- Letter from Frederick D. Rossini, NRC to LP RE: Details on the NRC Committee on Physical Chemistry meeting (which LP cannot attend as he is in London). [Filed under LP Science: National Research Council, 1925-1950: Box #14.027 Folder #27.4]
- Letter from Herman F. Mark, Scientific Planning Committee, American Committee for the Weizmann Institute of Science to LP RE: Informs LP of their decision to postpone the scientific gathering they were going to have in May in Palestine because of uncertain political conditions, mention that the physics laboratories have been finished, ask for his preferred time of year to meet so he can be at the opening of the Institute. [Filed under LP Correspondence: 441.4]
- Letter from L.J. Witts to LP RE: Is looking forward to LP's talk on “The Structure of Antibodies” at the Medical Consilia on February 25th. Invites both LP and AHP to dine with he and his wife afterwards. [Witt's last letter: November 24, 1947, LP's reply: February 20, 1948] [Filed under: LP Speeches, 1948s.18]
- Letter from LP to D. R. J. Boyd, Esq., Balliol College RE: Says he would be pleased to come to their sherry party, and thanks them for inviting him. [Note from Boyd to LP February 15, 1948] [Filed under LP Correspondence: (Oxford University, [re: Eastman professorship and residency in Oxford] 1946-1948), #299.8]
- Letter from LP to Dr. Robert Corey. [Notes from Corey to LP February 11, 1948, February 25, 1948] [Filed under LP Correspondence: Box #67.6 file:(Corey, Robert B., 1937, 1943, 1947-1952, 1954-1957, 1960, 1965, 1967-1968, 1971)]
Feb. 18, 1948
Dr. Robert B. Corey
California Institute of Technology
Pasadena 4, California
I am glad to have your letter, and to learn how you are getting along.
Has there been anything done about cooperation with Palmer? I am beginning to feel a bit uncomfortable about the English competition. They have a gift for driving straight at the heart of a problem, and getting its solution by hook or crook.
I enclose a copy of a letter to Carl Niemann, about an address that Chibnall gave here last night. They have not succeeded in crystallizing the quarter-molecules, with molecular weight 2,500 or 3,500, but they may succeed, and if they so they will [sic] the crystals to Mrs. Hodgkin. I think that the whole problem is so important that it would be worthwhile to tackle it independently in Pasadena, and see what progress we could make. Would you talk with Carl, and consider the question of how much effort should be put into an immediate attack along pretty much the same lines as those used by Chibnall. You know that the matter of crystallization of a new compound depends so much on chance that, despite the head start that Chibnall has, we might well succeed in obtaining the first crystals. Moreover, the structure determination of peptides with 26 or thereabout amino residues is such a difficult job that I think we could consider it the next step on the journey toward the complete solution of the crystal structure of a protein, a step that sooner or later we shall have to take.
Dr. Corey Feb. 18, 1948
My proposal is that Carl have a man or two begin work at once on the degradation of insulin, and that as fast as reasonably pure materials are made they be turned over to you, for crystallization and x-ray investigation.
The progress that has been made seems to me to be truly astounding. I judge that paper chromatography has been very largely responsible for it.
I am continuing to get along very well—perhaps being kept a little too busy, with so many extra lectures to deliver. However, I feel that when there is so much interest in what I have to say it is proper that I make the effort to say it.
- Letter from LP to Dr. Thomas Addis RE: Details his and AHP's journey from New York to Oxford, reporting that since his arrival he has been asked to speak in London and that his lectures are well received. Inquires into Dr. Addis' attempts to transfer to the University of California Medical School. [Filed under LP Correspondence: Box #2.3, File:(Addis, Thomas 1948-1949)]
- Letter from LP to Frank Aydelotte RE: Suggests that the salary for the Eastman Professor be raised to 2,500 pounds as to be comparable to average salaries at Oxford and to permit the caliber of professors desired to accept the position. Also raises the question of finding a permanent house to go along with the appointment to the Eastman Professorship. Goes on to report on the children's schooling. [Letter from Aydelotte to LP February 20, 1948] [Filed under LP Correspondence: Box #6.21, file:(Aydelotte, Frank, 1940-1956) and copy in #299.8 (Oxford University, [re: Eastman professorship and residency in Oxford] 1946-1948)]
- Letter from LP to Henry Allen Moe, Guggenheim Foundation. RE: Encloses a copy of a letter to Aydelotte. Informs him of the post-doctorate students working with him. Informs him that he is being kept busy. [Filed under LP Science: John Simon Guggenheim Memorial Foundation, 1946-1952: Box #14.014 Folder #14.3]
- Letter from LP to Mr. Whalley RE: LP asks that a room be reserved for both he and AHP at the Adelphi Hotel for the night of March 16th. [Whalley's letter: February 18, 1948] [Filed under: LP Speeches, 1948s.25]
- Letter from LP to Prof. Carl G. Niemann, Crellin Laboratory, Caltech. [Letter from Niemann to LP March 19, 1948] [Filed under LP Correspondence: Box #277.5, file:(Niemann, Carl)]
I have written to Corey that I thought it important to make an immediate and vigorous attack on the insulin problem, even though it involves duplication of work being done by Chibnall and his collaborators. Would you go to see him, and talk over the problem of what might be done at once. Chibnall spoke here before the Alembic Society last night. I judge that a good bit of what he said has been published already. The amino acid analysis of insulin indicates very clearly that there is a molecule of sub-molecule with molecular weight 12,000. The free amino groups have been determined by a method (due, I believe, to Saenger) involving treatment at about pH 7 with dinitrofluorobenzene, which couples dinitrobenzene groups onto the free amino groups, without changing the molecule otherwise. Then the molecule is hydrolyzed and analyzed by paper chromatography, the bright color of the dinitrobenzene group permitting easy identification of the substituted amino acid. It is found that the two lysine residues present in the molecule have their epsilon amino groups free, because these are coupled with the reagent. Also there are two glycine molecules that turn up as coupled derivates, and also two phenylalanine derivatives. It is accordingly concluded that there are four polypeptide chains in the molecule of molecular weight 12,000 (which contains 106 amino residues), two of these chains having glycine residues at their free amino ends, and the other two having phenylalanine residues at the free amino end.
There are six cystine residues in the molecule, and the four polypeptide chains are presumably held together by these sulfur-sulfur bonds of the cystine residues. These can be reduced, but the more effective method of destroying the bonds
is oxidation with performic acid, also carried out by Saenger. The oxidation produces sulfonic acid groups in place of the sulfide bonds, the residues then being cysteic acid. An ultracentrifuge study has been made by Gutfreund and Ogsten here at Oxford, which is reported to show that the boundary just barely moves, indicating molecular weight slightly less than 5,000. The molecular weight of four equal residues from the 12,000 molecule would be 3,000, and later evidence indicates that the two chains containing glycine at the end have molecular weight 2500 and the other two have molecular weight 3,500.
Saenger has separated the two kinds of chains. He has obtained a 30% yield - that is, 30% of the original protein, which would be about 75% yield - of the glycine-end polypeptide. He has carried out an amino-acid analysis, and has found that most of the simple amino acids are in this molecule, whereas the complicated ones are in the other polypeptide chains, with molecular weight 3,500. Each of the polypeptides seems to contain about 26 residues, the difference in molecular weight resulting from the difference in complexity. He has begun the analysis of the glycine-ended polypeptide by coupling it with the dinitrofluorobenzene reagent and then hydrolyzing, and then separating the various peptides by paper chromatography. He can identify the peptides that come from the end of the group where the glycine residue was by their color. He finds that the dipeptide is the substituted glycine attached to isoleucine. The tripeptide is the substituted glycine attached to isoleucine and valine, and the tetrapeptide is similar but with glutamic acid also. A pentapeptide has also been investigated. Thus it is found that in this peptide containing 26 amino acid residues the first four are, in this order, glycine, isoleucine, valine, glutamic acid, and the fifth one is believed to be serine.
It is clear that there is already considerable progress made on the job of a complete structure determination of insulin. However, there
is still a very great deal of work that remains to be done, and I do not think that it is assured that the British school will finish the job. I believe that this is the problem that we should begin to work on, with as much vigor as possible, under our insulin project. I would accordingly suggest, and I ask you to talk the matter over with Corey, that the thing to do is to get insulin, and to begin its degradation by essentially the same methods as those used by Chibnall, with such variations as seem reasonable to us. In particular, I think that the preparation of the 26-peptides should be carried out in quantity, and that the two (presumably two) kinds of molecules should be isolated in as pure form as possible. I suggest that the men working under you on the insulin project do this, and that the material obtained be turned over to Corey for crystallization. Chibnall has not succeeded in crystallizing either of the 26-peptides. It might be a very big job to do this crystallization, and I think that a specialist should have the job, namely Dr. Schroeder or some similar man. The effort should be made to grow crystals of many different possible kinds, in the hope that one derivative of the 26-peptide would crystallize, and in a suitable form for x-ray examination. It might not be necessary to determine by chemical methods the complete order of residues in the chain, because the x-ray structure determination should provide this information.
I would think that you might want to try to split the 26-peptides into half-size molecules by enzymatic methods. If these were made and crystallized their x-ray investigation would be, of course, much easier than that of the 26-peptides.
With best regards, I am
cc: R. B. Corey
- Letter from LP to Professor Rene Wurmser RE: LP is very pleased to accept his kind invitation to speak before the Society of Biological Chemistry and the Society of Physical Chemistry. He suggests the title of his talk be: “The Structure of Antibodies and the Nature of Seriological Reactions.” [Filed under: LP Speeches, 1948s.28]
- Letter from Mary E. Ray, Secretary, Emergency Committee of Atomic Scientists, to Mrs. Daniel Marsh. Apologizes for the delay in reply and writes to say they did check their records and that she has been added to their mailing list. She will receive the March issues in a few weeks; her original request may have been misunderstood and apologizes for the confusion. Writes that anyone wishing to subscribe to the Bulletin of the Atomic Scientists should make their checks payable to the Bulletin of the Atomic Scientists and checks made payable to the committee are seen as donations. Encloses a reprint from January 48, and Dr. Einstein's article "Atomic War or Peace," which may be of interest to her. [Letter from Marsh to Emergency Committee of Atomic Scientists, January 20, 1948, Letter from Marsh to Emergency Committee of Atomic Scientists, 3- 10-48]. LP Peace: Box 3.005, Folder 5.4