Life as an Infectious Diseases Physician Scientist: Science is Humanity’s Lifeline

My career as a physician-scientist grew out of my desire to address challenges to human health posed by infectious diseases. I went to college at the University of California at Berkeley in the early 1970s. The Vietnam War was still raging, and the assassinations of Martin Luther King, Jr., and Robert F. Kennedy and the horrors of Watts and Newark were still fresh in my mind. In the eyes of a 16-year-old freshman, the world seemed full of inequities and people who did not benefit from the fruits of human innovation and progress. I hoped my education would help me develop tools to make the world a better place for everyone. I had grown up in a home that valued education and equality, 4 decades before my old backyard became the lap of Silicon Valley. I was oblivious to STEM (science, technology, eEngineering, mathematics). In college, I studied art history and psychology, disciplines that gave me a perch from which to view how humans have represented history throughout the ages, depicted their identity, fears, and sorrows, and tools to better understand human behavior, differences, and dysfunction. I was particularly intrigued by artistic renditions of the Dance of Death, flagellants, and garbed doctors hoping to protect themselves from their patients, images of people ravaged by plague, cast off, mistreated, and disenfranchised from society. I wanted to learn more about the effects of disease on people and societies. So, as my college education drew to a close, I decided to pursue a career in medicine. I felt medicine would provide me with knowledge and tools that could help improve the human condition. As I immersed myself in premedical classes and learned about Mendel, Pasteur, Jacob, and Monod and others, basic science entered my radar screen for the first time and emerged as one of the most influential pieces of puzzle that would form my career. When I began medical school in the late 1970s, unbeknownst to me, my contemporaries, mentors, and the world, a new plague, one that would parallel the Black Death on so many levels, was brewing globally and in our own backyard in the Bronx. As I transitioned from my preclinical courses to the wards, I began to feel increasingly uncomfortable with the state of medical knowledge. It seemed that the very truths I had just learned in the classroom were insufficient to explain the condition of many of my patients as they failed to reveal the cause of their disease or lead us to the right treatment. This gap in our knowledge deepened further during my internal medicine training at Bellevue Hospital, where more than a quarter of the medical service suffered from a condition that was identified as human immunodeficiency virus (HIV)/ AIDS just as I was completing my residency. Taking care of patients with this disease was overwhelming and challenged my sensibilities intellectually and emotionally. Like those who were victims of the Black Death, my patients were young, dying, often alone, disenfranchised, and marginalized. In fact, like victims of plague centuries before, they were dying from a lack of understanding. It was clear that available knowledge could not explain the disease that appeared, progressed, and spread right before our eyes. It was also clear that this disease defied several long-standing tenets of infectious diseases. The edict that all we need to cure an infectious disease is the right antimicrobial agent, a tenet virtually written in stone, simply did not apply to many of my patients. There was often no treatment, and even when there was it didn’t work. Pneumococcal infections recurred despite treatment with highly active antibiotics. Pneumocystis pneumonia recurred despite the availability of active therapies. I still have the image of the desperate breathlessness of such a patient in my head. Cryptococcal meningitis could not be cured despite amphotericin and required lifelong treatment. Multidrug-resistant (MDR) tuberculosis surfaced, heralding the antibiotic resistance crisis. Neither the therapeutic paradigm nor the antimicrobial agents available to us were able to alter the course of our patients’ disease. Our inability to treat them effectively, as we watched them wither away and die was a transformative event in my training and led me to pursue a career in research. I wanted to translate what I observed at the bedside into paradigms to help us understand how the immune system affects the pathogenesis of infectious diseases. I wanted to develop S U P P L E M E N T A R T I C L E