Michael Levitt (Biophysicist)

Levitt was born in Pretoria, South Africa, on May 9, 1947, and grew up in a Jewish family.[1][3] His mother, Gertrude, was the daughter of a Czech immigrant, while his father, Nathan, had immigrated to South Africa as a child from Palanga, Lithuania.[4] He attended a Jewish primary day school.[3] In recollections published in 2025, he said his parents’ marriage deteriorated when he was eight and that his mother subsequently raised three children on her own, placing a strong emphasis on their education.[4]

Levitt’s later account of his childhood did not portray an uninterrupted early devotion to scientific study: he recalled being more interested in girls than in mathematics and physics and said he did not really begin reading books until he was 25.[4] He initially entered university in Pretoria to study applied mathematics, but a teenage visit to relatives in London changed the course of his education.[4] His aunt and uncle, Tikva Alper and Max Stern, were scientists, and Alper encouraged him to remain in Britain and seek admission to a university there.[4]

He studied at Acton Technical College before going on to physics at King’s College London, where he earned his bachelor’s degree in 1967.[4][1] Watching John Kendrew’s BBC lecture series, The Thread of Life, helped introduce him to molecular biology.[4] This introduction preceded his move from a physics education toward doctoral research on biological molecules and their structures.[4]

In 1967, Levitt sought a place at Cambridge’s molecular biology laboratory but initially found that there was no room for him.[4] After further discussion, he arranged to begin doctoral study the following year and spent the intervening period at the Weizmann Institute of Science in Rehovot, Israel.[4] His 1967–1968 appointment there was a visiting fellowship, also identified as a Royal Society Exchange Fellowship.[1][5] He arrived in Rehovot in October 1967 and met Rina ten weeks later; they married when he was 21.[4] He recalled that they subsequently moved to Cambridge and had children soon afterward.[4]

Levitt received his doctorate in 1971 through the University of Cambridge and the Medical Research Council Laboratory of Molecular Biology.[1] His doctoral training brought together the physics background he had acquired in London and the study of biological molecules that had drawn him to Cambridge and Weizmann.[1][4]

During his first appointment at the Weizmann Institute in 1967–1968, Levitt began working with Arieh Warshel, then a graduate student, on computer models of molecules using classical physics.[1] Their collaboration took place in the research environment of chemical physicist Shneior Lifson.[6] They developed a molecular-modeling program that ran on Weizmann’s Golem computer and was particularly relevant to large biological molecules.[6] The work established a collaboration that they would resume in the following decade, leading to simulations of protein folding and enzyme reactions.[1]

At Cambridge, Levitt also investigated transfer RNA, or tRNA.[4] In November 1969, he published his first sole-authored paper in Nature, presenting a model of that molecule.[4] He later recalled that the paper passed through submission, review, and publication in just 23 days.[4] Francis Crick had worked with him on the paper but submitted it under Levitt’s name.[4] Although Levitt said the proposed model later proved wrong, the publication brought invitations to conferences and helped introduce his work to other researchers.[4]

His recollections of the tRNA research also included the identification of base pairs in the molecule, a feature he said became known in some circles as the “Levitt Basepad.”[4] The episode was part of his early work on constructing models of biological structures, alongside the molecular-modeling research he had begun with Warshel.[4][1] It also remained an example he discussed much later when describing the role of error and experimentation in a scientific career.[4]

Levitt returned to the Weizmann Institute as a postdoctoral fellow from 1972 to 1974.[1] There he reunited with Warshel, and the two later continued working together at the Medical Research Council Laboratory in Cambridge.[1] In his retrospective account, Levitt identified the 1972 return to Weizmann as a period when a significant portion of the research later recognized by the Nobel Prize was carried out.[4] He alternated between the institute and Cambridge as the collaboration developed.[4]

In 1975, Levitt and Warshel published the results of a protein-folding simulation.[1] Their work on proteins included simplified representations of protein structure designed to analyze folding and packing.[3] These representations formed part of a wider research program in which Levitt pioneered molecular-dynamics simulations of proteins and DNA.[3] He also developed scoring systems for comparisons involving large protein sequences, protein structures, and other components of cells.[3]

The enzyme-reaction research addressed the problem of representing different physical processes within a single molecular system.[1] Levitt and Warshel developed a scheme in which some parts of an enzyme were treated with classical physics and others with quantum mechanics.[1] Crucially, the scheme accounted not only for the two sets of parts separately but also for their interactions with one another and with the surrounding medium.[1] In 1976, they published a paper applying it to the first computer model of an enzymatic reaction.[1]

The approach was not restricted to the particular enzyme reaction used in that paper: the modeling scheme could be applied to any molecule.[1] Their program gained efficiency by concentrating computational attention on the parts of a molecule of greatest interest.[7] The subsequent simulations helped researchers investigate how proteins work and contributed to the development of computational biology.[7] This combination of broad applicability and selective computational detail became central to the multiscale methods recognized by the Nobel Prize.[8]

The physical challenge behind the research was that classical and quantum approaches offered different advantages and limitations.[8] Classical-physics programs could model large molecules at rest but could not describe the subatomic dynamics of chemical reactions.[8] Quantum-physics programs could address those dynamics, but the computing power required made their application to entire large molecules impractical.[8] Combining the approaches made it possible to reserve the more demanding calculations for the region directly involved in a reaction while treating the remainder with classical physics.[8]

In this multiscale arrangement, quantum physics describes the electrons and atomic nuclei directly participating in a reaction, while classical physics describes the rest of the molecule.[8] The division reduces the computing power needed to track atomic movements and represent the breaking and formation of chemical bonds.[2] The broader program of simulations developed in the 1960s and 1970s sought to clarify the mechanisms of rapidly occurring, complex chemical reactions, including processes such as combustion and photosynthesis.[2]

A drug interacting with a target protein illustrates how the method can be applied.[9] Quantum calculations can be used for the atoms that interact with the drug, while the remainder of the large protein is simulated using less computationally demanding classical physics.[9] The calculation therefore combines detailed treatment of the interaction of interest with a representation of the larger molecular structure around it.[9] Such methods support computer simulations realistic enough to predict the outcomes of traditional experiments.[9]

The multiscale system drew on earlier programs developed through two related collaborations.[8] Karplus and Warshel had worked on a program for studying the human retina, while Warshel and Levitt had created a program for modeling enzyme reactions.[8] Together, these lines of work helped establish a way to combine classical and quantum physics in chemical modeling, allowing chemical processes to be investigated with greater sophistication and speed.[8]

Levitt’s institutional career during these years crossed repeatedly between Israel, Britain, and the United States.[1][4] He was a staff scientist at the Medical Research Council Laboratory from 1974 to 1979.[1] His later recollections also described moving to California in 1977 for a postdoctoral fellowship with Crick at the Salk Institute, before returning to Israel two years later.[4] He immigrated to Israel in 1979 and became an associate professor of chemical physics at the Weizmann Institute that year.[5][1]

He continued at Weizmann during the 1980s and had become a full professor by 1987.[1] In 1986, while on sabbatical in Cambridge, he received an offer from Stanford Medical School.[4] He subsequently became a professor of structural biology at Stanford University and held the Robert W. and Vivian K. Cahill Professorship in Cancer Research at its School of Medicine.[3][10] At the time of the 2013 Nobel announcement, his research affiliation was Stanford.[8]

Levitt later explained his move from Israel to the United States in terms of professional opportunities, saying he felt he could not progress professionally in Israel.[5] In another 2013 interview, he linked his decision to continue research abroad to Warshel’s failure to receive tenure in Israel, which he described as critical to their work during those years.[11] His career nevertheless retained continuing ties to Weizmann: in 2013 he was a visiting scientist there and divided his life between Israel and the United States.[10] A 2025 interview described him as dividing his time among Israel, China, and the United States.[4]

In 2013, Levitt, Warshel, and Martin Karplus received the Nobel Prize in Chemistry “for the development of multiscale models for complex chemical systems.”[8] The award recognized their development of accurate computer models of chemical reactions that combined classical physics with quantum mechanics.[8] All three chemistry laureates had received support from the United States National Science Foundation.[8] Levitt was an American, British, and Israeli citizen, and his work had included appointments in each of those countries.[9][1]

Responding to the award, Levitt said he had been “in the right place at the right time” and perhaps had had “a few good ideas.”[10] He also described computational biology as having once been treated as the “ugly stepchild” of experimental biology.[10] He welcomed the Nobel recognition as evidence that computational biology had become a substantial field, connecting the personal award to the standing of the wider discipline in which he had worked.[10]

Levitt’s later public and professional activities included involvement with Israeli biotechnology entrepreneurship.[12] A 2019 profile reported that he had joined the board of the Israeli startup Quantified Biology after meeting its founder, Shahar Barbash, through a personal connection.[12] Levitt said Barbash’s vision excited him even though it appeared difficult to realize.[12] The company’s software used mathematical methods to identify ambiguous objects in microscope images, including different kinds of cells.[12]

He described this image-analysis software as a shortcut for experiments, such as testing whether a drug kills particular cells.[12] In discussing the company’s approach, he favored solving precise customer problems rather than searching for a single algorithm capable of solving everything.[12] His interest in the startup thus concerned a practical use of mathematical methods to make biological experiments easier to interpret, rather than an attempt to replace all experimental problems with one general computational solution.[12]

In a 2025 interview, Levitt also discussed the place of failure in research.[4] He said that “a good scientist is wrong 90% of the time” and that a very good scientist might be wrong 99% of the time because the questions being investigated were difficult and did not already have known answers.[4] He connected this view to trying different approaches and remaining open to evidence rather than assuming the answer in advance.[4] His account placed the willingness to revise an unsuccessful model alongside the persistence required to investigate unfamiliar scientific problems.[4]

Levitt’s principal scientific legacy is the development, with Warshel and Karplus, of multiscale methods that allow classical physics and quantum mechanics to operate within the same chemical model.[8] The 2013 Nobel Prize recognized this framework as a way to investigate complex chemical systems without subjecting every part of a large molecule to the same computationally demanding treatment.[8] The methods combined the ability to describe chemical reactions at the quantum level with the ability to represent the larger molecular structures in which those reactions occur.[8]

The 1976 enzyme-reaction model was a particularly important demonstration because it included interactions between the classically and quantum-mechanically modeled parts of an enzyme, as well as their interactions with the surrounding medium.[1] Its importance extended beyond the original application: the scheme was usable for other molecules rather than being confined to one enzymatic reaction.[1] This general applicability distinguished the method from a model constructed only for a single narrowly defined system.[1]

His contributions also extended beyond enzyme chemistry to the computational study of biological structure.[3] Molecular-dynamics simulations of proteins and DNA, simplified models of protein folding and packing, and methods for scoring sequence and structural comparisons all formed part of his research.[3] The protein-folding simulation published with Warshel in 1975 was one early result of this work.[1] Their later simulations helped researchers investigate protein function and contributed to the growth of computational biology.[7]

The practical significance of these approaches includes the study of interactions between drugs and proteins.[9] Applying quantum calculations to the atoms directly involved in an interaction, while using classical physics for the surrounding protein, makes it possible to examine a chemically important region without treating the entire system at the most expensive computational level.[9] More broadly, the combination of the two kinds of physics increased the sophistication and speed with which chemical processes could be modeled.[8]

The biological applications were also described in terms of understanding and potentially influencing molecular processes.[10] The computational infrastructure developed by the laureates enabled the study of large, complex molecules, including proteins and nucleic-acid groups, by translating forces between atoms into physical equations and then into computer language.[10] Understanding how such molecules work could help researchers investigate ways to slow an unwanted biological process with drugs or other molecules.[10]

Weizmann occupies a central place in the history of Levitt’s work.[1][6] His collaboration with Warshel began there in the 1960s, included a program running on the institute’s Golem computer, and resumed there in 1972.[6] He later returned as a member of its faculty and continued his association as a visiting scientist after establishing his career at Stanford.[1][10] In his own retrospective account, a significant portion of the research that earned the Nobel Prize had been conducted during his return to Weizmann beginning in 1972.[4]

His career also reflects the international movement of researchers between Israeli, British, and American institutions.[1] His education in London and Cambridge, repeated appointments at Weizmann, work with Crick in California, and eventual professorship at Stanford connected the development of his research to institutions in several countries.[1][4] These institutional movements accompanied a continuing connection to Israel rather than a complete end to his professional involvement there.[10]

For Levitt, the Nobel Prize also carried significance as recognition of computational biology itself.[10] His description of the field’s earlier subordinate status relative to experimental biology contrasted with his response to the 2013 award, which he welcomed as evidence of its emergence as a substantial discipline.[10] The recognition therefore encompassed both particular molecular-modeling methods and the broader research approach of using computation to investigate biological and chemical processes.[10][8]

In March 2020, Levitt publicly discussed analyses and forecasts concerning the emerging COVID-19 pandemic, while acknowledging that he was not an expert in epidemiology or influenza.[13] He began examining early case counts after his wife, Shoshan Brosh, wrote to friends in China, and interpreted a decline in reported daily infections in Hubei from February 7 as evidence that the outbreak there was slowing.[13]

He offered forecasts about the timing of the outbreak’s decline and possible explanations involving social contacts, distancing, and natural immunity.[13] These were his contemporaneous interpretations, not established epidemiological findings.[13] In the same interview, he supported safety measures and said that the available Israeli data were insufficient to make estimates.[13]