November 17, 1969

C. Lockard Conley, M.D.

Hfeiratology Division

Johns Hopkins Medical Institutions

601 No, Broadway

Baltimore, Maryland

Dear Dr. Conley:

I was pleased to receive your letter, and to learn about your interest in the discovery of the abnormal human hemoglobins.

I know very well why it was that I decided to make an investigation to see whether or not sickle cell anemia involved the manufacture of an abnormal hemoglobin. The account given in my Harvey lecture is correct and nearly complete.

Last June I learned that Bill Castle had forgotten part of the story. He remembered that he and I had talked about the disease in 1945, when he told me about the observed birefrengence of sickled cells. He had forgotten the earlier episode, however - about two months earlier. This was the time in New York when he had talked about the disease at a small private dinner (just conversation among the seven or eight members of the Committee on Medical Research). M this earlier dinner, in the early spring of 1945, he mentioned that the cells were sickled in venous blood, and not in arterial blood. This fact immediately suggested to me that the hemoglobin molecule was, with little doubt, closely involved, and I formulated then the idea that it was an abnormal molecule with two complementary regions on its surface. I made a statement about this at the time, which, I think. Castle had forgotten later on, or confused with our second discussion.

There are several statements in the letter of 24 October, 1969, by George Burch to you that are new to me. Some of his statements are not quite right. It was 194 I, rather than 1940, when I developed nephritis, and came to Dr. Alfred Conn's laboratory for a diagnosis and met Dr. Burch. I remember that he made a check on me with the plethysmography and that we talked about some matters; but the only things that we talked about which I now remember were the disease, glomerulonephritis. I knew that my maternal grandfather had died of this disease, and I was, of course, concerned about having my illness diagnosed in this way. It is understandable that I do not remember much about that day except the tests that were made of me and the advice that was given to my wife and me, which was that we return to California and get in touch with Thomas Addis at Stanford Medical School.

I am sure that the idea that there was an abnormal hemoglobin did not occur at that time, but only four years later.

In 1945, after 1 had had this idea, Doisy wrote to me about a young physician who had studied with him at St. Louis, Harvey Itano. I accepted Itano as a graduate student working for a Ph.D. in chemistry, and wrote to him suggesting that he work on the hemoglobin problem. We built an electro-phoretic apparatus in our laboratory, and after a lot of effort succeeded in getting good evidence of the existence of the abnormal hemoglobin.

Dr. Burch says in his letter that he had sent all of the blood that we used to us. He also mentions Dr. Winsor as supplying blood from the Los Angeles County Hospital. He also obtained samples of blood from Children's Hospital in Los Angeles, through the courtesy of Dr. Evans. In our paper communicating the discovery of the abnormal hemoglobin we express our thanks to Dr. Burch, as well as to Dr. Winsor and Dr. Evans, for providing samples of blood.

As I have stated above, I am sure that my ideas about sickle cell anemia originated in early 1945, at the New York dinner, and that I talked with Bill Castle again in a Pullman car on the way to the meeting of the same committee, later that spring. Although T do not remember it, it is not unlikely that Dr. Burch talked about the disease when I first saw him in 1941.

The idea that Dr. Burch and Dr. Shedlowsky found definite differences of hemoglobin from sickle cell patients and normal persons in the early 1940's is new to me. Dr. Burch says that the hemoglobin from three patients was studied. I know from our own experience that it is, or was at that time, very difficult to get very definite evidence that the hemoglobin is an abnormal hemoglobin. Although Dr. Burch says in his letter that they have found definite differences from the normal in the electrophoretic patterns, I suppose that the Indications of a difference were not well enough defined to justify publication or even to justify further work. I assume that there is no publication about this, or I would know about it, and Dr. Burch would mention it.

I do not think that there is any justification for the sentence “Pauling then assigned Itano, his assistant, the responsibility of running through some samples and, of course, found the same electrophoretic patterns.”

I doubt very much that Dr. Burch and Dr. Shedlowsky had obtained the same electrophoretic patterns that we obtained. If they had, they surely would have published an account of their discovery.

Also, as described above, my decision to do some work in this field was made only four years later, and was consequent to some facts about the disease mentioned to me by Dr. Castle, and not at all to any discussion with Dr. Burch.

Dr. Burch was helpful to Dr. Itano and me not only in providing samples of blood but also, in the early i950's, in arranging for a test to be made of an idea that we had about controlling the crises of the disease.

I do not think that I have ever seen the article by M. B. Strauss published in Medicine in 1964. Could you send me a Xerox copy of this article, if you have it in your files, or the page reference?

Sincerely,

Linus Pauling

LP/mdm