Maxwell Berkow
December 5, 2014
Professor Lampousis
MHC 20301
Herbert Hauptman
The common saying, “knowledge is power,” is often applied to the field of
science, but it would be difficult to find a more applicable use than when describing
the work of Herbert Hauptman. Using his research to identify the structures of
molecules, scientists have engineered all of today’s invaluable drugs. Although the
common man may not know it, he or someone he knows has had their life saved by
Hauptman. Whether this lack of appreciation is due to Hauptman’s humble nature
or the public’s inattention to the scientific research that keeps them alive, this man
has helped to drastically increase U.S. life expectancy by ten years.
Interestingly, this advancement in the field of medicine came from a
mathematician. Contrary to this specification, Hauptman has had a self-‐described
love of both mathematics and science ever since he began to read. This interest in
science may have been the reason for his collaboration in chemistry that would
eventually win him his Nobel Prize. The New York City native attended Townsend
Harris Hall before graduating from The City College of New York in 1937 with a
bachelor’s degree in Mathematics and Columbia University two years later with a
master’s degree in the same field. Afterwards, the United States’ involvement in
World War Two forced Hauptman to take a break from his studies and become a
Naval weather forecaster in the South Pacific.
In 1947, after returning from the war, Hauptman enrolled in a Ph.D. program
at the University of Maryland and began a collaboration at Washington D.C.’s Naval
Research Center. This partnership, with physical chemist Jerome Karle, became the
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focal point of Hauptman’s career. The research he did on x-‐ray crystallography, a
process by which molecules are identified, with Karle was the source of his eventual
Nobel Prize and the dissertation that earned him his doctorate in 1955. He and Karle
published their results in a book, Phase Problem I: The Centrosymmetric Crystal, but
their findings were quickly dismissed because of the difficulty of the problem they
had solved. The question of determining the exact structure of a molecule was
considered unsolvable to most chemists at the time. It would take until the 1970s
for their work to be accepted and 1985 for it to be recognized with the Nobel Prize
in Chemistry. Hauptman would study this process of x-‐ray crystallography for the
rest of his career.
In 1970, not wanting to shift his research towards laser-‐guided missiles,
Hauptman left the research center. He continued his work in relation to endocrines
at the Medical Foundation of Buffalo. He became the director of research for the
foundation in 1972 and its president in 1988. By this time, Hauptman was an
internationally renowned scientist: a member of the National Academy of Sciences,
honorary degrees from universities worldwide, and recipient of a Nobel Prize. He
became the first mathematician to win the award based solely on his work in
mathematics. Due to these distinctions and Hauptman’s contributions to the
foundation, the Medical Foundation of Buffalo has since been renamed the
Hauptman-‐Woodward Institute. Quoted as saying “There is no such thing as
working too hard or too long,” Hauptman exemplified his beliefs, working daily at
the Hauptman-‐Woodward Institute even into his nineties. He died on October 23,
2011.
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X-‐ray crystallography is the process of changing a compound to its crystalline
form and analyzing the scattering patterns observed when x-‐rays are shone on this
crystal. Scientists use this technique to determine the position of specific atoms in a
compound and create an image of the molecule in three-‐dimensional space. This
knowledge is key to the production of all drugs. It provides researchers with
information about the substances they are studying and molecules they have
created, both of which are vital to understand how a proposed treatment may
interact with the body.
Hauptman and Karle made this process into what it is today. At the time of
their research, the idea of calculating the position of an atom in a molecule was
actually deemed impossible by most researchers. Prior to their research, x-‐ray
crystallography could only be used to infer the structures of a compound. Chemists
knew that there was a relationship between the scattering patterns of the x-‐rays and
the composition of the molecule, but they could not determine the exact correlation.
One major difficulty in x-‐ray crystallography is the phase problem. Inconveniently,
the x-‐ray detector can record the intensity of different beams but not the phases of
each electromagnetic wave. This limitation means that vital information, such as
electron density distribution in the crystal, is lost. Hauptman used probability
theory to devise a series of equations, called “direct methods”, that could determine
the phase and translate the diffraction patterns to pinpoint the positions of atoms in
a small compound. In the 1980s Hauptman addressed this limitation, applying his
research to larger molecules and successfully altering his equations to do so.
Although they had revolutionized medicine and the pharmaceutical industry,
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Hauptman and Karle’s theories were dismissed, unused until they were finally
accepted twenty years later.
Hauptman’s formulas even reduced the time required to determine a
compound’s structure. During the 1960s, it could take two years to find the
structure of an antibiotic with only fifteen atoms. Using Hauptmann and Karle’s
research, it became possible to determine the structure of a compound with 100
atoms. Hauptman’s later improvements to his own direct methods, made from his
research at the Hauptman-‐Woodward Institute, further increased this limit to 1000
atoms. Currently, using direct methods in conjunction with modern computing
capabilities, it is possible to quickly determine the position of atoms in a protein
with over ten thousand atoms. A determination that once took years to complete is
now done in hours with much larger molecules. Although computing power has a lot
to do with this increase in efficiency, the impact of Hauptman’s research is
undeniable.
In an interview with the Associated Press, Eaton Lattman, chief executive of
the Hauptman-‐Woodward Institute stated, “I don’t think there’s a single
pharmaceutical that’s been developed in the last 30 years that hasn’t been studied
using derivations of what Dr. Hauptman and his colleagues won the Nobel Prize for.”
Although Hauptman’s influence on modern medicine is demonstrated by his
prestige and awards, Lattman’s quote is a much greater measure of his work.
Hauptman’s dedication to scientific advancement led him to further his research
even after decades without recognition. The lasting impact of his work shows that
society will forever be indebted to this commitment.
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Works Cited
Grimes, William. "Herbert A. Hauptman, Nobel Laureate, Dies at 94." The New York
Times. The New York Times, 24 Oct. 2011. Web. 28 Nov. 2014.
Hauptman, Herbert. "A Minimal Principle in X-‐Ray Crystallography: Starting in a
Small Way." Proceedings of the Royal Society A: Mathematical, Physical and
Engineering Sciences 442.1914 (1993): 3-‐12. JSTOR. Web. 30 Sept. 2014.
Hauptman, Herbert Aaron. An N-‐Dimensional Euclidean Algorithm. Thesis.
University of Maryland, College Park, 1954. N.p.: n.p., n.d. Print.
"Herbert A. Hauptman -‐ Biographical". Nobelprize.org. Nobel Media AB 2014. Web. 1
Oct 2014.
http://www.nobelprize.org/nobel_prizes/chemistry/laureates/1985/haupt
man-‐bio.html
Hauptman, Herbert. Crystal Structure Determination: The Role of the Cosine
Semivarients. New York: Plenum, 1972. Print.
"Herbert A. Hauptman, PhD." Hwi's Nobel Laureate. Hauptman-‐Woodward Medical
Research Institute, n.d. Web. 28 Nov. 2014.
"Herbert Hauptman." Jewish Virtual Library. N.p., n.d. Web. 28 Sept. 2014.
http://www.jewishvirtuallibrary.org/jsource/biography/hauptman1.html
Hauptman, Herbert Aaron, and Jerome Karle. Solution of the Phase Problem. I. The
Centrosystemmetric Crystal. Wilmington, DE: American Crystallographic
Association, 1953. Print.
Hauptman, H. "The Direct Methods of X-‐ray Crystallography." Science 233.4760
(1986): 178-‐83. JSTOR. Web. 02 Oct. 2014.
Lamont, Paul. "Herbert Hauptman: Portrait of a Laureate." Herbert Hauptman:
Portrait of a Laureate. PBS. 22 June 2008. Television.
"Nobelprize.org". Nobelprize.org. Nobel Media AB 2014. Web. 3 Oct 2014.
http://www.nobelprize.org/nobel_prizes/chemistry/laureates/1985/prese
ntation-‐speech.html
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