Carolyn R. Bertozzi, PhD, Nobel Laureate
On November 7-10, 2024, while attending the Annual Meeting of the Clinical Association of
Genitourinary Surgeons at Stanford University, hosted by Stanford’s Chair of Urology, Dr. Eila Skinner, Dr. Catalona was inspired by a presentation given by Nobel Prize Laureate, Dr. Carolyn Bertozzi, on the translation of discoveries in her field of “bioorthogonal chemistry” to improve the effectiveness of cancer immunotherapy, perhaps across all cancer types.
Dr. Bertozzi completed her undergraduate degree at Harvard, her doctorate at the University of California, Berkeley, and postdoctoral work at the University of California, San Francisco. As a faculty member at Stanford University, she holds the Anne T. and Robert M. Bass Professorship in the School of Humanities and Sciences. Her research focused on the sugars that coat the surface of all our cells and why changes in these complex sugar molecules occur.
In the 1980’s-1990’s, medical doctors discovered that cell surface sugars change in disease. The pattern on healthy cells is quite different than on cancer cells. Healthy cells have a well-manicured cover of sugars, while cancer cells have an overgrown jungle of sugars called sialic acid. Several decades of research have followed.
The scientists realized that changes in sugars have to do with our immune systems, which have an important role in protecting us from cancer. These immune cells (various types of white blood cells) sample other cells in our bodies and can chemically “taste” the surface of our cells. When all is working well, cancer cells have a bad taste and then are destroyed by immune cells. However, cancer cells can sometimes trick the immune cells by putting them “to sleep”.
About 15 years ago, scientists developed drugs (called immune therapies) to reactivate the immune system after these tricky cancer cells have put it to sleep. Immune therapies were first used to treat patients with deadly cancers. Jimmy Carter’s metastatic melanoma went into remission after it had spread to his brain after he received immune therapy. Revolutionary as they are, immune therapies don’t work in more than 50% of the people who were treated with them. This prompted several questions. Why is this the case? Could other immune therapies be more effective in patients who do not respond to those first-generation immune therapies?
Sialic acids send a different message to the immune cells. They make the normally bad cancer cells taste good. The immune cells are tricked, allowing the cancer cells to grow and spread. Dr. Bertozzi compares these cell surface sugar molecules (when viewed from above) to Earth’s vegetation, which includes grasses, trees, and shrubs. She had the idea of creating a medicine to strip the sialic acid sugars off the cancer cells so the immune system would recognize them as cancer and then act on them. She realized that making and testing a medicine would require the synergistic efforts of a medical center, hospital system, physicians, and MD-PhD student researchers. At that time, she moved her lab to Stanford to continue this important work and joined the interdisciplinary institute ChEM-H (Chemistry, Engineering & Medicine for Human Health).
During her first year at Stanford, Dr. Bertozzi met a graduate student named Melissa Gray, who studied the concept of removing the sialic sugars from the cells. This work was the emphasis of Melissa’s thesis. She created a medicine (part antibody) that parks on the surface of the cancer cell. An enzyme was attached to the antibody, and, like a lawn mower, revs up and mows the sialic acids off the cancer. This molecule is the foundation of the medicine that is currently in clinical trials at several hospital systems, including Stanford, and, in the future, may provide treatment for cancer patients.
Much of Dr. Bertozzi’s work in biology and chemistry is interdisciplinary and focuses on human health. When asked how she manages all of her diverse responsibilities, Dr. Bertozzi commented: “I do have a tendency to over-commit, and that makes it difficult to do a good job in every area, but I have outstanding people, and if you have an excellent team, you can expand your footprint quite a bit.” She also mentioned that she hires people who have areas of expertise in related fields that are not her specialty. She summarized, “The key is surrounding yourself with really good, talented people.”
Dr. Bertozzi has received many awards throughout her career. In 2022, Dr. Bertozzi received the Nobel Prize in Chemistry for the development of click chemistry and bioorthogonal chemistry.
Dr. Bertozzi’s revolutionary research is already providing hope to cancer patients. She co-founded Palleon Pharma of Waltham, Massachusetts, which focuses on investigating glycolimmune checkpoint inhibitors as a potential treatment for cancer. The long-term effect of her inimitable work could greatly improve longevity and quality of life for generations.
Dr. Bertozzi grew up in Lexington, Massachusetts. Her parents were the late Norma Gloria (Berringer) and William Bertozzi. Her father was of Italian descent. Her maternal grandparents were from Nova Scotia, Canada. Her father was a physics professor at the Massachusetts Institute of Technology. Dr. Bertozzi and her two sisters grew up around science, attending MIT camps during school breaks. As a young person, Dr. Bertozzi played softball and soccer and credited this involvement with helping her develop teamwork, resilience, work ethic, and grit. Dr. Bertozzi attended Harvard because the school offered strengths outside the science arena. While in high school, she briefly considered a music career, as she had won several awards for music compositions and musical accomplishments. Her talent on the keyboard earned scholarship offers as a music major, but she felt that she was always centered on the sciences.
