It's in the Blood! A Documentary History of Linus Pauling, Hemoglobin and Sickle Cell Anemia All Documents and Media  
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George W. Beadle
George E. Burch
Dan H. Campbell
William B. Castle
Robert B. Corey
Charles D. Coryell
Lee A. DuBridge
Vernon M. Ingram
Harvey A. Itano
Karl Landsteiner
Alfred E. Mirsky
Robert M. Nalbandian
James V. Neel
A. A. Noyes
Ava Helen Pauling
Linus Pauling
Walter A. Schroeder
S. Jonathan Singer
Stanley M. Swingle
Arne Tiselius
Warren Weaver
Ibert C. Wells
Paul L. Wolf
Emile Zuckerkandl

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Portrait of Linus Pauling.
Portrait of Linus Pauling. December 1949.
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Linus Pauling


Ava Helen and Linus Pauling Papers
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"It is very kind of you to consider the possibility of my working in Pasadena, an idea which certainly is attractive, especially since it would hold out the prospect of your cooperation or advice."

Karl Landsteiner. Letter to Linus Pauling. March 28, 1938.

"The item of $7,500 for apparatus, supplies, animals would permit us to use the large number of animals required for some of our projected researches, and should permit also the construction of a Tiselius apparatus for the electrophoretic separation of antibody fractions by the suggested method of combination with charged haptens, and for other investigations."

Linus Pauling. Letter to Warren Weaver. January 2, 1941.

"The meetings at Stanford...were very interesting. There were lots of times when people wanted to know what Pauling would say about different things, so [John] Edsall and I had to speak for you, taking of course, a fair amount of the credit."

Charles Coryell. Letter to Linus Pauling. July 4, 1941.

"Dr. Charles Coryell, who has worked on the metallurgy project at the University of Chicago for a couple of years, received his training here, and then became Assistant Professor at the University of California at Los Angeles, is an extremely able young inorganic and physical chemist, with a great amount of energy. I recommend him most highly."

Linus Pauling. Letter to George T. Felbeck. November 17, 1943.

"On the basis of the information available to me, I have formed the opinion that oxypolygelatin solution...may well be a thoroughly satisfactory blood substitute, which could be manufactured cheaply in large quantities. It is probably superior to gelatin itself with respect to fluidity of solution, retention in blood stream, and osmotic pressure."

Linus Pauling. Letter to Walter B. Cannon. March 14, 1944.

"I have been very pleased to find Dr. Seymour Singer at work here. He seems to me to be an excellent man, and we are looking forward to a good year's work from him."

Linus Pauling. Letter to Kurt G. Stern. August 14, 1947.

"Science cannot be stopped. Man will gather knowledge no matter what the consequences -- and we cannot predict what they will be. Science will go on -- whether we are pessimistic, or are optimistic, as I am. I know that great, interesting, and valuable discoveries can be made and will be made...But I know also that still more interesting discoveries will be made that I have not the imagination to describe -- and I am awaiting them, full of curiosity and enthusiasm."

Linus Pauling. "Chemical Achievement and Hope for the Future." 1947 lecture hosted by Yale University, reproduced in Science in Progress. Sixth Series. George A. Baitsell, ed. 100-121, 1949. October 15, 1947.

"Take care of yourself! That is more important than anything else I can think of. How glad I shall be to see you again!"

Robert Corey. Letter to Linus Pauling. February 25, 1948.

"I am very sorry you were not here during Warren [Weaver]’s visit because you started it all and are certainly the one responsible for getting Chemistry and Biology in a position where there’s a good chance of collecting some nice blue chips."

George Beadle. Letter to Linus Pauling. March 1, 1948.

"As to the Chemical-Biology building, we hope very much that Mr. Norman Church will make provisions so that we can start work on it in the near future. As Kirkwood has no doubt told you, Mr. Church has pledged himself to provide $1,500,000 for a Chemical-Biology building....It was the greatest good fortune, indeed, that he offered this gift just at the time when the Rockefeller gift came through."

Lee DuBridge. Letter to Linus Pauling. May 24, 1948.

"The rapidity and simplicity of this test suggests that it would be useful as a clinical laboratory procedure for diagnosing sickle cell anemia and sickle cell trait."

Linus Pauling. "A Rapid Diagnostic Test for Sickle Cell Anemia," Blood, 4(1): 66-68, 67. January 1949.

"It appears, therefore, that while some of the details of this picture of the sickling process are as yet conjectural, the proposed mechanism is consistent with experimental observations at hand and offers a chemical and physical basis for many of them. Furthermore, if it is correct, it supplies a direct link between the existence of “defective” hemoglobin molecules and the pathological consequences of sickle cell disease."

Linus Pauling. "Sickle Cell Anemia, a Molecular Disease." Science 110: 543-548. April 1949.

"Our postulate provides an obvious explanation of the action of oxygen in preventing the sickling of sickle-cell-anemia erythrocytes. We have visualized the sickling process as one in which complementary sites on adjacent hemoglobin molecules combine. It was suggested that erythrocytes containing oxyhemoglobin or carbonmonoxyhemoglobin do not sickle because of steric hindrance of the attached oxygen or carbon monoxide molecule. This steric hindrance effect might be the distortion of the complementary sites through forcing apart of layers of protein, as is suggested by the isocyanide experiments."

Linus Pauling. "The combining power of hemoglobin for alkyl isocyanides, and the nature of the heme-heme interéactions in hemoglobin." Science 114 (December 1951): 629-634 December 1951.

"Dr. St. George worked in collaboration with me for one year. The results of the work were published in a joint paper in Science, in December, 1951. I consider him to be a well-trained young man, with much native ability, and with deep and sincere interest in biochemistry."

Linus Pauling. Letter to Elmer H. Stotz. January 21, 1952.

"I believe medicine is just now entering into a new era when progress will be much more rapid than before, when scientists will have discovered the molecular basis of diseases, and will have discovered why molecules of certain drugs are effective in treatment, and others are not effective."

Linus Pauling. "Scientist Heralds New Era in Medicine Based on Studies of Molecular Action." Portland Oregonian.  February 13, 1952.

"...[I]t seems to be impractical to convert enough of the hemoglobin in a patient with sickle cell anemia to produce the desired therapeutic effects without injuring the patient from the point of view of toxicity and anoxia."

George E. Burch. Letter to Linus Pauling. August 5, 1954.

"The idea of Dr. Linus Pauling that an abnormal hemoglobin molecule might be responsible for the sickling process initiated the study of the hemoglobin molecule in hereditary anemias."

Harvey Itano. "Clinical States Associated with Alterations of the Hemoglobin Molecule." Archives of Internal Medicine, 96: 287-97, 295. 1955.

"The discovery by Dr. Itano of the abnormal human hemoglobins has thrown much light on the problem of the nature of the hereditary hemolytic anemias, and has changed these diseases from the status of poorly understood and poorly characterized diseases into that of well understood and well characterized diseases"

Linus Pauling. Nomination of Harvey Itano for the Theobald Smith Award. July 1955.

"Dr. Pauling explained the reasons behind his developing interest in the field of mental deficiency. His research in hematology has now developed this area to the point where other researchers have taken over and will carry on."

Ford Foundation. Official summary of a panel discussion titled "Basic Biochemical Research Related to the Problem of Mental Deficiency." July 7, 1955.

"[M]anufacture of abnormal determined by the genetic constitution of the patient; the disease is inherited. A disease of this sort, caused by molecules of abnormal structure present in the patient in place of the molecules of normal structure that are present in normal human beings, is called a molecular disease."

Linus Pauling. "The Molecular Basis of Genetics." Speech presented at the American Psychiatric Association Symposium, Chicago, IL. May 2, 1956.

"As to the degree of abnormality in sickle cell hemoglobin, it is astonishing how small it is..."

Linus Pauling. Molecular disease. Pfizer Spectrum, 6, no. 9 (May 1958): 234-235. May 1958.

"As more and more tests for heterozygosity are developed, predictions can be made with greater and greater reliability about the probability of birth of defective children, and advice can be given to prospective spouses or parents about the desirability of their contributing to the welfare of the human race as a whole by preventing the transmissions of seriously defective genes to the next generation."

Linus Pauling. "Molecular Structure and Disease." Disease and the Advancement of Basic Science, Henry K. Beecher, ed., pp. 1-7. 1960.

"It thus appears possible that there would be no evolution without molecular disease."

Linus Pauling. "Molecular Disease, Evolution and Genic Heterogeneity." Horizons in Biochemistry (Albert Szent-Györgyi Dedicatory Volume), Michael Kasha and Bernard Pullman, eds. New York: Academic Press 1962.

"In the United States about 10 percent of the Negro population (and a much smaller percentage of the remaining population) carry the gene for sickle-cell-anemia hemoglobin or the somewhat similar gene for hemoglobin C. About 1 child in 400 born in the Negro population in the United States inherits two of these genes and in consequence suffers from the very serious disease, sickle cell anemia (or the related diseases involving the hemoglobin-C gene)."

Linus Pauling. "Our Hope for the Future." June 25, 1962.

"The demonstration that sickle cell hemoglobin differs in electrophoretic mobility from normal hemoglobin led to the entitled inference: 'Sickle cell anemia, a molecular disease.' This astonishingly simple concept is of fundamental importance to medicine for the ultimate understanding of the origins of sickness, and to biology for the insight into what genes do. In the author's words, 'This investigation...reveals a clear case of a change produced in a protein molecule by an allelic change in a single gene involved in synthesis.'"

Samuel H. Boyer IV. Introduction to "Sickle Cell Anemia, a Molecular Disease." Papers on Human Genetics, 115-25. 1963.

"It is probable that the sickle cell gene represents a first step in the process of evolution toward the development of a mutant human being with effective protection against malaria and without the handicap of having half of the children die of either malaria or sickle cell anemia."

Linus Pauling. "Our Hope for the Future." In Birth Defects, Morris Fishbein, ed. Philadelphia: J. B. Lippincott. 1963.

"In 1949, application of methods of physical chemistry directly to the study of a protein produced by a mutated gene led Pauling, Itano, Singer and Wells to identify the specific change in the protein brought about by the gene. The discovery of the first of the abnormal human hemoglobins which they described as causing a 'molecular disease' -- sickle cell anemia -- was followed the identification of a large number of other proteins, each of which owed its difference from normal structure to a mutated gene. Ingram then showed that the change due to the mutation, in the case of each of two abnormal hemoglobins, was confined to a single amino acid residue at one point in one of the polypeptide chains composing the globin. There could be no doubt that genes controlled protein structure by specifying the sequence of amino acid residues in the polypeptide chains. The assumed basic functional correspondence was then altered from 'one gene-one enzyme' to 'one gene-one polypeptide.'"

L. C. Dunn. "Old and New in Genetics." Bulletin of the New York Academy of Medicine, 40(5): 325-333, 329. May 1964.

"I cannot imagine what would have happened to me, scientifically, if, in 1957, in a Hotel lobby in Paris, you had refused my request to come and work with you. I know that whatever field I would have been working in would not have been comparable in interest and scope to the one - or, rather, to the several - that you opened up to me."

Emile Zuckerkandl. Letter to Linus Pauling. May 28, 1964.

"I need scarcely say that I miss you very much. Indeed, I simply didn't realize how different it was going to be without you around the building. I hope that all is going well in your new endeavor and that it will not prevent you from paying an occasional visit to your friends in Pasadena."

Robert Corey. Letter to Linus Pauling. April 30, 1965.

"You know, hemoglobin is a wonderful substance. I like it. It’s a red substance that brings color into the cheeks of girls, and in the course of my hemoglobin investigation I look about a good bit to appreciate it."

Linus Pauling. "Science and World Problems." Speech sponsored by the Carl Neuberg Society for International Scientific Relations, New York City, NY March 30, 1966.

"It [hemoglobin] is a good substance from the standpoint of a chemist, because of its availability. All you need to do is to catch somebody, introduce a hypodermic needle and draw out a sample of blood. A standard victim of this practice, weighing perhaps 120 pounds (it's easier to catch them small!) contains in the red corpuscles in his blood one and two-tenths pounds of hemoglobin."

Linus Pauling. "Science and World Problems." Speech sponsored by the Carl Neuberg Society for International Scientific Relations, New York City, NY. March 30, 1966.

"Hemoglobin is complicated enough to be interesting. I began research in the nature of hemoglobin in 1935, and now 31 years later, I am still entranced by this wonderful molecule."

Linus Pauling. "Science and World Problems." Speech sponsored by the Carl Neuberg Society for International Scientific Relations, New York City, NY March 30, 1966.

"I have suggested that the time might come in the future when information about heterozygosity in such serious genes as the sickle cell anemia gene would be tattooed on the forehead of the carriers, so that young men and women would at once be warned not to fall in love with each other."

Linus Pauling. Letter to S. Leonard Wadler. August 15, 1966.

"[Zuckerkandl] found that in the beta chain of the human and the beta chain of the horse, for example, 20 of the 146 amino acids are different; but with human and gorilla, only one is different. It is the same amount of difference, just one amino acid residue, as between ordinary humans and sickle cell anemia patients, who manufacture sickle-cell-anemia hemoglobin."

Linus Pauling. "Medicine in a Rational Society." J. Mt. Sinai Hosp. N. Y. 36: 194-199. 1969.

"The National Institutes of Health have indicated that research into this disease is to be more than adequately funded over the next several years and it is hoped that the three year contract applied for will be funded early in the summer of 1972. It is worthy of note that the project director for this research performed pioneering work in the molecular understanding of this disease and has continued to play an influential role in continued research to date."

Linus Pauling. Excerpt from grant application, "The Involvement of Humoral, Metabolic, and Molecular Factors in Sickle Cell Crisis." 1972.

"How pathetically confused and misguided zealots can be!!"

Robert Nalbandian. Letter to Linus Pauling. May 1, 1972.

"In my current Institute there are the problems of any new experimental and research institute. It seems to be possible to get grants for our more conventional work but not for the problems that I would like to attack, which I consider to be the more imaginative ones."

Linus Pauling. Interview with David Ridgway for the Journal of Chemical Education, 53: 471-76, 475. June 20, 1975.

"I remember asking a new graduate student, Harvey Itano, what his research problem was. He said he was going to test your hunch that there was a difference in hemoglobin molecules between normal people and those with sickle cell anemia. I thought that was a crazy idea; a complicated human disease could not have any such simple cause. And so I learned to respect bold simple ideas -- especially those conceived by Linus Pauling."

Norman Davidson. Letter to Linus Pauling. January 26, 1976.

"I think that it is the duty of scientists to help their fellow citizens to understand the problems, and to give them the benefit of their own knowledge about the scientific aspects of the problems. In addition, however, to this work of helping to educate their fellow citizens, scientists have, I think, the obligation to express their own opinions, in order to help their fellow citizens."

Linus Pauling. "Preliminary Script for German TV Program." Interview by Harald von Troschke  May 26, 1976.

"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 the magnetic properties of hemoglobin was responsible in large part for the development of the now-accepted ideas about the binding of oxygen and carbon monoxide."

Linus Pauling. Letter to C. Lockard Conley. August 1, 1978.

Linus Pauling is one of that select group of individuals whose lives have made a discernible impact on the contemporary world. His contributions to molecular chemistry have been substantial and fully deserving of the recognition that he received in the form of a Nobel Prize in chemistry....Pauling continued to do productive scientific work throughout his lifetime, making a second outstanding contribution in his discovery of the molecular processes involved in sickle-cell anemia. This discovery, if made by anyone who was not already the only person to receive two unshared Nobel Prizes, might well have merited a third prize in medicine.

Ted Goertzel. "Linus Pauling: The Scientist as Crusader." Antioch Review, 38 (1980): 371-382. 1980.

"The hemoglobin molecule, with its striking color and its property of combining reversibly with dioxygen, seemed to me to be especially interesting."

Linus Pauling. "Hemoglobins and Hemoglobinopathies: A Current Review to 1981." Texas Reports on Biology and Medicine, University of Texas Medical Branch, Galveston, Texas, 40: 1-7. 1980.

"Ortho means 'right' -- the right molecules in the right amounts. Orthomolecular medicine is the use of the right molecules or orthomolecular substances that are normally present in the human body in the amounts that lead to the best of health and the greatest decrease in disease. It is the most effective prevention in the treatment of disease."

Linus Pauling. Interview by Deborah Kesten. Healthline. April 1983.

"I went to New York and gave a seminar at the Rockefeller Institute for Medical Research, in 1936. And at that time, I asked the director, Simon Flexner, to send Alfred Mirsky and his family to Pasadena to be with us for a year, because of my interest in hemoglobin. So Mirsky came. Mirsky was astonished that I would have the temerity to approach Flexner -- I was a brash young man, I think -- and then astonished that it worked out!"

Linus Pauling. Interview by John L. Greenberg, California Institute of Technology Archives Oral Histories Project. May 10, 1984.

"I'd built up this great research organization in structural chemistry, and I had discovered molecular diseases there at the Institute."

Linus Pauling. Interview with John L. Greenberg, California Institute of Technology Oral History Project. May 10, 1984.

"Life is too complicated to permit a complete understanding through the study of whole organisms. Only by simplifying a biological problem -- breaking it down into a multitude of individual problems -- can you get the answers. In 1935, for example, Charles Coryell and I made our discovery about how oxygen molecules are attached to the iron atoms of hemoglobin, not by getting a cow and putting it into our magnetic apparatus, but by getting some blood from the cow and studying this blood."

Linus Pauling. Interview with Neil A. Campbell, Bioscience, v. 36, no. 11. December 1986.

"If the bomb testing had gone on at the same rate for a few more years, it would have meant that...according to my calculations, which seem to have been essentially right, millions of children, infants, would have been born with gross physical and mental defects that otherwise would not have had the defect and millions of people would have died of cancer at an earlier age than otherwise."

Linus Pauling. Interview with Neil A. Campbell, Bioscience, v. 36, no. 11. December 1986.

"Many orthomolecular substances are so free from toxicity that they show beneficial effects over a 10,000-fold range of concentrations. Yet if you take even ten times the amount of aspirin that many patients take, for example, you’d be dead; hundreds of people do die every year from aspirin poisoning. And all of the other major drugs are highly toxic as well."

Linus Pauling. Interview with Neil A. Campbell, Bioscience, v. 36, no. 11. December 1986.

"Well, I thought that was a pretty nice idea that I had in 1945, about molecular diseases."

Linus Pauling. Interview with Nancy Touchette for "The First Molecular Biologist." Journal of NIH Research, vol. 2. 1990.

"[M]y recommendation to young people, which I have been making for fifty years, is that if you want to go into biology, biochemistry, molecular biology, why don’t you start out by majoring in physics and chemistry and mathematics and then move on later? I’ve even students interested in biology to take the Ph.D. in chemistry, rather than biology, and then...start work in...plant physiology or some other field. With your basic understanding you will be able to be successful in this field."

Linus Pauling. "Linus Pauling, Ph.D." Interviewed by Wayne Reynolds for the American Academy of Achievement. November 11, 1990.

"...I realized that I myself might discover something new about the nature of the world, have some new ideas that contributed to better understanding of the universe. For seventy years the motive to obtain greater understanding has dominated my life."

Linus Pauling. "The Nature of Life, Including My Life, Chapter 1 - How I Developed an Interest in the Question of the Nature of Life." May 5, 1992.

"To my surprise, I recieved the Nobel Peace Prize. I was at my home here in Salmon Creek, and I got back to Pasadena a couple of days later, and I was shown a copy of the Los Angeles Times where the president of the institute, Lee DuBridge said, 'It's really remarkable that any person should get two Nobel prizes, but there is much difference of opinion about the value of the work that Professor Pauling has been doing.' That's the work for world peace, you know. Well, I thought, that's a little too much so I decided to resign from the institute....DuBridge's statement caused me to make that decision."

Linus Pauling. "An Interview with Linus Pauling." Chemistry Education, 73, 1 (January 1996): 29-32. April 1, 1994.

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