As we face off against Covid-19, we urgently need physician-scientists who can quickly translate observations made at patients’ bedsides into therapies. Sadly, they are in short supply.
Physicians who also have extensive training in scientific methods, often a Ph.D., are ideally suited to learn from the unusual clinical manifestations of Covid-19, such as strokes in young adults and autoimmune Kawasaki syndrome in children. Physician-scientists, however, are becoming extinct in the United States, comprising only about 1% of all physicians today, and with few young clinician researchers joining their ranks.
A solution to this crisis might be found in a quiet research program at the National Institutes of Health that flourished in the shadow of the Vietnam War. It may well have been the greatest medical research program in modern history. The two-year program, officially known as the NIH Associates Training Program, was started in 1953 as a way to bring newly minted physicians to the NIH campus in Bethesda, Md., so they could do research for two to three years under the guidance of senior NIH investigators.
Applications for the program surged during the Vietnam War. Why? It was one of the only ways for medical students to avoid being inducted into military service through the “doctor draft” and sent to Vietnam. Between 1955 and 1973, almost 3,000 medical school graduates enrolled in the program.
Nine physicians who trained at the NIH during this period went on to win Nobel Prizes. From the class of 1968 alone, Robert Lefkowitz discovered a family of cellular receptors that one-third of all approved drugs target; Michael Brown and Joseph Goldstein discovered a cholesterol receptor that led to the development of cholesterol-lowering statin medications; and Harold Varmus discovered some of the fundamental mechanisms of cancer.
The impact of the program extends far beyond Nobel laureates. A 1998 survey showed that its graduates comprised one-quarter of professors of medicine at Harvard, Johns Hopkins, and other leading medical schools. Dr. Eugene Braunwald, one of the most iconic cardiologists of the modern era (the hospital tower I work in at Brigham and Women’s Hospital is named after him), also started his career in this NIH program in 1955. And the self-proclaimed “dummy” of this class has become the most influential physician-scientist of our time: Dr. Anthony Fauci, who has headed the National Institute of Allergy and Infectious Diseases since 1984 and is a powerful voice in the U.S.’s response to the Covid-19 pandemic.
Although they were officially called clinical associates, many at NIH and beyond came to call them the yellow berets, a term that started out as an insult inspired by Bob Seger’s satirical song about “men who faint at the sight of blood,” who “watched their friends shipped away, the draft dodgers of the yellow beret.”
I interviewed a half-dozen of the associates. All of those I spoke with opposed the war. Some told me they alternated between performing experiments in their NIH labs and joining anti-war protests. Yet many, including Fauci, resent the implication of cowardice in the yellow beret moniker. As the achievements of the clinical associates have accumulated, that once snide term has become a badge of honor.
Few who applied for the program had any prior research experience. “I avoided all sorts of opportunities to do research,” Lefkowitz said as we sat in his office, surrounded by framed accolades and memorabilia. The transition from the wards to the lab was daunting. “I had never before in my life met with such sustained and unremitting failure,” he told me. Now he sees the lack of experience as advantageous, “Knowing too much hems you in.”
Within 18 months at the NIH, Lefkowitz had purified adrenocorticotropic hormone, a hormone made by the pituitary gland, the first step in his journey to the 2012 Nobel Prize in chemistry.
The insights that physician-scientists receive from patients is essential to their discoveries. The research by Brown and Goldstein that led to the discovery of statins, for example, was inspired by two siblings born with high cholesterol. “The little girl had her first heart attack when she was 3 years old. She couldn’t walk across the room without angina [chest pain],” Brown told me. “If we hadn’t seen those two children, our lives would have been very different.”
Such insights will be paramount to overcoming Covid-19.
The only blemish on the program was its lack of diversity. In one analysis of 1,577 associates between 1955 and 1973, only four (0.3%) were women, and almost none were people of color. A widely acknowledged yet unspoken fact was that women were not accepted into the program because they would take a research spot that might keep promising young male scientists “out of harm’s way” in Vietnam.
“Whenever you have an endeavor that is meeting the general needs of the public and society, you always do better when the people who are actually performing the activity are representative of the society that it’s trying to help,” Fauci told me. “Just the way diversity is important in society to keep it enriched, diversity is important in the subspecialties of the things that contribute to society, like biomedical research.”
As the yellow berets reach the twilight of their illustrious careers, the future of American medical science and the fate of the physician-scientist is more uncertain than ever before. One solution to resurrecting physician-scientists might resemble scientific conscription. While many medical schools incorporate a year of research in their curricula, I believe that this model should be expanded by requiring students to spend at least one structured year exploring an area outside of clinical medicine, such as basic science research, statistics, data science, or the humanities.
“If we could have some sort of obligation to the country in the field of medicine and science,” said Fauci, “I would not be surprised if we got the same sort of extraordinary results that we got back then.”
Academic medical centers are essential purveyors of life support for physician-scientists. In China, scientists earn more money than clinicians. In the United States, physician-scientists give up substantial, guaranteed income from clinical work in exchange for dwindling and uncertain sources of grant funding. Their employers need to put the academic back into academic medical centers by being “run like a real intellectual enterprise rather than a money making enterprise,” said Brown.
That starts by giving young physician-scientists the freedom to creatively solve the greatest problems facing humankind.
The NIH took excellent physicians and scientists in the country and let them develop in an environment not governed by trying to get the next big grant or to bill for as many clinic visits and procedures as possible. “We had the freedom to pursue our own ideas in a way that was independent, with mentoring and coaching, but it wasn’t like you were working for someone and doing someone else’s work,” said Fauci. “We were so young and we were thrust into the big leagues, as it were.”
Covid-19 has made the need for physician-scientists starkly clear. The NIH continues to support physician-scientists through programs such as the Stadtman Investigators program, which provides ample freedom and support for emerging physician-scientists and which champions diversity and inclusion as a core pillar. Yet unless funding for research increases and the NIH and academic medical centers develop novel initiatives — even including a scientific draft — the yellow berets might well be remembered as the last of the great physician-scientists.
“It was a grand circus of ideas,” said 84-year-old Jesse Roth, one of Lefkowitz’s mentors, “a Garden of Eden for young investigators.”
Haider Warraich is a cardiologist and researcher at the VA Boston Healthcare System, Brigham and Women’s Hospital, and Harvard Medical School.
I was in the same internship and residency cohort at MGH as doctors Brown, Goldstein and Lefkowitz, and spent several years full-time and on the private staff at the Brigham during Eugene Braunwald’s tenure as chairman of the Department of Medicine. Unlike these renowned stars of academic and scientific medicine, however, I had taken a different turn in my career; despite starting out as a “pure” scientist with a biology major at Caltech before committing myself to being a hands-on physician, enrolling in the five-year program at Stanford and taking extensive elective time in cardiovascular medicine and surgery. I thoroughly enjoyed the brutal work schedule and challenges of my two years as intern and resident at MGH, and especially the simultaneous engagement of scientific knowledge and interpersonal relationships in a unique and real-time setting with immediate and real-world impact and consequences. Finishing my residency in June 1968, facing the doctor draft and knowing that many of my colleagues were going to NIH to establish research careers I instead enlisted as a medical officer in the active US Naval Reserve, serving one year as the medical officer for a destroyer division and one year as director of the general medical outpatient department at Long Beach Naval Hospital. My Navy colleagues also used the term “Yellow Berets,” but it was not as a compliment. I was in a sense fortunate to have postings that did not involve direct exposure to combat, though there was no question that I would go wherever I was needed; I did have a number of experiences, some involving physical risk and many entirely novel, and spent two years with colleagues and comrades who had entirely different backgrounds and skills and whom I came to respect deeply as well as on occasion entrusting with my life.
On the downside, however, as I rejoined the Boston academic medical centers to complete my specialty education in adult and pediatric cardiology it became very clear that the focus of the PBBH Department of Medicine and the path of academic advancement had become dominated by grant-funded research. The role of clinician-teacher-mentor became a career dead-end as these intensely clinically-focused activities, so central to the core values of medicine, clearly had no value in Eugene Braunwald’s department, where “productivity” was measured only in terms of publication and research grant funding. I maintained an academic appointment at Boston Children’s Hospital and established my own individual practice until my retirement.
I would not dispute the value of the contributions of the physician scientists who went through the NIH program impelled by their quest for knowledge and its application to the well-being of humanity. I would not call these people “Yellow Berets” and would reserve that epithet for those who chose the NIH primarily to avoid military service. I do consider it unfortunate that the path of academic advancement has been warped to put clinical programs in the hands of individuals who lack training, humanitarian motivation and even interest in the practice of medicine except as a source of revenue, and who have perverted the medical literature to focus on formulation of statistics-driven practices that ignore the individual, personal and specific characteristics of the unique human beings who represent the true foundational values of the profession of medicine.
I was a yellow beret and the experience defined my career path as a physician-scientist. It was an enlightening experience. I saw first class medical research up close. Indeed, my mentor won the Nobel Prize when I was in the lab Everything that I have done since can be traced to that two year experience. And not just techniques but rather the goal of ambitious problem solving with high integrity. As is said, physician-scientists are now an endangered species. Current careers in academic medicine are high stress, unstable since unstable NIH funding pays the bills, and income-compromised. The NIH Associates Program in the US Public Health Service included about 300 physicians post-residency per year. As a group their careers have been illustrious, greatly benefiting the American public, and also contributed to the stature of the NIH. A program that attracts the best and brightest into academic medicine is sorely needed today.