Isabella Karle was born of Polish immigrants in Detroit, Michigan in 1921. Her father was a Detroit city employee who painted the intricate hand-lettering on buses and streetcars. Her mother, who was self-taught, for a time operated a restaurant in an industrial area. Because he could speak Russian and Polish in addition to English, her father was an interpreter and censor for the newspaper in the town where he was stationed during World War 1. His stories about his experiences convinced Karle that there was an advantage to being able to speak more than one language. She is fluent in Polish and English, and also speaks some French and German. During the Great Depression the Detroit transit system managed to keep its employees working two or three days a week, so that salaries, if reduced, were still paid. When her family was able to buy a house in the suburbs, Karle initially attended a primitive schoolhouse where none of the children in the first grade could speak English. Eventually a new school, with better facilities, was built, and Karle continued her education there. Most of Karle's family had come to America from Poland before the outbreak of World War 2, except for one grandmother whom Karle never met. The war years were difficult times for the Polish people, and Karle had younger cousins who had to work in German factories. Karle did not have opportunity to visit Poland until after the war, when she traveled there to deliver lectures at the universities.

Isabella Karle remembers that news of what was happening in Europe was heard on radio and reported in the newspapers. Her father's ability to speak foreign languages gave him a better insight into what was happening, but Karle found it confusing. The Karles were concerned about relatives back in Poland, and it was impossible to get them out. Karle observed that because Poland is on the crossroads between Russia and Germany, there have been many wars conducted on Polish soil, even though Poland was not in the fight. There was always animosity between the Poles and Germans and Russians. In 1939, her parents set off driving with Karle and her brother to New York City to see the World's Fair. Two days before they arrived at the grand exposition, Germany invaded Poland and spoiled their vacation. Karle graduated high school at the age of 16. As there were no jobs available, she went straight into Wayne County Community College in Detroit. After one semester there, she took an exam, and was awarded a four-year scholarship at the University of Michigan where she majored in chemistry. There she met her husband. She was already married and a third year graduate student when Pearl Harbor was attacked. Neither she nor anyone she knew expected the tragedy that took so many lives.

Isabella Karle met her husband at the University of Michigan in a physical chemistry class. His undergraduate degree was in biology, and he was working on his doctorate in chemistry. The war had started and the draft board called up most young men over the age of 18, but allowed students of medicine and chemistry to defer enlistment until they got their diplomas. When her husband completed his studies, he thought he would get a draft notice, but instead got an offer letter from the University of Chicago. [Annotator's Note: Karle pauses, proposing to show Interviewer the letter.] It implied that instead of being a foot soldier, he would be doing something interesting and not wasting his time. Karle was happy that he would not be going too far away. Although he couldn't tell her about the job, he said it was interesting, something she could not imagine. They also told him that Karle could have a job there when she completed her doctoral studies. So, when she achieved her PhD, she joined him. She thought the University of Chicago was a beautiful campus, except for the temporary building in which they worked, although it was suitable for their purposes. She began her work with the assignment to wander around for a week to see if she could find out what was going on there, but she couldn't learn anything about the project. Karle found that peculiar, and figured they were testing their security systems. She was very happy to be reunited with her husband.

Isabella Karle's research involved isolating a purer form of plutonium. The laboratory was getting the oxide from Oak Ridge, Tennessee, and it was already about 95 percent pure, but still not sufficient for their purposes. Karle had to rework the material into a very pure crystalline form of chloride. It was a daunting task, especially since she had never studied heavy metals. Karle made several trips by train to a technical library in downtown Chicago to educate herself on how to work with this newly created substance. When she recognized she needed to work at about 900 degrees Centigrade, she had to build an apparatus, and use special silica glass rods, tubes, and stopcocks that would be stable to about 1,000 degrees. She wore very dark purple eyeglasses during her experiments. Because of security concerns, Karle could not rely on or share information with any other chemists. She and her husband did not discuss their respective projects. She developed a successful vacuum system, which was proven by Dr. William Zachariasen, who was then on the faculty of the university.

Isabella Karle said that certain measures were taken to insure against radiation sickness, including the daily consumption of a large calcium tablet. She also underwent periodic fingerprinting, as it was believed that overexposure to radioactivity could cause changes in identifiable ridges. Additionally, employees of the lab wore radiation meters on their wrists. Karle described an incident where an outside service man had appropriated a used lab tube and installed it in a Coca Cola machine. When she passed the machine, her device began ringing, causing general alarm and an investigation. Thankfully, the blunder was discovered before anyone had taken a drink. Karl said that her three healthy daughters proved that she suffered no ill effects from her research, nor does she know of anyone else who was adversely affected. Karle was ultimately aware of what she and the four others in her lab were creating. There was talk among the scientists, and they knew what other named scientists were working toward. They were under definite time pressure on this high government priority. They knew they had to complete their research before the Germans could complete theirs.

Isabella Karle worked at the University of Chicago labs during the year 1942. She and her husband ended their tenure there at the same time, and were both hired by the University of Michigan, where she had the distinction of becoming the first female chemistry professor. Karle did not particularly want to lecture; she preferred research. So it was a happy event when both she and her husband were offered jobs at the U.S. Naval research facility. The couple worked toward a better understanding of how atoms are arranged. Karle's husband also helped decipher a seemingly insoluble math problem, for which he was awarded the Nobel Prize. [Annotator's Note: Jerome Karle (1918 – 2013), jointly with Herbert A. Hauptman, was awarded the Nobel Prize in Chemistry in 1985.] She was awarded the President's Medal for advanced research using her husband's mathematical calculations.

Isabella Karle heard on the radio that the atom bomb had been dropped. At first she was amazed that it actually worked. The news of its horrible effects, she felt, was less of a shock than hearing about the disaster at Pearl Harbor. She noted that it wasn't the United States that started the war. She does not regret her contribution to the bombs' development, because she knew so many more soldiers would have been killed if the planned invasion of Japan had actually taken place. She thinks it regrettable that the Japanese did not respond to messages sent to them after the first bomb was dropped, and that surrender only happened after the second bomb. Karle doesn't think her family fully understood the extent to which she and her husband had been involved. She is pleased that their efforts proved useful. She later met a number of soldiers who were eternally grateful that they didn't have to engage in a final battle with Japan. Karle feels that World War 2 taught her that she could successfully solve intricate problems in an unfamiliar environment. She doesn't like the idea that it is possible to recreate the bomb in so many places in the world today. In World War 2, a lot of people put their life forward to protect the United States, Karle said, and we proved that our country could take care of itself. She believes it is important to teach future generations what happened in order to avoid a repeat of history.