A conversation with Jesse Roth

Ushma S. Neill

J Clin Invest. 2020;130(7):3331-3332. https://doi.org/10.1172/JCI138254.

Conversations with Giants in Medicine

We take it for granted today that all hormones and other intercellular messenger have their own specific receptors. But this was not the case until the groundbreaking work of Jesse Roth and his colleagues. Indeed, Roth (Figure 1), currently at the Feinstein Institutes for Medical Research of Northwell Health Zucker School of Medicine, is best known for his research on cell surface membrane receptors. His studies on the receptors for , , and adrenocorticotropic hormone (ACTH) in the early 1970s became the model for many others. See the JCI website for the full interview (https://jci.org/videos/cgms) to get a sense of whether Dr. Roth could have instead been satisfied as a clinician with a black bag doing house calls. JCI: Can you start by telling us a little bit about your parents and your upbringing? Roth: I have a accent notched into my tongue. I was born in 1934 in the depths of the Great Depression. I grew up in a happy middle-class family. My mother was an immigrant from Romania. My father’s parents emigrated from Austria. His father died when he was 12; my father left school to support his family. Despite the truncation of his school years, he was very well read. At the time I was growing up, science was just the hottest thing. Three […]

Find the latest version: https://jci.me/138254/pdf CONVERSATIONS WITH GIANTS IN MEDICINE

A conversation with Jesse Roth

We take it for granted today that all hor- ily. My parents said, “If the Jewish com- mones and other intercellular messenger munity is opening its first medical school, have their own specific receptors. But this of all people that should take a chance on was not the case until the groundbreak- them, I guess we ought to.” It was such a ing work of Jesse Roth and his colleagues. good choice. Indeed, Roth (Figure 1), currently at the JCI: After a life in , how Feinstein Institutes for Medical Research did you decide on St. Louis and Washing- of Northwell Health Zucker School of Med- ton University for your residency? icine, is best known for his research on cell Roth: In those days, the best of aca- surface membrane receptors. His studies demic medicine in the US was largely north on the receptors for insulin, growth hor- of the Mason-Dixon line and east of the mone, and adrenocorticotropic hormone Mississippi River. My professors of medi- (ACTH) in the early 1970s became the cine convinced us to shop more broadly, so model for many others. See the JCI web- my classmates and I actually went out and site for the full interview (https://jci.org/ looked; they were the ones who pointed videos/cgms) to get a sense of whether Dr. out that Washington University was really Roth could have instead been satisfied as a in the top echelon. They called ahead for clinician with a black bag doing house calls. me. It was much like horse trading, along Figure 1. Jesse Roth in New York City on JCI: Can you start by telling us a little bit the lines of, “Hey Jesse, where do you wish October 16, 2019. Photo credit: Alexey Levchenko. about your parents and your upbringing? to go?” “Oh, I thought St. Louis was ter- Roth: I have a New York accent notched rific.” My chief got on the phone, and the into my tongue. I was born in 1934 in the those days, you could compete in a six-hour arrangements were made. depths of the Great Depression. I grew up exam for a New York State Scholarship. JCI: What put you on a track towards in a happy middle-class family. My moth- Based on the score, the state paid $350 doing research? er was an immigrant from Romania. My out of the $600. The same thing happened Roth: The group I worked with in St. father’s parents emigrated from Austria. when I went to medical school with a New Louis were both very good clinicians and His father died when he was 12; my father York State Medical Scholarship. You sat for very good researchers. I started to see left school to support his family. Despite a multiple-choice exam and if you came out myself doing both. Near the end of my the truncation of his school years, he was above the cut line, you got $750 for each of residency, I was on a waiting list for a fel- very well read. the four years. At that time, medical school lowship when Irving London, my professor At the time I was growing up, science tuition was $1,000 per year. of medicine from Einstein, introduced me was just the hottest thing. Three or four of JCI: You were in the first medical to Solomon Berson and Rosalyn Yalow. us in each class in elementary through mid- school class at Einstein; why take a chance London knew they were doing very excit- dle school were turned on by science from on a completely new medical school? ing, cutting-edge research, but the greater the beginning. We did those silly exper- Roth: In those days, the prejudices in world of science didn’t yet realize it. I had iments — adding vinegar to bicarbonate medical schools were tough. If you were written to Berson and Yalow before that, soda and detonating small explosions. The Jewish and you were from New York, you and Berson had sent me back a very hes- school I went to was such a small school had a tough time getting into medical itating letter until he got the letter from that they had to hire a science teacher to school. I didn’t get into a fancy medical London. Berson then wrote back, “Forget come from the outside for an hour a week. school, and Einstein was just beginning the first letter. Come!” And that’s how I got That let them pick from among the best to admit its first class. My cousin, a physi- started in research. public school teachers. These were enthu- cian, was very impressed with the faculty Yalow and Berson had just published siastic and energetic people who in other that Einstein was putting together. When their landmark paper on insulin, the first times might have been active scientists I went to the interview, the only building radioimmunoassay [RIA]. International themselves instead of teachers. they had was a small one-family house in recognition was just starting for them. Ber- JCI: How did you end up at Columbia the Bronx. I needed imagination and cour- son and Yalow ran a small group, and they for your undergraduate studies? age, but I trusted my cousin’s opinion. were often at the lab bench. From the point Roth: It will surprise parents nowadays The other positive force came from my of view of the people who understood how that tuition back then was $600 per year. In parents. We were a committed Jewish fam- science and teaching were done, we saw that hands-on dedication right there. My project was working on an RIA

Copyright: © 2020, American Society for Clinical Investigation. for growth hormone with Shimon Glick. Reference information: J Clin Invest. 2020;130(7):3331–3332. https://doi.org/10.1172/JCI138254. Growth hormone was slow in emerging as

jci.org Volume 130 Number 7 July 2020 3331 CONVERSATIONS WITH GIANTS IN MEDICINE The Journal of Clinical Investigation an important factor among the hormones. the rest of my life. I recall him adding, “But [now Northwell Health] asked me to stay. It turned out that the animal growth hor- this is an exciting place. Why don’t you see They offered me the position as geriatri- mones were different from human growth what else you might want to do?” While I cian-in-chief of the medical system. It was hormone, unlike almost all the other pep- continued working on growth hormone to at that time they decided that they were tide hormones. It was a big puzzle. pay for lunch and the month’s rent, Pastan going go major league, start a medical JCI: Given this exciting research, how and I decided to focus on one question: how school and invest in cutting-edge research. did you end up as a clinical associate at the does the cell know when insulin is present? It was yet another exciting opportunity. NIH? We started in 1963 and succeeded, but it And so far, Northwell has been very pro- Roth: In those days, the Vietnam War took us much longer than we expected to phetic in which way to go. They are now was going on, and young MDs were being define that first step in insulin action. the largest health system in New York drafted. I didn’t want to go to war, so I went JCI: How difficult was it for the field State. down to NIH to try to look for a job, because to accept the fact that insulin could have a JCI: Your trainees over time have if you went to NIH or CDC or FDA, that receptor? included Nobel Prize winners, National was considered a full government job and Roth: I remember presenting some of Academy members, a who’s who of the you would not be deployed. I looked at the the receptor work at several excellent aca- metabolism field with Bob Lefkowitz, Bar- endocrine jobs, and I didn’t get one. I risked demic centers and the audience just look- bara Kahn, Ron Kahn, Jeff Flier, among that year not having a deferment, and I was ing at me, wondering why I would be doing others. lucky I didn’t get drafted; the next year, this. We persisted; the concept of cell-sur- Roth: I think that we were lucky. I the plum job that I wanted was open and it face receptors eventually started to gain always thought that my job was to con- came to me because Berson called the guy wide acceptance. vince my trainees that if they worked hard, at the NIH and said, “I got this kid for you.” JCI: Why did you leave NIH to go to they would have every chance to succeed. The group leaders at NIH were terrific. Johns Hopkins? And why did you pivot Many of the MDs came with relatively lit- Another terrific thing about the NIH was towards geriatric medicine? tle research background compared to the there seemed to be no walls. It was not like Roth: I was at NIH for 26 years. By that PhDs. We worked very hard with them, universities where they had lots of differ- time, I was entitled to a pension and my and our job was to encourage them and ent groups, but not much talking between three children were approaching college help them do the right experiments. groups. NIH was just one big, wide, open age. If I had stayed at NIH, I was worried JCI: Turning from mentoring to being house. We lived all in one giant red brick that my kids would wind up with big col- mentored: Yalow was notoriously fiery. monster of a building, Building 10. We all lege debts and I thought that was such a What was that relationship like? ate in the same cafeteria, had our hair cut burden; I had gone through college with no Roth: For much of my research career, in the same barber shop, covered night debt. That prompted me to look around, Yalow treated me as a favorite, including calls in the same places. Science was also and Hopkins had a job open in geriat- me and my wife Susan in Yalow family much easier in those days. You could get ric medicine. The big advantage of that events, including the party in Stockholm the help you needed, complete a competi- position was that the National Institute at the time of her Nobel Prize. On the oth- tive piece of work in a year or two, and have on Aging (NIA) had a very good research er hand, she often went out of her way to it published and recognized. The time was program in Baltimore (adjacent to Hop- challenge (in public) work from my lab. In right and the environment was right, and kins) which included a very rich endocrine my early years at NIH, it took me months we were in heaven. group. On paper, the move looks big, but in to convince her that the immunoassayable JCI: You rose from being clinical asso- reality, it was not a great leap. insulin in blood also included proinsulin ciate all the way to being the scientific JCI: After nine years at Hopkins, you and other insulin precursor molecules. In director of the National Institute of Dia- moved again to become the president and later years, she challenged our findings betes and Digestive and Kidney Diseases CEO of the Picower Institute in New York. that bacteria have bioactive peptides that (NIDDK), with the rank of assistant sur- Was that driven by a desire to return to are very similar to mammalian hormones. geon general. And this coincided with the New York or the opportunity for a leader- Regrettably, she did not live to see our time when you came up with your extreme- ship position? recent publication of the 33–amino acid ly controversial idea that hormones could Roth: It was really an opportunity peptide released by E. coli that resembles have receptors. for a leadership position. I was just turn- α-MSH and ACTH in structure, but espe- Roth: That was really fun. Ira Pastan ing 65. A lot of the universities want to cially in bioactivity in vitro and in vivo. was my scientific partner at the time. He move you along at that point. The Picow- JCI: What other career could have kept was just finishing up a research project in a er Institute had good young people. I had you engaged over your life? major biochemistry lab at NIH. I was com- a long-standing record of helping young Roth: I’m increasingly convinced that ing from the Berson and Yalow lab. There researchers develop, so I was a good fit for this was the right path for me. I’m not sure was a tendency in those days that whatever their job. I was there for about a year when I would have been as happy and fulfilled success you had, you continued in that line the Picower sponsors started to consider doing anything else. What else could I have for the rest your career. When I came to the a change in direction. I was considering done? I could see teaching. I like teaching. NIH, my new boss (Ed Rall) told me I could going back to Hopkins, when the Picower’s continue researching growth hormone for neighbor, North Shore–LIJ Health System Ushma S. Neill

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