Jerome Karle, 94, Dies - Nobelist for Crystallography - NYTimes.com Jerome Karle, who shared the 1985 Nobel Prize in Chemistry with a former college classmate for creating what is now an essential tool in the development of new drugs, died on June 6 at a hospice in Annandale, Va. He was 94. The death was confirmed by Isabella Karle, his wife of 71 years, on Thursday. The technique developed by Dr. Karle and Herbert A. Hauptman, called X-ray crystallography, is now routinely used by scientists to determine the shapes of complex molecules like proteins. "These structures are solved all over the world on a daily basis," said Louis J. Massa, a professor of physics and chemistry at Hunter College in Manhattan and a collaborator with Dr. Karle on more recent research. It's one of those things that's taken for granted now. In X-ray crystallography, an X-ray beam bounces off the crystal form of a molecule to produce a pattern of points of light. The positions of the atoms in the molecule are then deduced from the pattern. But when Dr. Karle and Dr. Hauptman started working on the problem after World War II at the Naval Research Laboratory in Washington, it was "thought to be not just difficult but mathematically impossible to solve," Dr. Massa said. Dr. Karle and Dr. Hauptman, who had met at City College in New York, published their main ideas in the 1950s, but it took many years for them to convince others that their technique worked. "In the beginning, people didn't understand what my father was saying," said Dr. Karle's daughter Louise Karle Hanson, adding that she could "remember his frustration." Isabella Karle, who was also a chemist at the Naval Research Laboratory, joined her husband in the work, employing X-ray crystallography to determine the structure of previously intractable molecules. "After I found some structures that no one could have dreamt of solving before, it started to get a lot of attention," she said. With a clearer picture of the structure of biological molecules, drug researchers now have a much better idea of the chemistry going on inside the body and how to formulate drugs to treat illnesses. Jerome Karle was born in Brooklyn on June 18, 1918, and attended public schools. Routinely placed in advanced classes, he graduated from Abraham Lincoln High School around his 15th birthday, then enrolled at City College. "He could have gone at 14," Isabella Karle said. I think his mother thought at five feet tall, he was a little short to go to college. Dr. Karle and Dr. Hauptman both graduated from City College in 1937. Dr. Karle obtained a master's degree in biology at Harvard in 1938 and then worked at the New York State Health Department in Albany to earn money for further studies. He enrolled in graduate school at the University of Michigan in 1940. The student sitting next to him in the physical chemistry laboratory was Isabella Lugoski, whom he married in 1942. "That was alphabetical order," Isabella Karle said. Just as precocious a student as Dr. Karle, she had finished her undergraduate studies at 19. After the couple completed their doctorates, they both worked in Chicago helping develop the atomic bomb as part of the Manhattan Project, concentrating on the chemistry of extracting and purifying plutonium. In 1946, they moved to the Naval Research Laboratory, which was expanding into basic science research. Dr. Hauptman joined the laboratory the following year, and he and Dr. Karle began thinking about X-rays and crystals. In the early years, the X-ray crystallography calculations were laborious. "These things were done by hand and by eye, originally," Dr. Massa said. They would make estimates by the human eye how bright something was or not. With faster computers in the 1970s, the use and acceptance of X-ray crystallography accelerated. In jointly awarding the two men the Nobel Prize in 1985, the Royal Swedish Academy of Sciences cited their achievement "in the development of direct methods for the determination of crystal structures." It noted that "in order to understand the nature of chemical bonds, the function of molecules in biological contexts, and the mechanism and dynamics of reactions, knowledge of the exact molecular structure is absolutely necessary." Dr. Karle was a member of the National Academy of Sciences. In addition to his wife and his daughter Louise, he is survived by two other daughters, Jean Karle and Madeleine Karle Tawney, and four grandchildren. Dr. Hauptman died in 2011. Dr. Karle continued to work at the Naval Research Laboratory and advanced his studies of X-ray crystallography. With Dr. Massa and Lulu Huang, another scientist there, he helped develop a technique to glean from the X-ray patterns not only the positions of the atoms but also the shapes of the electron clouds and the strength of the molecules" bonds. Dr. Karle and his wife retired from the Naval Research Laboratory in June 2009. After the academy announced the Nobels, Dr. Karle and Dr. Hauptman were at a meeting of the American Crystallographic Association, Dr. Massa recalled. Three decades earlier, Dr. Karle had appeared before the same group, only to leave frustrated by his inability to explain his work to his colleagues. The meeting was being held in a large auditorium, Dr. Massa said, and Dr. Karle and Dr. Hauptman walked in unannounced. "They were immediately recognized, and everyone stood up and clapped," Dr. Massa said. That gives you the sense of the enormous importance of the problem these guys solved. I've never seen anything like it, before or since.