By applying electron and X-ray diffraction to molecular structure problems, Isabella Karle (born 1921) was able to develop procedures for gathering information about the structure of molecules.
Isabella Karle is a renowned chemist and physicist who has worked at the Naval Research Laboratory in Washington, D.C., since 1946 and heads the X-Ray Diffraction Group of that facility. In her research, she applied electron and X-ray diffraction to molecular structure problems in chemistry and biology. Along with her husband Jerome Karle, she developed procedures for gathering information about the structure of molecules from diffraction data. For her work, she has received numerous awards such as the Annual Achievement Award of the Society of Women Engineers in 1968, the Federal Woman's Award in 1973, and the Lifetime Achievement Award from Women in Science and Engineering in 1986. Her work has been described in the book Women and Success.
Isabella Lugoski Karle was born on December 2, 1921, in Detroit, Michigan. Her parents were Zygmunt A. Lugoski, a housepainter, and Elizabeth Graczyk, who was a seam-stress. Both her parents were immigrants from Poland, and Karle spoke no English until she went to school. While still in high school, she decided upon a career in chemistry, even though her mother wanted her to be a lawyer or a teacher. She received her B.S. and M.S. degrees in physical chemistry from the University of Michigan in 1941 and 1942. Determined to continue her studies, Karle ran into serious financial problems since teaching assistant positions at the University of Michigan were reserved exclusively for male doctoral students. She managed to stay in school on an American Association of University Women fellowship, however, and in 1943 also became a Rackham fellow. She received her Ph.D. in physical chemistry from the University of Michigan in 1944, at the age of twenty-two.
After receiving her doctorate, Karle worked at the University of Chicago on the Manhattan Project (the code name for the construction of the atomic bomb), synthesizing plutonium compounds. She then returned to the University of Michigan as a chemistry instructor for two years. In 1942 she had married Jerome Karle, then a chemistry student. In 1946 she and her husband joined the Naval Research Laboratory, where she worked as a physicist from 1946 to 1959. In 1959 she became head of the X-ray analysis section, a position she maintained through the 1990s.
When Karle began her work at the Naval Research Laboratory, information about the structure of crystals was limited. Scientists had determined that crystals were solid units, in which atoms, ions, or molecules are arranged sometimes in repeating, sometimes in random patterns. These patterns or networks of fixed points in space have measurable distances between them. Although chemists had been able to investigate the structure of gas molecules by studying the diffraction of electron or X-ray beams by the gas molecules, it was believed that information about the occurrences of the patterns—or phases—was lost when crystalline substances scattered an X-ray beam. The Karles, working as a team, gathered phase information using a heavy-atom or salt derivative. The position of a heavy atom in the crystal could be located by scattered X-ray reflections, even though light atoms posed more serious problems. When a heavy atom could not be introduced into a crystal, its structure remained a mystery. In 1950 Jerome Karle, in collaboration with the chemist Herbert A. Hauptman, formulated a set of mathematical equations that would theoretically solve the problem of phases in light-atom crystals. It was Isabella Karle who solved the practical problems and designed and built the diffraction machine that photographed the diffracted images of crystalline structures.
While investigating structural formulas and the makeup of crystal structures using electron and X-ray diffraction, Karle made an important discovery. She found that only a few of the phase values—no more than three to five—are sufficient to evaluate the remaining values. She could then use symbols to represent these initial values and also numerical evaluations. This process for determining the location of atoms in a crystal was amenable to processing in high-speed computers. Eventually, it became possible to analyze complex biological molecules in a day or two that previously would have taken years to analyze. The rapid and direct method for solving crystal structure resounded through chemistry, biochemistry, biology, and medicine, and Karle herself has been active in resolving applications in a range of fields.
In addition to describing the structure of crystals and molecules, Karle also investigated the conformation of natural products and biologically active materials. After a crystallographer determines the chemical composition of rare and expensive chemicals, scientists can synthesize inexpensive substitutes that serve the same purpose. Karle headed a team that determined the structure of a chemical that repels worms, termites, and other pests and occurs naturally in a rare Panamanian wood. The team was then able to produce a synthetic chemical that mimics the natural chemical and is equally effective as a pest repellent. In another application, Karle studied frog venom. Using extremely minute quantities of purified potent toxins from tropical American frogs, the team headed by Karle established three-dimensional models, called stereoconfigurations, of many of the toxins and showed the chemical linkages of each of these poisons. The inexpensive substitutes of the toxins were of great importance in medicine. The venom has the effect of blocking nerve impulses and is useful to medical scientists studying nerve transmissions. Karle has also researched the effect of radiation on deoxyribonucleic acid (DNA), the carrier of genetic information. She demonstrated how the structural formulas of the configurations of amino acids and nucleic acids in DNA may be changed when exposed to radiation. Her research into structural analysis also established the arrangement of peptide bonds, or combinations of amino acids.
Karle has held several concurrent positions, such as member of the National Committee on Crystallography of the National Academy of Science and the National Research Council (1974-1977). She has long been a member of the American Crystallographic Society and served as its president in 1976. She was elected to the National Academy of Sciences in 1978. From 1982 to 1990 she worked with the Massachusetts Institute of Technology, and she has been a civilian consultant to the Atomic Energy Commission.
Karle has received numerous awards including the Superior Civilian Service Award of the Navy Department in 1965, the Hildebrand Award in 1970, and the Garvan Award of the American Chemical Society in 1976. She has received several honorary doctorates. Her most recent awards have been the Gregori Aminoff Prize from the Swedish Academy of Sciences in 1988, the Bijvoet Medal from the University of Utrecht, the Netherlands, in 1990, and a National Medal of Science in 1995, the United States' highest scientic honor. She has written over 250 scientific articles.
The Karles have three daughters, Louise Isabella, Jean Marianne, and Madeline Diane. All three have become scientists like their parents. Jerome Karle, who is chief scientist at the Laboratory for Structure and Matter of the U.S. Naval Laboratory, received the Nobel Prize in chemistry in 1985 for developing a mathematical method for determining the three-dimensional structure of molecules.
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