Vox Meditantis

Isabella Karle’s story is a damning indictment of how scientific recognition has systematically sidelined women’s contributions. While her husband Jerome received the Nobel Prize in 1985 for developing mathematical methods to determine molecular structures, it was Isabella’s practical brilliance that proved these theories worked in the real world. Her experimental prowess revolutionised crystallography and transformed pharmaceutical development, yet her contributions remain scandalously underacknowledged in the annals of scientific history.

A Brilliant Mind Emerges Against the Odds

Born in Detroit on 2nd December 1921 to Polish immigrants, Isabella Helen Lugoski didn’t speak a word of English until she entered primary school. The daughter of working-class parents in Depression-era America, she faced the dismissive attitudes typical of the time. When a teacher told her that “chemistry was not a proper field for girls,” Isabella didn’t capitulate to this small-minded nonsense. Instead, inspired by Marie Curie’s biography, she surged ahead with remarkable determination.

Her academic brilliance manifested early. By age 23, she had completed not only a bachelor’s degree but also a master’s and doctorate in physical chemistry from the University of Michigan. This accomplishment becomes even more impressive when we consider that teaching assistantships were reserved exclusively for male students – a blatant discrimination that didn’t deter her resolve.

It was at Michigan that fate intervened. Seated alphabetically in a chemistry laboratory (her surname was Lugoski), she found herself next to Jerome Karle, a fellow student. Their shared passion for science blossomed into romance, and they married in 1942. This personal union would evolve into one of science’s most productive partnerships – though one where recognition would be shamefully unequal.

War Work and Professional Beginnings

Like many scientists of their generation, the Karles’ early careers were shaped by World War II. In 1943, Isabella joined the Manhattan Project at the University of Chicago. Her task was profoundly consequential – developing methods to extract plutonium chloride from mixtures containing plutonium oxide. The work was so classified that she and Jerome, who also worked on the project, couldn’t discuss their research with each other.

After the war, Isabella briefly became the first woman faculty member in Michigan’s chemistry department – a milestone that speaks volumes about the gender barriers of the era. In 1946, both Karles joined the US Naval Research Laboratory (NRL) in Washington, DC, beginning an extraordinary 63-year tenure that would reshape molecular science.

Revolutionary Scientific Contributions

The great scientific challenge facing crystallographers was the “phase problem” – determining the phases of X-ray waves scattered by crystals. Without this information, scientists couldn’t accurately determine molecular structures. Jerome Karle and mathematician Herbert Hauptman developed a theoretical approach to solve this problem, but their methods were greeted with widespread scepticism.

This is where Isabella’s genius proved decisive. While the men worked on abstract mathematical theory, Isabella focused on practical application – the essential bridge between theoretical possibility and scientific reality. She developed the “Symbolic Addition Procedure,” a revolutionary method that transformed the theoretical equations into practical laboratory techniques.

Her experimental design was ingenious. Working at a time before computer-controlled diffractometers were available, she borrowed an X-ray tube and constructed her own experimental arrangement. Using the human eye to estimate intensities on photographic film, she demonstrated with remarkable precision that the theoretical approach actually worked.

The consequences were transformative. Isabella’s techniques allowed scientists to determine the structures of complex biological molecules, including peptides, toxins and antibiotics. Her work on frog venoms led to the identification of pumiliotoxins, a previously unknown class of compounds. She determined the structure of valinomycin, an antibiotic that became commercially important. Her studies of antamanide, a substance from death cap mushrooms, identified a potential antitoxin and treatment for oedema.

These weren’t merely academic accomplishments. Isabella’s methods drastically improved drug development by allowing scientists to understand how medications interact with proteins in the human body. Her work enabled researchers to study nerve transmissions and helped chemists synthesize pest repellents. The practical applications touched countless lives.

The Nobel Prize Controversy

Science is meant to reward innovation and impact, but all too often, recognition follows existing patterns of power and privilege. When the 1985 Nobel Prize in Chemistry was awarded to Jerome Karle and Herbert Hauptman “for their outstanding achievements in the development of direct methods for the determination of crystal structures,” Isabella’s crucial contributions were inexplicably ignored.

Let’s be crystal clear: without Isabella Karle’s experimental validation, the mathematical approach would likely have remained an interesting theoretical curiosity. Her husband himself was “devastated that Isabella was not included” in the Nobel recognition, as were many in the crystallography community. As she later recounted, “I told him to forget about it – I had enough awards as it was”.

This magnanimity shouldn’t obscure the fundamental injustice. The Nobel Committee’s failure to recognise her contributions reflects a persistent pattern where women’s scientific work is minimised or attributed to male colleagues. It is precisely this sort of oversight that continues to discourage talented young women from pursuing careers in STEM fields.

Recognition and Legacy

Despite the Nobel oversight, Isabella Karle’s brilliance couldn’t be completely denied. She received the Navy Superior Civilian Service Award (1965), the American Chemical Society Hillebrand Prize (1970), the Women in Science and Engineering Lifetime Achievement Award (1986), and the Swedish Royal Academy of Sciences’ Aminoff Prize (1988). In 1995, President Bill Clinton presented her with the National Medal of Science, America’s highest scientific honour.

Beyond accolades, Isabella’s legacy lives in the thousands of molecular structures solved yearly using methods she pioneered. Her techniques revolutionised crystallography and made it an indispensable tool in modern biochemistry, biophysics and drug discovery. When she and Jerome retired from the Naval Research Laboratory in 2009, they had accumulated a combined 127 years of government service – an extraordinary testament to dedication.

Isabella Karle died on 3rd October 2017 at age 95 from a brain tumour, leaving three daughters and a scientific legacy that deserves far greater recognition.

The Greater Injustice

Isabella Karle’s story illustrates a fundamental question about how we value scientific contribution. Is theoretical work inherently more valuable than experimental validation? Is the mathematician who proposes an equation more important than the scientist who proves it works? And why do these judgements so often break along gender lines?

The uncomfortable truth is that science doesn’t operate in a vacuum. It reflects and often reinforces the prejudices of the societies in which it operates. Women scientists have historically been relegated to supporting roles, their achievements attributed to male colleagues or supervisors. Isabella Karle’s case is not an anomaly but part of a pattern that includes Rosalind Franklin, Jocelyn Bell Burnell, and countless others whose contributions were diminished or overlooked.

The scientific establishment owes these women not just recognition, but a fundamental rethinking of how we attribute credit and celebrate achievement. How many other brilliant minds have we marginalised? How many young women have abandoned scientific careers after seeing their role models denied proper recognition?

Isabella Karle’s legacy should include not just her revolutionary crystallography methods but also a call for greater fairness in scientific acknowledgement. Her story remains a powerful reminder of the brilliant women whose work underpins modern science – often without the recognition they so clearly deserve.

Bob Lynn | © 2025 Vox Meditantis. All rights reserved.