"for their outstanding achievements in the development of direct methods for the determination of crystal structures"

Hauptman

Karle

Herbert A. Hauptman, (b. 1917), The Medical Foundation of Buffalo
Buffalo, NY, USA;
Jerome Karle (b. 1918), US Naval Research Laboratory
Washington, DC, USA. The Nobel Prize in Chemistry 1985.
From the presentation by Professor Ingvar Lindqvist, the Royal Academy of Sciences

...It was not, however, possible to determine crystal structures without some assumptions or guesses, because the phase differences between the different scattered X-rays were not known. The crystallographers had to use a trial and error method.

Several methodological improvements have since taken place, but it has for a long time been considered a great scientific achievement to determine the molecular structures of organic molecules as large as penicillin or vitamin B12. As late as 1964 Dorothy Hodgkins was awarded the Nobel Prize in chemistry for such structure determinations.

It therefore was met with great interest and much opposition and discussion when Herbert Hauptman and Jerome Karle during the years 1950-56 published a series of papers in which they claimed to have found a general method, a "direct" method for solving the phase problem, thus opening the possibility to determine the structure directly from the experimental results without any further assumptions. Hauptman and Karle built their method on two established facts. One was that the electron density in a molecule can never be negative - there are electrons or there are not.
The other fact was that the number of experimental results is large enough to permit application of statistical methods. Recent developments have shown that they were right and the production of modern computers has strongly contributed to the rapidity and efficiency of their methods. These methods are now so efficient that structure determinations for which the Nobel Prize was awarded in 1964 can today be made by a clever beginner.

At the same time it has been more and more important for the chemists to know the exact structures of molecules which take part in important chemical and biochemical reactions. One could without exaggeration say that it is only in the last ten years that chemistry has developed into a truly molecular era. Molecules with desired structures and properties can be produced and the molecular mechanism is known for increasingly more reactions.

It is this importance to chemistry which has motivated a Nobel Prize in chemistry to the mathematician Herbert Hauptman and the physicist Jerome Karle. Another way to express it is, that the imagination and ingenuity of the laureates have made it unnecessary to exercise these qualities in normal structure determinations. On the other hand they have increased the possibilities for the chemists to use their imagination and their ingenuity.