Isabella L. Karle, whose experiments elucidating the shapes of molecules contributed crucially to her husband’s Nobel Prize in Chemistry, died on Oct. 3 in Arlington, Va. She was 95.
The cause was a brain tumor, her daughter Louise Karle Hanson said.
Dr. Karle was an expert in bouncing X-rays off crystals to deduce the structure of molecules by observing patterns in the deflected rays. When she and her husband, Jerome Karle, joined the Naval Research Laboratory in Washington in the mid-1940s, the technique was limited and arduous. Scientists did not know how to apply it to most molecules, like large biological ones.
In the 1950s, Jerome Karle, together with Herbert A. Hauptman, a mathematician, developed a technique that could be used for more complex, three-dimensional structures. But they had trouble convincing anyone that it would work.
“My father never actually did a crystal structure in his life,” Ms. Hanson said.
It was her mother who showed that the technique did work.
Isabella Karle had taught herself X-ray crystallography and came up with practical applications of her husband’s theory, which she used to puzzle out the structure of molecules in substances like drugs, steroids and frog toxins.
Bhakta B. Rath, a former associate director of the naval laboratory, said, “Isabella Karle took the task of deciphering the theory to provide not only a solution but also to show that it could be used to solve very complex molecules, such as proteins.”
Other scientists took notice in the mid-1960s.
With a clearer picture of the structure of biological molecules, drug researchers now have a much better idea of the chemistry going on inside the body and how to formulate drugs to treat illnesses.
“After I found some structures that no one could have dreamt of solving before, it started to get a lot of attention,” Dr. Karle told The New York Times in 2013.
When Jerome Karle and Dr. Hauptman were awarded the Nobel for their work in 1985, Jerome Karle was deeply disappointed that his wife was not also honored. “He wanted to not accept it,” Ms. Hanson said, “and she told him, ‘Go ahead, that’s silly, you should accept it.’”
Isabella Helen Lugoski was born in Detroit on Dec. 2, 1921, the daughter of Polish immigrants. Her father, Zygmunt Lugoski, worked for the city’s transportation system. Her mother, the former Elizabeth Graczyk, ran a restaurant — eventually with Isabella’s help.
“My mother realized fairly early that I like numbers,” Dr. Karle recalled in an interview in 2015. “I soon became the accountant, so to speak. Fresh meat was delivered every day, and the butcher left the bill that had to be paid once a week. So once a week I added up all the numbers of the money that was owed him.”
She skipped a couple of grades in elementary school. Later, she learned she would need to take a science class in high school to attend a university. By whim, she said, she chose chemistry, and the teacher, a woman, sparked her passion for the subject. (Her father was initially disappointed. He had hoped she would be a lawyer, as he had wanted to be.)
She attended Wayne University (now Wayne State University) in Detroit for a semester before obtaining a four-year scholarship to the University of Michigan, where she received her bachelor’s, master’s and doctoral degrees, all before she turned 23.
She met her husband while an undergraduate: The spaces in the physical chemistry laboratory were assigned in alphabetical order, so Karle was seated next to Lugoski.
“I walked into the physical chemistry laboratory and there’s a young man in the desk next to mine with his apparatus all set up running his experiment,” Dr. Karle said. “I don’t think I was very polite about it. I asked him how did he get in here early and have everything all set up. He didn’t like that. So we didn’t talk to each other for a while.”
Eventually, they did talk again. They married in 1942.
Both worked in Chicago on the Manhattan Project, the government effort during World War II to develop an atomic bomb. Isabella Karle developed processes to synthesize plutonium chloride out of lumps of impure plutonium oxide.
The Karles moved to the Naval Research Laboratory after the war and stayed there until both retired on the same day in July 2009.
Jerome Karle died in 2013. In addition to her daughter Louise, Dr. Karle is survived by two other daughters, Jean Karle Dean and Madeleine Karle Tawney; four grandchildren; and a great-granddaughter.
Isabella Karle published more than 350 papers. She was a member of the National Academy of Sciences, the American Academy of Arts and Sciences and the American Philosophical Society. In 1993, the Franklin Institute presented her with the Bower Award and Prize for Achievement in Science, and in 1995 she received the National Medal of Science from President Bill Clinton in a White House ceremony.
Dr. Rath, who supervised Dr. Karle’s work in Washington, said that her renown within the scientific community was so wide that when scientists from around the world visited the Naval Research Laboratory, they would very often make one request. “They all wanted to see Isabella,” he said.
