David M. Livingston, who died unexpectedly on 17 October 2021 at the age of 80 years, was a superb scientist and generous man whose tireless enthusiasm and inspired approach to science made him one of the world’s most highly respected cancer researchers. He was equally passionate about training future generations of scientists and mentored nearly 200 fellows and students in his laboratory at the Dana-Farber Cancer Institute (DFCI), creating an enduring legacy of cancer discovery.

Born in Cambridge in Massachusetts, USA, David was educated at Exeter, Harvard (AB, 1961) and Tufts (MD, 1965). He completed training in internal medicine at the Peter Bent Brigham Hospital. In 1973, following postdoctoral training at the National Institutes of Health (NIH) and Harvard Medical School (HMS), David was recruited by Sidney Farber to what is now the DFCI, where he maintained an active laboratory and served in numerous leadership positions. He was the Emil Frei III Distinguished Professor of Medicine and Genetics at HMS, and the Charles A. Dana Chair in Human Cancer Genetics at DFCI at the time of his death. David was a valued and trusted advisor to the National Cancer Institute (NCI), where he served as Chair of the NCI Board of Scientific Advisors from 1995 to 1999. He was a member of numerous scientific advisory committees at cancer centers around the world and, for more than 30 years, belonged to the Board of Directors of the Damon Runyon Cancer Research Foundation. Most recently, David was appointed to the Governing Board of Directors of the Breakthrough Cancer Foundation in Cambridge. He was elected to the National Academy of Medicine, National Academy of Sciences and American Academy of Arts and Sciences, and was a fellow of the American Association for Cancer Research. A lover of all things Italian, he was especially proud of receiving the Pezcoller Foundation–AACR International Award for Cancer Research in 2017.

David’s early research focused on the DNA tumor virus SV40 and its oncoproteins, namely the large T- and small T-antigens or, as he more vividly referred to them, “big T and little t”. Following Ed Harlow’s discovery that the adenoviral E1A protein interacted with the retinoblastoma (RB) protein, David’s laboratory identified RB as an SV40 large T-binding protein and showed that RB phosphorylation during the G1/S transition allowed cells to progress through the cell cycle. Based on these discoveries, David and his group cloned and characterized the molecular functions of the E1A-binding proteins EP300 and EP400.

Soon after the cloning of the breast cancer BRCA1 gene, David’s laboratory was the first to show that BRCA1 is a nuclear protein that forms foci at sites of double-strand DNA breaks and, along with Maria Jasin’s laboratory, that BRCA1 directs homologous recombination-directed double-strand DNA break repair. This discovery led the field into focusing on the role of BRCA1 and BRCA2 in DNA damage repair. For more than 25 years, David’s work contributed to the reclassification of breast cancer, leading to new treatment paradigms and fundamental insights into the process of homologous recombination.

David was instrumental in bringing people together in the fight against cancer and led the effort to establish the Dana-Farber/Harvard Cancer Center (DF/HCC). In doing so, he brought together a prestigious yet somewhat reluctant group of leaders and investigators from seven Harvard institutions and served as its Deputy Director from 1999 to 2019. In securing an academic–industry partnership between DFCI and Sandoz (now Novartis) in the early 1990s, David’s vision played a key role in the development of several US Food and Drug Administration (FDA)-approved targeted cancer therapies. More recently, he worked with Tyler Jacks at the Massachusetts Institute of Technology (MIT) to develop the Bridge Project, aimed at bringing MIT and DF/HCC scientists together in peer-reviewed proposals. In these — and many more — endeavours, David understood the power of connecting people to facilitate unexpected discoveries and important breakthroughs.

In one of his most inspired moves, David invited his scientific competitors to his country home in western Massachusetts for three days in the fall of 1988, to discuss their unpublished data. Over home-cooked meals, camaraderie replaced competition. The collective brilliance of those gathered was amplified by collaboration, teamwork and David’s charm. That first retreat became an annual event that continues to bring competing laboratories together for innovation and friendship.

David has long been a pillar of the scientific community — but he was not one to be complacent in his standing, no matter how much he accomplished. His voracious appetite for a good experiment knew no bounds and invigorated those around him. His curiosity led to questions that few others would think to ask. In the lab, his daily catchphrase of “what’s new and different?” would provide every postdoctoral researcher and graduate student the chance to discuss their latest results. Even the smallest findings brought him joy and excitement. David would immediately seize on the slightest hint of discovery and build complete — if sometimes challenging — hypotheses, for his trainees to test. While he loved a beautiful scientific story, he demanded rigorous experimentation to support his ideas.

Although David was justifiably proud of his own accomplishments, he often said that he derived his greatest pleasure from the achievements of those he trained, including William G. Kaelin Jr, who was awarded the 2019 Nobel Prize in Physiology or Medicine.

Few things could pull him away from his work — but his family always came first. He was an adoring husband, father and grandfather who enjoyed fine dining and traveling with loved ones. A lifelong fan of the Boston Bruins and Red Sox, sporting events were the place where David’s energy could fly untethered. He cheered on his teams with a passion usually restrained in professional settings, burning just beneath an academic exterior.

David Livingston was bighearted, affectionate and caring. He was brilliant, yet humble; intimidating, yet encouraging; a leader who lifted those around him. His outsized impact will continue in future research — in lives saved, in treatments developed, in the institutions he nurtured, and in the careers of so many trainees and colleagues around the world. His legacy will live in those he loved, who will remember David as a dedicated father, husband and friend.