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NEWS | Oct. 24, 2017

Isabella Karle, Renowned Crystallographer and Chemist, Dies at 95

By Gabrielle Gibert

WASHINGTON -- Dr. Isabella Karle, former U.S. Naval Research Laboratory (NRL) scientist and renowned crystallographer, died Oct. 3, 2017, at the age of 95 due to complications from a brain tumor.

Isabella Karle was born Isabella Helen Lugoski in Detroit, Michigan, Dec. 2, 1921, the daughter of two Polish immigrants. After graduating high school, Isabella attended the University of Michigan on a full scholarship, earning her Bachelor of Science in Chemistry at the age of 19. She went on to earn her Master of Science and doctorate in physical chemistry. It was during this time that Isabella met the man who became her husband and lifelong collaborator: Dr. Jerome Karle, another decorated alumnus of NRL and 1985 Nobel Laureate in Chemistry.

Together, the Karles revolutionized the field of small molecule structure research by developing methods to determine structures of crystalline substances indispensable to the solutions of problems in numerous scientific disciplines such as chemistry, biochemistry, biophysics, mineralogy, material science, pharmaceuticals, drug design, and medicinal chemistry. By the end of their tenure at NRL, the two had accumulated a combined total of 127 years of scientific research.

The Karles were highly esteemed NRL scientists, with Isabella receiving the NRL Lifetime Achievement Award in 1998. In their honor, NRL has dedicated a conference room on its Washington, D.C. campus to them that displays highlights of their careers and their congratulatory letters and awards. NRL has also established the Jerome and Isabella Karle Distinguished Scholar Fellowship Program which consists of the Karles Fellowships, awarded to young NRL researchers just starting their scientific careers, and the Karles Senior Research Fellowships, open to outstanding established researchers. In addition, NRL hosts the annual Karles Invitational Conferences, started in 2011, to commemorate their achievements and broad scientific impact.

Isabella mentored many young scientists, teaching the direct methods that she developed at international “summer schools” and workshops across the globe. She even influenced her own family: each of her three daughters became a woman in science.

“I remember from a young age that my parents were always very excited about their work,” said Jean Dean, chemist and Isabella’s middle daughter, with fondness. “They always brought that enthusiasm for science home with them, so I got that enthusiasm instilled in me as well very early on.”

“Although they would never say it, it was expected that we find our path in science,” chimed Isabella’s eldest daughter Louise Hanson, a chemist herself, laughing.

Isabella helped pave the way for women in science, becoming the first female faculty member in the University of Michigan’s chemistry department and being an inspirational example of an outstanding professional scientist with more than 350 published papers in her name.

“Dr. Isabella Karle was a pioneer in the scientific community whose legacy will live on through many future generations of scientists,” said Meredith Hutchinson, Ph.D., and president of NRL’s chapter of Women in Science and Engineering (WISE) in which Karle was involved. “Dr. Karle was an icon for women scientists everywhere. NRL WISE is eternally grateful for her hard work, sacrifice and contributions to the field of chemistry.”

Isabella’s first scientific breakthrough came at the age of 22 shortly after earning her doctorate from the University of Michigan, working in Chicago on the Manhattan Project, the World War II research project that led to the invention of the first atomic bombs. Isabella developed the techniques used to synthesize pure plutonium chloride from plutonium oxide mixtures.

At the conclusion of World War II, Isabella began her 63-year tenure at NRL in 1946. It was here that Isabella achieved her second scientific breakthrough working in electron diffraction, improving pre-existing electron diffraction instrumentation used to determine the structure of small molecules in the gaseous phase.

At the time of this new electron diffraction device, the field of X-ray crystallography was severely limited by what was known as the phase problem. Scientists at the time knew that the X-ray diffraction patterns of crystalline materials were determined by the three-dimensional atomic structures of their constituent molecules, but for most substances, they did not know how to deduce these structures from the observed diffraction patterns.

Jerome Karle (with Herbert Hauptman) created mathematical formulas that successfully addressed the phase problem. At first, these mathematical methods were not well understood and were received skeptically by the scientific community. It was then that Isabella taught herself X-ray crystallography through textbooks and transitioned the mathematical concepts developed by her husband and Hauptman from the theoretical into the experimental. She also simplified the mathematics, thereby creating what is now known as “direct methods.” Isabella's direct methods revolutionized the field of X-ray crystallography and has been used to determine the three-dimensional atomic structures of hundreds of thousands of molecules by scientists all over the world.

“Through their persistent and dedicated research, they opened the doors to our understanding of the complexities of atomic arrangements in large biological and organic molecules,” said Bhakta Rath, Ph.D., former associate director of research for the Materials Science and Component Technology Directorate. “Their theoretical and experimental research, which is now commonly known as the direct method for solving the multivariable complex functions extracted from X-ray diffraction data, has made immeasurable contribution to our understanding of the structure and function of biomolecules and, consequently, to the development of various pharmaceutical products.”

In addition to her work in crystallographic methodology, Isabella is noted for her research investigating the conformation of natural products and biologically active materials such as peptides, steroids, and alkaloids. The structural information she provided has been invaluable to the prediction of folding of new peptide and protein molecules and to the field of computational chemistry.

Isabella also did extensive research with frog toxins, elucidating three-dimensional stereoconfigurations of the toxins and determining their chemical linkages. This allowed for synthesis of these toxins and their subsequent use in the medical community to block nerve impulses, integral to the study of nerve transmissions.

In recognition of her scientific accomplishments, Isabella received many awards, the first being presented by the Society of Women Engineers in 1968. In 1973, she received the Federal Woman’s Award, presented by President Richard Nixon. In 1993, she was awarded the prestigious Bower Award and Prize for Achievement in Science from the Franklin Institute, and in 1995 she received the National Academy of Sciences Award in Chemical Sciences and the National Medal of Science from President Bill Clinton.

Isabella was elected to the National Academy of Sciences, the American Academy of Arts and Sciences, and the American Philosophical Society. She received the Garvan Award of the American Chemical Society, the Hillebrand Award, the WISE Lifetime Achievement Award, the Gregori Aminoff Prize from the Royal Swedish Academy of Sciences, the Bijvoet Medal from the Netherlands, Robert Dexter Conrad Award from the Office of Naval Research, and eight honorary doctorate degrees, among them one from the University of Athens (Greece) and one from Harvard University.

She served as President of the American Crystallographic Association, on several editorial boards of journals and a number of national committees concerned with various aspects of chemistry and crystallography. Other recognitions include her biography in both "Women in Chemistry and Physics" and "The Door and the Dream," a symposium in her honor at an American Chemical Society meeting, and honors at the New York Academy of Sciences. In 2007 she was the recipient of the highly esteemed Merrifield Award from the American Peptide Society.

Upon her retirement from NRL, Isabella and her husband received the Department of the Navy Distinguished Civilian Service Award, the highest honor possible for a civilian employee.

Isabella is survived by her three daughters; Louise Hanson, Jean Dean, and Madeleine Tawney, four grandchildren, and one great-grandchild.

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