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.

After World 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 solids.

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 concept.

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 molecules.

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 of inequalities.

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.

Sources: Wikipedia; "Herbert A. Hauptman Autobiography"; britannica; Nobelprize.org. Photo: Jewish Buffalo

Herbert Hauptman