By Luise Z. Moskowitz

She looks like many other mothers and wives: abundant white hair arranged in a neat pageboy, a smart navy blue suit covering a comfortable frame, a silk scarf and Aztec-inspired pin adding some color and flair to an understated ensemble. But then this mother and wife, Isabella Lugoski Karle '41, '44 PhD, steps up to a podium in Philadelphia's venerable Franklin Institute Science Museum and shows the expectant audience another side of herself. For this mother and wife also happens to be a groundbreaker in x-ray crystallography, a researcher whose work has contributed critical information to the disciplines of molecular biology, chemistry, physics, metallurgy, geology, genetics and pharmacology, and one of the 1,000 most cited authorities worldwide in all scientific fields.

She addresses the audience of scientists, teachers and students as the most recent recipient of the Bower Award and Prize for Achievement in Science, an honor bestowed annually by the Franklin Institute on an outstanding contributor to the advancement of science. The award, the riches American prize given in science today, has added a quarter of a million dollars to Isabella Karle's bank balance and a prestigious medal to her already impressive list of official accolades.

In a breathy voice colored with a tinge of an Eastern European accent, Karle takes her listeners on a tour of her career with humor and self-effacing charm. She is the senior scientist for structural chemistry at the Naval Research Laboratory in Washington, DC, and is best known for developing the "symbolic addition method," a way of determining the three-dimensional structure of molecules using both x-ray and electron diffraction. This widely adopted procedure has allowed Karle to reveal the crystal structures of a range of complex organic substances, work that has significantly facilitated studies in chemistry, biology and medicine–all fields that rely on the determination of molecular structure to advance their research.

Karle was not steeped in the sciences as a child. Her parents, a seamstress and a house painter, were Polish immigrants, her father from a small town west of Warsaw, near where Chopin was born. "My father was all self-taught and my mother was very adept at all sorts of things, but neither one knew anything about science. For various reasons they did not have the opportunity for much formal schooling, but they were very anxious that my younger brother and I be educated."

One of the benefits of foreign-born parents was bilingualism. In fact, though born in Detroit, Karle never spoke a word of English until she entered school. "My parents, although thy did speak English, didn't want to speak English at home because they thought that perhaps they didn't speak it well enough, and they worried that I would not learn in well enough from them. I spoke Polish at home, and I spoke Polish with all my relatives, and that worked very well until my parents bought a new house in the suburbs. There, a different language was spoken in every house. I learned a little Flemish so I could play with the girls next door, and the boy on the other side spoke Ukrainian. When we started school every child spoke a different language and only the teacher spoke English. But it didn't take long for everybody to pick up the new tongue."

High School Chemistry
Karle began her lifelong fascination with the natural world at Denby High School in Detroit when an advisor informed her she'd have to take a science course. "Well, what's a science?" was Karle's first reaction. "My advisor told me I had to take either chemistry or biology or physics, so we decided on chemistry and I was lucky to have a really good teacher. Her name was Mrs. Demming and from the very first day in class I decided that it was the most interesting thing I had ever studied."

Karle graduated from high school in the middle of the year at the age of 16. "I went down to what is now Wayne State and there, by some administrative mix-up, I was put into a chemistry class that was intended for chemical engineers. I was the only girl and there were something like 99 boys. Well, that didn't faze me a bit! I did very well academically in that class and the professor took and interest in me–his name was Joseph Jasper–and before the semester was over I was awarded a four-year scholarship to the University of Michigan. When I told him I was leaving, he said, 'The University of Michigan is a good school, and you'll like it very much, and you will of course go on to graduate school.' To which I replied, 'What's that?'"

She indeed did go on to graduate school, completing her BS, MS, and PhD degrees in just seven years, and earning her place as the first American woman to receive a doctorate in physical chemistry from Michigan, and the first woman to teach chemistry at the University.

It was in her senior year that Isabella also learned a thing or two about human chemistry when she found herself seated in class next to a graduate student, Jerome Karle, who was switching from biology to chemistry, and therefore had to take some undergraduate courses to continue in that field. (Jerome Karle went on to share the 1985 Nobel Prize in Chemistry.)

An Alphabetic Romance
"His last name started with K, mine with L, and we were assigned adjacent laboratory benches in physical chemistry," Isabella explains. "Well, it was a competition to begin with because I was always accustomed to being at the head of the class and here was somebody who was maybe better than I was! But it didn't take too long before we realized that we had similar aims."

Several years later, the Drs. Karle had wed and she received her PhD a year after his. Stimulated by a physical chemistry course taught by Lawrence O. Brockway while at Michigan, the Karles had chosen to study electron diffraction by gaseous molecules. It was 1944, and the 22-year-old chemist and her young husband took their knowledge to the Manhattan Project in Chicago. After the end of WWII, the couple began to search for permanent positions, but found that nepotism rules at most academic centers barred the hiring of spouses. Then they discovered the Naval Research Lab, which offered both of them labs and funding to research gas electron diffraction. Dr. Karle's relationship with the lab has been a fruitful one, allowing her the freedom and flexibility to take her research in a variety of directions, including her current interest in ion transfer via peptides.

A woman known for her mentoring skills, Karle is quick to provide a layman's explanation of her work. "X-ray crystallography allows us to see what a molecule looks like, to see which atoms are attached to which, to see the shape of a molecule, whether it repels water or attracts oily things. These physical properties are very important, really vital to know. One of the big uses for crystallography now, for example, is in drug design. Imagine there's a receptor, a big protein that attracts various things. That receptor may or may not do something good, and so the idea is, if you can block it by pushing a small molecule into it, you can stop its action-sort of a lock-and-key concept that has been around for a long time. Supposing you already know that there are some substances that do this, but they have terrible side effects. To try to alleviate some of these side effects, people want to design or discover a molecule with a slightly different shape or grouping, which will still be attracted to the receptor by fitting in like a Lego set. X-ray-diffraction techniques have given drug companies a library of molecular shapes to help solve these problems."

Karle's experience as a Michigan undergraduate did a great deal to maintain her commitment to scholarship. "I lived in a place called Alumni House, which was one of the grand old houses on the intersection of Hill and Washtenaw and another street right off campus. It's all paved over now. It was a cooperative dorm with only 16 girls living there. Amongst them were students who were the better students, mostly on scholarship, those that were awarded places to live as long as they were willing to cook and houseclean and so forth!"

Karle found this living situation very supportive, and useful for a fledgling female in a predominantly male field. "My housemates there were musicians and English majors, but also the first girl engineer, Tenho Sihvonen, and she and I had a lot in common. I also had a lot in common with my roommates who were not in scientific fields, but both the variety and the shared interests were very good. I think the current plant o offer female undergraduates in the sciences a shared dormitory space is a good one. Such an atmosphere would be useful and encouraging."

Isabella and Jerome's children clearly found a "useful and encouraging" atmosphere at home. Of their three daughters, Louise '67 MS and Jean '71 are chemists and Madeleine is a geologist.

In the Franklin Institute's auditorium with guests who are here to applaud her, Karle stops on her way to a cup of coffee to answer a question here, to take a young girl's chin in her hand there, teaching and explaining and encouraging at every pause. Her vibrant aspect completely belies her septuagenarian status, a fact which can be at least partially attributed to her lifelong work.

"Work that is really a lifelong career does keep you young," she says. "It is very meaningful. New, interesting problems keep coming up all the time, and because new techniques develop too, you can do more and more difficult things, more complicated things that weren't possible 20 years ago. If I wanted to, I could have retired 17 years ago. But I've been lucky enough to spend my life doing what I've always wanted, in a field that keeps unfolding all the time, and I intend to keep looking for answers, and new questions, for as long as I can."

Luise Z. Moskowitz is a Philadelphia writer and a publicity and external affairs coordinator at the University of Pennsylvania.