I packed my three pieces of furniture and my luggage into the rented Ryder trailer attached to my oil-burning, gas-guzzling 1960 white Pontiac Bonneville and headed toward the Lincoln Tunnel and Interstate 95 south. I arrived at the NIH on June 27, 1968, twenty-seven years old, fresh out of my medical residency training, to begin my fellowship in Bethesda, Maryland, a sleepy country town especially in comparison to the hustle and bustle of midtown Manhattan. One person who shared this feeling of culture shock with me was my good friend Bob Curran, who had just completed with me our years of internship and residency at The New York Hospital–Cornell Medical Center and by some quirk of fate also had obtained an NIH fellowship, his at the National Cancer Institute. Counting our rivalry on the basketball court in high school, this was Bob’s and my thirteenth year in lockstep.
I had had the honor of being the best man at his recent wedding, and Bob arrived with his new bride, Peggy.
My training over the next three years was under Shelly’s tutelage. He was an excellent physician and scientist, a street-smart, self-made, down-to-earth guy from Newark, New Jersey. His major asset was an uncanny ability to sense talent in young physicians and to put them on projects that they could ultimately develop on their own. He would then get out of their way and be available for support and encouragement. Ten years my senior, he not only became my mentor but filled a spot somewhere between an older brother and an uncle. Whenever my emotions got the best of me and I went to him to vent about some perceived academic injustice, such as not getting a scientific paper that I submitted immediately accepted by a journal, he just looked at me, shook his head, said, “Anthony, Anthony,” and laughed; Shelly was the only person outside my family who called me by my full first name. Years later, when I got married, he was my best man.
My basic research laboratory project was involved in the newly emerging field of human immunology, the study of the component of the body that protects one against attacks by infectious diseases and cancers. I was fortunate that Shelly assigned me to a clinical project that was just in its earliest stages. It involved the study of a group of diseases characterized by profound inflammation of blood vessels leading to collapse of the function of various organs such as the kidneys and the lungs. They were referred to as the vasculitis syndromes. Most deadly among these was Wegener’s granulomatosis (now called granulomatosis with polyangiitis). It had a devastating mortality rate of almost 100 percent. We studied our NIAID patients on the wards of the NIH Clinical Center Hospital. Other NIH institutes such as the National Cancer Institute, the National Heart, Lung, and Blood Institute, and the National Institute of Diabetes and Digestive and Kidney Diseases, among others, also studied their patients there. In addition, the Clinical Center was the hub for the multi-institute research laboratories including the one where I worked. The plan was to treat our patients with drugs such as cyclophosphamide (a drug that kills certain immune cells in the body) and steroids (anti-inflammatory drugs) that were being used by the National Cancer Institute researchers working two floors up from us. We used these drugs at much lower doses than those used to wipe out cancers, but high enough doses to suppress the out-of-control inflammatory and immunological responses that were harming the patients whom I was personally taking care of. Because our lab was located within yards of the patients’ rooms, we drew blood, did bone marrow biopsies, and examined these specimens back in our lab for effects of our therapy as we monitored the patients for improvement in their disease. Shelly put me on that project for the three years of my fellowship, and the preliminary results were striking, resulting in a 93 percent remission rate.
My hands-on experience with patients during the years of my fellowship was not limited to work in the Clinical Center. In the spring of 1971, the anti–Vietnam War movement was at a high pitch. There was a massive demonstration in Washington, D.C., involving tens of thousands of protesters who congregated on the Mall and in a nearby park. Calls went out for physician volunteers to be on hand, and I and a few of my colleagues answered the call. We were stationed at a makeshift clinic inside a small church just north of the Mall. After tending to several people with a variety of medical conditions, from poorly controlled diabetes to heat exhaustion, we heard that a group of demonstrators had been tear-gassed and a guy about my age with severe asthma was in distress. His clothes reeked of tear gas when a pickup truck dropped him off in front of the clinic. I was focused strictly on his breathing, and with tears flowing from my irritated eyes, I brought him inside to treat his asthma. Really bad idea! Within seconds, the tear gas that had permeated his clothing had contaminated the inside of the church, causing us to evacuate for about half an hour. There is always something to learn in clinical medicine. If I ever had to take care of a tear-gassed person again, I would remember to take off their clothes before bringing them inside.
As I approached the end of my fellowship, which is a classic decision point in a young investigator’s career, Shelly offered me a highly desirable position at NIAID as a senior tenured investigator, an amazing offer for someone at such an early stage in their career. At the same time, I was offered the position as chief medical resident in the Department of Medicine back at The New York Hospital–Cornell Medical Center, a stepping stone to a lucrative hospital-based or private practice there. Being the resident in charge of the care of internal medicine patients and the training of younger physicians in a globally preeminent hospital was very appealing. Before I came to the NIH, this is exactly what I thought I wanted to do. I still cherished the opportunity to be chief medical resident, although as much as I loved the hands-on care of patients and totally respect and even admire physicians who do this full time, I now did not want to do only clinical work without a research component. I wanted to do both, and I felt that I could do this best at the NIH. I had begun to think about and appreciate more and more the concept of my work having a multiplier effect. As the leader of a research team at the NIH, I felt we could use the information we gathered from the detailed study of our patients to contribute to the medical literature. This knowledge could then inform hundreds of physicians throughout the world who could use that knowledge to benefit many thousands of patients. As good as I was in a one-to-one interaction with an individual patient, the impact of my studies could potentially go well beyond the patient for whom I was caring.
I worked out a deal with Shelly that I would go back to New York, serve the year as chief medical resident, and then resume my work at the NIH as the head of my own laboratory doing basic and clinical research on the interface between infectious diseases and the human immune response.
My year of chief residency was one of the most challenging and exhilarating years of my life. It was clinical medicine at its best. I had about fifty younger physicians under me, and I liked the role of teaching them the art and science of clinical medicine. I was called to see the sickest and most clinically complicated patients in the hospital: diabetic coma, GI bleeds, heart attacks, congestive heart failure, overwhelming infections, patients without a clear diagnosis but who were desperately ill. I was on call every other night and every other weekend. I was single and this was my entire life. I learned an enormous amount and honed my clinical skills to the point that I felt there was no medical problem that I could not handle and handle as well as anyone, and I loved it, every minute of it.
When I returned to the NIH in July 1972, I picked up where I had left off at the Clinical Center. I continued my basic research studies on the regulation of the human immune response while expanding my clinical studies on patients with the vasculitis syndromes. As with our earlier studies on granulomatosis with polyangiitis, we were now getting equally dramatic results with our therapeutic regimens on other related inflammatory vascular diseases such as polyarteritis nodosa, which often led to death by renal failure, heart attack, and/or stroke.
Five years after I returned, Shelly left the NIH to become chairman of the Department of Medicine at Tufts Medical Center in Boston, and I carried on with the vasculitis program with even greater success over the next several years. Although the diseases were uncommon, our research led to the saving of many lives directly by us, and by physicians throughout the world who were now using our protocols. My upward career trajectory was steep. I was becoming well-known and respected nationally and internationally in this somewhat narrow field (at the time) of the treatment of autoinflammatory diseases. Several years later, a Stanford University Arthritis Center survey of the American Rheumatism Association membership ranked my work on the treatment of polyarteritis nodosa and Wegener’s granulomatosis as one of the most important advances in patient management in rheumatology over the past twenty years.
I had already been elected into several honorific academic societies and was being offered endowed chairs in Departments of Medicine in prestigious medical centers throughout the country. But I felt at home in the intellectual atmosphere of the NIH and had no interest in leaving for an exalted title at another institution.
Despite these professional milestones, for reasons I could not fully understand at the time, part of me felt unfulfilled. For the prior few years, I had the nagging feeling that although I was academically successful and our work was saving lives, something was missing. I had met the main challenge of developing effective therapies for formerly fatal diseases. But we were dealing with unusual diseases that lacked a broad public health impact. Certainly others would come along and improve on what we had done, but what I was doing now seemed to me to be only incremental. I had been on a clear path ever since I had decided as a student at Regis High School twenty-five years earlier to become a physician. Now I was forty years old, and I was starting to feel unchallenged. I was at a crossroads.