March 11, 1953
Dr. Linus Pauling
Gates and Crellin Laboratories of Chemistry
California Institute of Technology
Dear Dr. Pauling:
It goes without saying that the recent proposal concerning nucleic acid structure
by Dr. Corey and yourself is a milestone in biological chemistry. I am taking the
liberty of enclosing a copy of a paper by Mr. Thomas W. James and myself which we
think may have some bearing on your theory. It deals with the properties of DNA films
at an air-water interface, and raises the following questions:
1) How can we account for the stability of a DNA film over a salt solution in which
the DNA is soluble? None of the formulations of nucleic acid structure yield a hydrophilic-hydrophobic
axis. Since spreading is possible only over strong electrolyte, we might image that
we are exploiting the surface activity of pure water relative to strong salt solutions
to spread the thinnest possible layer of aqueous solution, and that the DNA molecules
interact to form a sheet-like polymer which is less soluble in the underlying salt
solution. Note, however, that this film, after being deposited on a solid surface,
can be dissolved in water. I wonder whether your model would predict the behavior
of the material at an interface.
2) We observe a thickness of approximately 22 Å whether we "weight" the DNA represented
by a given area of film or measure it directly by means of the ellipsometer. Since
this thickness is 1.5 times the length of a nucleotide, we speculated in terms of
some sort of spiral arrangement. But if there were a single spiral, it should not
be very tightly packed, and the thickness calculated from the weight of a given area
of film should be less than that observed optically. It seems to us that your model
does account for the agreement between the thickness calculated from the two types
of observation. I am not certain, from reading your remarks on page 86, what thickness
you predict for the 3-helix thread.
3) We wonder if your proposal does not account for our observation – for which we
have had no explanation – that lowering the pH under the film causes it to tend to
expand. Would this not be a reasonable consequence of a structure in which the basic
residues would be facing the water? The seeming hysteresis of the effect of lowered
pH is something else again, and here our data are incomplete because we did not determine
the pH limits within which the pH effect was reversible.
We would appreciate very much any comments you might make on these questions and would
at the same time hope that these data, representing a somewhat different experimental
approach from those that you cite, might be of some use to you in further elaboration
of your theory. I hope that the points we have raised will be intelligible despite
the chemical illiteracy that they reflect.
I must add that all the credit for the technical accomplishments in the enclosed paper
should go to Mr. James.