On Dec. 2, 2022, 2017 National Inventors Hall of Fame® (NIHF) Inductee Carolyn Bertozzi joined “Science Friday” host Ira Flatow to discuss her research, her 2022 Nobel Prize in Chemistry and the importance of diversity in her field. Read on for highlights of their thought-provoking conversation.
Developing a New Field
Flatow began the segment by asking Bertozzi to explain bioorthogonal chemistry, the field she developed, which earned her a shared Nobel Prize with Morten Meldal and Barry Sharpless.
“The word orthogonal is one that we usually use when we’re trying to describe two things that don’t interact with each other,” Bertozzi said. “When someone is really thinking outside the box or in a very different way, we like to think of that as orthogonal thinking. So bioorthogonal means not interacting with biology.”
She went on to explain that this new type of chemistry began with a longstanding interest she had in the biology of complex carbohydrates, comparing them to a “forest that decorates the entire surface of every cell in your body.”
However, until her work in the late 1990s, there was no way to observe and study these complex carbohydrates using a microscope or PET scan and look at the sugars on the cells while they were still alive and in the body.
While working as a postdoctoral fellow, Bertozzi was frustrated that she was not able to specifically visualize the carbohydrates. By chance, she attended a conference in Southampton, England, where German biochemist Werner Reuter explained the process of feeding cells chemically altered sugars to change the structures of these complex carbohydrates.
“You could actually make the cells turn into what they eat,” Bertozzi said. “You’ve heard the phrase ‘you are what you eat,’ right? And these cells actually were putting altered sugars on the surface just because they were eating the little simple precursors. And so that gave me an idea for how you could sneak a little bit of chemistry into cell surface sugars, and then use the chemistry to attach probe molecules for imaging.”
Applying Bioorthogonal Chemistry
For the first decade of her independent career, Bertozzi developed these ideas, engineering chemical groups that were bioorthogonal and would only react with other bioorthogonal groups and with nothing that exists in nature.
The applications of this are profound. Bioorthogonal chemistry has the potential to revolutionize drug delivery, specifically in cancer treatment, where current chemotherapy methods kill both cancer cells and healthy cells at the same time.
“One of the challenges is to figure out, how do you send that toxic drug to the cancer cell specifically, like a guided missile, and keep it away from all the other cells in the body?” Bertozzi said. “And bioorthogonal chemistry has turned out to be useful for this.”
Bertozzi went on to explain how companies are currently conducting human trials for the application of bioorthogonal chemistry to treat cancer, noting that these promising developments have the potential to radically improve current cancer treatment methods.
Bioorthogonal chemistry is a field still in its relative infancy, and the next major step, according to Bertozzi, involves developing additional bioorthogonal chemistries that can be performed inside humans.
“There are other bioorthogonal reactions that we and others developed and have used in animals, in cells in a dish, in lots of other settings,” Bertozzi said. “But to actually do the chemistry in the human body is a whole new layer of complexity. And right now we only have one chemistry that is good enough for that.”
Promoting Interest and Diversity in Chemistry
Flatow and Bertozzi concluded their conversation by discussing the misconception that chemistry is boring or uninteresting.
“I think the misconception of chemistry being boring might be our own fault,” Bertozzi said. “Because I think chemists teach students in a somewhat boring way during their first exposure in high school.”
Bertozzi admitted that when she was first introduced to chemistry in high school, she did not really appreciate its relevance and therefore did not really enjoy the subject. It wasn’t until she took organic chemistry in college that she realized how central the field was in biology and medicine.
“I’m really glad that I stuck with it long enough to discover organic chemistry because that sealed it for me,” Bertozzi said. “But I think if we did a better job teaching in the early stages, people wouldn’t have this bias against chemistry. It’s fascinating. And there’s so much we don’t know and so many discoveries yet to be made, it’s a field I think of as still very young.”
As a newly minted Nobel laureate, Bertozzi has started to notice that more people are paying attention to the things she has to say, and the additional gravity her words might have on others.
It’s for this reason that she plans to continue promoting the importance of having a diverse group of scientists in labs across the country in order to produce the best ideas and outcomes.
“Lots of chemists, including myself, have been advocating for greater diversity among our ranks,” Bertozzi said. “But if you are awarded the Nobel Prize, and your strategy for success has been to have the most diverse lab that you can have, I think that that gives some validation to the idea that diversity breeds success.”