W. B. CASTLE, M.D
BOSTON CITY HOSPITAL.
November 25, 1946
Dr. Linus Pauling
Gates and Crellin Laboratories of Chemistry
California Institute of Technology
Pasadena 4, California
How nice it is to have a word from you and probably to learn something more as a result of your work about that most interesting
condition, sickle cell anemia. With regard to the facts about sickling, it is well established that oxygen and carbon monoxide
prevent sickling, and that exposure to other gases produce sickling by the removal of one or the other of these. Naturally,
there is some effect from carbon dioxide in so far as it alters the saturation curve for oxygen of the hemoglobin by a change
in the pH of the system. I would agree with you that Doctor Burch's papers can all be interpreted in terms of removal of
oxygen and, indeed, I wrote a critique of one of them for the Year Book of Medicine in which I simply interpolated the abstract
of his communication in terms of this explanation.
I think that the literature that would be most useful for you, both for its content and for the references given, is the following:
Scriver, J. B., and Waugh, T. R. Canad. Med. Assn. J. 1930, 23, 375-380.
Murphy, R. C., and Shapiro, S. Arch. Int. Med., 1944, 74, 28. (Cf. Bibliography)
Same authors, Annals Int. Med. 1945, 23, 376. (Cf. Bibliography)
Our own observations here confirm those of Scriver and Waugh that sickling begins at about 35 to 40 millimeters oxygen tension.
We were interested to determine the sickling by the effect on the "viscosity"; that is, the timed flow of blood through a
viscosimeter with appropriate arrangements to maintain the blood in equilibrium with various tensions of oxygen. The viscosity
of the blood begins to increase at about 40 millimeters oxygen tension, and rises
Dr. Linus Pauling, November 25, 1946—2
sharply in the range between 20 and 40. As you know, the tension of the capillary blood is in this range, and consequently
the sickling phenomenon probably is the basis of the rather uniform and striking pathology of sickle cell disease. We have
published only a sentence or two on this topic, but, as far as I know, it is the first observation of the "viscosity" of the
blood. The reference is:
Ham, T. H. and Castle, W. B. Tr. Assn. Am. Phys., 1940, 55, 127.
I hope this is the information you want. It would be pleasant to see you sometime, and in the meantime I send all best regards
William B, Castle, M.D.