Herbert Hauptman & Jerome Karle: Perfect Symmetries | CUNY Laureates

What is it about crystals that make them so beautiful? Is it their shape? Their color? Or maybe it's the way that the light passes through them. But did you know that the way light moves through a crystal turned out to be the key to developing a whole generation of new medicines? This is a story of two CUNY graduates who became Nobel laureates and the invention of direct methods. For as long as history records, crystals have always mesmerized us. From the youngest child to the most powerful kings and queens, something about these strange little rocks can get just about anyone's attention. Scientists, too, had this share of interest, wanting to know what exactly makes them unique from other products of nature. Early on, it was discovered that crystals have a unique structure. On a microscopic level, the atoms and molecules inside crystals are highly organized, forming what's called a crystal lattice, where multiple identical atomic structures can stack together endlessly, fitting like puzzle pieces. Although some of these patterns were well known, taking precise measurements of the atomic structures within crystals proved difficult. For many years, the beautiful symmetries of crystals remained a mystery to scientists. Jerome Karl and Herbert Hauptmann had some symmetries of their own. Both were born in New York City to Jewish immigrants a year apart. Herbert, born in 1917 to a printer and a sales clerk, was a quiet boy who preferred reading to athletic pursuits. When the other boys were out playing baseball, Herbert was at the local library reading philosophy books by Bertrand Russell and math books by Pierre de Fermont, the subject that would become his life's passion. Across the city in Brooklyn, Jerome was not so foreign to sports. Born in 1918, young Jerome enjoyed all kinds of physical activity, from swimming in the packed waters of Coney Island to ice skating in a frozen neighborhood parking lot. But like Herbert, Jerome also discovered an early fascination with science at the local library, as he pored over books by the physicist and astronomer James Jeans. To me, it was obvious that there was nothing else to do in this world, he once said. Somehow or other, I would manage to do something science related. Fueled by their intellectual pursuits, Herbert and Jerome both progressed rapidly through the public school system, and in 1933, the two enrolled at the City College of New York at the ages of 16 and 15. Although their paths came close, it wasn't yet their time to meet. Unbeknownst to one another, Jerome and both thrived at City College, and the two graduated in 1937. Jerome began studying for his Ph.D. in chemistry at the University of Michigan, where his life was about to move in an exciting new direction. On the first day of his physical chemistry lab, Jerome arrived early and began conducting experiments before class. The student assigned to sit next to him soon appeared, asking how he got in instead of before anybody else. An argument followed, and the two lab mates stopped speaking for several days. After some time, however, chemistry prevailed, and in 1942, two years after their contentious introduction, Jerome Karl and Isabella Lugoski were married. Herbert, meanwhile, continued his love affair with mathematics at Columbia University, where he received his master's degree. When World War II began, he joined the Navy and hastily trained as a weather forecaster and fire marshal in the Pacific Theater. It was a difficult time for Herbert, faced with the destruction of war and nearly losing his life on multiple occasions fighting fires. Herbert grabbed a few precious moments of solace every evening by studying a calculus textbook he had brought from home. Away from the front line, Jerome and Isabella also had their part to play in the war. In 1943, the husband and wife team joined the Manhattan Project, where they worked on isolating and extracting plutonium for the world's first atomic bomb. After the war, Jerome and Isabella both went to work at the Naval Research Laboratory. After some initial work studying electron diffraction in gases, Jerome decided to shift his focus to x-ray crystallography, the study of crystal structures by use of x-rays. It was around this time in 1947 that Herbert Hauptman joined the Naval Research Laboratory. After years of parallel but distinct paths, the two scientists finally met one another formally, and using Jerome's initial research as a starting point, they decided to work on crystal structures. Since the early 20th century, scientists had known that x-rays passing through a crystal would be diffracted by the atoms inside of it, and that the pattern of the diffracted x-rays on the other side of the crystal could partially indicate the position of those atoms. But determining the precise position of atoms in three-dimensional space was not an easy task. To do so required three crucial pieces of information. The direction of the diffracted x-rays, the intensity of the rays, and the phase of the rays, that is, how the rays' waves align with one another. While diffraction patterns could tell scientists the direction and intensity of the x-rays, they could not provide the phase. Without this crucial piece of information, the inner structures of crystals remained a mystery. This dilemma was known as the phase problem, and by the 1950s, it had been considered impossible to solve. Jerome and Herbert speculated that the phase problem might be solved by mathematics. With Jerome's background in chemistry, and Herbert's in math, they realized they were the perfect team for the job. Building off a recently developed equation that could calculate probable values for phases in diffracted rays, the two scientists created their own formula. With these new calculations, researchers could quickly predict possible structures for a crystal. And if the process was repeated enough times, the observation would eventually match one of the predictions, giving a precise image of the crystal's molecular structure. This process came to be known as direct methods, since it only used data collected directly from an experiment and would vastly cut down on the amount of time required to determine a crystal's structure. There was only one problem. The entire process was theoretical, since Jerome and Herbert had no x-ray diffraction equipment of their own. And when they released a paper detailing their methods in 1953, the scientific community remained skeptical that it could actually work. For years, their method was largely ignored. Eventually help came not from afar, but from very near. Jerome's wife and fellow chemistry lover Isabella became fed up with the lack of attention paid to direct methods. In order to prove the utility of Jerome and Herbert's technique, Isabella bought a stack of textbooks, taught herself x-ray crystallography, and eventually procured an x-ray diffraction facility for their lab. Now, with equipment of their own, the three scientists turned theory into practice, and direct methods took the science world by storm. Jerome and Herbert's solution to the crystal structure problem went on to be used for countless molecules, and not just those found underground. By applying direct methods to biomolecules, scientists could see how they worked and reacted to one another, allowing them to study and develop new pharmaceuticals for bacterial infections, heart ailments, and malaria, and to gain a much deeper understanding of the natural world. In 1985, Jerome Karl and Herbert Hartman were awarded the Nobel Prize in Chemistry for their outstanding achievements in the development of direct methods and the determination of crystal structures. Although Jerome always felt that Isabella should have shared in their Nobel Prize, she received her share of accolades as well, including the National Medal of Science in 1995 and eight honorary doctorates. When the award was announced, one Nobel judge stated, it is almost impossible to give an example in the field of chemistry where this method is not being used. So, while the inside of a crystal ball may not hold your future, it just might hold a secret to a few more medicines and cancer treatments. Not such a bad fortune now, is it?