Growing up on a kibbutz
Arieh Warshel was born on November 20, 1940, on Kibbutz Sde Nahum in the Beit She’an Valley, in what was then British Mandate Palestine. He was the eldest of four sons of Tzvi and Rachel Warshel, Jewish immigrants from Poland who had arrived in 1936 and 1929 and helped build the kibbutz. Much of both sides of the family were murdered in the Holocaust; his father’s sister Chana, who had studied engineering at the Technion, was killed in Lachowicze in Poland. His father bred carp in the kibbutz fishponds and, despite only an elementary education, became the kibbutz accountant.
Warshel grew up in the kibbutz children’s house, sleeping alongside his classmates and spending a couple of hours a day with his parents, which he remembered as a happy way to grow up. Every Saturday morning the children raced a kilometre from the kibbutz fence to the old Damascus-Haifa railway tracks. He usually started at the back but often finished first, an early lesson in perseverance that he says stayed with him: if he keeps working long enough on a scientific problem, he will probably solve it. On the football field he liked to play attacking midfield, connecting defence and attack; connecting different parts, he later reflected, became the theme of his scientific life.
Soldier and student
The kibbutz school was relaxed about exams, and there was little science, but young Arieh built home-made gadgets and worked in the fishponds, the dining room, the gardens and as an electrician’s apprentice. He joined the army in 1958, serving as a communications specialist with the Golani infantry brigade and then as an officer in a radio surveillance unit, carrying physics and mathematics books in his kitbag the whole time. Because the kibbutzim of the day did not encourage members to go to university, he had no matriculation certificate; he studied for it on night shifts at army headquarters and then passed the demanding entrance exam of the Technion in Haifa.
He began studying chemistry in 1962, almost at random, and soon became fascinated by how enzymes, the catalysts of living cells, can speed up chemical reactions by factors of up to a hundred billion billion. A summer job spent doing eight hours of hand calculations a day for irrigation research showed him how much a computer could help. He graduated in 1966 with top honours and the same year married Tamar Fabrikant.
Molecules as balls and springs
Warshel went to the Weizmann Institute of Science in Rehovot to work with Shneior Lifson, who was beginning to model molecules on computers. There he developed what became the consistent force field, which treats molecules as balls connected by springs so that a computer can calculate their shapes, energies and vibrations. His breakthrough was to describe atoms by simple Cartesian coordinates, which made the mathematics far easier. Lifson at first thought it could not be right, but Weizmann’s computer, named the Golem after the creature of Jewish legend, confirmed it. Lifson later told people not to argue with Arieh, because he would always turn out to be right.
In 1967 Warshel was called to the reserves and fought in the Six-Day War as communications officer of a tank battalion that helped take the Golan Heights; his wife carried his doctoral proposal down to the shelter during air raids. Back at Weizmann, he and a young student from South Africa, Michael Levitt, built general computer programs that could model any molecule. He earned his doctorate in 1969 and went to Harvard as a postdoctoral researcher with Martin Karplus, where he combined quantum and classical calculations to study the molecule that lets our eyes detect light.
Teaching computers to see enzymes at work
Returning to Weizmann in 1972, Warshel went back to his old dream of understanding enzymes. He fought again on the Golan Heights in the Yom Kippur War of 1973, when a bullet pierced his helmet; he called the war traumatic and said it pushed him to move faster into biology. With Levitt he built a simplified computer model that folded a small protein into a realistic shape, an early attack on one of biology’s great puzzles. In 1974 he joined Levitt at the Medical Research Council Laboratory of Molecular Biology in Cambridge, England.
There, in 1976, the two published the method that would earn them a Nobel Prize. Chemical reactions involve electrons, which obey quantum physics, but quantum calculations were far too demanding for a whole protein of thousands of atoms. Classical physics could handle big molecules but could not describe bonds breaking and forming. Warshel and Levitt combined the two: the computer uses quantum mechanics for the few atoms where the reaction happens and simpler classical physics for the rest of the enzyme and the surrounding water, coupling the two parts consistently. They used it to model the reaction of lysozyme, an enzyme in tears and saliva that attacks bacteria. The approach, known as QM/MM, is now one of the main methods of theoretical chemistry and biophysics.
Also in Cambridge he ran what he describes as the first molecular dynamics simulation of a biological process, modelling the first step of vision, when light makes the retinal molecule in the eye change shape. His calculation predicted that the step takes about 100 femtoseconds, a tenth of a millionth of a millionth of a second, a result later confirmed by experiment.
How enzymes really work
In 1976 Warshel joined the University of Southern California, where he has worked ever since. Around 1978 he arrived at what he believes is the answer to the puzzle of enzyme power. In water, a reaction is slowed because the water molecules must turn and rearrange around the developing electric charges. In an enzyme, the charged and polar groups are already arranged in exactly the right positions, so that cost is largely avoided. He developed the empirical valence bond method to calculate this and showed that the effect accounts for almost all of the catalytic power of enzymes. In 1987, within two weeks of receiving the structure of the photosynthetic reaction centre, his team used its ready-made programs to work out the first step of photosynthesis, correctly predicting the mechanism.
Acceptance was slow. His ideas, he wrote, were first called wrong, then called trivial and attributed to others; his battles with hostile journal referees became legendary. A USC colleague called him fearless.
From computer to medicine cabinet
In 2013 the Royal Swedish Academy of Sciences awarded the Nobel Prize in Chemistry to Martin Karplus, Michael Levitt and Arieh Warshel for the development of multiscale models for complex chemical systems. The Academy said that computer models mirroring real life have become crucial for most advances in chemistry, and that the computer is now as important a tool for chemists as the test tube.
The methods Warshel helped found are used every day. When drug companies want to see how a candidate medicine binds to its target protein, they use exactly the approach he pioneered: quantum calculations for the atoms at the binding site and classical physics for the rest. The Nobel committee noted that such models help scientists optimise drugs, the catalysts in car exhausts, and solar cells, and to pursue artificial photosynthesis for clean fuel. Warshel has argued that understanding enzymes in detail allows better treatments than experimenting blindly, giving improved cancer chemotherapy as an example. His laboratory has also modelled molecular machines such as the rotary motor that makes the cell’s energy molecule ATP, and the voltage-sensing ion channels that let nerve cells fire.
A Jewish and Israeli story
Warshel’s life traces modern Jewish history: parents who left Poland for a pioneering kibbutz, relatives lost in the Holocaust, two wars fought on the Golan Heights, and an education at Israel’s great scientific institutions, the Technion and the Weizmann Institute. He holds both Israeli and American citizenship. The Jewish Virtual Library lists him among Jewish Nobel laureates and notes that he is credited with founding computational enzymology. He is a member of the US National Academy of Sciences and has published hundreds of scientific papers.
Family and character
Warshel and his wife Tami have two daughters, Merav and Yael. He has thanked Tami for following him through his scientific life and helping him both endure difficulties and enjoy successes. In the punch-card era, when the computer centre returned results only twice a day, the couple would stop at the centre on the way home from a show so he could submit one more job before bed. Colleagues describe him as creative, funny, stubborn and original; one said he could see into the future. A few days after the Nobel announcement, he was back in his USC laboratory working with students.
Legacy
Warshel helped move chemistry from the test tube to the computer. The idea that a simulation can combine quantum physics for the heart of a reaction with simpler physics for everything around it is now built into the software used across the pharmaceutical, chemical and energy industries. He believes that the merger of experiment and computation has only begun. For a boy from the fishponds of Sde Nahum, it is a remarkable legacy: a way for scientists everywhere to watch life’s chemistry unfold, atom by atom, before they ever step into the laboratory.
Sources & further reading
Arieh Warshel, Biographical, NobelPrize.org · Press release: The Nobel Prize in Chemistry 2013, NobelPrize.org · A Nobel victory, USC Dornsife · Arieh Warshel, Jewish Virtual Library · Arieh Warshel, 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.