The Stochastic Method and the Structure of Proteins

Address at opening ceremony, 10:30 AM, 29 July 1953.

Concert Hall, Stockholm

Ladies & Gentlemen: I am conscious of the honor that has been given me in permitting me to present the opening address of the 13th International Congress of Pure and Applied Chemistry, and I express my appreciation to the Committee.

I am going to speak about the stochastic method in scientific progress. First I must apologize to philosophers and students of scientific methodology for the naiveté that they will no doubt discern in my remarks.

Twenty years ago the physicist Karl Darrow in New York asked me to explain to him what I was doing. Then he said "You should call your method the stochastic method." [From the] Greek stochastikos - apt to divine the truth by conjecture. Alexander Smith.

Already 1923 Roscoe Dickinson, to whom I had expressed some thought about the structure of complex crystals, said to me "That sounds very good to me - I must say, however, that I would never do anything like that." Dickinson and Wyckoff were, in fact, the leading exponents of the "rigorous" school of x-ray workers. They contended that each conclusion about the structure of a crystal should be rigorously required by the experimental data. The rigorous method was not really rigorous - it involved the assumption that x-ray reflections not observed were really absent, not just very weak. and it was soon exhausted - it was not powerful enough to permit the determination of the structure of any but the simplest organic compounds.

The stochastic method consists in guessing the exact structure - that is, formulating a reasonable structure, with use of general principles of some sort - and then checking it by experimental test. This is, of course, what a chemist (synthetic organic chemist) does all the time. He obtains a product and assigns it a structure - a stochastic structure - on the basis of his knowledge of chemical principles; then he checks one or two points - ultimate analysis, molecular weight, presence of a methyl side chain or a carboxyl group - and is satisfied. I shall give some examples of the stochastic method later.

I learned from Dr. Karl Landsteiner that people differ in their methods of attacking scientific problems - some like the stochastic method, and some do not. In 1936 he asked me about the structure of antibodies.

Protein structures ---

Finally, we may ask more in detail about the stochastic method - what are its principles.

I have not been able to get beyond the first two - the guess must be characterized by simplicity and also by quasi-uniqueness. Everybody should be allowed one guess - but not 100. Corey and I guessed wrong on collagen - we were overly enthusiastic 3 years ago; now we would better be right the second time.

As for simplicity - it is clear that living organisms are not simple, and yet there is a striving for simplicity - the use of a structural element or mechanism over and over - heme in hemoglobin, cytochrome, etc; 2 amino acid residues in proteins instead of same two proteins and same 1; use of complementariness in antibody-antigen, gene reduplication, enzyme activity.

Perhaps we would do well to make a serious study of the stochastic method, to get a better understanding of it, to make it more powerful. The problems of biology and medicine are of great importance, and they are so difficult that we cannot afford to overlook any possible aid to their solution.