A musical family in Brooklyn
Jerome Karle was born Jerome Karfunkle in New York City on June 18, 1918, to Louis Karfunkle and Sadie Helen Kun, immigrants from Eastern Europe, in a Jewish family with a strong interest in the arts. His father ran a business on Coney Island. His mother was an excellent pianist and organist who hoped her son would become a professional pianist, and as a boy he competed in New York’s Music Week piano competitions. An uncle by marriage, Ivan Olinsky, taught for many years at the Art Students League. Jerome had some success at the keyboard, but he found early that he had no taste for public performance and that science attracted him far more.
He grew up near the ocean, swimming, skating on a parking lot the fire department flooded each winter, and playing single-wall handball. He went to Abraham Lincoln High School in Brooklyn, which also produced the Nobel laureates Arthur Kornberg and Paul Berg. The public schools let advanced students move at their own pace, and Karle finished high school at fifteen, an age gap he remembered most vividly from dancing practice with classmates who were seventeen and eighteen.
Free college and a first contribution
In 1933 Karle entered the City College of New York, which charged no tuition; the only fee was one dollar a year for a library card. He spent three hours a day on the subway, which ended his piano practice, and studied mathematics, physics, chemistry and biology. Among his classmates was a mathematics student named Herbert Hauptman. Karle graduated in 1937 and earned a master’s degree in biology at Harvard in 1938.
To save money for further study he took a job with the New York State Department of Health in Albany. Fluoridation of drinking water to prevent tooth decay was just getting under way, and Karle developed a procedure for measuring the amount of fluorine in water supplies that became a standard method. He called it his first modest contribution to science.
Isabella
In 1940 Karle entered the chemistry department of the University of Michigan. On his first day in physical chemistry class, students were seated alphabetically, and Karle found himself at the desk next to Isabella Lugoski. They married in 1942 and both earned doctorates under Lawrence Brockway, a specialist in determining the structure of gas molecules by electron diffraction. Karle finished his research in 1943, though his degree was awarded in 1944.
During the Second World War he worked on plutonium chemistry for the Manhattan Project at the University of Chicago, and Isabella soon joined him. In 1944 they returned to Michigan, where he worked on a Navy project on the structure of lubricant films, and in 1946 both joined the U.S. Naval Research Laboratory in Washington, D.C., where they would spend the rest of their working lives. Isabella became a great crystallographer in her own right and was elected to the National Academy of Sciences two years after him.
The phase problem
X-ray crystallography is the main way scientists see the arrangement of atoms in a molecule. A beam of X-rays shone through a crystal is scattered into a pattern of spots. The brightness of each spot can be measured, but each scattered wave also has a phase, its position in the wave’s cycle, which is lost in the measurement. Without the phases, the pattern cannot be turned back into a picture of the atoms. For decades crystallographers relied on laborious tricks, such as attaching heavy atoms to their molecules, or simply guessed. Solving a single structure could take months or years, and many scientists believed the phases could never be recovered from the intensities alone.
Around 1947 Herbert Hauptman joined Karle at the Naval Research Laboratory, and the chemist and the mathematician set out to prove otherwise. Starting from the physical fact that the density of electrons in a crystal can never be negative, they derived mathematical relationships among the measured intensities and used probability theory to estimate the missing phases directly from the data. They set out the main ideas in a 1953 monograph, Solution of the Phase Problem I: The Centrosymmetric Crystal. These were the direct methods of crystal structure analysis.
From disbelief to routine
The reception was cool. Many crystallographers doubted that the phase problem could be solved this way, and in his Nobel autobiography Karle wrote that in the early 1950s a large number of fellow scientists did not believe a word they said. He credited the Naval Research Laboratory with standing by them.
What changed minds was practical success, and much of it came from Isabella Karle. In the late 1950s she established an X-ray diffraction laboratory in their group, and in the 1960s, largely through her efforts, the team developed the symbolic addition procedure, a step-by-step way of applying the theory to real crystals of all kinds. The first application was published in 1963, and in 1964 the group published the first structure of an essentially equal-atom noncentrosymmetric crystal, the hardest kind, solved by direct phase determination. By the end of the decade laboratories around the world were adopting direct methods, and with growing computer power they became the standard way to solve the structures of small and medium-sized molecules.
Why it matters for medicine
Knowing the exact three-dimensional shape of a molecule is the starting point for understanding how it works and for designing new ones. Direct methods allowed chemists to determine structures that once took years in days or hours, and they helped reveal the shapes of vitamins, hormones, antibiotics and countless newly made compounds. Pharmaceutical chemists use crystal structures to confirm what they have made and to understand how a drug fits its target, and the technique has played a major role in the development of new medicines and materials.
Karle continued to extend the field. In 1980 he published an exact algebraic theory for multiple-wavelength anomalous dispersion, a method for finding phases by measuring a crystal at several X-ray wavelengths. Late in his career he also helped originate quantum crystallography, which uses X-ray data to describe the quantum state of a crystal’s electrons, and his last paper, published after he retired, applied quantum mechanics to predict the properties of high-energy molecules. Early at the laboratory he had also designed an electron diffraction instrument that was a considerable advance on existing machines. His colleague Wayne Hendrickson and others applied the anomalous dispersion theory, using synchrotron radiation, to large biological molecules, and it became a widely used technique for solving the structures of proteins, including many targets of drug research.
Jewish roots and public service
Karle grew up in a Jewish family of Eastern European immigrant origin in Brooklyn and Coney Island and rose through New York’s free public schools and tuition-free City College, the path that carried so many children of Jewish immigrants into science in the twentieth century. He later changed his surname from Karfunkle to Karle. He did not write publicly about religious practice.
He spent his entire career in government service. Asked why he never went into industry, he said that it was quite possible to do good research for the Navy and the Department of Defense and at the same time do good science. In his later years he spoke of the need for societies to give every child an education open to all and of the urgency of protecting the environment.
Nobel Prize and later life
On October 16, 1985, Karle learned that he had won the Nobel Prize in Chemistry, shared with Hauptman, while on a Pan Am flight from London to Washington; the captain announced to the passengers that America’s newest Nobel laureate was on board. Karle felt strongly that Isabella’s experimental work deserved a share of the prize. He served as president of the American Crystallographic Association in 1972 and of the International Union of Crystallography from 1981 to 1984, and had been elected to the National Academy of Sciences in 1976.
In 1968 he founded the laboratory’s Laboratory for the Structure of Matter and led it as chief scientist. Jerome and Isabella Karle retired from the Naval Research Laboratory together in 2009, after a combined 127 years of federal service, and the Secretary of the Navy presented both with the Navy’s highest civilian award. They had three daughters, Louise, a theoretical chemist, Jean, an organic chemist, and Madeleine, a museum specialist trained in geology. Jerome Karle died of liver cancer in Annandale, Virginia, on June 6, 2013, at the age of 94, and was buried at Columbia Gardens Cemetery in Arlington. Isabella, his partner in science for seven decades, died in 2017.
Legacy
Colleagues remembered Karle as modest, kind and steady, a man who made others feel equal in conversation; his coauthors wrote that no characteristic was more manifest than his humility. One said that he turned chemical crystallographers into crystallographic chemists, freeing them to concentrate on the molecules rather than on the mathematics of finding them.
Today direct methods run inside the software of crystallography laboratories everywhere, usually without users giving them a thought. Each time a chemist confirms the structure of a new drug candidate in hours rather than months, the work of Jerome Karle, Herbert Hauptman and Isabella Karle is quietly at work.
Sources & further reading
Jerome Karle, Biographical, NobelPrize.org · Jerome Karle obituary, Physics Today · Jerome Karle obituary, American Crystallographic Association · Jerome Karle, Wikipedia · Researched from the sources above and checked against them. Spotted an error? Tell us.
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