Isabella L. Karle, who was once told that chemistry was not a “proper field for girls” but went on to help her husband, Nobel laureate Jerome Karle, devised a pathbreaking method for determining molecular structure, died Oct. 3 at a hospice center in Arlington, Virginia. She was 95.

The cause was a brain tumor, said her daughter Louise Karle Hanson. Dr. Karle, who along with her husband spent more than six decades at the Naval Research Laboratory in Southwest Washington, resided in the Lake Barcroft area of Fairfax County.

Jerome Karle shared the 1985 Nobel Prize in chemistry with the mathematician Herbert Hauptman, also a colleague at the Naval Research Laboratory, honoring “their outstanding achievements in the development of direct methods for the determination of crystal structures.” Isabella Karle, a crystallographer, received the National Medal of Science in 1995, bestowed by President Bill Clinton, among other major honors in her field.

The Karles worked side by side at the Laboratory for the Structure of Matter, accumulating a combined 127 years of federal service. “I do the physical applications, he works with the theoretical,” she once told The Washington Post. “It makes a good team. Science requires both types.”

Before the prize-winning work that the Karles pursued with Hauptman in the 1950s, scientists could discern molecular structure only through the time-consuming and painstaking process of X-ray crystallography, in which X-rays were reflected off a molecule and their patterns then examined.

The Karles’ “direct method” permitted scientists to use mathematics to discover molecular structure via a less circuitous route, saving time and gaining precision.

For many years, the method languished, unnoticed by other scientists. “It was Isabella’s work that drew attention to its usefulness,” according to a tribute to the couple by the Naval Research Laboratory, which credited her with preparing the way for “the analysis and publication of the molecular structures of many thousands of complicated molecules annually.”

Among those molecules were toxins and antitoxins; drugs to treat bacterial infections, malaria and heart ailments; anticarcinogens; and explosives.

“It is almost impossible to give an example in the field of chemistry where this method is not being used,” a judge for the Nobel Prize remarked when Jerome Karle’s award was announced.

Isabella Helen Lugoski was born in Detroit on Dec. 2, 1921. Her father painted the numbers and letters on city trolley cars. Her mother ran a restaurant and sewed automobile upholstery for Detroit carmakers.

In her youth, the future Karle drew inspiration, her daughter said, from a female high school chemistry teacher and from a biography of Marie Curie, the Nobel Prize-winning physicist who, like Karle’s parents, was born in what is now Poland.

Karle’s career required her to overcome the discouragement of another teacher, she once told an interviewer, Elga Wasserman; this teacher advised her on the impropriety of chemistry as a topic of study for young women.

She went on to study chemistry at the University of Michigan, receiving a bachelor’s degree in 1941, a master’s degree in 1942 and a Ph.D. in 1944. She met her husband in a physical-chemistry lab where alphabetical seating dictated that the two of them — Karle, Lugoski — would sit next to one another.

After working on the Manhattan Project during World War II, Karle joined the Naval Research Laboratory in 1946, two years after her husband was hired there. Early in her career, she studied molecules in the vapor state. Both Karles retired in 2009.

Isabella Karle’s honors included the 1988 Gregori Aminoff Prize from the Royal Swedish Academy of Sciences, the 1993 Bower Award and Prize for Achievement in Science (worth $250,000), and the Navy Distinguished Civilian Service Award. She was a member of the National Academy of Sciences.

Her husband died in 2013 after 71 years of marriage. Survivors include their three daughters, who are all scientists, Louise Karle Hanson of Ridge, New York, Jean Karle Dean of Vienna, Virginia, and Madeleine Karle Tawney of Lake Barcroft; four grandchildren; and a great-granddaughter.

When Jerome Karle received the Nobel, he said he hoped the honor would one day be extended also to Isabella.

“I can’t think of anyone,” he told The Associated Press, “who is more qualified than my wife.”