CALIFORNIA INSTITUTE OF TECHNOLOGY
PASADENA, CALIFORNIA

DIVISION OF BIOLOGY

March 13, 1958

Dear Josh,

Fetal Hb is known to differ markedly from normal
adult Hb (Hb A) in amino acid composition. For one
thing, it contains about 5 times as much isoleucine as
Hb A (see Huisman et al., Nature 175, 902, for example).
This contrasts with Hb S and the other mutant hemoglobines,
whose chemical compositions can be distinguished from
normal only by the special methods developed by Ingram.

According to Itano (pers. comm.), the fetal Hb
of sickle-cell anemic individuals is normal in its electro-
phoretic and other properties. This means that fetal Hb
is determined by a different gene from the one that
determines Hb A. It seems to be a special protein that
is formed in resvonse to anoxia. This would account for
its presence in the fetal circulation and in adults
with wkhex either hereditary or acquired anemia.

I don't think you understiod my multiple allele

argument—--certainly I do not understand your reply to
it--but I won't labor the point.

Yours,

Norman Horowitz