The Chemist Who Taught Reactions to Mind Their Manners: Carolyn Bertozzi at Sixty

Most chemistry happens in flasks because flasks are empty. A living cell is the opposite: a crowd of water, salts, proteins, sugars and thousands of reactive groups, any of which might intercept a reagent before it reaches its target. Much of Carolyn Bertozzi’s career has been an answer to the question that follows. Can a chemist run a reaction inside that crowd, on purpose, and have nothing else in the cell take notice?

Her answer earned her a share of the 2022 Nobel Prize in Chemistry, with Morten Meldal and K. Barry Sharpless, “for the development of click chemistry and bioorthogonal chemistry,” in the words of the Royal Swedish Academy of Sciences. It has also made her one of the most cited scientists at Stanford. OpenAlex, the open bibliographic index, credits her with 1,012 works, 87,280 citations and an h-index of 144 (retrieved Oct. 27, 2026). On Oct. 9, former students and postdocs gathered at Paul Berg Auditorium for CRB60, a symposium marking her 60th birthday. It is a fitting moment to take stock of what she built.

From Harvard to the Farm

Bertozzi earned her A.B. in chemistry at Harvard in 1988 and her Ph.D. at the University of California, Berkeley, in 1993, then did postdoctoral work in cellular immunology at UCSF, according to her Stanford profile. She joined the Berkeley faculty in 1996 and has been a Howard Hughes Medical Institute Investigator since 2000. She came to Stanford in June 2015 as co-director and Institute Scholar of Sarafan ChEM-H, the university’s institute joining chemistry, engineering and medicine, and has led it as Baker Family Director since 2020. Her title runs long: she is also the Anne T. and Robert M. Bass Professor in the School of Humanities and Sciences and a professor, by courtesy, of chemical and systems biology and of radiology.

The sprawl is deliberate. “To advance science, I think it’s important to blur the boundaries between the disciplines,” she told Stanford Chemistry in January, in a profile where she described her work plainly: “I am a chemical biologist. My lab develops chemical technologies to study biological systems and to make new kinds of medicines.”

A forest of sugars

Her subject from the start was glycans, the chains of sugar that coat the outside of cells. “Cells have a forest of glycans on their surfaces, so they’re kind of the first point of contact when cells are touching each other and exchanging information,” she said in the same profile. Glycans are awkward to study with biology’s usual tools, because genes do not spell them out directly the way they spell out proteins. Her approach was to slip chemistry in through the cell’s own supply lines.

The first landmark came in 1997. In “Engineering Chemical Reactivity on Cell Surfaces Through Oligosaccharide Biosynthesis” (Science, doi:10.1126/science.276.5315.1125), Lara Mahal, Kevin Yarema and Bertozzi fed cells an unnatural version of the sugar N-acetylmannosamine carrying a ketone, a chemical handle cell surfaces do not normally display. The cells’ own machinery turned it into sialic acid and set it out on their surfaces, where the ketone could be tagged with a hydrazide. Tagged cells, the authors showed, could then be “selectively killed in the presence of a ricin A chain-avidin conjugate,” an early sketch of targeted delivery. OpenAlex counts 796 citations (Oct. 27, 2026).

Reactions the cell ignores

Ketones, though, are not wholly foreign to biology. The real advance was a pairing in which neither partner belongs to the cell at all. In 2000, Eliana Saxon and Bertozzi reported “Cell Surface Engineering by a Modified Staudinger Reaction” (Science, doi:10.1126/science.287.5460.2007), in which an azide placed on cell-surface sugars was joined by an engineered triarylphosphine to form a stable amide bond. “Both reactive partners are abiotic and chemically orthogonal to native cellular components,” the paper reads. Two chemical halves that recognize only each other in a sea of biology: that idea is what came to be called bioorthogonal chemistry. OpenAlex lists 2,462 citations (Oct. 27, 2026).

The next problem was safety. Click chemistry’s signature reaction, which joins an azide to an alkyne, relies on copper, and as Nicholas Agard, Jennifer Prescher and Bertozzi wrote in 2004, “the Cu(I) catalyst is toxic to cells, thereby precluding in vivo applications.” Their solution was to build the energy into the molecule itself, using a ring-shaped alkyne strained tightly enough to snap onto an azide unaided. The strain-promoted cycloaddition (Journal of the American Chemical Society, doi:10.1021/ja044996f) “proceeds under physiological conditions without the need for a catalyst,” the authors reported, “with no apparent toxicity.” With 3,027 citations in OpenAlex (Oct. 27, 2026), it is her most cited paper.

The method then moved from dishes to animals. A 2005 review with Prescher, “Chemistry in living systems” (Nature Chemical Biology, doi:10.1038/nchembio0605-13; 1,461 citations), set out the field’s ambitions. In 2008, Scott Laughlin, Jeremy Baskin, Sharon Amacher and Bertozzi used the approach to image membrane glycans in developing zebrafish (Science, doi:10.1126/science.1155106; 1,027 citations). The Nobel committee’s summary was compact: “Carolyn Bertozzi took click chemistry to a new level,” and “her bioorthogonal reactions take place without disrupting the normal chemistry of the cell.”

From tools to medicines

Over the past decade, the lab has turned more squarely toward therapy. Her Stanford profile lists inventions beyond bioorthogonal chemistry: next-generation antibody-drug conjugates, lysosome-targeting chimeras (LYTACs), antibody-enzyme conjugates and antibody-lectin chimeras, several of which have been “translated into clinical candidates for treatment of cancer and autoimmune diseases.”

LYTACs arrived in a 2020 Nature paper by Steven Banik, Kayvon Pedram, Simon Wisnovsky, Green Ahn, Nicholas Riley and Bertozzi, “Lysosome-targeting chimaeras for degradation of extracellular proteins” (doi:10.1038/s41586-020-2545-9; 1,171 citations). The title carries the ambition. Many disease-relevant proteins sit outside cells or on their surfaces, and the aim is to send them to the lysosome, the cell’s digestive compartment, to be broken down.

Antibody-lectin chimeras, or AbLecs, appeared in Nature Biotechnology last December (doi:10.1038/s41587-025-02884-6), with Jessica Stark as first author and Jeffrey Ravetch among the collaborators. The paper describes “bispecific antibody-like molecules comprising a cell-targeting antibody domain and a lectin ‘decoy receptor’ domain,” which reduced tumour burden in a humanized mouse model and, the authors report, “synergize with blockade of established immune checkpoints.” Bertozzi put the direction in her own words in January: “Now, we are trying to develop medicines that target the surface of cancer cells to chop up these immune-suppressive glycans. We have a couple of new candidates that are going through tests in animal models now.”

The output has not slowed. In July, Nature Chemical Biology published the group’s “Tumor immune cell targeting chimeras reprogram tumor-associated macrophages” (doi:10.1038/s41589-026-02258-2), and Nature Chemistry a paper on genetically targeted photocatalytic organic dyes (doi:10.1038/s41557-026-02195-6). The Nobel announcement itself noted that bioorthogonal reactions have improved the targeting of cancer pharmaceuticals, “which are now being tested in clinical trials.”

The lab as legacy

The CRB60 program read like a map of chemical biology. Speakers included Agard, now at Genentech; Mahal, at the University of Alberta; Prescher, at UC Irvine; Banik, now on the Stanford faculty; Christina Woo and Ryan Flynn of Harvard; Xing Chen of Peking University; and Ellen Sletten of Dartmouth. Baskin and Pamela Chang of Cornell were among the organizers. The Stanford Daily reported on Oct. 14 that Bertozzi has mentored “almost 300 researchers, 60 of whom now lead independent academic laboratories,” and that her lab’s discoveries have helped launch at least 12 biotechnology companies. Stavroula Hatzios of Yale, another organizer, was quoted by the Daily: “These aspects of her inspiring, compassionate mentorship have transformed the lives of so many, and will ultimately be her lasting legacy.”

The formal honors are long. Her profile lists membership in the National Academy of Sciences, the National Academy of Medicine, the National Academy of Engineering, the American Academy of Arts and Sciences and Germany’s Leopoldina, along with Foreign Fellowship of the Royal Society. Her prizes include a MacArthur Fellowship in 1999, the Lemelson-MIT Prize in 2010, the Wolf Prize in Chemistry, the Priestley Medal, the Welch Award and the Heineken Prize. In February the Royal Society of Chemistry made her an Honorary Fellow, its highest honor, citing her “invention of bioorthogonal chemistry,” the School of Humanities and Sciences reported.

Announcing the 2022 prize, committee chair Johan Åqvist said it “deals with not overcomplicating matters, instead working with what is easy and simple.” That simplicity was hard-won. A reaction that does exactly one thing, and nothing else, amid everything a cell contains, is among the hardest things in chemistry to design. Bertozzi spent the better part of three decades making such reactions ordinary, and the people who learned to do it in her lab now run laboratories of their own.

Photo: Armin Kübelbeck (Kuebi) / Wikimedia Commons, CC BY-SA 3.0. Bertozzi at the Emanuel Merck Lectureship, TU Darmstadt, Nov. 14, 2011.