Dr. Karle was a scientific polymath, schooled in biology and chemistry but proficient as well in physics and mathematics. He shared the 1985 Nobel Prize in chemistry with the late Herbert A. Hauptman, a mathematician with whom he pursued his pioneering research in the 1950s and ’60s at the Naval Research Laboratory in Southwest Washington.
The two men and their colleagues — including Dr. Karle’s wife, Isabella Karle, a chemist at the lab — took on a problem that had vexed scientists for years: the challenge of discerning the structure of three-dimensional molecules, combinations of atoms that were the simplest units of chemical compounds. They were too small for the most powerful of optical microscopes.
In the early part of the 20th century, the development of a technique called X-ray crystallography had made it possible to determine the probable shape of molecules. The technique involved buffeting a crystallized form of the molecule with X-rays and studying the patterns made on photographic film by the reflected beam, an effect compared to the reflection of light off a mirrored disco ball.
But it was a laborious process that could take months or years to complete. Dr. Karle and his colleagues devised an alternate, mathematical process relying on measurements including the intensity of the reflected X-rays. It allowed scientists to determine molecular structure more directly, precisely and quickly.
First published in the early 1950s, the discovery was overlooked for years. Dr. Karle credited his wife with drawing attention to the method’s usefulness. (“I do the physical applications, he works with the theoretical,” she told The Washington Post. “It makes a good team. Science requires both types.”)
The applications were numerous and transcended fields of science. Dr. Karle’s work has been applied to research on the structure of DNA, the development of painkillers and drugs to treat breast and other types of cancer, the study of hormones and antibiotics, and military research on propellants for missiles.
“It is almost impossible to give an example in the field of chemistry where this method is not being used,” a Nobel judge was quoted as saying when the prize was announced. The citation honored Dr. Karle and Hauptman for making “outstanding achievements in the development of direct methods for the determination of crystal structures.”
Dr. Karle had worked for the Naval Research Laboratory for more than six decades when he retired in 2009 as chief scientist in the laboratory for the structure of matter. He was once asked why he had never joined the private sector, where his earning potential would have been much greater.