A boy from Pretoria
Michael Levitt was born on May 9, 1947, in Pretoria, South Africa, to a Jewish family. His father had been born in Plungė, Lithuania, and came to South Africa at the age of ten; his mother, Gertrude, was born in Johannesburg to parents who had emigrated from Czechoslovakia. He remembers a happy childhood of seaside holidays in Durban and trips to the Kruger game reserve, school that was enjoyable but not challenging, and a model car he built from fibreglass and powered with a petrol engine before he was thirteen. In 1960 he heard about computers for the first time and was impressed that they could play chess.
His parents separated when he was nine. One night in December 1962 he came home at two in the morning after playing snooker with friends, and the ensuing family discussion led to a decision that he was bored with school. He crammed the last two years of high school into a summer vacation with private tutors, passed his matriculation exams, and entered Pretoria University a few months before his sixteenth birthday, studying applied mathematics in lectures given in Afrikaans.
London and the thread of life
In November 1963 Levitt went to London to spend the holidays with his uncle, Max Sterne, who had developed an effective and safe vaccine against anthrax, and his aunt, Tikvah Alper, a radiation biologist whose work laid groundwork for the discovery of prions. He decided to stay. His mother soon followed with his brother and sister, and at fifty she became a schoolteacher to support the family. Watching a BBC television series on molecular biology by the Nobel laureate John Kendrew, Levitt was captivated by the idea that physics could help explain life. He studied physics at King’s College London, where Maurice Wilkins had helped reveal the structure of DNA, and spent a summer at the Radiation Laboratory in Berkeley writing his first computer programs on punched cards. In London he also learned to programme, first on paper tape at a computer course his mother sent him on, and he made friends who would later push him to chase his ambitions.
Determined to join the famous Medical Research Council Laboratory of Molecular Biology in Cambridge, he was first turned down for lack of space. Wearing the suit from his bar mitzvah, he drove to Cambridge, waited outside the office of Max Perutz and politely ambushed him in the corridor. It worked: he was accepted for 1968, and Kendrew arranged for him to spend the year before at the Weizmann Institute in Israel.
A watershed year in Rehovot
Levitt arrived in Israel by boat on the eve of Yom Kippur in October 1967. He called the year that followed the real watershed of his life. Working with the Israeli chemist Arieh Warshel in the group of Shneior Lifson, he wrote the computer program that allowed them to calculate the structure, energy and vibrations of any molecule using the consistent force field. He applied the method to the two protein structures then known. And ten weeks after arriving, at a Christmas party, he met Rina, an Israeli biology graduate and later a multimedia artist. They married in August 1968, when he was 21.
Back in Cambridge he did his doctorate, completed in 1971, and as a young father became an early telecommuter, cycling to the laboratory for four hours each morning to type punched cards and caring for his son the rest of the day. One reviewer ridiculed his thesis methods as worth an F in an undergraduate course; those methods of calculating molecular forces are now standard. Working closely with Francis Crick and Aaron Klug, he built a model of transfer RNA; it was wrong in its overall shape but right in many details, and Crick submitted it on his behalf to Nature, which published it 23 days later.
Folding proteins on a computer
Proteins are long chains of amino acids that fold into precise three-dimensional shapes, and their shape determines what they do. In the early 1970s it seemed impossible to simulate folding, because there were far too many atoms and possible arrangements. Back in Israel during and after the Yom Kippur War of 1973, Levitt and Warshel spent hours a day talking about science as an escape. Joking that protein models would be easier to fold in the zero gravity of a spacecraft, they had a serious idea: simplify the protein drastically, replacing the ten or so atoms of each amino acid with one or two interaction points. Their 1975 paper in Nature showed that a small protein could be folded on a computer into a realistic shape, an early example of the coarse-grained models now used to study huge molecular machines.
Their second collaboration was even more influential. Levitt had argued that the enzyme lysozyme works through electrical rather than mechanical strain, which ordinary models could not capture. Warshel proposed combining quantum mechanics for the reacting atoms with classical physics for the rest of the enzyme. Their 1976 paper introduced this hybrid approach, now known as QM/MM, which lets scientists simulate chemical reactions inside proteins. Levitt also pioneered molecular dynamics simulations of proteins surrounded by explicit water molecules, and with Cyrus Chothia classified the common patterns of protein structure.
From models to medicines
At the Salk Institute in California from 1977, where there was no computer, he used a federal grant to buy one of the new VAX minicomputers, kept it at a local company and worked on it from a teleprinter in his beachside home, driving to the institute at lunchtime to talk science with Crick and Orgel. Back at the Weizmann Institute from 1979, with strong support from its president, Michael Sela, he wrote nine sole-author papers in three years and, with Ruth Sharon, solved the hard problem of simulating the motion of a protein in a large box of water molecules, an approach that underlies the molecular dynamics simulations run by thousands of laboratories today.
Having chaired Weizmann’s Department of Chemical Physics, Levitt moved in 1987 to Stanford University, where he chaired the Department of Structural Biology from 1992 to 2004. At Stanford he consulted for Protein Design Labs, a company that used computer modelling to humanise mouse antibodies so that the human immune system would accept them as medicines. He was an author of the landmark 1989 paper describing a humanised antibody against the interleukin-2 receptor, in which a computer model of the antibody guided the design. That antibody became daclizumab, approved to help prevent the rejection of kidney transplants, and the company’s humanisation method was used in a series of later antibody medicines, including treatments for cancer. Levitt also founded a software company, Molecular Applications Group, to sell molecular graphics programs.
The Nobel committee said that computer models mirroring real life have become crucial for most advances in chemistry, and that the methods are used to optimise drugs, catalysts and solar cells. Today the simulation methods Levitt helped invent, together with protein-structure prediction to which his students and he contributed, are part of everyday work in drug discovery.
The Nobel Prize and a controversy
In October 2013 Levitt shared the Nobel Prize in Chemistry with Martin Karplus and Arieh Warshel for the development of multiscale models for complex chemical systems. He was woken by the call at 2:16 in the morning and adopted a motto: no one should expect the Nobel Prize. He said he wanted to use the attention to make sure young scientists today receive the opportunities his generation enjoyed, warning that failing them would dry up the well of innovation.
In 2020, during the COVID-19 pandemic, Levitt used his modelling experience to make public predictions that the outbreak would be far smaller and shorter than it proved to be; in March 2020, for example, he predicted fewer than ten deaths in Israel. He opposed lockdowns and signed the Great Barrington Declaration. His forecasts were widely criticised by epidemiologists, and fellow laureate Randy Schekman wrote that he had crossed a boundary from data to public policy.
Jewish and Israeli ties
Levitt grew up in South Africa’s Jewish community and celebrated his bar mitzvah there. His deep connection to Israel began in 1967 and has shaped his whole life: he met his wife there, became an Israeli citizen in 1980, and raised his three sons partly in Rehovot, where all three served in the Israel Defense Forces while he commuted between Israel and Stanford. He holds American, British, Israeli and South African citizenship.
Family and legacy
Michael and Rina Levitt had three sons, Daniel, Reuven and Adam, all born in Cambridge, and several grandchildren. Rina, an artist who studied at the Avni art school in Tel Aviv and later made large monotypes in California, died in 2017. Levitt has described his sixties as the most enjoyable years of his life, filled with long hikes in Patagonia and a solo sea-kayaking trip in the Swedish archipelago, and he continues to work at Stanford.
His legacy is the idea that a computer can be a laboratory for the molecules of life. The protein simulations and models he helped create in the 1970s, once greeted with scepticism, now underpin structural biology and computational drug design, and they were a foundation for later advances in predicting how proteins fold.
Sources & further reading
Michael Levitt, Biographical, NobelPrize.org · Press release: The Nobel Prize in Chemistry 2013, NobelPrize.org · A humanized antibody that binds to the interleukin 2 receptor, PNAS 1989 (PubMed Central) · Michael Levitt (biophysicist), Wikipedia · Researched from the sources above and checked against them. Spotted an error? Tell us.
A life of tikkun olam. This is part of tikkun olam, the Jewish idea of repairing the world, and every one of us can add to it.