Herbert Hauptman

In 1985, American mathematician Herbert Hauptman (born 1917) won the Nobel Prize in Chemistry, becoming the first non-chemist to win in that category. He shared the honor with a colleague, Jerome Karle, both of whom were honored for their towering discoveries that made mapping the chemical structures of small molecules easy and efficient. Over the years, scientists have used their method to develop new drugs that combat diseases such as cancer, high blood pressure, and heart disease. Shortly after Hauptman won the prize, the Buffalo News reported that Hauptman "undoubtedly saved more lives … than anyone else in recent history," according to the Hauptman-Woodward Medical Research Institute Web site.

Born on February 14, 1917, Hauptman grew up in the Bronx borough of New York City and attended Townsend Harris High School. He was the oldest of three boys born to Israel and Leah (Rosenfeld) Hauptman. Hauptman credits his parents for playing an integral role in his development as a scientist because they gave him the choice to study whatever he wanted. Early on, science caught his eye, and he devoured every scientific book he could find. "My interest in most areas of science and mathematics began at an early age, as soon as I had learned to read, and continues to this day," Hauptman said in his 1985 Nobel acceptance speech, posted on the Nobel e-Museum Web site.

Hauptman attended City College of New York during a time when it was common for qualified students to obtain a free education. He later noted that without such financial help, he never would have been able to receive the higher education necessary for his discoveries later on. Hauptman graduated from City College in 1937 with a bachelor of science degree in mathematics. He continued his studies, earning a master of arts degree in mathematics from Columbia University in 1939. On November 10, 1940, he married Edith Citrynell, a teacher, and they settled in the Washington, D.C., area. That same year, Hauptman began working in Washington as a U.S. Census Bureau statistician. In 1942, with World War II in full swing, and Hauptman found employment as a radar instructor for the U.S. Air Force.

Revealed Breakthrough Research

Following the end of the war in 1945, Hauptman decided to continue his graduate studies, aiming for a career in basic scientific research. By 1947 he was working at the Naval Research Laboratory (NRL) in Washington, D.C., where he teamed up with Jerome Karle, a fellow New Yorker who was also a 1937 graduate of the City College of New York. At the same time, Hauptman enrolled at the University of Maryland and began studies toward his doctorate.

Hauptman's and Karle's backgrounds complemented each other: Hauptman was a mathematician, whereas Karle was an expert in chemistry. Over the next several years the two began the preliminary studies that would ultimately lead to their breakthrough research and which also became a part of Hauptman's doctoral dissertation. Around 1950 the two began research into a technique whereby they could decode the structural makeup of crystals, a dilemma that had daunted scientists for decades.

Since about 1912, scientists had known that when an X-ray beam strikes a substance that has been crystallized, the rays diffract—or scatter—producing fuzzy spots of variable intensities that can be recorded on film. Scientists, however, wanted to be able to work backward, using the diffraction data to determine the atomic arrangement of the substance. The problem was that scientists were basically looking at a molecule's "shadow" and from that attempting to reconstruct the three-dimensional object. Writing for the Buffalo News, Henry L. Davis described the task this way: "Imagine yourself on a sandy shoreline as waves move past wooden posts in the water. Depending on the position of the posts, some waves will break on the beach stronger than others. Now, work backwards, and based on the intensity of the waves hitting the shore, figure out the location of the posts in the water."

X-rays, like water, travel in waves, and for years scientists had been stymied trying to work backward looking at the pattern on the film to figure out the position of the atoms from a substance that had been crystallized. Hauptman and Karle took a mathematical approach to the problem. Over several years, they developed a mathematical formula to figure out the location of the atoms in the crystal. This procedure, known as "direct methods" was not understood initially. Decades passed before anyone realized the significance of their work, but by the mid-1980s Hauptman and Karle's discoveries were being used by crystallographers around the world. With the duo's mathematical formula and the correct computer program, crystallographers were able to determine the structures of thousands of molecules for the first time. This new mapping information assisted in the development of many new drugs.

Interestingly, Hauptman's mathematical insights at first had gone virtually unnoticed. By 1954 he had studied the problem for five years and had presented 13 scientific papers on molecular structure determination, yet hardly anyone supported his ideas. "There was a lot of resistance to it, mostly because it wasn't understood," Hauptman explained to New York Times writer John Noble Wilford. "It was highly mathematical and crystallographers didn't have the training to understand it. It was not generally accepted until the middle 1960's or so when more and more people began to use it."

Balanced Family, Research, Doctoral
Work

While working on his doctorate and researching crystallography, Hauptman balanced studies with parenthood. One daughter, Barbara, was born in 1947, and younger daughter Carol followed in 1950. Hauptman recalled his graduate student years as frantic, as he commuted between campus, his Bethesda, Maryland, home, and the lab where he worked. However, he made it a priority to spend time at home in the evenings to help his wife take care of the children before going back to his studies until the pre-dawn hours.

Hauptman's daughter, now Carol Fullerton, was five years old when her father received his doctorate in 1955. "He would do his work on the dining room table," she told the Washington Post's Barbara Vobejda. Once, she decided to play a joke on him by adding a minus sign to one of his formulas. "But right away, he knew," she added

After receiving his graduate degree, Hauptman continued part-time as a professor at the University of Maryland and later joined the biophysics faculty at the State University of New York at Buffalo. By 1965 he was head of the NRL's mathematical physics branch and began a collaboration on steroids with the Medical Foundation of Buffalo, which eventually lured him to their offices. In 1970, after 20 years at the NRL, he left to join the crystallographic group at the Medical Foundation of Buffalo. He became research director of the foundation in 1972. In 1979 and 1980 he was elected president of the Association of Independent Research Institutes.

Awarded Nobel Prize

Hauptman jumped into the limelight in 1985 when the Royal Swedish Academy of Sciences chose to recognize his long-ago work from the 1950s and award him the Nobel Prize for chemistry. He shared the honor with Karle, and the two split the $225,000 award. Karle explained the lag time this way to Science News writer Julie Ann Miller: "Initially it was hard for people to believe that the mathematics would, even in principle, do what it does." William Duax, a colleague of Hauptman's, told the New York Times that before the Hauptman-Karle method, it took two years to map out the structure of a simple 15-atom antibiotic molecule. Using Hauptman and Karle's methods, it took only two days to determine the three-dimensional structure of a 50-atom molecule. Over the years, the Hauptman-Karle method has been used to analyze hormones, vitamins, antibiotics, potential anti-cancer drugs, and plant-growth promoters. The U.S. Department of Defense was also interested in the methods as a way to investigate the structure of certain propellants, which could be used for rockets.

In 1986 Hauptman was named president of the Medical Foundation of Buffalo and in 1994 the foundation's name was changed to the Hauptman-Woodward Medical Research Institute (HWI) to honor both Hauptman and foundation benefactor Helen Woodward Rivas. HWI continues as an independent, not-for-profit biomedical research facility located in Buffalo, where one of its missions is to understand diseases at the molecular level.

Discoveries at HWI led to better insulin and a new antibiotic to fight strain-resistant bacterial infections. Under Hauptman's direction, HWI has also developed research experiments that have flown with NASA crews. The institute is also working on a way to determine the chemical interactions that cause polycystic kidney disease and breast cancer, with the hope of determining new treatments or even a cure. "Solving the structures that control our bodies gives us a deeper understanding of how things work, how things go wrong and how we can design drugs that destroy diseases while causing minimal collateral damage," Hauptman told Buffalo News writer Davis. At HWI, Hauptman also continued his original, Nobel Prize-winning research, hoping to extend its capabilities. In time, HWI was successful in formulating a new "shake-and-bake" procedure to his original "direct methods" formula, giving scientists the ability to map the structure of even larger molecules than the original breakthrough allowed.

Hauptman's research is recognized by many universities around the world, and the honorary degrees he has received include those from the University of Maryland, 1985; City College of New York, 1996; University of Parma, Italy, 1989; D'Youville College, Buffalo, 1989; Columbia University, 1990; Bar-Ilan University, Israel, 1990; the Technical University of Lodz, Poland, 1992; and Queen's University, Kingston, Canada, 1993. Over the years, he has published his findings in journal articles, research papers, and book chapters.

Continued Research

When he is not working, Hauptman listens to classical music, and in his spare time designs geometric-patterned stained glass. He also swims nearly every day. Although well past retirement age, Hauptman continued his work as a research professor at the State University of New York at Buffalo and also at the research institute, which expanded its state-of-the-art research laboratory in 2003. Though some of the institute's work has gone unnoticed, Hauptman remained unfazed. As he remarked on the HWI website, "When you look at the great strides that were made against polio and tuberculosis, those breakthroughs could not have been made without research that was done 50 or 100 years earlier.… And once in a while, with a little luck, lightning strikes."

Books

American Men and Women of Science, Gale, 2003.

Periodicals

Buffalo News, January 30, 2000; November 1, 2003.

New York Times, October 17, 1985.

Science, January 24, 1986.

Science News, October 26, 1985.

Washington Post, December 21, 1985.

Online

Hauptman-Woodward Medical Research Institute Web site,http://www.hwi.buffalo.edu/ (December 19, 2003). "Herbert A.

Hauptman," SUNY Buffalo Web site,http://www.cs.buffalo.edu/pub/WWW/faculty/hauptman (December 4, 2003).

Nobel E-Museum,http://www.nobel.se/chemistry/laureates/ (November 30, 2003).

HAUPTMAN, HERBERT AARON

HAUPTMAN, HERBERT AARON (1917– ), U.S. mathematician and Nobel laureate in chemistry. Hauptman was born in New York City and received his B.S. at City College (1937), M.A. at Columbia University (1939), and Ph.D. from the University of Maryland (1954) in mathematics after serving in the U.S. Navy in World War ii from 1942. He was a staff member of the Naval Research Laboratory in Washington, d.c. (1947–70), before joining the crystallography group of the Medical Foundation of Buffalo (now the Hauptman-Woodward Medical Research Institute), where he became research director in 1972 and then president. He was also research professor in the departments of biophysical sciences and computer science of the University of Buffalo. Hauptman's research work stems from his collaboration with the physicist Jerome Karle starting in 1947. They developed mathematical methods for establishing the structure of complex molecules which could previously only be determined by time-consuming, classical crystallographic techniques of more limited scope and accuracy. He was awarded the Nobel Prize jointly with Jerome Karle (1985), the only mathematician to have received the award in chemistry. His Nobel lecture discusses the integration of direct and mathematical techniques for establishing molecular structure. Subsequently he continued to refine these methods, which are in universal use in basic and medical research and in drug design. He remained actively involved in the work of the institute named after him, which studies protein structure, protein interactions, and the alterations predisposing to disease. His many honors include the Gold Plate Award of the American Academy of Achievement (1986), election to the U.S. National Academy of Sciences (1988), and an honorary degree from Bar-Ilan University (1990).

[Michael Denman (2^nd ed.)]