Herbert A. Hauptman was born on February 14, 1917,
in New York City. He graduated from the City College of New York in
1937 with a B.S. in mathematics, and received his M.A. degree in mathematics
in 1939 from Columbia University.
War II, Hauptman moved to Washington,
D.C. to work in the Naval Research Laboratory.
At the laboratory Hauptman paired up with Jerome
Karle. Simultaneously, Hauptman began
studying at the University of Maryland,
College Park for his Ph.D. Karle and Hauptman’s
proficiency in mathematics and physical
chemistry permitted the partners to study
the phase problem of X-ray crystallography
(a technique in crystallography in which
the pattern produced by the diffraction of
x-rays through the closely spaced lattice
of atoms in a crystal is recorded and then
analyzed to reveal the nature of that lattice).
Crystallography is the experimental science
of determining the arrangement of atoms in
Hauptman and Karle’s 1953 monograph, “Solution
of the Phase Problem I. The Centrosymmetric Crystal,” introduced
probabilistic methods, which were crucial for phase determination of
X-ray crystallography. They formed mathematical equations for reasoning
the molecular structure of chemical compounds from the configurations
formed when X-rays are diffracted. By 1954, Hauptman had received his
Ph.D. and laid the foundations of the direct methods of X-ray crystallography.
In 1970, Hauptman moved to join the crystallography
team at the Medical Foundation of Buffalo. He became a professor of
biophysics at the State University of New York at Buffalo. In 1972,
he was elected Research Director of the institution. It was during this
period, that Hauptman devised the neighborhood principle and extension
Hauptman received the Nobel
Prize for Chemistry in 1985 along with Jerome
Karle for their work
with X-ray crystallography.
The following press release
from the Royal Swedish Academy of Sciences
describes Hauptman and Karle's work:
This year's Nobel Prizewinners
in Chemistry, Herbert A. Hauptman and Jerome
Karle, have developed what are termed "direct
methods" for the determination of crystal
structure. This development of a method
merits a Nobel Prize since the method now
plays an increasingly important role in
chemical research. It is therefore of importance
to consider the method first.
As early as the turn of the century, chemists possessed
a good understanding of the geometrical arrangement
of the atoms in carbon compounds. But it is only through
structure determination using X-ray crystallography
that we have been able to obtain a detailed picture
of the distances between the atoms and of the angles
between the various bonds. Spectroscopy and electron
diffraction have played a complementary role, especially
in the case of simpler molecules.
The need for exact knowledge
of structure is great within two areas
of chemistry. One of these areas concerns
structural problems, especially those associated
with the function of molecules in biological
contexts. Here, a large number of processes
are considered in similar ways under the
heading "signal - receptor processes".
Examples of these processes are enzyme activity,
antigen - antibody and scent substance
- scent receptor. For understanding these
signal-receptor processes it is necessary
to gain as detailed a knowledge as possible
of both signal molecules and receptor molecules
(active site). The signal molecules are
relatively small and their structure can
be determined. The structure of the receptor
molecule can also be perceived by analogy
with low-molecular compounds. Where giant molecules
are involved, structure determination of the type
for which Perutz and Kendrew received a
Nobel Prize is required. For determining
the low-molecular signal molecules the
Hauptman-Karle direct method must be used.
In the other important area, the mechanism and chemical
dynamics of reactions are studied. Questions being
asked also by chemists working with organic synthesis
are, for instance: How, at molecular level, does a
chemical reaction take place? How does a molecule move,
and how is the structure changed in chemical reactions?
The most important answers are coming from researchers
within theoretical chemistry, but these must in turn
have accurate knowledge of the structures of reacting
To summarize: the last
fifteen years have seen a large increase
in structure determinations accomplished
within both inorganic and organic chemistry,
including natural product chemistry. These
determinations have been carried out predominantly
using "direct methods". Looking into
the future we can predict a further increased need
for structure determinations of this kind.
While it is easy to explain the importance for chemistry
of the two prizewinners' development of the methods,
it is considerably more difficult without recourse
to mathematical formulae to describe the achievement
itself in a way that is easy to understand.
When X-rays strike a
crystal, they will be deflected only in
certain definite directions, where the
intensity of irradiation may be measured.
To determine the arrangement of atoms in
a crystal, however, it is not enough to
know the direction and intensity. The "phase" of each
ray so deflected must also be known. In special cases,
it has been possible to solve this "phase problem" by
making use of the fact that "heavy" atoms containing
many electrons spread the X-rays more strongly than "light" atoms
do. This property of heavy atoms is used both in "Patterson
methodology", which has been very important in structural
inorganic chemistry, and in "isomorph substition".
The latter is used when determining the structure
of giant molecules such as proteins. In this case
the heavy atoms can be bound to the protein without
its structure being appreciably altered. This however
is not possible for the large number of compounds.
Two facts have created
the conditions for the development of the "direct" methods.
The first is that electron density, which
diffuses the X-rays, can never be negative.
The other is that the number of measurements is
much greater than the number of equations
to be solved, which permits the use of
statistical methods. In work done between
1950 and 1956, Hauptman and Karle laid
the foundations for a rational exploitation
of these possibilities, specially the use
The immense importance
of this work for subsequent development
may easily be followed in the literature.
This is not to say that Hauptman and Karle alone
are responsible for the development, and
other names must be mentioned in particular.
Before Hauptman and Karle published their
work, D. Harker and J.S. Kasper proposed
the use of one inequality, which represents a special
case in the Hauptman-Karle system, and determined
a complicated structure using it. Important
conceptual contributions were also made
by D. Sayre, who anticipated the practical
approach which has later come to be used.
Isabel Karle´s and M. Woolfson's contributions
to the practical utilization of direct methods
have been crucial, and in this connection the development
of fast computers has been a prerequisite for the
full realization of the value of the method.
A. Hauptman Autobiography"; britannica; Nobelprize.org.