In Memoriam
Ignacio Tinoco, Jr.
Professor of Chemistry, Emeritus
UC Berkeley
1930-2016
Ignacio (“Nacho”) Tinoco, Jr. passed away on November 15, 2016. I first met Nacho in 1975, when I approached him about the possibility of joining his group. I had come from Perú a few months earlier to start a Ph.D. in the Biophysics Graduate Group and Donald Glaser, my academic advisor in the program, suggested Nacho as a possible research advisor. I told Nacho that I wanted to do theory since I wanted to go back to Perú. He asked me several questions, and, after reminding me that “theory is a very lonely work”, he said that I could join the group the following summer. From the very beginning, I was truly impressed by Nacho’s creativity, his unique insight into scientific problems, and the apparent ease and relaxed attitude with which he pondered them. “How does he do it?” I wondered. “Where did that idea he suggested at group meeting come from?” All 15 of us in his group were present and heard the same information, but Nacho was the one who came up with what seemed like a true clarifying thought. So it was that, during my student years at Berkeley, I decided that I would not only work on my Ph.D. thesis but I would try to uncover the mystery of how to get to think the way Nacho did. I am not sure that I succeeded, since the act of creation is always a private one, but over the years—first as a graduate student and then as one of his colleagues—I have continued to ponder this question.
Nacho was born in El Paso, Texas, on November 22, 1930. Both of his parents were from Mexico. When he was barely 12 years old, he got himself a chemistry lab at home. El Paso, as he explained in one interview, was a mining town at the time, and one could get many chemicals without restrictions: “with these I set up a chemistry lab in my backyard and came up with experiments out of chemistry books—of course, I liked making explosions”, he explained. Nacho obtained his bachelor’s degree in chemistry in 1951 at the University of New Mexico. He was 21, the youngest graduate in the history of the department. He then moved to the University of Wisconsin for his graduate studies, obtaining his Ph.D. in chemistry with John Ferry in 1954, working on the viscoelasticity and linear birefringence of polymers, including fibrinogen. At that point, Nacho, his wife Joan, and their daughter Kathy, moved to Connecticut where he joined the group of John Kirkwood at Yale University. He recalled years later: “My father—who had left Mexico escaping from Pancho Villa—used to mispronounce ‘Yale’ and instead told his friends that his son was working in ‘jail,’ to which they replied, “too bad, when does he get out?” In Kirkwood’s group he picked up what was to be a constant in his approach to science: formulate hypotheses, design experiments to test them, and formulate theoretical models to account for the results.
In 1956, Nacho and his family drove from Connecticut to Berkeley, where he had been hired as an instructor. He was 25. Kirkwood, he recalled, had advised him to take the job, warning him, however, that he should not expect to be given tenure because Berkeley hires only its own Ph.Ds. Nacho recalled: “On arriving at Berkeley, I presented myself to Miss Kittredge, the all-powerful administrative assistant who ran the chemistry department. Her first comment was, ‘You’re very young looking.’ My apparent youth also worried others: Dean Pitzer told me to wear a coat and tie so that I would be distinguishable from the students. Luckily, I no longer have to wear a tie or coat to be distinguishable.” During the next three years, Nacho taught courses and did experiments to try to understand the circular birefringence of polymers, and in 1958-59, he derived a quantum mechanical perturbation theory that explained for the first time the so-called hypochromic effect in DNA, which is the observation that double stranded DNA absorbs approximately 40% less light than its independent units or nucleotides. His theory elegantly explained the phenomenon, the cause of which had been a mystery until then, showing that the effect was due to interaction between the transition dipoles on the stacked bases.
In the early 1960s, biophysical chemistry came into being, in part due to the efforts and guidance of scientists like Nacho, who correctly saw that doing experiments on purified and simplified complex biological systems was an essential way to understand their behavior inside the cell. One impressive aspect of Nacho’s career is that he seemed permanently to be at the beginning of a new career. His ability to start anew, moving to recent approaches and making contributions to them, is legendary among his students and close colleagues. Some people learn a trade and keep at it, as it becomes their comfort zone. Not Nacho. He was well aware that his job as a scientist was to constantly challenge himself and so he did, moving from one technique to another as necessary to answer the questions he was interested in at the time. As a result, he became first interested in optical activity of biopolymers, developing the exciton theory of circular dichroism; then in NMR, which he used to study the structure of RNAs in solution; then in the theory and experiments of light scattering of circularly polarized light, in order to investigate the higher order chiral organization of nucleoprotein complexes; and then in single molecule biophysics, where he investigated RNA folding, fluctuation theorems in non-equilibrium processes, and the mechanism of translation by single ribosomes, among other problems.
In retrospect, this ability to “re-invent” himself over and over seems to me an unavoidable corollary of that relaxed attitude towards challenging problems which I had admired in him as a graduate student. I still remember that, as I was deriving the theory of differential scattering of right and left circularly polarized light in collaboration with Marcos Maestre, he came to my desk to tell me that he wanted to include the work in an Annual Review of Biophysics article he had been asked to write. I was, of course, very happy that he had thought my work good enough to be included in his review, so I applied myself eagerly to write my part of the paper. Then, one day, as I was discussing the work with him, he noticed that I had made a mistake (an omission, actually) in the derivation. I had failed to take explicit account of the transversality of the scattered fields, and very calmly he went to the blackboard and suggested one way it could be done. I was devastated. The deadline to submit the paper was in 15 days, and I had to correct my equations with new terms that were likely to be three times bigger than the ones I had derived. Nacho must have seen the despair in my expression, and he told me: “You know, Carlos, everything is going to be fine. You can derive the terms that are needed. I am sure of that.” Having that reassurance from him gave me the courage to work frantically for two weeks, re-derive the theory, and carry out the computer simulations to finish before the deadline. I had learned a lesson: keep your cool. He always did.
And that brings me to a reflection about Nacho as a person, about his character and about his attitude towards science and towards others. He was a brilliant man who enjoyed doing science as much as interacting with other scientists. He had what I would imperfectly define as an irreverent sense of humor. He was having fun doing science and had fun talking and discussing science with colleagues and students. At times, his comments, and his challenges to us, reminded me of the kid in school who is always making jokes, feeling at ease with everyone. He was always in command and enjoyed keeping others on their toes. I still remember his exchange with a famous European scientist during a NATO conference to which Nacho invited Art Pardi and me, as graduate students, to accompany him. We were having lunch, and at some point this scientist said to him: “But for fun, I like to scuba dive. What do you like?” Nacho immediately said to him: “I thought science was supposed to be fun!” Art and I looked at each other and smiled as we saw this man at odds to try to get out of the situation he had gotten himself into! I also remember that when translation frameshifting was demonstrated, Nacho challenged his students at a group meeting to come up with a sentence that when read moving down first by one letter, then by two letters, retained some meaning. The prize for the winner: a six-pack. As a foreigner, and language-challenged as I was, I got second prize: a handshake from Nacho. At other times he challenged us to come up with what we thought were the 10 most important problems to solve in biophysics in the next 10 years. He truly loved science, and he knew that he was very good at it. What others perceived as a challenge (sometimes an anguishing challenge) had the attractiveness of an amusement park to Nacho, and he reacted accordingly. All his students, I believe, recognized this unique aspect of his personality and silently—he would not have allowed it to be otherwise—revered him for that.
Nacho Tinoco is one of the few towering figures and one of the founding fathers of molecular biophysics. His seminal contributions to our understanding of the physical foundations of macromolecular science are now textbook material. With his unique, quiet, even understated, demeanor, with wit and humor, he taught many generations of scientists how to do science, how to ask the most important questions, and how to reduce the most complex problems to their central and most essential core. But all of us who had the privilege of knowing him knew that he was more than a great scientist. He was a fantastic mentor, an example, a model, and a teacher who taught his students the much more difficult task of always being honest scientists. Through his personal example, he showed us how to be fair to our colleagues and to our competitors. He showed us how to be humble before our own ignorance, and to love the very process of searching for knowledge and understanding. And he taught us how to be generous with our knowledge and to be unafraid of posing the most complex questions. His love for science inspired us all, and his intellectual honesty was the reference and archetype to which we all aspire. Having had the privilege of working with him for many years and seeing how serene he appeared before any new challenge, seeing his clear, sharp mind at work dissecting a problem, I was reminded of Ernest Hemingway’s dictum that “the true measure of courage is to show grace under pressure.” Indeed, Nacho’s approach to science embodied the poetic, imperishable grace that Hemingway attributed to the bullfighter.
Carlos Bustamante
2020
Nota Bene: I want to thank Dr. Bibiana Onoa for providing me with some of the material used in this memorial. Nacho and Bibiana married in 2006, and she was his partner and accompanied him through his final ailment with immense love and care.
Nacho was born in El Paso, Texas, on November 22, 1930. Both of his parents were from Mexico. When he was barely 12 years old, he got himself a chemistry lab at home. El Paso, as he explained in one interview, was a mining town at the time, and one could get many chemicals without restrictions: “with these I set up a chemistry lab in my backyard and came up with experiments out of chemistry books—of course, I liked making explosions”, he explained. Nacho obtained his bachelor’s degree in chemistry in 1951 at the University of New Mexico. He was 21, the youngest graduate in the history of the department. He then moved to the University of Wisconsin for his graduate studies, obtaining his Ph.D. in chemistry with John Ferry in 1954, working on the viscoelasticity and linear birefringence of polymers, including fibrinogen. At that point, Nacho, his wife Joan, and their daughter Kathy, moved to Connecticut where he joined the group of John Kirkwood at Yale University. He recalled years later: “My father—who had left Mexico escaping from Pancho Villa—used to mispronounce ‘Yale’ and instead told his friends that his son was working in ‘jail,’ to which they replied, “too bad, when does he get out?” In Kirkwood’s group he picked up what was to be a constant in his approach to science: formulate hypotheses, design experiments to test them, and formulate theoretical models to account for the results.
In 1956, Nacho and his family drove from Connecticut to Berkeley, where he had been hired as an instructor. He was 25. Kirkwood, he recalled, had advised him to take the job, warning him, however, that he should not expect to be given tenure because Berkeley hires only its own Ph.Ds. Nacho recalled: “On arriving at Berkeley, I presented myself to Miss Kittredge, the all-powerful administrative assistant who ran the chemistry department. Her first comment was, ‘You’re very young looking.’ My apparent youth also worried others: Dean Pitzer told me to wear a coat and tie so that I would be distinguishable from the students. Luckily, I no longer have to wear a tie or coat to be distinguishable.” During the next three years, Nacho taught courses and did experiments to try to understand the circular birefringence of polymers, and in 1958-59, he derived a quantum mechanical perturbation theory that explained for the first time the so-called hypochromic effect in DNA, which is the observation that double stranded DNA absorbs approximately 40% less light than its independent units or nucleotides. His theory elegantly explained the phenomenon, the cause of which had been a mystery until then, showing that the effect was due to interaction between the transition dipoles on the stacked bases.
In the early 1960s, biophysical chemistry came into being, in part due to the efforts and guidance of scientists like Nacho, who correctly saw that doing experiments on purified and simplified complex biological systems was an essential way to understand their behavior inside the cell. One impressive aspect of Nacho’s career is that he seemed permanently to be at the beginning of a new career. His ability to start anew, moving to recent approaches and making contributions to them, is legendary among his students and close colleagues. Some people learn a trade and keep at it, as it becomes their comfort zone. Not Nacho. He was well aware that his job as a scientist was to constantly challenge himself and so he did, moving from one technique to another as necessary to answer the questions he was interested in at the time. As a result, he became first interested in optical activity of biopolymers, developing the exciton theory of circular dichroism; then in NMR, which he used to study the structure of RNAs in solution; then in the theory and experiments of light scattering of circularly polarized light, in order to investigate the higher order chiral organization of nucleoprotein complexes; and then in single molecule biophysics, where he investigated RNA folding, fluctuation theorems in non-equilibrium processes, and the mechanism of translation by single ribosomes, among other problems.
In retrospect, this ability to “re-invent” himself over and over seems to me an unavoidable corollary of that relaxed attitude towards challenging problems which I had admired in him as a graduate student. I still remember that, as I was deriving the theory of differential scattering of right and left circularly polarized light in collaboration with Marcos Maestre, he came to my desk to tell me that he wanted to include the work in an Annual Review of Biophysics article he had been asked to write. I was, of course, very happy that he had thought my work good enough to be included in his review, so I applied myself eagerly to write my part of the paper. Then, one day, as I was discussing the work with him, he noticed that I had made a mistake (an omission, actually) in the derivation. I had failed to take explicit account of the transversality of the scattered fields, and very calmly he went to the blackboard and suggested one way it could be done. I was devastated. The deadline to submit the paper was in 15 days, and I had to correct my equations with new terms that were likely to be three times bigger than the ones I had derived. Nacho must have seen the despair in my expression, and he told me: “You know, Carlos, everything is going to be fine. You can derive the terms that are needed. I am sure of that.” Having that reassurance from him gave me the courage to work frantically for two weeks, re-derive the theory, and carry out the computer simulations to finish before the deadline. I had learned a lesson: keep your cool. He always did.
And that brings me to a reflection about Nacho as a person, about his character and about his attitude towards science and towards others. He was a brilliant man who enjoyed doing science as much as interacting with other scientists. He had what I would imperfectly define as an irreverent sense of humor. He was having fun doing science and had fun talking and discussing science with colleagues and students. At times, his comments, and his challenges to us, reminded me of the kid in school who is always making jokes, feeling at ease with everyone. He was always in command and enjoyed keeping others on their toes. I still remember his exchange with a famous European scientist during a NATO conference to which Nacho invited Art Pardi and me, as graduate students, to accompany him. We were having lunch, and at some point this scientist said to him: “But for fun, I like to scuba dive. What do you like?” Nacho immediately said to him: “I thought science was supposed to be fun!” Art and I looked at each other and smiled as we saw this man at odds to try to get out of the situation he had gotten himself into! I also remember that when translation frameshifting was demonstrated, Nacho challenged his students at a group meeting to come up with a sentence that when read moving down first by one letter, then by two letters, retained some meaning. The prize for the winner: a six-pack. As a foreigner, and language-challenged as I was, I got second prize: a handshake from Nacho. At other times he challenged us to come up with what we thought were the 10 most important problems to solve in biophysics in the next 10 years. He truly loved science, and he knew that he was very good at it. What others perceived as a challenge (sometimes an anguishing challenge) had the attractiveness of an amusement park to Nacho, and he reacted accordingly. All his students, I believe, recognized this unique aspect of his personality and silently—he would not have allowed it to be otherwise—revered him for that.
Nacho Tinoco is one of the few towering figures and one of the founding fathers of molecular biophysics. His seminal contributions to our understanding of the physical foundations of macromolecular science are now textbook material. With his unique, quiet, even understated, demeanor, with wit and humor, he taught many generations of scientists how to do science, how to ask the most important questions, and how to reduce the most complex problems to their central and most essential core. But all of us who had the privilege of knowing him knew that he was more than a great scientist. He was a fantastic mentor, an example, a model, and a teacher who taught his students the much more difficult task of always being honest scientists. Through his personal example, he showed us how to be fair to our colleagues and to our competitors. He showed us how to be humble before our own ignorance, and to love the very process of searching for knowledge and understanding. And he taught us how to be generous with our knowledge and to be unafraid of posing the most complex questions. His love for science inspired us all, and his intellectual honesty was the reference and archetype to which we all aspire. Having had the privilege of working with him for many years and seeing how serene he appeared before any new challenge, seeing his clear, sharp mind at work dissecting a problem, I was reminded of Ernest Hemingway’s dictum that “the true measure of courage is to show grace under pressure.” Indeed, Nacho’s approach to science embodied the poetic, imperishable grace that Hemingway attributed to the bullfighter.
Carlos Bustamante
2020
Nota Bene: I want to thank Dr. Bibiana Onoa for providing me with some of the material used in this memorial. Nacho and Bibiana married in 2006, and she was his partner and accompanied him through his final ailment with immense love and care.
