Crystallography: a science for all seasons

Bill Lipscomb also appreciates being surrounded by women at the Philadelphia ACA meeting, seen here with Judy Flippen-Anderson and Penelope Codding. (Photo W. L. D.)

The number of Nobel Laureates associated with crystal diffraction is now 26. Since the total world population of crystallographers, most of whom use X-rays, is less than 10,000, the young crystallographer would appear to have better odds of winning a Nobel Prize than a worker in any other field of endeavor. One may ask why this is so.

Herbert Hauptman, Jerome Karle and Isabella Karle at the symposium honoring Herb and Jerry's 75th birthdays in October 1992 in Buffalo. (Photo, W. L. Duax)

Thirteen years after the discovery of X-rays by W. Roentgen (Nobel Prize in Physics, 1901), M. von Laue (Physics, 1914) discovered X-ray diffraction. But it was W. H. and W. L. Bragg (Physics, 1915), both of whom were educated as mathematicians, who exploited those findings to determine the atomic structure of crystals. These discoveries, together with the development of X-ray Physics by C. G. Barkla (Physics, 1917), K. M. G. Siegbahn (Physics, 1924), and A. H. Compton (Physics, 1927), removed crystallography from its 300-year-old association with mineralogy and moved it to the domain of physics. The physics laboratories of the Braggs, first in Leeds, then in Cambridge and London, were the meccas for disciples of the new science of X-ray crystallography.

Aaron Klug at the anniversary party for DNA in Chicago 1993. (Photo W. L. D.)

Two other radiations, electron and neutron, that also can have wavelengths suitable for atomic diffraction, joined the X-rays, and diffraction became the primary source of precise quantitative information about the three-dimensional structure of matter in gases, liquids, and amorphous solids, as well as crystals. Because it is this three-dimensional atomic structure that determines the physical, chemical, and biological properties of substances, use of these diffraction methods became a common interest for a broad spectrum of sciences. This interdisciplinary theme started with P. J. W. Debye (Chemistry, 1936) and runs through the history of the later Nobel laureates. L. Pauling (Chemistry, 1954) used his experience in crystallography extensively in writing The Nature of the Chemical Bond. G. Natta (Chemistry, 1963) applied crystallography to his polymer research. F. H. C. Crick, who had been a physicist, collaborated with J. D. Watson, a biologist, in interpreting the X-ray diffraction patterns of physicists M. H. F. Wilkins and R. Franklin, and so discovered the double helix (Physiology and Medicine, 1962) with a little help from J. Donohue, a chemist.

Sir John Kendrew and David Harker at the ACA meeting in Philadelphia in 1988. (Photo W. L. D.)

Once the simpler inorganic crystal structures had been determined, the methodology of crystal structure analysis became very difficult, especially when applied to organic molecules. This was because of the phase problem. While this gave the research considerable intellectual appeal - like playing chess against Nature - it made it very time consuming and often tedious. Nevertheless, some scientists with special combinations of curiosity, insight, and determination persisted, such as M. F. Perutz (Chemistry, 1962), D. M. C. Hodgkin (Chemistry, 1964), O. Hassel (Chemistry, 1969), W. N. Lipscomb, Jr. (Chemistry, 1976), and M. Robertson. Although the last named was not awarded a Nobel Prize, he was elected president of the Chemical Soc. (UK) in recognition of his crystallographic contributions to chemistry. Assisted by the rapid development of computer technology, but using methods developed for small molecules by A. L. Patterson (a physicist) and Robertson (a chemist) in the 1930's, Perutz and J. C. Kendrew (Chemistry, 1962) demonstrated the use of X-ray crystallography to determine the atomic structures of very large molecules, namely, proteins, Physicist A. Mug (Chemistry, 1982) extended this work to methods for the structure analysis of even larger molecules, the viruses.

John Deisenhofer at the ACA meeting in Seattle in 1989. (Photo W. L. D.)

Herb Hauptman and Robert Huber receive the title Commandeur d'Honneur from the Ordre du Bontemps Medic et Desgraves at the IUCr congress in Bordeaux in 1990 at the wine tasting. Hauptman commented that it was one of the two best wines he had ever tasted. The only other glass he had ever had was probably Mogen David. (Photo W. L. D.)

With recognition of the importance of molecular shape or conformation, by Hassel and D. H. R. Barton (Chemistry, 1969), X-ray crystallography begin having a tremendous impact on chemistry. Crystallography was able to play such a major role in chemistry because of the invention of a mathematical method, based on probability theory, for solving the phase problem. It was for this invention that Hauptman, a mathematician, and Karle, a chemist, were awarded the Nobel Prize (Chemistry, 1985). Hauptman and Karle acknowledge their debt to D. Harker and J. Casper, who used inequality relationships to determine the structure of one of the first boron-containing compounds. Deisenhofer, Huber, and Michel received the Prize for elucidating the crystal structure of a membrane protein (Chemistry, 1988). The most recent Nobel Prize that has an X-ray crystallographic connection is the 1992 Prize in Physics awarded to G. Charpak, inventor and developer of particle detection devices, particularly in the multiwire proportional chamber. A counting chamber he built in 1984 is in continuous use by protein crystallographers at the synchrotron light source in Orsay.

Honest Jim Watson at a celebration of the 40th Anniversary of the discovery of the double-helix, 1993. (Photo W. L. D.)

Interdisciplinary transfer or collaboration between the major disciplines in science is a theme that runs through these discoveries. Yet the increasing sophistication of the sciences has led to a segregation in university education that drops the curtain between them at increasingly earlier stages. It is rare that a graduate physicist can, or wishes to, understand the language of even an undergraduate chemistry course. A solid-state physicist can be surprised to learn that proteins and viruses can be crystals. Similarly the mathematical logic of physics undergraduate courses is a mystery to most biochemistry and biology students.

Maureen and George Jeffrey at the 50th Anniversary celebration of the Pittsburgh Diffraction Conference, 'Behind every great man...' (Photo W. L. D.)

At present the major thrust of crystallography seems to be in molecular biology, but I wonder what the crystallographers will turn to when they get tired of tracing α-helices and pleated sheets.

This article is an update of one published in Physics Today, Nov. 1986.