Anthony Monaco, the Peter Medawar Professor of Surgery Emeritus at Harvard Medical School (HMS) and Director Emeritus of the Division of Transplantation at Beth Israel Deaconess Medical Center, was a pioneering transplant surgeon, scientist, teacher, mentor, collaborator, and friend to many. Tony dedicated his entire career to clinical and experimental organ transplantation and scientific research related to immunology. He founded the organ transplantation service in the Harvard Division of Boston City Hospital, which subsequently became the Transplant Division at Beth Israel Deaconess Medical Center (BIDMC). Today, this division is named in Tony’s honor.
Dr Monaco’s major research breakthroughs came from his laboratory early in his career, setting the foundation for decades of research and clinical advances formative to the growth and development of transplantation, benefitting all those needing organ transplants. He was a pioneer in the field whose first research breakthrough demonstrated that antibodies generated by animals to immune cells could suppress organ rejection. This research produced “antilymphocyte serum” and opened the door to the large and growing class of therapeutic products that remain in use today in and beyond organ transplantation. Tony’s work also critically contributed to our current understanding of how to achieve transplantation tolerance.
Dr Monaco was President of The Transplantation Society (1986–1988) and Editor-in-Chief of Transplantation, and among the many recognitions for his contributions and scientific achievements, he received the Medawar Prize in 1998. He was also a founding member and Chairman of the New England Organ Bank, President of the American Society of Transplant Surgeons, and an Honorary Fellow of the Royal College of Surgeons of England. Most importantly, Tony developed and maintained extraordinary and lifelong friendships and was a mentor and friend to many whose lives and careers have been critically impacted by Tony.
Some of those have come together to share thoughts, recognizing Tony’s many contributions. Although reading this piece, we can see the characteristically uplifting, calming, and at the same encouraging smile on Tony’s face.
Human qualities including kindness and honesty shaped Tony’s whole life on his way to the many pioneering achievements and especially to his extraordinary mentorship.
Working closely with Tony, how did his characteristic traits shape his immediate environment and our field in general?
MH: I feel more blessed than others because I was his first fellow at the Harvard Division of Boston City Hospital in 1968, after he left Massachusetts General Hospital (MGH). Drawn to him by his book on basic immunology, I ended up learning not only basic immunology but also how to set up a new Hemodialysis and Transplantation Service that became the Beth Israel/Deaconess Transplantation Service. Tony inspired everyone to do more than their best by being an extraordinary role model. He dealt with all equally, with respect and friendship. He was generous with praise, and silence was his greatest sign of dissatisfaction. He loved to hear new ideas and facts, from science to politics. Tony and his friend Gene McDonough taught me how to do renal transplants and how to recover organs. Tony also taught me how to organize and deal effectively with administrators and how to immunosuppress and take care of patients and even how to hemodialyze.
Transplantation was a hobby in those early days, but for Tony, it was a passion from the start and remained so. He had incredible determination to continue to contribute to the development of transplantation, even after his “retirement.” The weekend announcements in those early days always included the mission of “tolerance on Monday.” In the laboratory, the work was at the cutting edge of what was known and was always novel, honest, and exciting. The team led by Mary Wood (his collaborator and his unofficial “co-editor” for Transplantation) and Ingrid McDonough, his chief technician, taught us everything we needed to know about mice and cells. It is remarkable how many ideas and initiatives Tony pursued with the ultimate goal of reaching the “holy grail” of tolerance.
Loss of his larynx did not slow him down, and he became an example to us all on how to overcome major adversity and keep on going. The team published and presented in distinguished journals and at national and international meetings. It was a beehive of activity interrupted only briefly on winter weekends by ski trips after the Monacos bought a new house in Vermont and by travel to meetings where Tony introduced and praised his mentees to all who would listen. As Sir Peter Medawar once said, “It was a golden era in transplantation,” and Tony was one of its main angels.
Teaching, doing good, and loving and caring for his family and his mentees were his goals while making major contributions to the field of immunobiology. He accumulated many well-deserved honors along the way, but his greatest satisfaction and pride came from the love of his wife, Mary Lou, the accomplishments of his children, and those of the many fellows whom he had trained.
Dr Monaco adopted the concept of using antibodies to human lymphocytes generated in animals to suppress immune effector cells, leading to a product called antithymocyte globulin that is being used in and beyond organ transplantation. What are recollections of the development of this immunosuppressive milestone?
BC: I first met Tony in 1966 during my second year of surgical training. Tony had just completed his residency and had joined the MGH Transplant Division 3 y earlier. He was already well on his way to becoming a leader in the field, especially in studies of the biologic immunosuppressive agent, anti-lymphocyte serum (ALS). The MGH team had observed remarkably prolonged survival of skin allografts in mice treated with serum taken from rabbits, previously immunized with mouse lymphocytes. Tony was now combing the operating rooms, looking for “spare” lymph nodes to inject human lymphocytes into his rabbits for production of ALS to treat human kidney transplant recipients.
Tony was a tireless surgeon-scientist, committed to bringing ALS to the bedside. He was always bubbling over with recent findings, often scribbling the data on whatever writing surface was available. During a plane trip, Tony told me about his new large animal model. Some of his dogs that had received kidney transplants and treatment with rabbit anticanine lymphocyte serum had survived for more than a year.1 In his excitement, Tony had written the data on the fold-down seatback table in front of him. It was only Tony’s Italian, boyish charm that saved us from the ire of the flight attendants.
In early 1967, Tony was one of only 24 investigators, judged to be the world’s foremost experts, who were invited to a special study session on ALS in London. At that meeting, Tony presented his observations alongside such renowned giants as Medawar, Gowans, Woodruff, Humphrey, Starzl, and Russell. Tony had clearly made it to the “Major Leagues.” These seminal reports were immediately published in the widely cited Chemische Industrie Basel Foundation Study Group series.2
The initial MGH cautious studies in humans were primarily limited to in vitro assays and skin grafts in volunteers.3 Positive results encouraged moving forward to clinical trials. To provide adequate supplies for clinical use, Tony’s production of ALS was eventually extended to horses that were immunized with human thymic tissue. This approach was adopted by the Upjohn Company to provide the first commercial product (antithymocyte globulin) in the United States, which remains in clinical use nearly 50 y later.
Tony’s greatest dream was to direct ALS’s remarkable lymphodepleting effect to achieve tolerance. He felt that, in combination with donor antigen, ALS could produce specific unresponsiveness in adults, comparable with that described in neonates by Sir Peter Medawar. In fact, early murine observations suggested he was right,4,5 although extending this approach to humans proved to be much more difficult.6 It took more than another decade for us to define treatment protocols that could reproducibly induce tolerance in humans. Not surprisingly, Tony’s basic concept of combining profound lymphodepletion with donor antigen infusion provided the concept with the most successful approach to achieving tolerance.
In contributing to novel concepts of tolerance and other sentinel findings, Tony Monaco focused on the critical collegial and productive interaction of clinicians and basic scientists. What were the principles that he emphasized, and how have they shaped our current approach to problem solving?
DS: Tony Monaco will be remembered both for his scientific contributions and for his ability to get people with different talents to work together for a common purpose. His knack for achieving cooperation among his colleagues was best exemplified by his leadership role as Editor of Transplantation, in which his warm tolerance for different opinions allowed him to mediate frank discussions among colleagues, leading to compromise rather than arguments.
I met Tony Monaco shortly after joining the Russell Laboratory at MGH as an HMS elective medical student in 1965, and I learned quickly about the important work he had done in that laboratory before my arrival. We then met many times as colleagues at various meetings during the 20-y period I spent at the National Institutes of Health before returning to the MGH in 1991. However, it was not until I accepted his invitation to join him as 1 of 3 new North American Editors of Transplantation in 1997 that I began to know him well. I learned quickly that it was difficult to say no to a request from Tony, which made it possible for him to bring together scientists and clinicians and make them aware of their common interests and goals. Who couldn’t help but be impressed and inspired by his courage, his ability to overcome obstacles, and his will to contribute to both the scientific and the clinical advances in our field? He had a way of analyzing problems and helping to find solutions that were very convincing. He used these talents to rejuvenate Transplantation and to construct a highly productive collaboration between the publisher and the editors. He was indeed the guiding force in bringing the journal Transplantation to success as the official journal of The Transplantation Society, of which he was President. This became the first international journal at the interface between the basic and clinical arms of this exciting field.
As an editor of the journal Transplantation, Dr Monaco took it from an embryonic effort to the major clinical and scientific information source that it is today. What were some of Tony’s contributions and his lasting impact on the success of the journal?
MS: My first exchanges with Tony were from submitting articles to Transplantation. Although I would have preferred a higher percentage of my submissions to be accepted, I found Tony as the Editor to be highly ethical, fair-minded, unbiased, and scientifically rigorous. These much-needed qualities were central reasons for me to accept Tony’s invitation as he expanded the journal to serve as 1 of the 3 North American Editors. I never approached him for this prestigious position, and there was no quid-pro-quo except to preserve and protect the scientific integrity of the journal. Imitation is perhaps the sincerest form of flattery, and I followed his example of editorial decision-making not based on the impact factor or reprint purchasing potential but exclusively based on the originality and scientific rigor of the submitted article. The legendary editor of the Washington Post, Ben Bradlee, is quoted to have said, “Editors decide.” In the highly competitive academic field, editorial decisions, especially for young investigators, can make or break their careers, and it was refreshing to witness firsthand Tony handling submissions from budding scientists with the same respect as the submissions from more established ones.
Several years into my own tenure as the Editor, Tony stepped down as the Senior Editor of the North American Editorial office, and I took on (without campaigning for it!) the responsibility of managing the North American Editorial Office. We wanted to retain Tony’s wisdom, and we created the position of Special Features Editor, who would write without fear or favor on areas including policies pertinent to our chosen field and reject or accept the never-ending requests for special interest supplements. When Sir Peter stepped down as the Senior Editor of the European office, the dynamic duo of Tony and Peter became Special Features Editors and never let mercantile interests supersede scientific priority.
In every religious persuasion, a prevailing theme is that we must leave this world better than we found it. Tony is an exemplar of this axiom.
Rounding with Tony was always full of stories and a learning experience of how to care for patients and how to be innovative in treatments. What are the recollections of his role as a mentor?
LP: I was introduced to Tony at the beginning of my career as an intern. He stood up and shook my hand—very polite and very formal. I was struck by his gracious cordiality. Tony was unfailingly polite and compassionate. I also remember the time when I realized that I was now a full-fledged member of the team on the day he said “damn” in front of me and did not apologize. Dr Monaco taught me how to do a kidney transplant as a second-month intern, and his calming demeanor and dignified patience were greatly appreciated by a nervous trainee.
Tony had a legendary unease around computers that was ironic. Somehow, he was never able to remember his password, motivating his staff to ingeniously change it to “Medawar” for all to remember. As a transplant fellow, he treated us like colleagues and entrusted us to review some seminal papers that appeared in Transplantation.
Tony’s perseverance after his medical hardship was inspiring. Most people thought he would retire after undergoing a total laryngectomy. It is impossible to overstate how difficult that time was. Mastering esophageal speech was a slow process. He had a talk to give—the first since surgery—about innovations in transplantation. He was nervous but stood at the podium, held his voice synthesizer up for the audience to see, and said that “innovation in medicine was alive and well and he was the proof.” The audience stood and cheered. Through his determined mastery, he was able to influence future generations in the same manner he had done with me.
Tony Monaco was a true leader in all aspects of our field. What were the experiences of clinical collaborations and daily interactions as a door-to-door office neighbor, friend, supporter, and colleague?
MP: I knew about Dr Tony Monaco when I entered the field of kidney transplantation as a research fellow in Terry Strom’s laboratory at Beth Israel Hospital. Tony’s reputation was legendary even then. However, it was not until 1999 that I had the opportunity to know him as a colleague. At that time, I assumed the medical directorship of the kidney and pancreas transplant programs at the newly merged BIDMC. In the ensuing few years, as Tony was ready to pass the reins of the surgical directorship to Doug Hanto, I wondered how such a strong and prominent surgeon will take to having someone else in charge. I must admit I worried that Tony would struggle with his new role as a “simple” transplant surgeon who was no longer the chief. I learned about Tony’s true strength as I saw him, almost seamlessly, transition to the role of a wise elder statesman who “only” operated. He was available for counsel when asked as he continued to attend our conferences, meetings, and events. His advice reflected his years of experience, his wisdom, and his decency. On one occasion, he listened quietly while we struggled to figure out how best to address a patient’s difficult posttransplant issue. When asked, Tony simply said, “I’d leave the guy alone and let him heal.” That is exactly what we did, leading to a successful outcome. He often voiced the wise restraint in the face of uncertainty and the urge of younger clinicians to “do something” when patience was what was required.
When Tony stopped seeing patients in the clinic, his request was that I inherit all of them. It was a great honor. To this day, I care for patients asking me at the end of their visit, “and how is Dr Monaco?”
Tony’s example of how to work and live your values in the latter stages of a successful career is what I found truly inspiring and a model for all of us.
Beth Israel Deaconess Hospital under your leadership has recognized Tony’s many contributions, dedicating the transplant unit in his name. Can you share details and comment on your relationship with Tony after he discontinued his surgical career?
DH: While I was a surgery resident working in Dick Simmons’s transplant immunology laboratory at the University of Minnesota, Mary Wood, who was Tony’s right hand in the laboratory and in editing Transplantation for many years, visited the laboratory to learn about our sponge matrix allograft model so they could study cellular infiltration in their mouse tolerance model. It was through this chance interaction in 1981 that I later met and got to know Tony and his wife Mary Lou, often meeting at national and international meetings. After I succeeded Tony as Chief of the Division of Transplantation at BIDMC in 2001, our friendship and mutual respect grew from our shared interest for patient care, teaching, and research and our desire to see transplant flourish at BIDMC. He was a supportive and wise counsel in all things, and we often met in his office for wide-ranging discussions of issues of work and home.
Tony continued his laboratory research until his longtime friend and collaborator Takashi Maki retired and returned to Japan, but he continued working on moving his tolerance induction protocols into patients. Tony also continued to operate and see patients for several more years while also doing special projects for Transplantation. When he turned 75 y old, he decided to stop operating, not because he had to (he was still an excellent technical and clinical surgeon) but because he wanted to make room for the younger surgeons. Always putting others first.
Before leaving BIDMC, I suggested to the Chair of Surgery, Dr Elliott Chaikof, that the Transplant Service be named after Tony because of his many groundbreaking contributions to transplantation and his long-term commitment to BIDMC. Dr Chaikof enthusiastically agreed, and the service was named the “Anthony P. Monaco Transplant Service” at an event in Tony’s honor at the Harvard Club in 2016. After I left BIDMC in 2012, Tony and I maintained our close friendship.
In 2019, I started commuting between St Louis and Boston on a weekly basis while pursuing a Master’s degree in Bioethics at HMS. Sadly, Mary Lou had died the year before, but Tony was still living in their home in Newton where he and Mary Lou had raised their daughter, Lisa, and 3 boys, Peter, Mark, and Christopher. He invited me to stay during my overnight stays in Boston. I would come to his home after class in the evening, and he would prepare a 3 course (often Italian) meal that we would enjoy together while talking about transplant—past, present, and future world events, bioethics, and any recent books we had read. We also bragged about our kids and grandkids, of which we were both proud. We retired to his study after dinner, and under the watchful eye of Tony’s visage, painted by Sir Roy Calne, that hung above the leather sofa, we would watch the news and continue our conversations. Some weeks I would stay for 2 or 3 d, and other weeks I would leave the next day, but we both looked forward to my return the next week and the continued renewal of our close relationship. This routine was interrupted by coronavirus disease 2019 in 2020, but it could not undo the bond that was our close and enduring friendship.
New transplant centers were established following early clinical progress and an improved understanding of immunity. Tony was instrumental in the development of many centers around the world. His contributions to the establishment of the Transplant Center at Rhode Island Hospital, which he also directed for some time, was also critical. What are lasting memories of these shared times?
PM: At New England Deaconess Hospital (known today as BIDMC), Tony had grown a world-class transplant program that quickly became the main kidney transplant referral center for patients from Rhode Island.
In 1996, at the request of the Rhode Island nephrology community, Tony established the kidney transplant program at Rhode Island Hospital along with Reginald Gohh, a recent graduate of the Brown University Renal Fellowship, who coordinated the medical aspects of the program. This was the beginning of the Rhode Island Hospital’s Transplant Clinic, which initially consisted of 1 nephrologist, 1 nurse, and 2 Boston surgeons, and where Rhode Island patients were evaluated and followed.
On March 23, 1997, 2 Rhode Island residents were transplanted at Rhode Island Hospital by Tony Monaco and Peter Madras, marking the first kidney transplant operation to be performed in Rhode Island since 1973. Fast-forwarding to today, the Rhode Island program is happily anticipating its 1500th transplant procedure this winter. Our program is an example of Tony’s selflessness and dedication and his willingness to put his patient’s best interests far ahead of his own. Our Transplant Division flourished under his tenure as Director for a decade, at which time he took on the role of Emeritus, leaving the day-to-day affairs of the program to my current team. Although he was a Harvard-affiliated surgeon his entire career, it was natural for Tony to recognize the local desires of patients and the necessity to establish a new transplant program in Rhode Island to serve its residents. It has been my honor to carry on Tony’s work here in Rhode Island and, in some small way, to build on his remarkable legacy and generosity.
What contributions including shaping the international impact of transplantation on the public, governments, and practitioners have been particularly outstanding and long-lasting?
REM: Tony was an important transplant surgical research role model during my first exposure to the field of transplantation in the late 60s as an undergrad at Stanford and later as a Stanford University School of Medicine Medical Scientist Training Program medical student doing research in transplantation. We Stanford alumni refer, with thinly veiled envy, to Harvard as “The Stanford of the East.”
The >3 dozen publications Tony managed to publish when he was President of The Transplantation Society from 1986 to 1988 and his publications in 1989 from his work when he was President are a testament to Tony’s basic and clinical research contributions to our field.
The best autobiographies can often be superior to the best attempts at biographies, so I recommend Tony’s book chapter titled “A Personal Memory of Antilymphocyte Serum and Its Impact on Transplantation” in the History of Transplantation: Thirty-Five Recollections (Paul I. Terasaki, Ed, 1991, UCLA Tissue Typing Laboratory). Tony’s research focus on ALS and, later, ALG recapitulated the history of anti-infectives. Just as treatment of syphilis began with Paul Ehrlich’s small, synthetic organic drug and the field evolved to von Behring’s biologic therapeutic anti–diphtheria toxin antibody treatments, transplant immunosuppression also began with small molecules and later added “biologics,” ALS being the first followed by monoclonal antibodies.
Tony’s presidential address published in Transplantation7 provides evidence of Tony’s deep and broad insights about areas in transplantation far beyond his basic and clinical research contributions. The title of his address was “Problems in Transplantation—Ethics, Education and Expansion.” In this address, Tony does not focus on a recitation of his research accomplishments; rather, he starts by reviewing critical ethical guidelines including donor organ trafficking, preference for transplants in wealthy foreign nationals to the exclusion of transplants in US citizens, and guidelines for living donor transplantation. Tony is very clear that basic or applied transplantation research needs to be an integral part of the education and training of transplant surgeons. The final topic of Tony’s address focuses on the expansion of clinical transplantation that had become all too influenced by some hospitals’ primary rationales for creating transplant programs primarily to increase their market shares for all types of patients.
Tony ended his address on a typically positive and enthusiastic note by writing, “Transplantation is a vibrant, vital field, ever changing, ever challenging, ever stimulating, ever accomplishing…So to you younger members I emphasize this wonderful vitality of transplantation…You get from it and you give to it depending on your hard work and contributions.”
That quote is how I will always remember Tony most; he radiated his love for both basic and clinical transplantation and for his patients, who benefitted so much from his dedicated care.
Dr Monaco was a thoughtful and inspirational mentor to many who are now in leading positions around the world. What was his mentoring “secret?” How did his teaching help you and others as current leaders in the field?
SN: It is an impossible task to relate, in a paragraph, what Tony Monaco meant to me as a mentor and what he meant to our field as an educator and a scientist. If I had to choose 1 word to describe Tony, I would say that word is “dedication.” Tony was fiercely dedicated to his craft, his patients, and the training of the next generation of transplant surgeons. I had the distinct privilege of training under Dr Monaco and remember vividly my first operative transplant experience when I saw, for the first time, a transplanted kidney pink up after reperfusion. I was so amazed by what I had just seen that I whispered under my breath something to the effect of “that’s awesome.” Dr Monaco, on hearing what I said, immediately stopped what he was doing, took my hand in his, looked me dead in the eye, and said something to me that I will remember for the rest of my life: “Don’t ever lose that sense of awe. If you ever reach a point in your career when you are no longer awed by the organ making urine, or bile, or insulin, it’s time to step away.” Over the last 5 decades, Dr Monaco has made innumerable contributions toward bettering our understanding of immunosuppression that had a major clinical impact on the life of our patients and their grafts. His legacy as the quintessential surgeon-scientist will be carried forward into the future by all his mentees, in whom he fostered a love of transplantation and a respect for science. I feel fortunate beyond words to be numbered among them.
The transplant community has lost a true trailblazing pioneer, a world-class surgeon-scientist and a towering, inspirational figure, a friend, and a colleague who always had an open door to his home and office.
ACKNOWLEDGMENTS
The author appreciates the contribution of the following individuals for this article: Mark A. Hardy, MD, PhD (Hon), FACS, Auchincloss Professor of Surgery, Director Emeritus and Founder Transplantation Program, Columbia University Medical Center, New York, NY; Dr A. Benedict Cosimi, Claude E. Welch Distinguished Professor of Surgery, Chief Emeritus, Transplantation at the Massachusetts General Hospital, Boston, MA; David Sachs, MD, Professor of Surgery in the Center for Translational Immunology at Columbia University and the Paul S. Russell Professor Emeritus at Harvard Medical School, Boston, MA, and New York, NY; Manikkam Suthanthiran, MD, Stanton Griffis Distinguished Professor of Medicine, Medicine, Weill Cornell Medical College, New York, NY; Elizabeth Pomfret, MD, PhD, Chief of Transplantation; Igal Kam, MD, Endowed Chair of Transplant Surgery, Executive Director, Colorado Center for Transplantation Care, Research and Education University of Colorado Anschutz Medical Campus, Aurora, CO; Martha Pavlakis, MD, Medical Director, Kidney Transplantation, Beth Israel-Deaconess Medical Center, Boston, MA; Douglas W. Hanto, MD, PhD, MBE, Co-Chair, Surgical Ethics Working Group, Harvard Medical School Center for Bioethics Lewis Thomas Professor of Surgery Emeritus, Harvard Medical School, Boston, MA; Paul Morissey, MD, Professor of Surgery, Warren Alpert Medical School at Brown University, Director, Division of Organ Transplantation, Rhode Island Hospital, Providence, RI; Randall E. Morris, MD, FRCP, Research Professor of Cardiothoracic Surgery and, by courtesy, Medicine and Surgery (Emeritus), Stanford University School of Medicine, Stanford, CA; Satish N. Nadig, MD, PhD, FACS, Edward G. Elcock Professor Surgery, Microbiology/Immunology, and Pediatrics; Chief, Division of Abdominal Transplant Surgery; Director, Comprehensive Transplant Center; Co-Director, Comprehensive Transplant Immunobiology Laboratory, Northwestern University, Feinberg School of Medicine and Northwestern Medicine, and Lurie Children’s Hospital, Chicago, IL.
