Today, the Huang fellows had the honor to meet Dr. Lefkowitz, the Nobel prize winner of 2012, known for his groundbreaking discoveries about G protein-coupled receptors, the most important and widely used drug targets in pharmacology. Dr. Lefkowitz told us the story behind every picture in his powerpoint slides and unveiled his journey from an aspiring medical student to a Nobel Laureate.

Dr. Lefkowitz’s career path, which he named “A Tale of 2 Callings”, was filled with coincidence, change of plans, and soul searching. Dr. Lefkowitz’s “first calling” was to become a practicing physician. Upon completing his medical studies at Columbia University in 1966, Dr. Lefkowitz intended to continue his training through medical residency. However, the onset of the Vietnam War disrupted his plan. Newly graduated medical students were drafted to military and national institutions, and Lefkowitz was assigned a research position in the National Institutes of Health (NIH). At that time, little did he know that this mandatory draft would steer him towards a path that he had never envisioned – a career in research. However, this transformation did not occur immediately. In fact, with no prior research experience, Dr. Lefkowitz found himself in the middle of a series of unsuccessful experiments, playing catch-up during his first year in research. His second year in NIH saw some success, yet his focus remained on becoming a doctor as he began his cardiology fellowship at Harvard after fulfilling his NIH service. The pivotal moment of realization struck during his medical practice at Harvard, when he realized that he missed the curiosity, exploration, and excitement of research that he experienced at NIH. Here came his “second calling” that beckoned him towards the world of fundamental research. He decided that research must be a part of his career and became a physician scientist professor at Duke. He eventually shifted his entire focus to his research on G protein-coupled receptors (GPCR) and was awarded the Nobel Prize of Chemistry in 2012.

Looking back at Lefkowitz’s successful research career, what I found interesting was his unwavering sense of optimism. In discussing his work, Dr. Lefkowitz highlighted the value of innate curiosity, focus, and persistent experimentation, but what truly tied these elements together and propelled him to his success was his optimism towards science and research. With a strong faith that his innate curiosity will lead him to fruitful findings and an optimistic belief that the medical community will always find ways to leverage his work, he allowed himself to focus exclusively on experimentation and be driven primarily by curiosity without concerns on the real-world application or the potential impact of his research. As Dr. Lefkowitz puts it, succeeding in research requires someone who is “a bit obsessive and stubborn”. His optimism provided the extra dose of tenacity needed to unravel the mechanisms of GPCRs, a discovery that helped the production of ⅓ of all pharmaceutical drugs.

Dr. Lefkowitz’s optimism extended beyond his research as we saw glimpses of his positive outlook and sense of humor throughout the talk. Knowing that his passions would eventually lead him to where he belongs, he optimized his career decisions by reflecting on his inner callings. Although having a twisty career path due to numerous coincidences, his unwavering optimism and faith for his inner callings made his decision process simple and straightforward. From his decision to be a medical student, to an NIH researcher, to a cardiology doctor, and eventually to a physician scientist, he always made the decision that resonated the most with his inner callings without overthinking about concerns in the future.

The power of optimism lies in its ability to help us maintain a positive mindset on coincidences that we cannot control, while empowering us to focus on aspects of life that we can control. It is through his unwavering optimism, Dr. Lefkowitz turned coincidences to serendipities, leading him into a hugely successful career in research.