Beth Cindy Levine (1960–2020)

Beth Cindy Levine, founder of the field of modern mammalian autophagy, died on 15 June at the age of 60. Beth seamlessly integrated the molecular and cellular mechanisms of autophagy—in which cellular cargo is captured and degraded, “cleaning” the cell—into new understandings of disease pathogenesis, often challenging dogma and winning. Born on 7 April 1960 in Newark, New Jersey, Beth graduated from Brown University in Providence, Rhode Island, in 1981 with a degree in French studies and obtained an M.D. from Weill Cornell Medical College in New York City 5 years later. She completed training in internal medicine and infectious diseases before accepting her first faculty position at Columbia University in New York City in 1992. In 2004, she left Columbia to become chief of the Division of Infectious Diseases at the University of Texas Southwestern Medical Center, a position she held until 2011, when she became the director of the university's Center for Autophagy Research. Beth was selected as a Howard Hughes Medical Institute investigator in 2007, and she was elected to the National Academy of Sciences in 2013. The following year, she received the American Society for Clinical Investigation's Stanley J. Korsmeyer Award for her work in autophagy. Early in her independent career, Beth performed a yeast two-hybrid (Y2H) experiment that, unexpectedly, showed that the apoptosis-blocking protein Bcl-2 bound a previously unknown protein, which she named Beclin 1. In pivotal papers in 1998 and 1999, Beth identified Beclin 1 and proved that it is an autophagy protein that functions as a tumor suppressor in breast cancer cells, a finding later confirmed in animal studies. Beth was fond of showing the original plates from this Y2H experiment as the introduction for her many talks at scientific meetings. Beth had a knack for combining diverse disciplines, molecular mechanisms, and experimental approaches to forge new concepts of biology. By studying Beclin 1, she made fundamental discoveries linking autophagy to the pathogenesis of cancer, developmental disorders such as Fanconi anemia, and neurodegenerative and infectious diseases, and the physiologic processes of development and aging. She linked exercise to autophagy, and thus to metabolic regulation, and showed that innate immune Toll receptors, surprisingly, connect Beclin 1 to metabolic signaling, muscle function, and disease. Beth created an autophagy-inducing peptide that she and others have used to probe the physiologic effects of autophagy induction in vivo. This subset of her accomplishments exemplifies the consistency with which Beth and her group, often in collaboration with colleagues from varied fields and backgrounds, coupled previously unconnected concepts to create new paradigms. Her work spanned structural biology, cell biology, virology, and animal physiology, a difficult challenge that Beth regularly met with rigor and exceptional experimental insight. Beth imbued the field of autophagy with a sense of community, a feeling of purpose, and a moral commitment to nurturing young scientists. She was proud to be the founder, in 2003, of the ongoing Gordon Research Conference on Autophagy in Stress, Development, and Disease, bringing together a scientifically eclectic and international community of scholars. Many of the first meeting's participants, including two of us (H.W.V. and A.M.C.), remain friends to this day. Beth's meetings featured wide-ranging talks on yeast, worms, flies, mice, structural biology, and human biology. She had a clear vision of the field's potential, and she set the tone of integrity and collegiality that has characterized our meetings ever since. We will miss her polished-to-perfection talks, her fearless defense of the data, her insightful remarks, and her intelligent questions, as well as her laugh at the dinner table, her fine sense of humor, her look of complicity when somebody pulled a prank, and her free spirit on the dance floor. We all benefited from Beth's exceptional mentoring skills, which ushered generations of bright young scientists into the field. Many of the women in the autophagy community are indebted to Beth for her support. She told things as she saw them and did not indulge in self-pity when that precious time could instead be dedicated to resolving scientific problems for the benefit of humanity. Beth would always stop to listen to those in need of scientific advice, career guidance, or just a patient, friendly ear. Beth's vibrant approach to work and to life was immediately apparent to anyone who spent time with her. Her visionary creativity, innate curiosity, rigor in thought, and unparalleled commitment and dedication to science and medicine made it impossible not to gravitate toward her, to bear witness to science at its best; she was a leader whom people liked to follow. Beth made courageous sacrifices for the benefit of science and those in the field of autophagy, in later years attending autophagy meetings with her portable oxygen tank in tow while somehow retaining her natural elegance. During her final weeks, she was actively participating in advisory panels, planning for the continuation of her work and the future of her trainees, holding lab meetings, and even submitting a major manuscript the day before she left us. She planned for her own death with the dedication and care she brought to all aspects of her life. Beth's love for science was matched only by her profound love for her family. Listening to her proudly bragging about her children's talents, creativity, and passion was always uplifting. As in everything else, Beth excelled in balancing career and family. Given her dedication as a true physician scientist committed to alleviating human suffering and maximizing human potential, we believe that the best way to honor Beth is by continuing the work that she so obviously loved. Someday, human diseases will be remediated on the basis of her discoveries. If she were to witness such success, she would be exceptionally proud and then ask, “So what is the next step forward?”