CAMBRIDGE — It was the simple parental desire to avoid having two boys blow stuff up in the basement of their Newton home that helped set Martin Karplus on a path that culminated Wednesday in science’s most prestigious prize: the Nobel. After Karplus begged his parents for a chemistry set like the one his brother, Robert, was using to create all kinds of awful smells and small explosions, they gave him a microscope instead.
At first it felt like a consolation gift, but soon, Karplus could not be torn away from his microscope, preferring to gaze at tiny critters found in pond scum instead of eating meals. That led him to a love of nature and birds. And eventually, he decided he wanted to understand biology — really understand it.
“I was supposed to be a doctor,” said Karplus, whose family was Jewish and fled Austria after the Nazi takeover in 1938. But in Brighton and later Newton — where he learned to be an American kid, playing stickball and even shoplifting candy — he found himself drawn to something quite different.
“I realized what I really wanted to do was understand biological systems, and the only way to do this was to do chemistry and physics,” Karplus said during a news conference at Harvard, where he is now an emeritus professor. “Because all of what goes on inside of us is governed by chemistry and physics.”
The 83-year-old Karplus is sharing the Nobel Prize in chemistry with Michael Levitt, 66, of Stanford University, and Arieh Warshel, 72, of the University of Southern California. The Royal Swedish Academy of Sciences cited the trio, all of whom were born abroad, for creating computer programs that laid the groundwork for a sea change in how chemistry is done, using software in addition to test tubes and bunsen burners to understand how molecules will behave.
The computational methods the three pioneered in the 1970s are now routinely used by chemists to understand how molecules will interact, including understanding how drugs interact with proteins in the body. The approach has been used to understand how to inhibit an enzyme in HIV, for example, and to understand the formation of amyloid fragments in the brains of people with Alzheimer’s disease.
Despite his success, the early Wednesday morning phone call came as a surprise. Karplus was half asleep in his Cambridge home and still not quite able to grasp what was happening when a voice on the other end of the phone told him he would share the Nobel Prize, he said. To the octagenarian scientist, who continues to do research today, the call was more than just personally gratifying; it reinforced his belief that young scientists need to be courageous, and that originality and hard work are the qualities that lead to success.
“When we first began doing the type of work that was honored today, my chemistry colleagues thought it was a waste of time. . . . My biology friends at the time said, ‘Well, even if we could do this, it wouldn’t be of interest,’ ” Karplus said. “I think now it has become a central part, not only of chemistry, but of structural biology. I think that what the Nobel Prize does . . . is it in a way consecrates this field.”
Karplus’s achievements in the laboratory were profoundly shaped by the turns his life took, he wrote in an essay published in the Annual Review of Biophysics and Biomolecular Structure in 2006.
At a young age, Karplus, born in Vienna, seemed destined for a career in medicine — a profession that Jews could then practice without as much discrimination. He came from a family of physicians, and as a child, he would bandage broken furniture as practice for one day healing bones.
As a refugee in the United States, he wrote that he aspired to be a “street kid in every sense, hanging around with my friends, playing stickball and other such games, occasionally stealing candy just for the fun of it.”
His intellectual curiosity, however, took him to the serious study of birds, and eventually, chemistry.
Elias J. Corey, also a Nobel laureate in chemistry and emeritus professor at Harvard, recalled meeting Karplus when they were both young faculty members at the University of Illinois. Karplus’s recommendation letter from Linus Pauling, an eminent chemist who would receive two Nobel prizes, was glowing, Corey recalled.
“He said that Martin was his most brilliant PhD student,” Corey said in an interview.
The two then-unmarried scientists ate meals together and talked science intensively, and Corey continued to follow Karplus’s career, until they both ended up as faculty members at Harvard.
“We work in very different fields,” Corey said. “But he has made contributions of a high order of excellence over many years, and it probably would take quite a long lecture for him to summarize his major achievements.”
It was at Harvard that Karplus decided to focus on questions that fell between chemistry and biology. He used quantum mechanics, which describes the behavior of matter at a very small scale, to model the structure of molecules.
The two scientists who are being honored alongside him, Warshel and Levitt, had utilized a computer at the Weizmann Institute of Science in Israel called the Golem to model the behavior of molecules using classical physics. Warshel joined Karplus’s laboratory in Cambridge, and the two began working on an approach that would integrate Karplus’s interest in applying quantum mechanics to predict the small-scale behavior of molecules with a more classical approach.
He and Warshel modeled quantum and classical effects in a molecule called retinal, involved in vision.
Warshel later worked with Levitt on understanding the interactions and behavior of enzymes, proteins involved in basic processes in cells.
The techniques are now used widely in the drug industry, and by companies trying to optimize chemical processes for any number of reasons — to design more efficient solar panels, for example, or materials used in cars.
“He really did change biomedical research in foundational ways,” said Stuart Schreiber, a founding core member at the Broad Institute, a genetics research center in Cambridge, who said Karplus’s creativity and intellectual curiosity were clear from the first time they met.
Perhaps more important was his passion and his ability to make his own path. Schreiber, too, was a pure chemist who became interested in working in biology.
“It was inspiring to me to know this can be done,” Schreiber said. “A more established person, fearlessly moving into this world of complexity.”
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