A Conversation with Cornelia Bargmann
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CONVERSATIONS WITH GIANTS IN MEDICINE A conversation with Cornelia Bargmann How are behavioral decisions modified JCI: How did you decide to go work on by context and experience? Cornelia Barg- oncogenes with Bob Weinberg for your PhD? mann of Rockefeller University has made Bargmann: I joined the Weinberg lab this her life’s work, exploring the intersec- right at the time that the lab discovered tion between genes, the environment, and that changes in the Ras genes were associ- the nervous system in the roundworm, ated with the transforming ability of human C. elegans. Bargmann (Figure 1) is also seek- tumors. In my first summer, the lab identi- ing to help cure, manage, and prevent all fied the exact molecular change at Ras ami- disease by the year 2100 by serving as Head no acid 12 that occurred in tumor cells. This of Science for the Chan Zuckerberg Initia- was work done by graduate students — Cliff tive. Watch the full interview at www.jci. Tabin and Luis Parada. It was an easy deci- org/videos/cgms to hear her tell the story of sion for a graduate student to go there! how blowing up a toilet got her interested in The early work on oncogenes led to science and what she finds most interesting incredible discoveries, and yet at the time, about studying 37 trillion cells all at once. it didn’t feel like we were in control of this JCI: What were you like as a child? huge problem. We were graduate students Bargmann: I grew up third of four sis- trying to make things work, and most ters. My parents were immigrants from Figure 1. Cornelia Bargmann on May 15, 2018 in of the time they didn’t, and we dropped Europe, and like many immigrants, what New York. Image credit: Alexey Levchenko. things on the floor and contaminated our they believed in was education. It was a cultures. Somehow, we kept at it and these very scholarly household full of books: we Then my sister Eve went to medical discoveries happened. all played the piano, we all read. There was school. I worshipped my older sister, so I I feel really proud to be part of what art, literature, math. My sisters all went to decided I was going to be a doctor too. When the lab accomplished at that time. My proj- college, which was somewhat unusual in I was 12 years old, I signed up to be a volun- ect was to clone a gene that was associated the town that I grew up in; in Athens, Geor- teer at the hospital to learn to be a doctor. I with rat neuro- and glioblastomas. Most gia at the time, maybe only 20% of stu- lasted two days. It was so upsetting to be with of the people in the lab were working on dents went to college after high school. My people in need and not be able to help them. human tumors, but there were reasons to father was in the Department of Statistics But that idea led me to science. Not long after think that these tumors were interesting. and Computer Science at the University that, I started working in a chemistry lab, and One reason was that sometimes the immune of Georgia and before that, he had been at then a biology lab. The combination of the system attacked the transformed cells and IBM in the early days of computing at the lab being very much about learning and also the tumors spontaneously regressed. Ulti- Watson Research Center. immediate and concrete — you work with mately several of us were able to identify I remember that whenever we would your hands, you spend all day talking with the gene that was altered in those tumors. toast glasses around the dining room table, smart people — was incredibly compelling. It turned out that the reason that the tumors we had to calculate how many times the I was not a natural. The way I remem- regressed is that the gene, neu, encoded a glasses were going to clink. I still look around ber my first summer in the lab as an under- transmembrane protein, a growth factor a room and think, “Hmm, 6 times 5 divided graduate is that every day I would plate out receptor. It was accessible on the surface of by 2.” These kinds of games were part of bacteria, and then go home. The next morn- the cell and could be recognized by antibod- the vocabulary of the house, and part of ing I would come in and the experiment ies that would ultimately lead to its destruc- understanding that whatever you learned — would have failed. I would go to the vending tion. After that discovery was made, Genen- whether it was about math or music — would machine and eat some Twinkies, and then tech developed an antibody (Herceptin) that be something that would apply in life. go back in and do the experiment again. could be used to attack the transmembrane JCI: When did you start to think seri- There was something about eventually get- protein to target a class of human breast can- ously about science? ting it to work that was such a thrill. The cer in which this gene is altered. Bargmann: I grew up in the 1960s dur- potential that molecular biology opened up JCI: Why did you turn from such an ing the space era. And if you talk to scien- in understanding biological problems in a exciting discovery toward studying neuro- tists from that generation, we all wanted to new way was obvious even to a college stu- science in roundworms? be astronauts. At some point, I realized that dent, and the excitement of being able to Bargmann: I had always been interested being an astronaut was not practical, since I learn new things using new approaches was in neuroscience and particularly behavior. got sick every time I got on an airplane. what drew me into genetics. What became clear to me in graduate school was that the molecular approaches that we were using in cancer might also be applicable Reference information: J Clin Invest. 2018;128(7):2655–2656. https://doi.org/10.1172/JCI122804. to problems in the brain and nervous system. jci.org Volume 128 Number 7 July 2018 2655 CONVERSATIONS WITH GIANTS IN MEDICINE The Journal of Clinical Investigation At that time, a lot of people argued there UCSF had a fantastic interdepartmen- decided on the birth of their first child that couldn’t possibly be genes that regulate tal neuroscience program, and that was the they were going to give away their wealth to behavior. This was despite the fact that the place that I learned about brains and how try to make the world that their children live existence of innate behaviors implies that if neural systems work. You just never know: in better. Priscilla is a pediatrician and was there’s something invariant in every individ- you’re starting out, you’re an Assistant Pro- very motivated by seeing children that she ual in a species, it is probably encoded in the fessor, you’re trying to set up your lab, you’re could not help. That led to the Chan Zucker- genome. But still, how that might work was trying to figure out how much ice buckets berg Initiative’s mission to support science a real puzzle. I came to C. elegans because cost. The Assistant Professor in the lab next and technology to help cure, prevent, or it had great genetics. Also, I was interested door was going through the same thing. He manage all diseases by the end of the cen- in behavior and genetics, but it was clear knew a ton about neuroscience, and we were tury. This mission is a lot to wrap your head that there was going to be a nervous system interested in similar things. That was Marc around, but: One, the end of the century is between point A and point B. Right then, a Tessier-Lavigne, who went on to become a long way away. Two, science is powerful. connectivity map of the C. elegans nervous one of the great developmental neuroscien- Three, this is a community effort. The Chan system was published that would serve as a tists, the President of Rockefeller University, Zuckerberg Initiative is not going to be the way to move back and forth between what and now the President of Stanford Universi- one group that solves all diseases. What we molecules, neurons, and the organism did. ty. I had the great experience of having a col- can do is think about where we might be able That wiring diagram is still the foundation league who, at the time, seemed just as clue- to make a differentiated impact with new of what goes on in my lab every day. less as I was but was smart and thoughtful resources. How can we accelerate progress? One of the things I’ve learned about and stimulating, and helped my lab advance How can we make science better? Mark and studying behavior is that you’re doing your- in its science. And I think our lab helped his Priscilla are in Silicon Valley, which has new self a big favor if you study something that lab advance its science as well. perspectives on making systems more effi- the animal wants to do. To the extent that JCI: After 14 years at UCSF, you transi- cient through software engineering, data you can use an animal in a setting that it tioned to Rockefeller University.