When Barry R. Bloom was diagnosed with pancreatic cancer, he decided to be a data point. He signed up for clinical trials, and, as was his way, he read all the papers and came to his appointments with questions and wanting to learn as much as he could. When he entered a Phase 1 study of a molecular inhibitor of his tumor’s KRAS mutation and saw a tremendous response, he knew it was temporary. A single inhibiting agent was bound to select for resistance — he knew it was a matter of time.
He used that time well: writing his memoir for his 5-year-old grandson, seeing friends, going to the symphony.
Barry, who died March 18 at his home in Cambridge at the age of 88, began his career as a chemist and became a world-famous immunologist. He took the unusual step for a laboratory scientist of immersing himself in global health, becoming a serial founder of and adviser to programs and institutes around the world, as well as dean of the Harvard School of Public Health, where he remained on the faculty until his death, having just recently submitted his final immunology paper for publication. He brought rigor, integrity, and humanity to science and public health, pushing both forward by force of example and personality.
We were among the very many people fortunate enough to have Barry take an interest in our careers. More than that, he took great joy in scientific matchmaking. When I (Marc) — an evolutionary biologist with a budding interest in microbiology — was the second choice for a faculty position in epidemiology at Harvard, Barry pushed the department to hire both their first and second choices, and then offered me space in his laboratory to start my own.
To seal the deal, he told me that Eric Rubin (now the editor of the New England Journal of Medicine) had just accepted a job with adjacent lab space and would be a kindred spirit. Meanwhile, he had told Eric, who was also considering whether to move to the School of Public Health, that Marc Lipsitch was a kindred spirit who had just accepted a job and would be fun to work with. We did, in the end, both accept, and when we worked out the chronology came to admire Barry’s social engineering.
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Barry was a key architect of the modern field of immunology. At the start of his career, the field had not yet discovered most of what we now consider basic facts: the endless parade of cell types, chemicals they secrete, the mind-blowing genetic changes they undergo to create memory of previous encounters with pathogens and toxins. Barry established much of the information that set the field on its modern path.
Two categories of immune cells already known when Barry entered the field were lymphocytes and macrophages. The immune system’s magic is to remember prior exposure to pathogens or vaccines and mount a faster, bigger response on seeing the same invader a second time.
It was Barry who discovered that lymphocytes — not macrophages, as some hypothesized — that carry immune memory. With his collaborator Boyce Bennett, he showed that lymphocytes signal to macrophages through a chemical they termed migration inhibitory factor (MIF) — which, together with interferon, were the first cytokines discovered.
The discovery of MIF led to an invitation that changed his research approach and opened up a new stage of his career. After the paper appeared in Science in 1966, he was invited by the director of immunology at the World Health Organization to a meeting to define how research could help to solve the scourge of leprosy (now called Hansen’s disease), a disfiguring and stigmatizing mycobacterial skin disease that at the time had only one effective treatment, for which drug resistance was a constant threat.
The meeting at WHO headquarters in Geneva, which he described in a draft of his memoir as “one of the most intense and exhilarating experiences I ever had,” helped him to see the possibilities of studying the immune system, not through the well-characterized workhorse molecules that immunologists typically used, but through “real antigens from real pathogens.” As he later told an interviewer, “This just wasn’t done” at the time, but for him it was transformative to work on immune responses to mycobacteria, the genus that causes tuberculosis and Hansen’s disease, bringing the discoveries in his lab a step closer to translation to treatments and diagnostics for major infectious diseases.
Research in mycobacteria was slow and hard because the tuberculosis bacteria were dangerous to work with, and the leprosy bacteria almost impossible to grow. Moreover, it was impossible to do the basic tricks of genetic engineering because what worked in lab organisms like E. coli didn’t work in mycobacteria.
Barry played key roles in solving all these problems. With Bill Jacobs, he developed the first genetic engineering system in mycobacteria, developed “phasmids” — hybrid phage-plasmid vectors. He established the harmless bacterium Mycobacterium smegmatis as a model system to study mycobacterrial genetics and set up a global system to share stocks of Mycobacterium leprae, the cause of Hansen’s disease. With his long-term collaborator Robert Modlin, he characterized human immune responses to this organism and discovered a role for vitamin D in enabling macrophages kill the TB bacillus, a collaboration that was still active until weeks before his death.
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Beyond providing critical questions to drive his science, this turn in Barry’s work toward immunology of mycobacteria launched his efforts to improve global health. Like the science, the list is too long to do justice to, but it started with leadership of WHO panels on mycobacterial diseases and tropical diseases and included advisory roles to President Carter and the CDC, among many others.
This global health work continued while he was dean at Harvard: establishing the first U.S.-China Health Forum; helping to found the Public Health Research Institute of India, now a full university; leading the executive board of the Human Heredity and Health in Africa initiative of the Wellcome Trust; and championing the university’s efforts to help combat HIV in Nigeria and Botswana.
The HIV work put Barry and the school of public health at odds with then-Harvard President Larry Summers, who feared that Harvard’s launching the arm of President George W. Bush’s new program, the President’s Emergency Fund for AIDS Relief (PEPFAR), in Nigeria, Tanzania, and Botswana would expose Harvard to liability and reputational risk. Instead, it treated hundreds of thousands of people, as part of the larger PEPFAR program, which Barry called “probably the most successful international engagement by the United States since World War II.”
Reading a draft of his memoir (which will be published soon as an e-book), it’s hard to fathom how he found the time, energy, and imagination to engage so widely in a range of activities to benefit science, global health, and those around him. A reflective and thoughtful person, Barry took great joy in meeting people and in learning from those genuinely different from himself, from the poet Robert Frost (whom he met when he was an undergraduate at Amherst College), to Pope John Paul II (whom he met when presenting advances in leprosy treatments to the Pontifical Academy of Sciences) to students and colleagues from around the world. He continued taking long flights to attend advisory board meetings in Africa, China, and elsewhere well into his 80s.
He constantly sought opportunities to create some benefit for others. We experienced that personally, both in his matchmaking and in his often blunt criticism of our ideas, embodying the true but rare belief that feedback is a gift. He would say with a huge smile, “Marc, it is amazing how little you understand immunology,” and proceed to school me, but always with the goal of improving my work. He set an example for all of us by attending student talks and sending comments on both substance and presentation, taking everyone seriously, engaging with their ideas, and making suggestions for improvement.
His humanistic passions, particularly for classical music, history, and Chinese ceramics, gave him energy and joy, matched only by his passion for good Chinese food. He was an enthusiastic trombone player from high school into adulthood. His wife, Irene, a Chinese philosophy scholar who passed away in 2010, gave him a harpsichord as a surprise present in 1980. In recent months, he was learning a piece by the Baroque keyboard virtuoso and composer Froberger. His faith in the power of science to improve lives was inspiring.
Interacting with Barry, listening to his stories, one got the sense that he always found lessons to learn from his many and varied experiences, and he shared these lessons with us, through his good humor and wonderfully told anecdotes and sometimes through pithy, aphoristic admonitions. A memorable one he shared with me (Yonatan) after I sought his advice — and that he attributed to former Harvard Medical School Dean Joe Martin — went like this: “At Harvard, you can get anyone to come to a discussion of a new idea — once. For the next meeting there has to be money on the table.”
His legacy includes landmark contributions to immunology, infectious diseases, and global health, as well as the example he set for so many as a leader, a mentor, and a mensch.
Marc Lipsitch was hired by Barry Bloom to the faculty of Harvard School of Public Health, where he was professor of epidemiology until 2025, when he moved to join the faculty of Stanford University. Yonatan Grad is a professor in the Department of Immunology and Infectious Diseases at HSPH, the department in which Barry was also a faculty member and then emeritus professor.