Max continues to churn out these fundamental discoveries.  He’s making the rest of us look bad.

I’d like to end with a few words about the man.  I’ve had the good fortune to get to know Max pretty well, spending time together not only as colleagues but as friends.  We’ve travelled together, fished together (there’s another story there, but not for tonight), eaten some amazing meals together and shared confidences.  My wife Wendy and Max’s son Chris were partners in an architecture practice for 7 years.  I’ve had the pleasure of visiting the Coopers at their home in Birmingham and then Atlanta and their summer home in Brittany, drinking too much of Max’s favorite Italian wine and talking late into the night.  And from all those experiences one simple fact emerges.  Max is the finest person I know. His reputation among our colleagues is unequalled. In a world of pettiness and temperament, Max is the voice of reason and encouragement.  He carries himself with grace and humility, with a deep and genuine concern for the welfare of others, respecting and admiring the work of his colleagues. Like his science it defies explanation. And so say we all.

Max, I congratulate you on your remarkable career, your terrific family and your unfailing commitment to your science and your colleagues. It has been my privilege to work with you and to count you as a friend.  And now I can count you as a colleague on the Rockefeller faculty.  We’ve honored to have you join our ranks.