Irving Lerner Weissman (1939– )

Irving Lerner Weissman is a researcher and professor in developmental biology at the Stanford University School of Medicine in Stanford, California. Weissman is also a professor of pathology and the Virginia & D. K. Ludwig professor of clinical investigation in cancer at the Stanford University School of Medicine. Weissman studies the biology of stem cells and immune cells and has conducted research in those fields during the late twentieth and early twenty-first centuries. In the late 1980s, Weissman’s team developed methods to identify hematopoietic stem cells, or HSCs, which give rise to the body’s blood and immune cells. Also, in the early 2000s, Weissman co-authored California’s Proposition 71, which secured three billion dollars in state funding for stem cell research after the federal government restricted human embryonic stem cell work. Weissman’s efforts have demonstrated the therapeutic potential of stem cell transplantation in the treatment of diseases, including blood cancer.

Weissman was born on 21 October 1939 in Great Falls, Montana. His family had first immigrated to the US when his father, a Jewish person, left Russia in the early 1900s to avoid being drafted into World War I. Weissman’s father developed steel supply, plumbing supply, and hardware stores across Montana and Wyoming. His mother was a classical pianist who briefly attended The Juilliard School in New York City, New York, before settling down due to economic pressures from the Great Depression in the 1930s. As a result of his mother’s musical background, Weissman also developed musical skills, learning to play both the flute and piccolo.

According to an oral history interview in 2013 with the American Association of Immunologists, or AAI, Weissman reported that he developed an interest in science at an early age. At ten years old, he found a book titled Microbe Hunters by Paul de Kruif, which detailed major developments and contributors to the field of microbiology. Microbiology is the study of micro-organisms called microbes, which are organisms that cannot be seen with the naked eye due to their small size. Weissman asserted that despite him being so young, the book fascinated him due to its applications to the field of medicine.

Also, in the interview with AAI, Weissman stated that through exposure to research in high school, he realized that learning through direct experimentation was more valuable to him than memorization. Weissman recalled being a good but unexceptional student, particularly struggling with science classes such as physics. At fifteen years old, his friend mentioned a pathologist named Ernst Eichwald, who had been hired at a local hospital in Great Falls, Montana. Eichwald was conducting skin transplantation research in mice and had been researching the H-Y antigen, which was one of the first known genes encoded by the Y chromosome. Weissman asked Eichwald for a job, who initially hired him over summers to take care of the laboratory mice and aid in lab research. Weissman claimed that Eichwald’s mentorship allowed him to think and learn like a scientist.

In the interview with AAI, Weissman described how Eichwald taught him about transplantation genetics and explained an experiment in which Eichwald investigated the genes related to skin transplantation in mice. Eichwald taught Weissman to piece the results of the experiment together and fit them into the broader field of research. In Eichwald's lab, Weissman began some of his first experiments. Weissman reported that he had an interest in transplantation biology and wanted to uncover more about tissue transplantation in mice. By the end of high school, Weissman had received high marks on the Scholastic Aptitude Test, or SAT, and became a National Merit Scholar. He graduated high school forty-first in his class in 1957.

After high school, Weissman attended Dartmouth College in Hanover, New Hampshire. Weissman stated in the interview with AAI that after attending Dartmouth for two years, the education had disappointed him. According to Weissman, his professors were teaching him older biology rather than new advancements in biology at the time like in the field of transplantation biology. Weissman also stated that he felt disappointed because, as a Jewish person, he felt uncomfortable with the growing anti-Semitism at Dartmouth College. As a result, Weissman transferred to Montana State University in Bozeman, Montana, after completing two years at Dartmouth College. Weissman asserted that at Montana State University, his fascination with genetics grew through his coursework. At the same time, Weissman went back to do research in Eichwald’s laboratory over the summers.

After graduating in 1961 from Montana State University, Weissman began medical school at Stanford University. According to the interview with AAI, Weissman asserted that he felt particularly drawn to Stanford University’s option of a five-year medical school curriculum rather than four years, which gave him more time to conduct research. Weissman quickly became involved in research on immunological tolerance with Henry Kaplan, a professor of radiology at Stanford University who conducted immunological research. Weissman received his own research lab and a part-time research associate to work with.

In 1964, Weissman went to Oxford University in Oxford, England, to work with Jim Gowans, who studied immunology. Weissman found that immune cells can develop directly in the thymus, an organ in the upper chest, and can move through the blood to the organs involved in the immune response. That finding challenged other notions that the thymus produced hormones that caused the precursors of immune cells to develop outside the thymus. After that finding, Weissman continued doing research rather than completing a medical internship or residency after finishing medical school.

Weissman returned to Stanford University, where he continued his immunological research and focused on identifying and investigating different types of immune cells. He investigated the production of those immune cells in the thymus. Weissman also investigated the process of how bone marrow produces immune cells. In the mid-to late-1960s, Weissman visited Gowans, and together, they developed a method for investigating specific immune cells in the lymph nodes. Weissman and Gowans stained lymph nodes and used antibodies that lit up and showed a part of the lymph node rich with T cells, which are immune cells that help fight disease and infection. They repeated the experiment and found another region rich with B cells, another type of immune cell that makes antibodies to fight infections.

In addition, Weissman investigated T cells and found that one cell could create all different types of T cells in the thymus. That finding led to the development of a quantitative assay that could count the amount of T cells. Weissman then researched the role of the bone marrow in making B cells and developed a quantitative assay for B cells. He found that the cells in the bone marrow that made B cells also had the ability to make myeloid cells, which protect the body from pathogens, and erythroid cells, which are red blood cells that deliver oxygen throughout the body. As a result, Weissman’s lab began to search for what cells in the bone marrow produced B cells and T cells.

That search led to one of Weissman’s contributions to immunological research in 1988 when his group at Stanford University proposed an array of markers useful for isolating blood-forming stem cells in mice. In 1992, Weissman and his colleagues built off of that study and proposed another set of markers that can help identify those blood-forming stem cells, known as HSCs, which form the body’s blood and immune cells. Weissman identified multiple proteins on cell surfaces that could be used to identify HSCs in humans, including the proteins CD34+, CD59+, Thy1+, CD38-, C-kit-, and lin-. Weissman’s team used a method called fluorescence-activated cell sorting to isolate HSCs from white blood cells, in which fluorescent proteins can bind to those specific cell surface protein markers. The technique allowed Weissman’s team to identify what cells were HSCs and isolate them. The ability to isolate HSCs suggested the possible use of such stem cells in treating diseases by allowing the regeneration of damaged cells, tissues, and even organs.

Weissman and his colleagues founded the company SyStemix Inc. in 1988 in Palo Alto, California, to investigate the therapeutic potential of HSCs, where they began working on clinical trials. In 1996, together with physicians at Stanford University, SyStemix Inc. began a clinical trial with fifteen women with metastatic breast cancer who had received a high dose of chemotherapy, which is a drug treatment used to kill cancer cells in the body. Since chemotherapy also damages healthy cells, including stem cells, Weissman’s company and the physicians at Stanford University transplanted purified HSCs back into the women to regenerate damaged cells. As a control group, their team also transplanted unpurified blood into seventy-eight women with the same cancer.

In 1996, a pharmaceutical company named Sandoz, which owned 60 percent of SyStemix Inc., merged with another company named Ciba to form Novartis Pharmaceuticals. Later, Novartis decided to no longer support SyStemix Inc.’s stem cell therapy programs. Although the original trial did not finish, fifteen years after the start of the trial, one-third of the fifteen women who received the purified stem cell transplantation remained alive, compared to only 6 percent of the seventy-eight women who got the unpurified blood transplant.

In 2001, George W. Bush, then president of the US, and his administration began to limit the amount of federal funds allocated to support human embryonic stem cell research. Parents of children with diabetes had started a movement in California to get a proposition passed in the state to fund stem cell research. Weissman, along with Robert Klein, a member of the Juvenile Diabetes Foundation and a lawyer, drafted the proposition, which became known as Proposition 71. In 2004, Proposition 71 passed and allocated three billion dollars for stem cell research over ten years. Proposition 71 led to the creation of the California Institute for Regenerative Medicine, or CIRM, to oversee and fund stem cell research in the state of California.

Weissman and his team at Stanford University continued to carry out their research and identified the “don’t eat me” signal in 2009. Weissman’s lab had investigated an antibody called CD47, which they identified as present in all human leukemias. The CD47 antibody is a protein on the surface of cells that tells the immune system not to attack those cells. Weissman’s team termed that the "don't eat me" signal. Cancers like leukemia use the CD47 antibody to avoid attacks from the body’s immune system. Weissman’s lab found that CD47 binds to a protein called SIRPalpha, which exists on the surface of macrophages, or immune cells that detect and destroy harmful materials like pathogens. That binding inhibits the macrophage’s ability to kill the cancer cells. Building on that study, Weissman, along with colleague Ravi Majeti at Stanford University, developed an antibody therapy that blocks CD47, which prevents cancer cells from evading immune attack. Studies in mice have demonstrated the potential efficacy of the therapy to treat cancer. Later, in 2017, Weissman’s lab also identified another “don’t eat me” signal that cancer cells use to evade macrophages. That study described a protein structure on the surface of cancer cells called complex class 1. The researchers found that human tumors with a higher presence of that protein structure have greater resistance to CD47 antibody therapies.

In the 2020s, Weissman continued to make contributions to the fields of stem cell biology, cancer biology, and regenerative medicine. Weissman’s lab published a paper in the journal Nature in 2024, which explained that depleting myeloid-biased hematopoietic stem cells can decrease age-related markers of immune decline and restore aspects of a healthy immune system. In addition, as of 2025, Weissman has expanded his research in regenerative medicine, with a company that he co-founded named Bitterroot Bio. The company completed the treatment of participants in a Phase I trial for the treatment of atherosclerotic cardiovascular disease with an anti-CD47 drug.

Outside of science, Weissman frequently goes fly fishing, even going on trips multiple times a year to fly fish in places like Russia and Argentina.

Weissman has received many awards and appointments throughout his career. In 1989, Weissman began to serve on the AAI council, where he continued until 1996. Weissman served as president of AAI from 1994 to 1995. In 2004, Weissman began to serve as director for the Stanford Institute for Stem Cell Biology and Regenerative Medicine until he stepped down in 2021. In 2019, Weissman received the Albany Medical Center Prize in Medicine and Biomedical Research for his research in stem cell and cancer biology, including the identification of HSCs and the role of CD47 and the “don’t eat me” signal in cancer cells. In 2022, Weissman received the Wallace H. Coulter Award for Lifetime Achievement in Hematology by the American Society of Hematology, or ASH. The ASH stated that Weissman’s notable achievements include the isolation and transplantation of hematopoietic stem cells and the isolation of hematopoietic progenitor cells, central nervous system cells, and solid tumor cells. Other awards include the Rabbi Shai Shacknai Memorial Prize in Immunology and Cancer Research, the Linus Pauling Medal for Outstanding Contributions to Science, the Simon M. Shubitz Award for Excellence in the Field of Cancer Research, and the Cockrell Foundation Award in Clinical or Translational Research.

As of 2025, Weissman leads research in stem cell biology and regenerative medicine research at Stanford University.

Sources

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14. Weissman, Irving. “From Immunological Tolerance to Stem Cell Therapy and Back: An Interview with Irving Weissman.” By Sarah Allan. The Company of Biologists. September 1, 2011. https://journals.biologists.com/dmm/article/4/5/559/53588/From-immunological-tolerance-to-stem-cell-therapy (Accessed May 27, 2025).