Isabella Helen Lugoski Karle, widely acknowledged as one of the greatest crystallographers of her generation, died on 3 October 2017 in Arlington, Virginia.
Born in Detroit, Michigan, on 2 December 1921, Isabella received her bachelor’s, master’s, and PhD from the University of Michigan before she turned 23. While an undergraduate, she met Jerome Karle, who sat next to her because the school customarily assigned lab positions alphabetically. They were married while working as graduate students under Lawrence Brockway, an early student of Linus Pauling. Their work was in the field of electron diffraction, which provided a foundation to their entering the field of x-ray diffraction a few years later.
After completing her PhD, Isabella joined the Manhattan Project at the University of Chicago. She was tasked with investigating the chloride chemistry of plutonium. At the end of World War II, she became the first woman professor of chemistry at the University of Michigan. About a year later, she and Jerome transferred to the US Naval Research Laboratory in Washington, DC, where they made their greatest discoveries.
Isabella did the experimental work that proved beyond doubt that the mathematical solution explicated by Herbert Hauptman and Jerome for the x-ray crystallographic phase problem was in fact correct. The only contention with the mathematics was that almost no one in the field of crystallography thought Jerome and Hauptman could actually solve the phase problem as they claimed. And that disbelief prevailed for decades. But Isabella’s experimental work proved the pair right. The two men were awarded the 1985 Nobel Prize in Chemistry. Isabella did not share in the Nobel, although she should have.
To appreciate the enormity of Isabella’s accomplishment, one must remember that at the outset, in the 1950s, the automatic computer-controlled diffractometers so common today had not yet been invented. She had to borrow an x-ray tube and design an experimental arrangement that would allow the scattering and collection of x rays. She read a book by Martin Buerger of MIT to help her design and analyze the x-ray experiment because her experience with x-ray diffraction was new. Two especially amazing things were that she recorded the x-ray scattering on photographic film and that she was able to judge relative intensities using her eyes as a detector.
Isabella was able to solve structures no one else could. At first, even that was not sufficient to overcome disbelief in the mathematical model. But as she solved more and more impressive structures, crystallographers slowly came to understand that the new mathematical framework informing the experimental structures was correct. It was Isabella’s experimental work that legitimized and proved the solution that made possible the Nobel Prize for Jerome and Hauptman.
What we find so impressive about Isabella is that being overlooked for the Nobel did not hinder the progress of her science. She continuously solved important structures of remarkable variety. The structures included peptides, toxins from colorful frogs, and drugs to treat infections, heart problems, and malaria. She also looked at carcinogens and explosives, to name a few of the endless stream of structural problems that coursed through her laboratory.
Isabella published more than 300 scientific papers and won accolades from every direction for her work. Among the many honors she received were the US’s highest scientific award, the National Medal of Science, in 1995 and the 1988 Gregori Aminoff Prize, considered to be the preeminent award granted in the field of crystallography, from the Royal Swedish Academy of Sciences. We personally are indebted to her for helping us with our development (together with Jerome) of the quantum kernel energy method. She provided the first 15 peptide structures against which the theory was tested.
While Isabella was working at the highest levels of US science, she and Jerome raised three daughters; all went into scientific work. At the Naval Research Laboratory, Isabella worked with a group of young people, many of them aspiring women scientists. She did not much talk about being a woman scientist; she was a scientist who was a woman.
History will remember Isabella for the work she did solving structures and proving experimentally the value of mathematical direct methods to deliver crystal structures. Those who knew her will also remember her as a humble, brilliant, and kind person.
