Charles L. Sawyers, MD
During his undergraduate years at Princeton University, Charles L. Sawyers, MD, studied history. Now, well into his career as a physician and translational scientist, Sawyers is busy making it. Currently chair of the Human Oncology and Pathogenesis Program at Memorial Sloan-Kettering Cancer Center and a Howard Hughes Medical Institute investigator, he has played a seminal role in the discovery of three groundbreaking cancer drugs. And in developing these drugs, he has helped to create an approach to the treatment of cancer that has transformed cancer research.
Although Sawyers’ most recent discovery concerns his work in developing enzalutamide (Xtandi), a drug therapy for the treatment of patients with metastatic castrationresistant prostate cancer (mCRPC), he applied many of the same scientific methods he developed while working with leukemia earlier in his research career. Sawyers, over the course of his career, had explored how signaling pathway aberrations in cancer cells could be exploited as targets for new drugs. In his work with enzalutamide, Sawyers focused on how prostate cancer cells develop resistance to drugs that target the androgen receptor (AR) pathway. To appreciate and understand his approach to solving scientific problems, one has to go back to when Sawyers began his career, first as an undergraduate, then as a medical student, and, finally, as a physician scientist.
History Provides a Lesson in Research
Sawyers was born and raised in Nashville, Tennessee, into a family of physicians: a grandfather, father, two uncles—all surgeons—and a mother, an anesthesiologist. As a young student, he excelled in mathematics and science, so one would have thought that a career in science, especially medicine, was inevitable. Yet, when he headed off to Princeton University for his undergraduate education, those areas of study were far from his mind. Instead, he chose to major in history. A liberal arts education, he felt, would broaden and enrich his outlook on life. Ultimately, he said, it contributed to his ability to isolate and analyze science problems.
“It exposed me to a certain style of research. You select a topic, investigate and master a body of evidence using original sources, and come up with a conclusion. You grab onto something you think is controversial or fascinating in some way, and try to get to the heart of it,” he said. “I actually think that that’s what research in science is all about, and frankly, that’s how a liberal arts education works.”
It was during this time that he encountered the work of science historian Thomas S. Kuhn, PhD. Kuhn, through his magisterial work, The Structure of Scientific Revolutions, argues that scientific progress is the result not so much of an evolution in ideas, but rather a revolution in ideas—one led by “intellectual mutineers,” insurgents who overthrow one conceptual worldview or paradigm to replace it with another; thus, Galileo and Copernicus upended astronomy, Newton rewrote physics, and Darwin revolutionized biology. The idea that new discoveries in science could result not from the logical extension of older ideas but from an overturning of those ideas was intriguing to the young Sawyers, and ignited his interest in and passion for the scientific method that has informed his life’s work.
Learning to Be a Scientist
After graduating from Princeton, Sawyers enrolled in Johns Hopkins University School of Medicine in Baltimore. “Hopkins had an outstanding faculty made up of people who were involved both in teaching medical students and running a laboratory, combining research with clinical activity,” he said. At Hopkins, Sawyers was greatly impressed and influenced by Donald S. Coffey, PhD, a faculty member and researcher who worked on prostate cancer. “He is a man of great personal charm and charisma, with a renegade spirit that I greatly admire,” said Sawyers. Coffey, according to Sawyers, also has a unique talent: to get students genuinely interested in a problem, to get them to dig into it, and to get them excited about biomedical science.
“It was inspiring. And don’t forget, this was a time when the tools of molecular biology were just being broadly applied to questions in medicine. The ability to understand the genetics of a disease was leading to fascinating new insights,” said Sawyers. “Cancer was a fascinating challenge. A lot of the features of biomedical science are part of cancer research, so you’re pretty much in the mainstream of all research. You can draw on many different lines of investigation. Solving problems that arose from the research was incredibly interesting. The real question was whether I could stomach the clinical part of it.”