A Viennese childhood cut short
Martin Karplus was born on March 15, 1930, in Vienna, into what has been described as an intellectual and successful secular Jewish family. His grandfather, Johann Paul Karplus, was a well-known professor of psychiatry at the University of Vienna. The physicist Robert von Lieben was a great-uncle, the philosopher Theodor W. Adorno became an uncle by marriage, and his older brother Robert would grow up to be a respected physicist and science educator at the University of California, Berkeley.
The comfortable world of his early childhood did not last. In his Nobel autobiography, Karplus recalled that in the spring of 1937 two neighbourhood boys who had been his and his brother’s best friends suddenly refused to play with them and began taunting them as “dirty Jew boys.” On March 13, 1938, German troops crossed into Austria. A few days later his mother took the two boys by train to Switzerland on what was presented as a “ski vacation.” Train tickets and a room in Zurich had been arranged well in advance, and an aunt had spent three years teaching the boys English. His father was not allowed to leave and had to give himself up to the Vienna city jail, held partly as a hostage so that the family’s money could not leave the country. One of Karplus’s great-aunts, the ethnologist Eugenie Goldstern, was later murdered in the Holocaust.
Refugees in America
The family spent months in Zurich and then in La Baule, France, waiting for American visas. When the visas came at the end of the summer, his father, released from jail, turned up unexpectedly at Le Havre a few days before their ship sailed. He told the boys cheerfully that he had passed his time in prison teaching the guards to play chess. Karplus later wrote that his father’s habit of making something positive out of any experience shaped both him and his brother.
They reached New York Harbor early on October 8, 1938, and the eight-year-old stood on deck watching the Statue of Liberty appear through the mist. The family was first lodged in a mansion in Brighton, near Boston, that had been turned into a welcoming centre for refugee families, where they took English lessons and learned how to stay in the United States as refugees. His parents soon moved to Newton because its public schools were better. There his father gave him a microscope instead of the chemistry set he wanted, and he became so absorbed in watching tiny rotifers swim that he refused to leave them even for meals. A free public lecture series on birds then turned him into a dedicated birdwatcher, and his teenage field studies won him a top place in the national Westinghouse Science Talent Search, which brought him to Washington to meet President Truman.
Harvard, Caltech and Linus Pauling
Karplus entered Harvard in 1947, intending at first to study medicine. Research soon changed his mind. He enrolled in a combined programme in chemistry and physics, convinced that to understand life at a basic level he needed a solid grounding in both, and worked with the biologists Ruth Hubbard and George Wald on retinal, the light-sensitive molecule in the eye. He graduated in 1951 and went to the California Institute of Technology for graduate work.
At Caltech he began in the biology group of Max Delbrück but moved to chemistry, and eventually became a student of Linus Pauling, one of the century’s greatest chemists. Because quantum mechanical calculations still had to be done with desk calculators and tables, Karplus chose a deliberately simple system for his thesis: the bifluoride ion, which holds the strongest known hydrogen bond. He finished his doctorate in 1953. Pauling later called him his most brilliant student. Karplus then spent two years as a postdoctoral fellow at Oxford with Charles Coulson, travelling around Europe and taking the photographs that later formed the basis of several exhibitions.
A theorist who wanted to be useful
From the start Karplus wanted theory to help working scientists. At the University of Illinois, where he taught from 1955 to 1960, he used one of the first university computers, the ILLIAC, to calculate how the magnetic signals of hydrogen atoms in a molecule depend on the angle between their chemical bonds. The result, known as the Karplus equation, became a routine tool for chemists using nuclear magnetic resonance to work out the shapes of molecules, and it is still taught to chemistry students today. He later warned, in a widely quoted paper, that the equation was often used with more confidence than it deserved.
After five years at Columbia University and the IBM Watson Laboratory in New York, where he studied how chemical reactions happen atom by atom, he returned to Harvard in 1966. He would remain on its faculty for the rest of his career, supervising more than 200 graduate students and postdoctoral researchers.
Molecules that move
Around 1970 Karplus turned back to biology. A visit to Shneior Lifson’s group at the Weizmann Institute in Israel introduced him to simple mathematical descriptions of the forces between atoms, and one of Lifson’s students, Arieh Warshel, joined him at Harvard as a postdoctoral fellow. Together they wrote a program that treated most of a molecule with the simple equations of classical physics while handling the electrons that matter most with quantum mechanics. In 1974 they used it to model how retinal changes shape when it absorbs light, the first step in vision.
With his graduate student Bruce Gelin, Karplus then built a program that could take the sequence and structure of a protein and calculate the energy and forces on every atom. The next step was to let those atoms move according to Newton’s laws. In 1977, with Andrew McCammon, his group published the first molecular dynamics simulation of a protein, a small molecule called bovine pancreatic trypsin inhibitor. Colleagues had told him such calculations were impossible, or a waste of time if they were possible. The simulation showed that proteins are not rigid sculptures, as crystal structures suggest, but constantly flexing and jiggling, and that this motion matters for how they work.
CHARMM and the computer as laboratory
The program grew into CHARMM, short for Chemistry at HARvard Molecular Mechanics. It was developed over decades by Karplus and a wide circle of former students and is distributed worldwide to universities and companies. Methods that came out of his group’s early simulations, such as techniques for searching how small molecules fit into pockets on a protein, became widely used in drug design. Former students led some of the world’s most important simulation laboratories and wrote other major programs in the field.
In awarding the 2013 Nobel Prize in Chemistry to Karplus, Michael Levitt and Arieh Warshel for multiscale models of complex chemical systems, the Royal Swedish Academy of Sciences said that computer models mirroring real life had become crucial for most advances in chemistry. It gave as an example how a drug couples to its target protein in the body, with quantum calculations for the atoms that touch the drug and classical physics for the rest. Today researchers use such simulations to study how proteins fold and misfold, how enzymes speed up reactions, how viruses and antibodies interact, and how candidate medicines might bind before anyone makes them in a laboratory. “Today the computer is just as important a tool for chemists as the test tube,” the Academy wrote.
Jewish roots and a refugee’s outlook
Karplus’s family was secular, but their Jewishness determined the course of his life. The taunts of former friends, his father’s imprisonment, the hurried flight from Vienna and the murder of relatives in the Holocaust all came from the Nazi persecution of Austria’s Jews. His family told The Harvard Crimson after his death that fleeing the Nazi regime as a child shaped his approach to science.
He wrote about these experiences frankly, and with gratitude for the country that took his family in. Recalling his first sight of the Statue of Liberty, he noted in 2013 that its symbolism might seem trite today, and somewhat deceptive given present immigration policies, but that in 1938 it was special for him. He is counted among the Jewish Nobel laureates in chemistry. One of his daughters, Reba, a physician, made her home in Jerusalem.
Strasbourg, food and photographs
In the 1990s Karplus set up a second research group in France, at the Louis Pasteur University in Strasbourg, after sabbatical visits there, and for years he divided his time between Strasbourg and Cambridge, Massachusetts. His wife, Marci, ran the laboratory as its administrator, which made the commuting possible. He had two daughters, Reba and Tammy, both physicians, from his first marriage to Susan, who died in 1982, and a son, Mischa, with Marci.
Outside science he was a serious photographer and a lover of food and wine. A former student recalled that he even spent short periods working in restaurants to learn the craft. Colleagues remembered him as demanding about quality and accuracy, generous with detailed comments on their papers, and eager for young scientists to become independent. He dedicated his Nobel lecture to the 244 “Karplusians” who had worked in his laboratories in Illinois, New York, Cambridge, Paris and Strasbourg.
Legacy
Martin Karplus died at his home in Cambridge, Massachusetts, on December 28, 2024, at the age of 94. In his own account of his life he argued that the real heart of the 2013 Nobel Prize was molecular dynamics, the idea of watching molecules move in a computer, which had grown from an esoteric specialty into a central part of modern chemistry and structural biology.
That idea is now everywhere. When scientists test how a new medicine might lock onto a protein, explore why a mutation makes an enzyme fail, or watch a virus protein change shape, they are using the approach he pioneered with crude models, small systems and very little computer time. For a boy who fled Vienna with his mother and brother in 1938, it is a remarkable legacy: a way of seeing the living world, atom by atom, that helps researchers everywhere design better treatments.
Sources & further reading
Martin Karplus, Biographical, NobelPrize.org · Press release: The Nobel Prize in Chemistry 2013, NobelPrize.org · Nobel Laureate Martin Karplus ’51 Remembered as Attentive Mentor, ‘Pioneering’ Chemist, The Harvard Crimson · Martin Karplus, 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.