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.
