Linus Pauling: My memory is that this was the occasion that Dr. Castle began to talk, to tell the story about what other people and he had
done on sickle cell anemia. And I was mildly interested in the fact that the red cells were twisted out of shape, but not
very interested, because I thought the red cell is so complicated that it will be decades before anyone gets any significant
understanding of it, its structure. And I wasn’t listening very hard, being polite of course, to suggest that I was paying
attention when he said that the red cells do not sickle in arterial circulation or in the presence of partial pressure of
oxygen, but sickle in, if the partial pressure of oxygen was low.
And immediately I said to him, and the others there, I wonder if this couldn’t be a disease of the hemoglobin molecule? That
the genetic constitution is such, that these people manufacture a sort of hemoglobin that is sticky, so that the molecules
stick together and form long rods which then attract one another by van der Waals attraction, forming a long, needle-like
crystal that twists the red cell out of shape. And these mutually complimentary regions must come into atomic contact, the
oxygen molecules in oxyhemoglobin are warts on the molecule that hold them four angstroms farther apart and the van der Waals
forces of attraction no longer operates effectively and so the sickling doesn’t occur in the oxyhemoglobin.
And I asked does carbon monoxide prevent the sickling; does carbon monoxide prevent the sickling? My memory is that Dr. Castle
said that he didn’t know whether it did or not, but he mentioned something about carbon dioxide, but...
William Castle: No, I should have said carbon monoxide today. Pauling’s [unintelligible]
Linus Pauling: Well Hahn and Gillespie. Carbon monoxide. Well, it may be that you answered that it did. At any rate I said, as I recall,
something like, "it’s pretty clear, it seems quite obvious that the hemoglobin and oxyhemoglobin are behaving differently,
and differently from normal hemoglobin, so I think it’s likely that this is a disease of the hemoglobin molecule. Do you think
that when I get back to Pasadena, I might check up on this?" And Dr. Castle said well he didn’t see why not, or who was there
to stop me, or something like that.
