1 August 1978
Professor C. Lockard Conley
Hematology Division
Department of Medicine
The Johns Hopkins Medical Institutions
601 N. Broadway
Baltimore, Maryland 21205
Dear Professor Conley:
In answer to your letter of 25 Jul 1978, about hemoglobin, let me say first
that my interest in hemoglobin was not specifically directed by someone at the Rockefeller
Institute.
I enclose a list of my papers from 1922 to 1967, About 25 papers on hemoglobin
are listed there. I also enclose a recent paper by me on hemoglobin.
I had been working on various problems of the structure of molecules and
crystals for about a decade when, about 1934, I began to wonder about the sigmoid
oxygen equilibrium curve of hemoglobin. My first paper on hemoglobin was a discussion
of this curve and nature of the heme-heme interactions in the hemoglobin molecule.
My first paper on hemoglobin was a discussion of this curve and the nature of the
heme-heme interactions in the hemoglobin molecule. While thinking about this problem
I realized that information about the nature of the bonds between oxygen and hemoglobin
could be obtained measuring the magnetic properties of hemoglobin and oxyhemoglobin.
Charles Coryell, who had just received his Ph.D. degree, became my assistant at that
time. We discovered the striking difference magnetic properties of hemoglobin and
oxyhemoglobin, and were able to draw significant conclusions about the nature of the
bonds and the structure of the hemoglobin molecule in the neighborhood of the iron
atoms from these observations. During the next few years we and others in our laboratory
made many measurement of the magnetic properties of hemoglobin and related compounds.
We were able to determine equilibrium constants and rates of reactions by using this
technique.
I lectured on this subject in the Rockefeller Institute for Medical Research.
Karl Landsteiner showed much interest in my lecture, and later he asked me many questions
about my interpretation of observations made by him and others in the field of immunochemistry.
I then wrote my 1940 paper on the structure of antibodies and nature of serological
reactions, and began an extensive series of experimental studies in immunochemistry,
my principal collaborators being Dan H. Campbell, whom I brought to Pasadena from
Chicago, and David Pressman.
In 1945 I was serving on a committee on medical research in the United States.
At a dinner in New York, we discussed various matters, and William B. Castle mentioned
some work that he was doing on sickle-cell anemia. I immediately pointed out that
some observations made on patients with sickle-cell anemia or on blood from these
patients could be accounted for if the assumption were made that the patients were
manufacturing an abnormal hemoglobin, with molecules containing two mutually complementary
groups, permitting them to aggregate into long helical rods and ultimately to form
a long crystal, which would twist the red cell out of shape. Attachment of oxygen
or carbon monoxide to the hemoglobin would prevent the molecules from achieving the
close proximity that would result in this aggregation, and hence would stop the sickling.
I asked Castle if he knew of anyone's having suggested this idea, and when he gave
me a negative reply I said that I though that I would work on the problem. A few months
later Ed Doisy wrote to me about a student he had had, who was interning in Detroit
and had a postdoctoral fellowship to permit him to work for a Ph.D. in chemistry.
He suggested that he come to Pasadena to come to work with me, which he did. This
man was Harvey Itano. I wrote to him in Detroit, after it had been decided that he
would come to Pasadena, suggesting that he work on the problem of the nature of the
hemoglobin in patients with sickle-cell anemia. This effort in course of time led
to the publication of our paper "Sickle-Cell Anemia, A Molecular Disease," and to
the discovery of several other hemoglobins in our laboratory, hemoglobins in our laboratory,
hemoglobins C,D, and E.
In related work in our laboratory we were able to show that the human hemoglobin
molecule contains polypeptide chains of two types, which we called the A chain and
the B chain. These designations were later changed to alpha chain and beta chain.
So far as I am aware, my idea in 1945 that human hemoglobinopathies exist
was the first time that this idea had been expressed. Our 1949 paper was the first
paper showing that there is in fact a human hemoglobinopathy, and it was followed
by work leading to a great development of this field. My earlier work on leading to
a great development of this field. My earlier work on a magnetic properties ofhemoglobin
was responsible in large part for development of the now-accepted ideas about the
binding of oxygen and carbon monoxide.
In your letter you ask if I would be willing to write a brief account of
my work on hemoglobin. the sketch in the above paragraphs is too superficial to be
of value. If you could tell me how much of my work you would like to have summarized
and how long the summary should be, I would be willing to write it.
Sincerely,
LP:dm
