Spinach on the Ceiling

The following sections are included:

• Dedication
• Contents
• Preface
• Acknowledgments

At the time of my birth in 1930, all four of my grandparents and most of their extended families were living in Vienna. However, their origins and, in particular, the history of their arrival in Vienna were different. It is clear to me now that the intellectual traditions of my family, those of my grandfathers in particular, and also those of my aunts and uncles, as well as my parents, played an important role in the future I sought for myself.

My childhood home, where we lived until 1938, was located in the Viennese suburb named Grinzing, which was reputed as a wine-growing area. There were small informal inns (Heurige), where we sometimes went in family groups for relaxed evenings of eating, and also drinking (mainly the adults) the fruity young white wine of the region (Figure 2.1)…

Our life was already changing significantly before the Nazis entered Austria in 1938, even from the viewpoint of an eight-year-old. Among our neighbors were two boys of comparable ages to my brother Robert and me. They were our “best friends,” and we played regularly with them, including splashing in the small pool in our garden. In the spring of 1937, they suddenly refused to have anything to do with us and began taunting us by calling us “dirty Jew boys” when we foolishly continued to try to interact with them. Similar problems occurred at school with our non-Jewish classmates. Before this, my school experience in the first grade (Figures 3.1a and 3.1b) and the beginning of second grade had been wonderful, in part because I had a great teacher, Herr Schraik, not the least of whose outstanding attributes was that his wife ran a candy store. When my class was ready to advance to second grade, the parents petitioned that Herr Schraik be “promoted” with us and, because of his outstanding record as a teacher, this request was granted. Nevertheless, in the middle of that school year (1937–1938), he was no longer allowed to teach. He was Jewish and the authorities had decided that any contact with him would contaminate the minds of the children. The new teacher was incompetent and blatantly anti-Semitic—he constantly criticized the Jewish students like myself, independent of how well or poorly we were doing. The situation soon became so bad that my parents took me out of the school…

When we arrived in New York early in the morning on October 8, 1938, I stood on the deck looking for the Statue of Liberty, which I had read about. As it appeared out of the mist, it was very special for me and probably for all those entering the United States during the war (Figure 4.1). The symbolism associated with the Statue of Liberty may seem trite (and somewhat deceptive given our present immigration policies), but then it really was a welcoming sign for people who had been living in fear. Most of the immigration formalities had been taken care of by Uncle Edu (Figures 4.2 a and b, 4.3), so that a few hours after our arrival we boarded a train to Boston with him…

Soon after we moved to Newton, our parents gave Bob a chemistry set, which he augmented with materials from the school laboratory and the drug store. He spent many hours in the basement generating the usual bad smells and making explosives. I was fascinated by his experiments and wanted to participate, but he informed me that I was too young for such dangerous scientific research. My plea for a chemistry set of my own was vetoed by my parents because they felt that this might not be a good combination—two teenage boys generating explosives could be explosive! Instead, my father had the idea of giving me a Bausch & Lomb microscope (Figure 5.1)…

I entered Harvard in the fall of 1947. There was never any question about my wanting to attend Harvard and I did not apply to any other school. My parents were concerned that I might not be admitted (Harvard was reputed to limit the admission of Jewish students, though apparently there was no quota at any time), and so they asked Richard von Mises, a Harvard professor who had received his doctorate in Vienna and come to the US as a refugee, to write a recommendation letter. He interviewed me for about thirty minutes and then agreed to write a letter, as he had done for my brother. In addition to the Westinghouse scholarship, I received a National Scholarship from Harvard to cover the cost of living on campus (Figure 6.1)…

In considering graduate school during my last year at Harvard, I had decided that I wanted to go to the west coast because I was interested in seeing other parts of the United States. This would offer me the opportunity to visit natural wonders such as the Grand Canyon and Yosemite National Park. I applied to the Chemistry Department of the University of California at Berkeley and to the Biology Department of the California Institute of Technology (Caltech). Accepted at both, I found it difficult to choose between them. Providentially, I visited my brother Bob in the spring of 1950 at the Institute of Advanced Studies in Princeton, New Jersey. He was working there as a postdoctoral fellow with J. R. Oppenheimer. Bob, who was always looking out for me and my future, introduced me to Oppenheimer. Einstein happened to walk by while Bob was showing me around and he introduced me to Einstein as well. Given Einstein’s fame, I am not sure I would have been able to think of something to say after we were introduced. Fortunately, he immediately inquired about my interests, to which I replied that I hoped to study biology from a chemist’s viewpoint. He gave me a warm smile, said, “That’s good,” with a German accent, and shook my hand. I remember Einstein as a large man, mainly because of his big halo of white hair, though actually he was not that tall…

One day in October 1953, Pauling came into the office I shared with several postdocs and announced that he was leaving in three weeks for a six-month trip and that “it would be nice” if I finished my thesis and had my exam before he left. This was eminently reasonable, since I had finished the calculations some months before and I had received a National Science Foundation (NSF) postdoctoral fellowship to go to England that fall. Pauling’s “request” provided just the push I needed, even though the introduction to my thesis was all I had written thus far. With so much to get done, I essentially wrote day and night, with my Caltech colleagues typing and correcting what I wrote. In this way, the thesis was finished within three weeks, and I was able to have my final PhD exam and celebratory party before Pauling left. I went back to Newton, Massachusetts, for a visit with my parents, before going to New York where I boarded a ship, the Ile de France, for England and arrived shortly before Christmas 1953…

As my postdoctoral fellowship in Oxford (1953–1955) neared its end, I decided to return to the United States to try to begin my academic career there. With my growing interest in magnetic resonance, I focused on finding an institution that had active experimental programs in the area. One of the best schools from this point of view was the University of Illinois in Urbana-Champaign, where Charles Slichter in Physics and Herbert Gutowsky in Chemistry were doing pioneering work in applying nuclear magnetic resonance (NMR) to chemical problems. The University of Illinois had a number of openings in the Chemistry Department at that time because it was undergoing a radical renovation. Several professors, including Roger Adams, who had been chairman for nearly thirty years, had retired. Pauling recommended me to the University of Illinois and the new chairman Herbert Carter offered me a job without an interview and without waiting for a recommendation from Coulson, which presumably was delayed by having been mailed from overseas. The latter was fortunate, because Coulson had written that, although he had no doubt about my intellectual abilities, I had done very little work on problems he had suggested. This was true; they seemed of limited interest to me. I accepted the offer from Illinois without visiting the department, something unimaginable today with the extended courtships that have become an inherent part of the academic hiring process. The University of Illinois offered me an instructorship at a salary of $5,000 per year. The offer did not mention start-up funds, unlike present-day offers, and I did not think of asking for research support. In my case, the latter would have involved a desk calculator as the most expensive item…

During the summer of 1960, I participated in an NSF program at Tufts University, whose purpose was to expose high school and college science teachers to what scientists actively engaged in research were doing. Our task was to present modern chemical concepts in a way that would help the teachers in the classroom. Ben Dailey, a Columbia professor and an organizer of the program, asked me one day as we were standing next to each other in the washroom whether I would consider joining the chemistry faculty at Columbia University. Because I had already been at Illinois for four of the five years I had planned to stay there, I responded positively. I heard from Columbia shortly thereafter and received an offer to join the IBM Watson Scientific Laboratory with an adjunct associate professorship at Columbia…

My interactions with the FBI appear to have begun when I was a graduate student at Caltech. I had participated in 1952 at a meeting concerned with organizing a protest movement against the death penalty sentences of Julian and Ethel Rosenberg. At the entrance to the meeting hall, there was a desk at which we were asked to write down our contact information and make a contribution. Apparently, an FBI agent was there to make a list of the participants. I first discovered this when, in the mid-1970s, my brother Bob was refused a security clearance to do research at the Livermore Laboratory. Because his participation was deemed important to the laboratory, the administrators appealed and found out that the reason for the refusal was my documented presence at a Rosenberg protest meeting two decades previously at the First Unitarian Church in Los Angeles led by the liberal minister, Stephen Fritchman. Once this unimportant item in his FBI file was found, Bob rapidly received the necessary clearance…

In 1965, it was time to move again. Columbia and New York City were stimulating places to live and work, but I felt that new colleagues in a different environment would help to keep my research productive. I had incorporated this idea into a “plan”: I would change schools every five years and when I changed schools I would also change my primary area of research. It was more exciting for me to work on something new where I had much to learn. Following this plan helped me to stay mentally young and have innovative ideas, in part because I was not encumbered by knowing all the literature in the field. Since I generally decided to start some research in areas where my new colleagues were doing experiments, the change in fields was also usually a plus for the institution…

The paper describing the hemoglobin work was written in Paris, much of it at Café Les Deux Magots, a left-bank café famous as a rendezvous for writers and philosophers such as Jean-Paul Sartre. I was on sabbatical leave in 1972–1973 and officially at the Université de Paris XI in Orsay, a suburb of Paris, associated with the group of Jeannine Yon-Kahn, a pioneer in experimental studies of protein dynamics. However, I was living (at that time with my wife Susan and our two daughters Reba and Tammy) in the heart of Paris in the 5th arrondissement. Since the trip to Orsay by the Réseau Express Régional (RER) (commuter rail) took about 45 minutes, I spent much of my time at the Institut de Biology Physico-Chimique on rue Paul et Marie Curie in the 5th arrondissement. Having found Paris a wonderful place to live during sabbatical visits, I began to consider the possibility of moving there on a permanent basis. I had been at Harvard for the canonical five years, and the idea of returning to live in Europe was tempting. Given my recollection of the escape from Austria and the Nazi-leaning parties still prevalent there, I had no inclination to return to the country of my birth. France offered many attractive aspects of European life and culture, and I believed that I could do high-level research in theoretical chemistry and its biological applications in Europe, as well as at Harvard. After the 1968 revolution, the immense Université de Paris, with more than 300,000 students, had been divided into a dozen campuses. With true French rigor, they were named Paris I, Paris II, and so on, although they now have names, in addition to their numbers…

Cy Levinthal, had pointed out, in what came to be known as the Levinthal paradox, that to find the native state by a random search of the astronomically large configuration space of a polypeptide chain would take longer than the age of the earth, while proteins fold experimentally on a timescale of microseconds to seconds or minutes. When Chris Anfinsen visited Rehovot, while I was in the Lifson group in 1969, I became aware that the mechanism of protein folding posed a difficult problem. He described the experiments that had led to the realization that many proteins can refold in solution, independent of the ribosome and other parts of the cellular environment [Anfinsen, 1973]. What most impressed me was Anfinsen’s film showing the folding of a protein with “flickering helices forming and dissolving and coming together to form stable substructures.” The film was a cartoon, but it led to my asking him, in the same vein as I had asked Perutz earlier about hemoglobin, whether he had thought of taking the ideas in the film and translating them into a quantitative model. Anfinsen said that he did not really know how one would do this, but to me it suggested an approach to the mechanism of protein folding, at least for helical proteins such as myoglobin…

Given that pre-CHARMM could calculate the forces on the atoms of a protein, the next step was to use these forces in Newton’s equation to calculate the dynamics. This fundamental development was introduced in the mid-1970s when Andy McCammon joined my group. An essential element that encouraged us in this attempt was the existence of molecular dynamics simulation methods for simpler systems. Molecular dynamics had followed two pathways, which come together in the study of biomolecule dynamics. One pathway concerns trajectory calculations for simple chemical reactions. My own research on the H + H₂ reaction [Karplus, Porter, and Sharma, 1965] had served as preparation for the many-article problem posed by biomolecules. The other pathway in molecular dynamics concerns physical rather than chemical interactions and the thermodynamic and dynamic properties of large numbers of particles rather than detailed trajectories of a few particles. Although the basic ideas go back to van der Waals and Boltzmann, the modern era began with the work of Alder and Wainwright [Alder and Wainwright, 1957] on hard-sphere liquids in the late 1950s. The paper by Rahman [Rahman, 1964] describing a molecular dynamics simulation of liquid argon with a soft-sphere (Lennard-Jones) potential represented an essential next step. Simulations of more complex fluids followed; the now classic study of liquid water by Stillinger and Rahman was published in 1974 [Stillinger and Rahman, 1974], shortly before our protein dynamics simulations…

Molecular dynamics simulations of proteins and nucleic acids, as of many other systems composed of particles (e.g., liquids, galaxies), can in principle provide the ultimate details of motional phenomena. The primary limitation of simulation methods is that they are approximate. Here, experiment plays an essential role in validating the simulation methods; that is, comparisons with experimental data serve to test the accuracy of the calculated results and provide criteria for improving the methodology. Although the statistical errors can be calculated [Yang, Bitetti-Putzer, and Karplus, 2004], estimates of the systematic errors inherent in the simulations have not been possible; for example, the errors introduced by the use of empirical potentials are difficult to quantify. When experimental comparisons indicate that the simulations are meaningful, their capacity for providing detailed results often makes it possible to examine specific aspects of the atomic motions far more easily than by using laboratory measurements…

When I completed my PhD, my family gave me a Leica IIIC, a superb camera, which my Uncle Alex had brought to the United States from Vienna. Throughout my travels as a postdoctoral fellow in Europe and since then, I took photographs, particularly of people, using a trick I had developed. The Leica had a long focus (Hector) lens with a reflex viewer, which enabled me to face away from my subject when I took their photograph. This made it possible for me to take photographs of crowds and individuals without their being aware of it. Often it is clear from looking at the photograph that the subjects do not know that I am taking a photograph, but that they are trying to see what I am photographing (Figure 17.1)…

Since the 1970s, my frequent sojourns in France were spent primarily in Paris, on the one hand, and at our chalet in Manigod in the Haute Savoie, on the other. However, this was changed by a serendipitous event…

An important part of our life in Europe was the accessibility of good food, not only that in outstanding restaurants but also the fresh produce that varied with the seasons at the local outdoor markets. In the part of Strasbourg where we lived there were no supermarkets. We were lucky to have a small local outdoor market twice a week (on Tuesday and Saturday) and a much larger market about a twenty-minute walk away. Even the local market had three vegetable stands, two meat stalls, and a booth that specialized in poultry products such as maigret de canard, whole chickens, and fresh fois gras. Given that and the local bakery with crusty French bread, we had no need for a supermarket…

Although the Nobel Prize committees make very clear that people who nominate someone for a Nobel Prize must not contact the individual, in my case at least I was well aware that I had been nominated various times by numerous individuals for over twenty years. In the 1990s, while living in Strasbourg, I would be at my computer at 11am the day of the chemistry prize announcement, working as usual but also waiting to find out who had been awarded the prize that year. After some years, I stopped this practice, having concluded that I would never receive the prize. The work on which I felt it should have been based was done in the mid-1970s and so it seemed that my chance had passed…

Shortly after the announcement of the Nobel Prize, we received an invitation to come to Washington and meet President Obama at the White House. Apparently it was a long-standing tradition that the President invites the American Laureates; this tradition was discontinued by President Trump. I was thrilled by the idea of meeting President Obama but wanted to know more about what this meeting was likely to entail. I contacted John Holdren, the science advisor to President Obama, for information about such a meeting and said that if it just a photo-op, I was not interested in going. He understood my feeling, but diplomatically said that when you are invited by the President, normally you refuse for only two reasons: (1) you are dead, or someone in your family has recently died, or (2) you are too ill to come. He then commented on what the meeting might involve and encouraged me to come. He said that the President would decide how much time he would spend with me and the other American Nobel Laureates. After this conversation, Marci and I decided that we would go to Washington, and it was indeed an honor to meet President Obama…

Some days after the October 9, 2013, announcement, we were contacted by the Nobel office in Sweden concerning the arrangements for our trip to Stockholm and our stay there during the Nobel Prize ceremonies in December. We were assigned Eva Nilson Mansfeld from the Swedish Foreign Ministry, who would be responsible for us during the Nobel week. This turned out to mean two things: she would help us by answering all our questions, and equally important, she would make sure that we did what was expected of us…

The Nobel Prize was awarded in 2013, 35 years after the BPTI molecular dynamics simulation on which it was based (see Chapter 15). Although both photography and cooking are activities that play an important role in my life, my primary focus continues to be on science and what I can do to contribute to the advancement of knowledge. In this chapter, I will outline how my research has evolved in a number of major areas since the first molecular dynamics simulation of a protein. Working to understand some of the systems involved has occupied me for much of my scientific life…

After receiving the Nobel Prize, I was invited to present keynote lectures at many more occasions than I could accept. I learned quickly that one has to turn down most invitations and accept only those where being a Nobel Laureate could have a positive effect. Many of the meetings were on subjects about which I knew little, certainly no more now than I did before receiving the Nobel Prize. An example is a meeting in Azerbaijan on economics with an honorarium of a $100,000, which I turned down. However, invitations to conferences concerned with climate change raised the possibility that I could be helpful in focusing the world on this vital subject. Since there were experts on climate change at Harvard (e.g., Michael McElroy, Steve Wofsy), I concluded it would be more constructive to write that they should be invited instead…

The following sections are included:

• Appendix 1. Karplusians: 1955–2019
• Appendix 2. Martin Karplus: LIFE IN COLOR—From the 1940s to 2019
• Appendix 3. Nobel Lecture
• Appendix 4. Haaretz Article
• Appendix 5. Supplementary Material

The following section is included:

• Index