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The “Giants in Obstetrics and Gynecology” series has thus far recognized the contributions of physician-scientists who have changed the practice of medicine, largely through research. These advances are made possible by the strategic decisions of leaders in academic medicine who use their knowledge of the human condition, podium, resources, and influence to improve patient care, stimulate discoveries, strengthen teaching and training, and contribute to the community and society. Deans of the schools of medicine are the leaders from whom we expect these decisions. I believe there is much to learn from the scientific humanism, transformative leadership, and creativity of Dr Arthur Levine. For this reason, he is recognized by the American Journal of Obstetrics & Gynecology.
Dr Levine, Distinguished University Professor, was the Dean of the School of Medicine and Senior Vice-Chancellor for the Health Sciences at the University of Pittsburgh for 22 years, and is now the Executive Director of the university's Brain Institute.
I first met Art in 1991 when he was Scientific Director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at the National Institutes of Health (NIH). There, he had been charged to establish an intramural Branch that would focus on pregnancy and pregnancy complications—the Perinatology Research Branch. I had a first-row seat to witness exceptional leadership and raw intelligence at work. Even though I saw Art in action at NIH, it is not easy to capture his holistic character and eclectic humanism to which science is so central. A good place to look for the philosophy behind his approach are the essays he contributed to the Pitt Med magazine throughout his tenure at the University of Pittsburgh, published under the title Jumping Spiders and One-Eyed Lambs (Figure 1). The essays have a timeless quality and touch every conceivable aspect of modern medicine, including teaching, research, and healthcare delivery.
What leaps from the pages of Art’s essays are the products of a fertile mind that grasps metaphorically “the magnificent but almost unimaginably complex molecular symphonies of structure and function,” which underlie the human condition and our multifaceted lives. To Art, the ability to perceive similarities among disparate things is the hallmark of creativity—“Great scientists make these connections freely...and they have a great capacity for metaphor and intuitive discovery.”
It is how he envisions a connection between a hypothesis about the origin of nuclei in our cells and “the ‘unspliced’ information that invades our lives through the internet, [and why] we often fail to translate that information in productive ways…fail to metabolize the information we absorb…[and] pay a price when our rate of accurate comprehension is challenged.”
And, it is the foundation of his faith in the saving power of science that “not only yields data and hypotheses about the world…[but] instructs us–even if by metaphor–as to how we might better live our lives.”
A propitious confluence of nature and nurture explains the provenance of Art’s creative mind. He is the son of Russian immigrants and, through his mother, comes “from a long line of rabbis; which is to say, my people have always been scholars and academics–philosophers, even.”
He grew up in Cleveland, Ohio, next door to his first cousin Donald Glaser. Ten years Art’s elder, Professor Glaser was awarded the Nobel Prize in Physics at the age of 34 for his invention of the bubble chamber used to identify subatomic particles.
Art steeped himself in the humanities during his formative years at Columbia College in New York. He majored in comparative literature with an eye toward the Russian literary masters, edited The Columbia Review, acted on the off-Broadway stage, and spent a great deal of time at New York’s museums. This experience may explain Art’s comprehension of the different forms of intelligence. “Interpersonal intelligence is needed to articulate ideas and to collaborate with colleagues,” he said. “Great science is often done by people who have more than mathematical or logical intelligence.”
Medical School, Residency, Fellowship, and then the National Institutes of Health
Art became interested in molecular biology at the Chicago Medical School (now the Rosalind Franklin University of Medicine and Science), and he pursued this interest once he completed his Residency in Pediatrics and a Fellowship in Hematology and Biochemical Genetics at the University of Minnesota. Joining the Pediatric Oncology Branch of the National Cancer Institute (NCI) was a serendipitous, unplanned move: “a consequence of the doctors’ draft during the Vietnam War.” He was accepted as a United States Public Health Service officer and as a Clinical Associate at the NCI, where he completed a three-year postdoctoral fellowship. Art was “fortunate to have superb scientific mentors and a bit of luck.” Notably, he and his collaborators completed the physical and genetic map of a small DNA virus—the simian vacuolating virus, or SV40—that is tumorigenic in rodents.
Art was awarded tenure as a result of that breakthrough, and he became a Senior Investigator. As an attending physician in the Pediatric Oncology Branch, Art treated patients with leukemia, lymphomas, and sarcomas. During that time, as the Section Head of Infectious Diseases, he was one of the first researchers to investigate opportunistic infections in immunocompromised hosts and became familiar with pneumocystis carinii
and blood-borne toxoplasmosis. This experience would prove invaluable when assessing the AIDS epidemic. Notably, Art was among the first to realize that the AIDS epidemic was probably attributable to an infection with a retrovirus.
Chief of the Pediatric Oncology Branch, National Cancer Institute
Art wanted to continue his work in the laboratory and care for patients with complex medical problems. He did not have a personal interest in administration, yet he took the position as Chief of the Pediatric Oncology Branch out of concern that if he did not, the person who did might not be as supportive of basic science as he felt was important. Although he knew that he was a good scientist, he did not think that he was a great one. He believed that his strength “had to do with integrating medicine and science and leading that integration.” So, Art continued along a career path that would lead him to become the Scientific Director of the NICHD.
Scientific Director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health
Art served as the Scientific Director of the NICHD from 1982 to 1998 (Figure 2) . During that time, he recruited gifted scientists and transformed the Intramural Program of the NICHD into one of the world’s top centers for developmental biology, while continuing to work on DNA damage and repair in his own laboratory. His administrative creativity, nose for talent, and mastery of a broad range of subjects in medicine and science made him an influential force not only at the NICHD but also at the highest levels of the NIH. He served on the search committees for Directors and Scientific Directors and became an important voice in shaping the direction of the NIH. Art knew the rules, understood the boundaries, and was comfortable challenging the regulations and policies in an open, direct way for the benefit of NIH, medicine, and science. As the Scientific Director, he earned the respect and loyalty of the scientists he recruited and of his colleagues throughout the NIH, and he left an indelible mark on the Intramural Program of the NICHD.
From the National Institutes of Health to the University of Pittsburgh
Given Art’s success, it is not surprising that he was asked to consider leadership positions in academic medicine throughout the United States. He had declined several offers from prestigious institutions until the opportunity at the University of Pittsburgh emerged. It took several visits before he agreed to become the Dean and Senior Vice-Chancellor (with responsibility not only for the School of Medicine but also for the Schools of Pharmacy, Nursing, Public Health, Dental Medicine, and Health and Rehabilitation Sciences). As the Dean, he was convinced that medicine and science could become the new “steel” for Pittsburgh.
As the Senior Vice-Chancellor, he believed that all six health sciences schools had much to teach one another and that their integration would greatly benefit patient care.
During his tenure at the University of Pittsburgh, he recruited all but three of the 31 current medical school department Chairs and propelled the University to become one of the strongest research institutions in the country. Moreover, during Art’s tenure, NIH funding at the University of Pittsburgh increased from $169 million to $578 million, which translated into an estimated 19,000 jobs, directly and indirectly, in Pittsburgh. When I asked Art what he considers his greatest contribution, he told me, “At Pittsburgh, as well as at NIH, it was the people I recruited. That is the most important thing I’ve done.”
“The Six Unlinked Genes” for success
When I asked Art about his gift for identifying talented people, he said that when he recruited physicians and scientists for the NIH and the University of Pittsburgh, he looked for “the six unlinked genes” on which he believes success depends, not only in science but in any walk of life: intelligence, creativity, drive, curiosity, social adroitness, and the ethic of hard work.
Moreover, he emphasized the one factor, often overlooked, that is key to the success of academic medical centers and universities—the chemistry between the people who have leadership responsibilities.
Creating a culture of excellence
An important part of a Dean's job comes after talented physicians and scientists have joined the faculty; the Dean must then put those gifted minds together. “One of the things I did at the NIH and at Pittsburgh was to introduce people to each other,” he said. “I would read something in Nature, Science, or the Proceedings of the National Academy of Sciences that I thought would be of interest to somebody and I would call them, send them the paper, and then I would say, by the way, there’s someone down the hall from you that you may want to talk to.” Knowing that talented individuals could leave, he argued that retaining talent is essential: “We don’t want the next Jonas Salk moving on to California or anywhere else,”
referring to the fact that Dr Jonas Salk left his position as the Director of the Virus Research Laboratory at the University of Pittsburgh to further develop the polio vaccine in La Jolla, California. Art was also successful at rallying the community and alumni to sustain the momentum achieved during his tenure; he wrote, “Pittsburghers reap the benefits of a fertile medical community…[and are] privy to new therapies often years before they’re commonplace”
The trait Art focused on in medical school applicants was the ability to think critically and imaginatively: “Do they direct plays, write poetry, compose sonatas, build organizations? We need physicians who can help us tackle the complex problems of our age.” He established collaborations with institutions, such as the Carnegie Museums of Natural History and Art, “to ignite the imaginations of our students and help expand their deepest sense of their potential as creative physicians and humanists.” For example, Art told me that partnerships were formed “to infuse evolutionary biology into our way of thinking about medicine.”
Furthermore, he wrote, “Perhaps someday we’ll hear about how the harmonic interplay of Brahms’ Requiem or Bach’s Die Kunst der Fuge inspired a young academic physician to build, for example, an accurate model of channel gating that finally reveals just how anesthetics work their molecular mysteries.”
Although the medical school’s goal was to produce more scientifically astute physicians, Art realized that neither scientific creativity nor committed humanism could be reduced to a metric. He wanted medical students to learn more than how to diagnose a disease, as scientific acumen is no substitute for compassion, insight, and understanding. Moreover, Art wanted future physicians to recognize the many social and psychological dynamics at work in their interactions with patients and family members, and to develop the communication skills that would allow them to establish high-quality doctor-patient relationships. To that end, medical students, on their first day, are paired with a patient diagnosed with a chronic disease. From close interactions with patients and their families, Art reasoned, students can acquire the necessary interpersonal skills, which they may have previously lacked, to sustain lasting, evolving relationships with patients.
“Our job is to nurture creative, analytical, evidence-based thinking in our students,” he said. For his part, that meant constantly reviewing the didactic curriculum because the technology that supports medical care is evolving at a greater rate than ever seen before in the history of medicine. “There has to be a continued evolution of what we teach in medical school,” he emphasized. “It is no longer enough to learn foundational subjects like anatomy, physiology, and even molecular biology. Students now have to really understand computational biology, artificial intelligence, and machine learning, and the building of structured and complex algorithms that could apply directly to the care of a patient and the prevention of illness.”
At the School of Medicine, Art encouraged an annual Curriculum Colloquium to which students were invited to review what was being taught and how.
The goal was to ensure that students metabolize new knowledge, generated by structural, molecular, developmental, computational, and cellular biology, as quickly as the data evolved to form the scientific basis of medicine.
Art resisted teaching “to an average stereotype.” He believes in “personalized” education. “I don't think that any two of our brains are hard-wired in exactly the same way, and some students do their best by reading a textbook, some by going to a lecture, some by using their laptop, some by a visual or auditory cue, and some by the intimacy of the mentor-mentee relationship,” he said. “We rarely try to teach to the way a particular brain is hard-wired. At least for me, I thought one of my roles was to introduce, incrementally, the notion of personalized education within a medical school.”
Supporting a new generation of physician-scientists
To address the concern about the steady decline in the number of physician-scientists in the United States, Art developed the Scholarly Research Initiative in 2004. Every student at the University of Pittsburgh was required to choose a mentor and a research project early in their career, and to see it through to graduation.
has now been shown to enhance medical student authorship rates in peer-reviewed publications, which, in turn, is linked to a higher likelihood of matching in a top-ranked residency training program (Figure 4).
In 2007, the School of Medicine at the University of Pittsburgh established a new program designed to enhance the pipeline of academic physicians, something quite different from the traditional MD-PhD path. The highly structured Physician Scientist Training Program for medical students at the University of Pittsburgh focuses on preparing MD-only physician-scientists who are interested in integrating basic and translational research into clinical medicine. A recent evaluation indicated that a large percentage of their graduates matched in top-10 NIH-funded residency programs in their specialty, published first-author papers, and exhibited confidence in research skills.
Art has been cognizant that the new generation of students face many obstacles that could deter them from a career in academic medicine. A major factor accounting for the dearth of physicians who undertake a career in clinical investigation is student debt—70% of academic centers had vacancies for junior physician-clinician investigators in 2008, one-third of which went unfulfilled. Most medical school graduates are in debt ($200,000 on average), making the choice of an academic career less likely. At the medical school, Art created a program to abate the debt of those who choose a career as physician-scientists, and he established an office to address the logistical problems created by the two-career family with child-care issues.
A prescient mind: healthcare equity during a pandemic
In the Fall of 2003, Art opened his essay with the words of William Shakespeare: “One touch of nature makes the whole world kin….”
He wrote: “One would think that the world of medicine, where we are in the privileged position of not only studying nature but are invited into others’ most private lives daily, would be flush in understanding and rich in fellowship. Yet, we’ve much work to do.”
He believed that we must address inequities “by providing evidence-based medicine to all people and fostering in our students (and physicians throughout their careers) greater understanding across cultures and a more nuanced ability to communicate.”
New scientific programs at the University of Pittsburgh
Perhaps the most innovative products of Art’s scientific eclecticism are the many programs he pioneered at the University of Pittsburgh—he established 10 new departments in the School of Medicine (Table).
Of interest, such a collision of disciplines resulted when one of the first medical school-based Departments of Structural Biology in the nation was established in 2005 at the University of Pittsburgh under Art’s watch. The goal was to relate one-dimensional knowledge about DNA sequences to the three-dimensional architectures that they encode, and to the complex chemical and physical transformations that underlie all living systems. Thus, by bringing X-ray crystallography, nuclear magnetic resonance imaging, and cryo-electron microscopy together in one department, he explained, “[My intent] was to combine structural information with other data to gain insight into cellular events and how these events translate into the form and physiology of entire organisms.”
TableThe Departments, Institutes, and Centers established by Dr Arthur S. Levine at the University of Pittsburgh
During his tenure, Art also realized that the system of drug development and research often fails patients, particularly in the field of orphan diseases, a group of more than 6000 defined as those afflicting less than 200,000 people. This led to the establishment of the Drug Discovery Institute, where innovative approaches to therapeutics—both traditional and novel—would be investigated, as the new field of quantitative systems pharmacology emerged in medicine.
To meet the goal of pursuing innovative, often unique, approaches to the prevention and treatment of human diseases, Art also commissioned a research facility, which opened in October 2005 and became the home of interdisciplinary programs (instead of traditional departments) such as structural biology, computational biology, neuroscience, developmental biology, and vaccine development. There, important translational studies on the zebrafish, the Caenorhabditis elegans, and the shark, among others, have emerged since. “There are limitless possibilities for advancing medicine by studying other species, as important biologic mechanisms are preserved through evolution,” he said.
Art’s own area of interest has always been DNA damage and repair, starting with his work 40 years ago on SV40 DNA damage and he has been fascinated by the fact that major DNA repair pathways are highly conserved in nature. “We find conserved DNA repair pathways in bacteria,” he said, “but as you move up the evolutionary chain, DNA repair becomes more complex. Events in evolution have evoked the emergence of whole new genes that encode the proteins that recognize specific lesions and specific forms of DNA damage. Depending upon what environment we find ourselves in, we may have a different type of DNA damage.” Moreover, knowing that unrepaired damage to DNA figures prominently in oncogenesis and that damage-induced inflammation is common both to cancer and neurodegeneration, Art has recently applied what he has learned about damage and repair in cancer cells to research on damage and repair in glia and neurons.
An extraordinary partnership between the School of Medicine and the University of Pittsburgh Medical Center
When Art joined the University of Pittsburgh in 1998, his charge was to strengthen the basic sciences while sustaining the clinical research enterprise. The success of medicine in the city of Pittsburgh can be traced to the synergistic evolution of the University of Pittsburgh School of Medicine and the University of Pittsburgh Medical Center (UPMC), which is recounted in an article written by the leadership of both organizations.
Art credits Jeffrey A. Romoff, the organizational and financial genius of UPMC, as key to this success story (Figure 5).
Most academic health centers fall into two organizational models: the fully integrated model in which clinical, academic, and research functions report to one person and one board, and the divided model where academic and clinical functions are managed separately and report to two different boards. The divided model, more prevalent in the United States, often generates substantial tension between schools of medicine at universities and their medical centers. The relationship between the University of Pittsburgh School of Medicine and UPMC would typically correspond to the divided model; however, throughout two decades of evolution, a unique organizational structure and management model has emerged. This model is inspired by one core principle: “what is good for one is good for both”.
The division of responsibilities is such that UPMC oversees all clinical activities, which include the consolidated physicians’ practice plan, whereas the School of Medicine is responsible for academic goals and, in particular, faculty-based research. The extraordinary success of UPMC, now a $23 billion healthcare provider and insurer, is central to this partnership. The UPMC is not only the largest nongovernment employer in the state of Pennsylvania but also has expanded its clinical operations to Italy, Ireland, Kazakhstan, and China.
Executive Director of the Brain Institute
After 22 years of innovation at the University of Pittsburgh, Art decided to step down as Dean, but not to retire. Given his recent interest in neurodegeneration and brain disorders and diseases that receive symptomatic treatment only, he has adeptly stepped into the role of Executive Director at the University’s Brain Institute. Art has focused on studies with genetically engineered marmosets as an animal model to study human diseases. Adapting to his role as a physician-scientist, he continues to investigate Alzheimer’s disease in his laboratory, pursuing the hypothesis that some people, as they age, either have an excess of oxidative damage to the DNA in their neurons from normal, everyday metabolism or they do not have DNA repair of the lesions they have sustained. Art and his colleagues have now submitted an article showing that experimentally induced DNA damage, particularly double-strand breaks, triggers the emergence of β-amyloid (the putative trigger of Alzheimer’s disease) in human neurons in vitro. I believe this work will show that Art Levine is not only an exceptional academic leader but also a great scientist.
This profile is based on conversations with Dr Arthur Levine during the COVID-19 pandemic in 2021.