1 September 1954

Mr. John Schuyten

5520 Esmond Avenue

Richmond, California

Dear Mr. Schuyten:

I am writing in answer to your letter of 30 June, which arrived in Pasadena shortly after I had started on an eastern trip.

I do not have any very good suggestions to make about places where you might apply for a position. I do not have very close contact with engineering work.

Have you had any experience on the investigation of alloys with x-rays - I mean the determination of their structure by x-ray diffraction? I hear about openings in this field occasionally, and might be able to refer you to a prospective employer.

Sincerely yours,

Linus Pauling:W

[handwritten note]

3 September 1954

Dear Peter:

I enclose a bill for 3 pounds 8 shillings from Easibind Limited. Would you please pay it, keeping track of the expenditure, so that I may reimburse you later.

Everything is going well here. I have continued to work on collagen. It seems to me unlikely that the Huggins structure can be correct. I have made a model of it, using, however, the approximate amide groups (120(degree) angles), and the model tends to coil up in a roll, instead of stretching out into a helix with the proper pitch. Moreover, Huggins' model, like our original one, has two thirds of the groups cis, and Badger says that the Infrared spectra show that the groups are practically all trans.

My structure, when built with the refined models, did not come out quite right. However, it is close enough so that I think it is not yet eliminated, and I still favor it -- perhaps because everything else that seems to me to be reasonable has been eliminated.

We have a stone mason working around the house today. He has been working during the past week. He and his helper took up the bituminous pavement extending from the road near the garage to the stone pavement near the swimming pool - 80 feet in all - and have replaced it with stone. The first 30 feet of stone, nearest the garage, is laid in cement, so that it will not be necessary to try to grow grass between the slabs, whereas the remaining 50 feet is still to have grass between it. It looks very nice. Today he is beginning on the construction of a low stone wall along part of this walk, similar to that just north of the swimming pool.

On Monday I am flying to Chicago, and, in fact, taking the train then to Kalamazoo, three hours' ride from Chicago. I am spending Tuesday with the Upjohn Company, giving a talk for them on the abnormal hemoglobins, and then returning to Chicago that evening. On Thursday I am speaking at Northwestern University on modern concepts in chemistry, before a meeting of the Society for Promotion of Engineering Education, and then flying back home Thursday evening.

Work on the revision of COLLEGE CHEMISTRY continues to take up most of my time. I have finished the major jobs, and am now working on the chapters that require only a small amount of change.

Two days ago we moved the Studebaker, which has been standing in our garage for a couple of months, over to Mrs. Brown's garage. The battery had gone dead, so Izzy, who is free again, and had stayed with us for a couple of weeks (he now has a room somewhere else) came over with his car, and pulled it over to Mrs. Brown's place. It was quite a strain for his car. Then he had to stop while the car was about 20 feet from the garage door, and drive his car over to one side. Then Mama, Izzy, Mrs. Brown, Edward, and I all pushed the Studebaker up the hill. We had to stop just before getting the front end of it into the garage, because the slope increased suddenly there, and we were too tired to get it up. Mama ran back to get a board, about 6 inches wide and three feet long, that we had put behind the rear wheel, and started to roll it toward the garage. As she rolled it once, it fell back instead of forward, and landed on her big toe, which has in consequence been sore for several days. It is apparently only a bruise. She would have been better off to have shoes on.

We have had a month of rather cool weather, but the last few days have been very hot -- temperatures around 97(degree)• We are happy to have the pool to swim in.

Love from

Linus Pauling:W

8 September 1954

Dr. Harold C. Urey

Institute for Nuclear Studies

University of Chicago

Chicago 37, Illinois

Dear Harold:

I was pleased to receive your letter, but sorry that you had been worried about the reception of your talk. I do not think that there is any use in my getting in touch with the editor of Frontier. I do not remember clearly what was said to me by a couple of people who heard your talk, but I think that they said that most of the members of the audience seemed to be dissatisfied with a statement that you made about the impossibility of getting along with Russia -of finding a way for peaceful co-existence in the world. However, as I have said, I am not sure that I remember correctly.

Is there an address that you could give me for about the time 20 September or 1 October? There is another matter that I should like to write to you about.

I am sure that you and Mrs. Urey are enjoying yourselves. I am glad to be spending a quiet summer at home - I am at work revising my textbook COLLEGE CHEMISTRY. I may say that both Ava Helen and I had a fine time traveling through Germany and Scandinavia last summer.

With best regards, I am

Sincerely yours,

Linus Pauling:W

I think that the time has now come for us to finish up the job on collagen.

I have finally become convinced that there is no reasonable alternative to the (10,10,a) structure for collagen, and that our job now is to refine the structure somewhat (this involves moving the atoms only a few hundredths of an Angstrom), and gathering and presenting the evidence about it.

I have just carried out another effort to find an alternative structure to (10,10,a), without success.

I think that it is very unlikely that I have overlooked the correct structure in my search. Moreover, the fact that three structures for collagen have been published in the last few months, by Crick, by Huggins, and by Ramachandran and his coworkers, shows that other investigators have been searching, too, and it is of some significance that they have not proposed a structure that is acceptable. It is, of course, true that they have apparently not discovered the (10,10,a) structure, and that accordingly they might have overlooked the correct structure, if it is a different one.

I shall summarize the present situation in the following paragraphs.

1. It is likely that the amide groups are all in the trans configuration, although possible that the proline amide group has the cis configuration. (I shall use proline in this discussion to refer to both proline and hydroxyproline, when discussing the main chain.) There is evidence, in the papers of Mizushima and Simanouti, that the trans configuration is more stable than the cis configuration, by significant amount. I think that the argument would, however the proline and hydroxyproline groups, because for them the nitrogen atom forms two single bonds to carbon atoms, which would behave in a nearly equivalent manner. Professor Badger says that the spectroscopic data pretty well show that the amide groups have the trans configuration. It is, I think, likely that the spectroscopic argument involves the N-H vibration, and that his conclusion accordingly applies only to the non-proline groups.

Our original structure was of the type cis-cis-trans. It does not agree with the x-ray data. I have not been able to formulate a cis-cis-trans structure that is acceptable. The Huggins structure, which is of this type, is probably unsatisfactory because of a non-coplanarity of the bonds formed by the nitrogen atom. I have not made a further detailed study of it.

I have not been able to find any satisfactory structure of the type cis-trans-trans. I think that all structures of this type can be ruled out if the assumptions are made that two hydrogen bonds must be formed for every three residues, the repeating unit being a three-residue unit, and that the orientation of the hydrogen bonds must conform roughly to the limitation set by the infrared dichroism.

The following detailed discussion relates accordingly to trans-trans-trans structures, involving a repeating unit of three residues.

2. Elimination of structures involving three chains twisted about one another. On 5 March 1954 Professor Badger told me that in glycylglycine the N-H vibration, 3300 cm^-1, lies about 10º from the N-H axis, in the N•••O direction, and that the amide II vibration (which is probably to be attributed largely to the wagging of N-H) is very nearly perpendicular to it, and in the plane of the group.

The direction assigned to the amide II vibration by Badger is within 2 degrees of the line stretching across the amide group between the two α-carbon atoms at its ends. Accordingly the observed dichroism of the amide II vibration, which occurs at about 1550 cm^-1, provides a very simple way of drawing conclusions about the folding of the polypeptide chain.

Let us assume that the amide II vibration lies within 10 degrees of the αC-αC axis, and draw conclusions from this.

If there are three chains, each amide group must stretch 2.86 A along the fiber axis. The distance between α-carbon atoms is 3.83 A. Hence the angle is 48º between the/axis and the basal plane. This corresponds to a positive dichroism of 2.54, which is far greater than the observed 1.22 (Badger). The observed dichroism corresponds to an angle of 38º, which is 10º less than calculated, and accordingly possible. However, there is no acceptable way of arranging three chains, with suitable hydrogen bonds.

3. Structures involving a single chain.

I have made an exhaustive analysis of structures involving a single chain, with a repeating unit of three trans groups, forming two hydrogen bonds.

Several of these structures have an axial length per unit of 2.86 A. The include (10,10,a), (14,14,a), (16,16,a), and (10,16,a). The last three of these four are easily eliminated by the observed infrared dichroism.

First let us consider the amide II vibration. The observed dichroism is positive, with value 1.22. If we assume that this vibration is along the α-carbon axis of the amide group, then the positive dichroism eliminates all structures of the single-chain all-trans type in which the x coordinates of the α-carbon atoms show only increase in value along the chain. The chain must progress the distance 2.86 A along the z axis, in the unit of three residues. If each residue is occupies one third of this distance, 0.95 A, the axis is at the angle 14.4º with the basal plane, and the dichroism is negative, the ratio being 17.6. The closest approximation to positive dichroism occurs when two of the residues have zero component along the figure axis, and the third the full component 2.86. The dichroism is still then negative, with ratio 1/2.2. This is so far from the observed 1.22/1 that we conclude that any three-chain all-trans structure must be a retrograde structure, with one residue having a negative component of its α-carbon axis along the fiber axis. (Or perhaps two residues having negative components.)

The structures (14,14,a), (16.16,a), and (10,16,a) are all non-retrograde in character. All have calculated dichroisms for amide II that are strongly negative, approximately 1/7 in each case. These structures may accordingly be ruled out.

All three structures may also be ruled out by consideration of the infrared dichroism for the N-H stretching vibration and for the amide I vibration (which is largely the C=O stretching vibration). These vibrations both show negative dichroism. The calculated dichroisms for the three structures just discussed are strongly positive, and the structures are hence eliminated.

4. The (10,10a) structure and the observed infrared dichroisms.

The calculated dichroism for the amide II vibration is 1.23 for the (10,10,a) structure when all three amide groups are counted, and 1.16 when 70 percent of one amide group is occupied by proline and hydroxyproline, and considered not to contribute to this vibration; these values correspond to positive dichroism, and are acceptable.

The calculated dichoirc ratios for the N-H and amide I vibrations, assuming them to be along the N-H axis or C=O axis, are approximately 1, whereas these vibrations are observed to show negative dichroism, 1/1.8 and 1/1.2, respectively. There is enough uncertainty about the effective directions of the dipole moments for these vibrations in the complex structure of the coupled hydrogen bonds that, however, the lack of complete agreement cannot be used to rule out the structure. The structure may be considered to be composed of three amide groups (alternating in the polypeptide chain) that are coupled together by two hydrogen bonds, and that may form a unit responsible for the infrared absorption. (The interaction is probably large for these vibrations, and small for the amide II vibration.) The configuration of this unit in space is such as to indicate that the effective dipole moments form a smaller angle with the basal plane than that formed by the N-H and C=O axes. This is presumably the explanation of the observed negative dichroisms. It may be desirable to carry out a somewhat detailed theroretical discussion of this question.

5. Dimensions of the structure.

The x-ray data indicate that there are three residues for collagen in the axial length 2.86 A, and that there probably is a repeating unit of three residues forming a helix with ten units in three turns or in seven turns. The (10,10,a) structure with planar amide groups and 110º bond angles gives 2.75 A per unit and 4.5 units per turn, rather than 3.3. If two of the residues in a unit are twisted about the C'N axis, through about 6º, the structure can be deformed to 2.86 A per unit and 3.3 units per turn. This corresponds to a strain energy of about 0.3 kcal/mole for each of the two residues. The same result can be achieved by distributing the deformation over several features of the structure – changing several bond angles by about 1 degree apiece, bending the double C'-N bond a little, and rotating about it through a smaller angle, perhaps three degrees. A total strain distributed over n features rather than one decrease the strain energy to 1/n of its value. It is accordingly probable that the amount of deformation involved here is not more than a few tenths of a kcal/mole per unit. The deformation is presumably the result of steric repulsion between the δ-carbon atom of the proline ring and the adjacent (once removed) amide group, and perhaps also between the carbonyl oxygens and the adjacent amide groups.

The orientation of the α-carbon atom adjacent to the proline nitrogen is a satisfactory/for formation of the proline ring.

6. Side chains.

The structure provides satisfactory positions for side chains. Of the two non-proline α-carbon atoms, one projects toward the axis of the compound helix, and one is on the outside. It cannot be concluded, however, that the former must represent only glycine residues, because there seems to be room enough for a larger side chain.

7. Radial distribution curve.

An experimental radial distribution curve published by Riley and Arndt has now been replaced by another one, sent to me by Dr. Riley. In the region from 6 A to 12 A the new curve shows acceptable agreement with the calculated radial distribution curve, made by Dr. Pasternak. There is a pronounced difference between the two curves, in that the experimental curve has a larger peak at 5 A, which is not shown on the theoretical curve.

It seems to me likely that the large peak at 5 A is to be attributed to the effect of atoms of side chains, not taken into consideration in the theoretical calculation. The (10,10,a) structure is in the form of a compound helix, which may be described as a rod with the 3₁₀ structure in which every third hydrogen bond is broken, permitting the rod to be twisted into a helix. The rod is about 6 A in diameter, including the Van der Waals radii of the atoms, and it is twisted into a helix with average radius about 3.5 A and pitch about 9.5 A. There is accordingly a helical cavity about 4 A in diameter, which must be filled up with side-chain atoms. Consideration of the model shows that an atom in this helical cavity will have some neighbors at about 3 A distance, and a number of neighbors at about 5 A distance.

I think that it would be wise to have Dr. Pasternak carry out, without delay, a determination of the radial distribution function for collagen. Possibly this should be done by Dr. Marsh, using the spectrometer and a disoriented sample of collagen or of gelatin, or perhaps both.

It might be worth while to repeat this work with a hydrated specimen, to see whether or not the same radial distribution curve is obtained.

8. The distribution of intensities along the equator.

I think that it would be worth while to make a comparison of observed and calculated intensities along the equator of a fiber diagram.

As for the calculated intensities, it would, I think, be enough to use the Bessel-function formula, which is given in our paper on Atomic Coordinates and Structure Factors for Two Helical Configurations of Polypeptide Chains. I think that you have a record of the atomic coordinates for the structure – the atomic coordinates were used by Dr. Pasternak in his radial distribution calculation. They may have to be refined somewhat later on, but I do not think that any changes that will be made are significant for this calculation. Could you have Mrs. Oberhettinger carry it out?

It might be worth while also to have Dr. Marsh make a spectrometer study of the equatorial intensities for kangaroo-tail tendon, both in the dried state and hydrated.

9. I feel that it would be well worth while to make some new collagen photographs, In particular, I think that we should examine the large-angle region along the meridian, to see whether reflections that at 1.43 A, 0.95 A, and 0.72 A can be picked up – perhaps even at 0.57 A. If the orders from 1 to 5 of the 2.86-A meridional reflection could be observed, and if their relative intensities were found to correspond to the proposed structure, we would have a pretty strong argument in favor of the structure. There will no doubt be a very heavy general background in this region, but I feel that it would be wise to make a vigorous effort to obtain experimental values of the intensities of these reflections. You remember how much more could be seen on the silk photographs than had been reported in the literature.

10. Ramachandran has stated that the 2.86-A reflection is not a meridional reflection. Perhaps a Weissenberg photograph could be made to check this point.

11. I think that it might be worth while to evaluate the complete form factor for the structure. I think that it should be done for only one azimuthal orientation of the helix. It is true that there are only ten orientations of different units, rather than eighteen in the α helix, but the result obtained by Dr. Yakel for the α helix, that the form factor varies only slightly with change in azimuthal orientation of the fiber relative to the x-ray beam, probably would apply pretty well to this structure also. The calculation would be made by use of the formula of Cochran, Crick, and Vand.

12. A simple calculation might be made to explain the observed meridional reflections on the third and seventh layer lines – perhaps also on the sixth layer line (I had thought that I could see such a reflection).

The chemical analyses of collagen indicate that in 30 residues there are about three hydroxyproline residues and four proline residues, a total of seven Pro + Hypro. There are, however, ten positions which might be occupied by these seven residues. Presumably three of the positions are occupied by some other amino acid.

I have assumed the sequence x, pro, hypro, x, pro, hypro, pro, x, pro, hypro, as a repeating sequence, in the identity distance 28.6 A.

I have assumed a scattering center with scattering power unity at each of the pro + hypro positions, and have calculated the following values of the structure factor for the first ten orders of reflection (00l): 0.4, 0.6, 2.6, 1.6, 1.0, 1.6, 2.6, 0.6, 0.4, 7.

We see that there should be a very strong tenth order, the observed 2.86 A meridional reflection. The two next longest reflections are the third and seventh; these are observed. Next are the fourth and sixth; of these the fourth is not present, but I have thought that I could see the sixth. It is calculated to be about 40 percent as intense as the third or seventh.

Perhaps the calculation should be carried out with use of the z coordinates of the atoms gamma-C and δ-C for the proline and hydroxyproline ring, and perhaps also for the oxygen atom of hydroxyproline. The β-carbon atom of the ring probably should not be included, because presumably there is a β-carbon atom in the residue taking the place of the ring. It might turn out that interference of the gamma-C, δ-C, and O would cause the intensity of 004 to be decreased, and perhaps that of 006 to be increased.

9 September 1954

Dr. Heinrich Heesch

Wilhelmplatz 4

Kiel, Germany

Dear Heinrich:

Your letter arrived in Pasadena just after I had left on an eastern trip, and since returning I have put off answering it, because I got very busy with the revision of a book.

I am glad to have the information that you give me about the four-color problem. I agree with Professor Peschl that you should prepare your present results for publication.

Have you decided on a place for publication? You might want to get in touch with Professor Phillip Franklin, in the Department of Mathematics at Massachusetts Institute of Technology. To reach him all that you need to do is to address the letter to M.I.T., Cambridge 39, Massachusetts. You mention in your letter that he worked with Birkhoff on the four-color problem long ago, and I suppose that he is still interested in it. He is the editor of a mathematics journal.

I think that it would be well worth while for you to publish also the classification that you have made of all maps in such a way that the four-color problem could be solved by a finite process. I think that you should try to carry out this process, but also it is worth while to see whether some of it might be done with electronic calculating machines, or at any rate whether the electronic calculating machines could be used to check the calculation.

In addition to revising my book, the textbook in general chemistry, I am working on the problem of the structure of collagen, which is a protein present in tendons, bones, and skin. This problem is a very difficult one, but I think that I have found a satisfactory structure now.

Cordially yours,

Linus Pauling:W

California Institute of Technology Inter-Office Memo

To L. Pauling From A.C. Allison, M. Murayama, J. Vinograd Date Sept 9. 1954

Subject Summary of Investigation on the Properties of S Hb solutions carried out at the Calif. Inst. Of Technology during August 1954.

Appended are summaries of research initiated during the visit of Dr. Allison. The work deals with the phenomena which occurs when concentrated solutions of S Hb are deoxygenated.

Since no part of the work is completed as yet tentative plans have been made to continue the work along the following lines:

1. Berreman and Murayama will continue to examine by x-ray diffraction methods the sickling of RBC, the formation of gels in deoxygenated S Hb, and possibility of fiber formation by S Hb.

2. Dr. Allison will continue the examination of effect of temperature and hydrogen bonding agents on gelation. It is anticipated that this work will be published in a short time since it is now well advanced.

3. Demonstration of the applicability of the phase rule to the system during gel formation will be carried out at C.I.T.

10 September 1954

Professor Edmund W. Sinnott

Graduate School

Yale University

New Haven, Connecticut

Dear Professor Sinnott:

I have received your letter of 30 August and am writing to say that Professor Corey, Roger Hayward, and I are pleased to give you permission to reproduce in your botany textbook one of the figures which appeared in our article on The Structure of Protein Molecules in the Scientific American for July 1954.

With best regards, I am

Sincerely yours,

Linus Pauling

W

cc: professor Corey

Mr. Hayward

14 September 1954

Dear Peter:

I shall pay the bill for the book when it arrives.

I am afraid that I do not have any very good suggestion to make about getting a heavy metal atom onto myoglobin or hemoglobin. It seems to me that it would be best if the atom were directly attached to the iron atom, and not dangling at the end of a chain somewhere. Our experience is that with hemoglobin a large molecule has difficulty in combining with the iron atom -- you remember that tertiary butyl isocyanide was found to combine with hemoglobin 200 times less strongly than ethyl isocyanide.

I was interested in making some alkyl isocyanides with an ionic group, such as a carboxyl group, attached to the side chain. Much to my surprise, the synthesis did not work out. I have a feeling that the ordinary isocyanide synthesis is sensitive to electronic interactions along the chain. I do not remember that anyone has ever made an isocyanide in which there is a heavy atom attached to the side chain. It might be possible to make an ethyl isocyanide with an iodine atom on the beta-carbon atom. On the other hand, I think that probably the treatment with alkali in the manufacture of the isocyanide would hydrolyze the carbon-iodine bond.

I have one suggestion to make. It seems to me possible that iodide ion would combine with ferrimyoglobin. You remember that hemoglobin combines preferentially with neutral molecules - oxygen, carbon monoxide, imidazole, the alkyl isocyanides. When the iron atom is oxidized to the tripositive state, hemoglobin combines with negative ions -- cyanide ion, fluoride ion, azide ion. Accordingly your best bet is to try to attach a negative ion to myoglobin. I think it is unlikely that iodide ion combines strongly, or I would remember that the compound has been made. Nevertheless, you might take some myoglobin, oxidize it to the ferric state (this can be done with ferricyanide ion), observe its spectrum, using a Hartridge reversion spectroscope, then add some potassium iodide solution, and see if the spectrum changes in the way that it does when you add cyanide ion. Roughton probably could lend you a Hartridge reversion spectroscope -- it is a little instrument in which there are two spectra, running in opposite directions. The wavelength of an absorption band or line is measured by moving the two spectra relative to one another until the line coincides in the two spectra, and then measuring the wavelength on a scale. Perhaps you have one in the unit.

I may say that it is still more likely that astatide ion would combine with ferrimyoglobin, but I do not know whether astatide ion can be obtained or not. Probably not.

I have just had another idea, although I hesitate somewhat to mention it to you. Ferrihemoglobin will combine with the hydrosulfide ion, HS^-. It is likely that it will combine with the hydroselenide ion, and also with the hydrotelluride ion. Accordingly, you might prepare some hydrogen telluride, H₂Te, by action of acid on a metal telluride, and run this gas into a solution of ferrihemoglobin -- or, better still, see if you can get some sodium telluride, Na₂Te, and add a small quantity of it to a solution of ferrihemoglobin. You must be very careful in working with hydrogen telluride or sodium telluride. Several chemists have been killed by it, because it is very poisonous. If I remember correctly, there was one such case in the chemistry department at Cambridge, about 50 years ago.

If this procedure works, and I think it likely that it will, you would have a tellurium atom attached directly to the iron atom of the heme group. The tellurium atom has one electron less than an iodine atom. It is accordingly far from being as strong a scatterer of x-rays as a mercury atom is, but it might be enough to do the job. Moreover, you can predict its distance from the iron atom, and you know that it will be out from the plane of the porphyrin ring. You might be able to orient the porphyrin ring by the optical properties -- except for azimuthal orientation around the iron-tellurium axis, which would have to be evaluated separately. If you had the coordinates of the tellurium atom and all of the atoms in the heme group, you would have a good start on the determination of phases.

I may say that I am not absolutely sure that the hydrogen telluride ion will combine with ferrimyoglobin. There is one argument against it, the fact that the electronegativity of tellurium is less than that of sulfur, and that the tellurium atom has accordingly a small tendency to form a bond with an iron atom. Nevertheless, I think feel pretty sure about making this prediction. You might want to try out hydrogen selenide first, perhaps determining the equilibrium constant of the HSe^- ion with ferrimyoglobin. You must be careful in working with selenium, also. It is not so poisonous as tellurium, although it is poisonous. On the other hand, most people who do any work with the element soon get a strong garlic breath, which causes their friends to be concerned.

I know that polonium can be obtained in at least microgram quantities, so that you might try the hydrogen polonide ion. Probably the difficulty of getting polonium is so great, however, as to make this not worth doing. Moreover, you would have trouble because of its fogging the photographic plate. I think that the tellurium idea is a good one, however.

I am interested to learn about the shrinkage states in the crystals of Finbak whale myoglobin. It is nice to have an orthorhombic crystal, but on the other hand four molecules are rather too much for the unit of structure -- I think that a monoclinic crystal with two molecules in the unit is the thing to look for, or even a triclinic crystal with one molecule in the unit. Dr. Corey has, I think, just about decided to give up on lysozyme as a crystal for an attempted complete structure determination, because of the four molecules in its unit (tetragonal).

I shall look forward to learning about any new results you obtain on the 1.5-A reflection.

I passed your comment about the rotating anode tube on to Holmes. He said that our rotating anode tube is pretty well along, and I went downstairs to look at it. Sheldon is installing the auxiliary apparatus for it now, and I hope that it will be operating in a few months.

The new laboratory is coming along in good shape. Concrete is being poured on the sub-basement walls and basement walls now, and on the columns along the center line of the building.

Give Millie Fowler my regards when you see him -- also Linda, when she gets back from France.

I am afraid that I cannot do anything about providing you with an index for your copy of Lucas. Professor Lucas left a couple of weeks ago -- he is going to teach organic chemistry full time in Columbus, Ohio, this year. It is unlikely that he would have an extra index, even though he might have saved page proofs of the book.

I am glad that you are taking a course on operation of the electronic computer. We have been having some trouble here with the electronic computer that was being used by our x-ray men - the Consolidated computer. The company now has enough business, I judge, to have caused them to break off the arrangement that had been made with us, before we were able to make the calculations that had been agreed upon. It seems possible, however, that we can arrange to use the Navy computer at UCLA. Moreover, it is not so much trouble to get to UCLA, now as it used to be. The freeway goes through Hollywood, and up into the San Fernando Valley. McCullough told me that he can get from the Institute to the point where he leaves the freeway -- probably Sunset Boulevard in Hollywood -- in the same length of time that it takes to get from there to UCLA -- altogether about 45 minutes from the Institute to UCLA, I think. I have not made the trip.

I have just been to Kalamazoo and Evanston, Illinois. I spent one day in Kalamazoo, visiting the Upjohn Research Laboratories. The Upjohn Company is an Industrial Associate of the Institute, and staff members are supposed to visit the Industrial Associates to give them some return for their $10,000 per year. I gave a talk on sickle cell anemia. At Evanston I attended a conference held by the Society for Engineering Education, and gave a talk on new concepts in chemistry. John Slater was there, and several other friends of mine. I was gone three days. Perhaps four days and three nights is more accurate.

I am still working hard on the revision of COLLEGE CHEMISTRY. I don't know just where I stand, because I have done some work on almost every chapter. Several people are reading the manuscript, and I have the job of going over it again, with their comments in mind.

Did I tell you that we have made some more dural models, in which the bond angles and bond distances are exactly right for an ordinary amide group? We have also made some in which the angles have the right values for a proline residue. I decided the other day that these models are with us to stay, and that we should order 10,000 Allen set screws, for $227, in order to get the reduction in price. This is enough for about 100 models, each with about 25 amino-acid residues in it.

If you do anything with tellurium, you probably should talk with Herman Emeleus first, and get advice from him. It is likely that he has some sodium telluride at hand. If so, there is no need to prepare the gas, hydrogen telluride -- all that you need to do is to add a milligram or two of the sodium telluride to your solution.

I may say that it might be well worth while, as a small extra investigation, to study the reaction of hydrogen selenide and hydrogen telluride (that is, of the hydrogen selenide ion and hydrogen telluride ion) with ferrihemoglobin and ferrimyoglobin, as a separate biochemical problem. These acids, H₂Se and H₂Te, are weak acids -- the first ionization constant of H₂Se is given in COLLEGE CHEMISTRY as 1.7 x 10^-4, and that of H₂Te as 2.3 x 10^-3. The second ionization constants are 1 x 10^-1 and 1 x 10^-5, respectively. These values mean that in the neutral range the solution that you would obtain by adding sodium selenide to the ferrihemoglobin solution would contain practically all of the selenium as HSe-, that is, in the form to combine with the ferrimyoglobin. The tellurium, however, would, if the value of the second ionization constant is correct, be largely in the form of Te^--. In order to convert it into HTe^- it would be necessary to acidify the solution somewhat, to about pH 5. I may say that it is quite possible that the ion Te^-- would also combine with ferrimyoglobin, so that you might have a compound at all pH values. You can follow the compound formation spectroscopically. It might be worth while for you to look through the literature, to see whether anybody has investigated possible compounds of ferrihemoglobin with the hydroselenide ion and the hydrotelluride ion, but no matter what you find, you should not be prevented from making your own investigation. See PPS

Do you know Joan Keilin? She published some work on compounds of isocyanides with heme, a few years ago, if I remember correctly. She might be willing to collaborate with you, if you wanted to get somebody to help you, in the investigation.

Crellin came back from Honolulu yesterday. He seems to have learned a good bit, in his work as an organic chemist. He leaves for Portland tomorrow. He is taking the little trunk, with a jog in it, which I bought before we went to Europe -- you remember we thought that it might have been a trunk on the back of an automobile. By the way, do you have two trunks with you in Cambridge? I tried to remember, and decided that you had taken the rawhide trunk for your books, and the big greenish trunk for your clothes. Is this right?

If you go to London sometime, you might be interested to hunt up Hermann Lehmann, pathologist in St. Bartholomew's Hospital. He spends his spare time traveling around in Africa, India, Arabia, the Andaman Islands, etc. testing blood samples for sickling. He visited us here last spring. Dr. Anthony Allison, of Christ Church and the Radcliffe Infirmary in Oxford, has just left, on his way home. He is another sickle-cell-anemia investigator -- the one who inoculated Africans with malaria parasites, and found that the sickle-cell-anemia hemoglobin provides protection against malaria. His wife is an American girl, interested in Egyptology, I believe.

I have not been able to do anything on collagen during the last week, but I hope to get some results before long.

Remember to be careful in working with tellurium. You should not have any trouble, because you need only a very small amount to combine with your heme groups.

Do you have any opportunity to speak in public -- that is, to talk before a group of people? You probably are going to follow an academic career, and it is important for you to be as good a speaker as possible. Practice counts for a lot. Are you a member of the Space Group, or does it not exist any more? I remember that I spoke before the Space Group in Cambridge in 1930 -- Bernal had organised it. The new group, in the Cavendish, probably is an outgrowth of the old one. If you could join some other group which has been formed for the purpose of holding seminars, I think that it would be a fine idea for you to do so.

Much love from

[Linus Pauling]

P.S. Have I told you that this summer I have been doing my work almost entirely in the new study, just west of the front porch. It is much cooler here than in my old study. In fact, I usually work in my old study for a little while in the morning, unless the morning is especially warm, and then I work in the new study in the afternoon. I have only been spending a couple of hours every day in the lab.

P.P.S. I am afraid that I have found a fatal flaw in the above suggestion about H₂Te. Hydrogen telluride and the hydrogen telluride ion are very strong reducing agents, their oxidation-reduction potentials being in the neighborhood of 1 volt. I do not remember the oxidation-reduction potential of the ferrihemoglobin-ferrohemoglobin couple, but I think it is a little above the ferricyanide-ferrocyanide value, about -0.3 volt. The difference of 1.3 volts is so great that there is, I think, no possibility whatever of adding hydrogen selenide to a ferrimyoglobin solution without getting reduction of the ferrimyoglobin to ferromyoglobin, and formation of metallic tellurium.

We might ask whether there is any chance that the hydrogen telluride ion or hydrogen telluride itself would combine with ferromyoglobin. I do not think that the ion would combine with ferromyoglobin -- the only negative ion that is known to combine with ferrohemoglobin is cyanide ion. Fred Stitt, when he was working here, discovered that ferrohemoglobin will combine with cyanide ion if the concentration is great, half saturation occurring at about 0.7 molal concentration of cyanide ion. Hence we are left with hydrogen telluride itself -- will it combine with ferromyoglobin? It might possibly be worth while to carry out the experiment, simply by reducing all free oxygen, say by the use of sodium dithionide in the usual way (atmospheric oxygen oxidizes hydrogen telluride), in the myoglobin solution, and then adding a bit of sodium telluride, if it is available. If there is a change in the spectrum, it would be worth while to try to crystallize the myoglobin-hydrogen telluride compound.

After thinking further about the matter, I have dug up another idea. It is seen that in general the singly-charged ions of weak acids combine with ferrihemoglobin. HF has acid constant 6.7 x 10^-4, H₂S has the constant 1.1 x 10^-7, HCN 4 x 10^-10, HN₃ 1.8 x 10^-5. In addition, we might include H₂0, with acid constant about 10^-16, because ferrihemoglobin in alkaline solution forms ferrihemoglobin hydroxide. I may mention that it seems likely that there is a water molecule attached to the iron atom in the ferrihemoglobin ion itself, and probably any ligand that attaches itself to the iron atom has to displace this water molecule.

It is true that not all weak acids combine with ferrihemoglobin. For example, acetic acid does not do so, nor do the other carboxylic acids. Their acid constants are about 10^-4. It may be that the strength of the bond that they can form with the iron atom is just not quite strong enough to do the job, but the example of ferrihemoglobin hydroxide [unreadable] an oxygen acid with acid constant small enough, approaching that of water, should work.

There is one obvious acid that you should try - this is telluric acid, H₆TeO₆, or Te(OH)₆. Its first acid constant is 1.6 x 10^-9. You might be able to get some telluric acid from Emeleus, but you could make it easily. I remember making telluric acid just thirty years ago, in order to study its crystal structure. If I remember correctly, it is made simply by dissolving tellurium in nitric acid. In checking on its combination with ferrimyoglobin you should work at moderately high pH, perhaps pH 8, or possibly even pH 9 -- I have forgotten when ferrihemoglobin is converted to ferrihemoglobin hydroxide, but I might as well check up on it. I find on referring to the paper on ferrihemoglobin that Stitt, Coryell, and I published in the J.A.C.S. in 1937 that the equilibrium constant for the formation of ferrihemoglobin hydroxide has p_k = 8.15. At pH 8.15 half of the ferrihemoglobin is in the form of the hydroxide. At this pH about 30 percent of the telluric acid is in the form of the single charged anion. You probably should work at about this pH, then, to see whether a ferrimyoglobin-tellurate is formed.

The experience with the alkyl isocyanides and hemoglobin suggests that the size of the tellurate ion might cut down its combination constant. At present there is no information as to whether this argument applies to myoglobin. I have a man here, Professor Lein from Northwestern University Medical School, who is, I think, working on this problem this year. At any rate, I have suggested that he do so. That is, he is going to investigate the combination of myoglobin with various alkyl isocyanides, in order to see whether or not the argument that St. George and I applied to hemoglobin applies to myoglobin also.

If we ask what other possibilities there are, we are left, I think, with only the acids of antimony as the answer. Antimonic acid, HSb(OH)₆, is a strong acid, and so is to be ruled out. Antimonous acid, H₃Sb0₃, is reported to have acid constant 10^-11; this is only a rough value. By reference to Latimer's book on oxidation potentials I find that the antimonite-antimonate potential is about -0.6 volt, and that accordingly antimonite ion could exist together with ferrimyoglobin. If tellurate ion does not combine with ferrimyoglobin, you probably should try antimonite ion.

Although lead and bismuth may form oxygen anions at high pH, it does not seem worth while to test them. The anions are, I think, not stable at pH below 10, and above pH 10 there would be strong competition with hydroxide ion, to say nothing about the denaturation of the protein.

To make Te(OH)₆

8 g Te dissolved in 50 ml HNO₃(conc) + 75 ml water. 5 g CrO₃ added. Evaporated on water bath to 15 ml. Residue washed 6 times with conc HNO₃. 100 ml of 50% HNO₃* added to dissolve TeO₃, and Te(OH)₆ crystallized out. Little octahedra. (A hydrate, monoclinic, may form.)

*Perhaps hot - my notes don't say

15 September 1954

Dr. Fred J. Allen

118 East Stadium

West Lafayette, Indiana

Dear Fred:

Thanks for your letters, Ava Helen and I were happy to have news about your sons. She has been busy the last couple of days getting Crellin ready to go off to Reed. He will leave this afternoon, and arrive in Portland tomorrow night, by train.

I am glad to have your comments on the working of problems. I think that I shall revise Chapter 8 accordingly, giving more than one way of working problems.

I shall need to have the manuscripts for Chapters 8 to 12 back, as soon as you have finished going through them. Perhaps you should mail them to me, airmail, individually, sending each one when you are through it. I want to get the first part of the book revised as soon as possible; but in particular I do not have a copy of these chapters, and I need to have the complete manuscript here for reference. You may keep Chapters 1 to 7, if you want, and write only your comments to me. If you have so many comments to make that it is much more convenient for you to put them on the manuscript itself, you might do so, and mail me the manuscript, or those pages that you have written on. I could mail them back to you.

Are you going to be too busy during the next six weeks to take on a job in addition to the one described in my letter? I think that I did not mention problems in the letter. Now I want to ask if you could give me some problems, or other exercises, especially for the first seven chapters. I should like to have ten or twelve simple exercises for each of the first few chapters, exercises in general simpler than those that are in the first edition. I shall be grateful if you can work this into your schedule.

Do not feel that you should limit the number of hours that you put in on this job because of a limitation on the amount of money that I can allocate to it.

I have not made a definite suggestion to you about payment. Let me say that I am very grateful to you for being willing to help me, and I do not consider that I can repay you adequately by writing a check. Nevertheless, I enclose my check for $400. I suggest that you keep track

Dr. Allen Page 2 15/9/54

of the hours that you spend on the job, and calculate the amount due you at the rate of $4.00 per hour. Is this satisfactory to you? Let me know when you have passed the 100-hour mark.

Please give my best regards to Mrs. Allen.

Sincerely yours,

Linus Pauling:W

17 September 1954

Professor E. B. Wilson

Harvard School of Public Health

695 Huntington Avenue

Boston 15, Massachusetts

Dear Professor Wilson:

I am writing to pass on to you a suggestion that has been made by Dr. Fritz Lipmann, of Massachusetts General Hospital.

He has suggested that the present system, under which the papers in the Proceedings of the National Academy of Sciences are classified according to the field of the work, be abandoned, and that perhaps they be divided into two sections, one on the physical sciences and one on the biological sciences. He suggests putting chemistry in the biological sciences.

I may say that I think that some simplification could be achieved, and I would go further than Lipmann. I suggest that papers not be labeled according to the field of science involved, in any way, and that they be published simply in the order of their receipt. I think that the title of a paper gives a good idea about its content, and that in general the number of papers in one field in a given issue is small enough so that there is not much value in having them classified together, nor in having an alphabetical sequence.

With best regards, I am

Sincerely yours,

Linus Pauling:W

20 September 1954

Dr. John S. Waugh

Department of Chemistry

Massachusetts Institute of Technology

Cambridge 39, Massachusetts

Dear Dr. Waugh:

I thank you for writing to me about the seminars at Harvard and M.I.T. I am afraid that I already have too many jobs down for the coming academic year to take on another one.

I may say that I am going to be in Cambridge during the spring of 1955 - I am to give the Prather Lectures at Harvard in May. Probably this is enough to let me off of the colloquium job.

Sincerely yours,

Linus Pauling:W

21 September 1954

Professor Ogden Baine

Southern Methodist University

Dallas, Texas

Dear Professor Baine:

I thank you for your letter. I enjoyed my visit with you very much, and should like to stop again to see you, but at the present time I do not have any trip arranged that will permit a stopover.

I have been working hard on my revision of COLLEGE CHEMISTRY this summer, and have been able to put to good use the advice that you gave me. I think that I have achieved a real simplification of the first few chapters in the book, but I am not sure that the problem is really solved yet.

With best regards to you and Mrs. Baine, I am

Sincerely yours,

Linus Pauling:W

22 September 1954

Mr. A. F. Reid

Auckland Teachers College

Auckland SE3, New Zealand

Dear Mr. Reid:

It is my understanding that the Dean of Graduate Studies is sending information about the regulations of the California Institute of Technology and application forms that you might use. I shall attempt to answer some of the questions in your letter to me.

The Division of Chemistry and Chemical Engineering has available some graduate assistantships, which are ordinarily given to men who are working for the Ph.D. degree. The assistantships provide about $1166, for the period of 9 months. In addition, some graduate students are given tuition grants of $600, income-tax free, which cover the annual tuition.

I may say that in the case of a foreign student some of the stipend of a graduate assistant is withheld until the time when he leaves the country.

Graduate assistantships are usually allocated to applicants during the month of March. Applications should be submitted about the first of the year.

Graduate students whose research is proceeding satisfactorily may receive a tax-free research grant of $300, to permit them to carry on their thesis research during the summer period.

The Institute requires three years of residence after the bachelor's degree, in order to fulfill residence for the Ph.D. I judge that your M.S. degree would excuse you from one year, and accordingly you would need at least two years to obtain a Ph.D. degree.

The work that you have been carrying on is such that you might be interested to do your research with Professor John D. Roberts. On the other hand, you mention molecular structure and valence-bond theories, and accordingly might be interested in work along these lines.

As to Miss Barwell, I would say that she might be able to obtain appointment as a research assistant, in connection with some research project being carried out in our laboratories. According to the regulations, she might be admitted as a graduate student. We have a girl

[page 2]

graduate student now, working in chemistry for the Ph.D. degree. She was admitted last year - the first woman to be admitted as a candidate for any degree in the California Institute of Technology for forty years. I think that the chances are reasonably good that Miss Barwell could get an appointment as a research assistant, and not very good for her being admitted as a candidate for a Ph.D. degree.

If she were to be given an appointment as research assistant her salary would be about $250 per month.

A decision about her appointment as research assistant could not be made for some time. We shall not know for several months what the need for research assistants will be in the fall of 1955.

Please write again about any matters that you want to have clarified.

Sincerely yours,

Linus Pauling:W

cc & Reid's letter to Grad office

24 September 1954

Mr. Max Hoffman

Industrial Home for the Blind

1000 Atlantic Avenue

Brooklyn 30, N.Y.

Dear Mr. Hoffman:

In answer to your letter, I must say that the problem of finding a cream that will remove hair is a really difficult one. I do not think that it would be possible easily to improve the preparation that you mention in your letter, which has a bad smell.

Let me mention, however, that one member of our staff has pointed out to me that an electric shaver should be perfectly satisfactory for a sightless person to use. An electric shaver is safe, and I should think that it would do the job.

Sincerely yours,

Linus Pauling:W

27 September 1954

Dr. Harold F. Blum

Department of Biology

Princeton University

Princeton, New Jersey

Dear Dr. Blum:

I shall look forward to seeing you in November. I expect to arrive sometime during the first week of the month, and to be in Princeton for about three weeks. The dates for my lectures have not been fixed.

I hope that you will get in touch with me after my arrival, in order that we may set a time for discussion. I am glad to learn that you are revising your interesting book "Time's Arrow and Evolution."

Sincerely yours,

Linus Pauling:W

Sept 28, '54

Tuesday Morning

Dear Mom,

Many thanks for the box of cookies that arrived yesterday. They certainly are delicious. The box from Taylor's arrived this morning. Everything was there, except they sent only four pairs of socks. So when you pay the bill be sure that you only pay for FIVE, not six. You remember that we took one pair with us when we bought the things.

I am suffering from a terrible cold. On Saturday I had a sore throat in the evening, and I went to bed rather early. I didn't go to the dance. I spent most of Sunday in bed, reading for Humanities, but on Sunday evening I had a runny nose and felt quite miserable. Yesterday afternoon I had a bio lab, which I almost didn't go to, because I felt so punk. But it was quite interesting; I'm glad that I went. I go again today.

I bought a copy of "The Handbook of Chemistry and Physics," and also a couple of volumes of a set of books that show some lovely Photographs of Europe. The two that I bought are of Paris and Rome, I have a great desire to buy a lot of books every time that I go into the bookstore, but I must try to choose carefully.

Well, I must go to lunch. I enclosed the copy of the receipt that came in the package.

Crellin

This typewriter is very useful. When Linda wants it back I fear that I will have to buy one myself.

30 September 1954

Dr. John T. Edsall

The Biological Laboratories

16 Divinity Avenue

Harvard University

Cambridge 38, Massachusetts

Dear John:

I was interested to see the paper on human hemoglobins, by Scheinberg, Harris, and Spitzer in the last issue of the Proceedings of the National Academy of Sciences. I am, of course somewhat disturbed by the difficulty of reconciliation of the conclusions of these authors and those reached by Schroeder, Kay, and Wells. I hope that something can be done to settle the question - perhaps Dr. Schroeder will be willing to repeat some of the analyses.

The main reason for my writing to you now is that I think that it is unfortunate that Scheinberg, Harris, and Spitzer used an odd nomenclature for the abnormal hemoglobins. During the last couple of years there has been general agreement as to the nomenclature to be used, involving capital letters rather than small letters, and in particular S rather than b for sickle-cell-anemia hemoglobin.

I also want to ask you about the first sentence in the paper. Do you think that the authors know something about the history of sickle-cell-anemia hemoglobin that I do not know; if so, I feel that I should be told about it. So far as I am aware, the statement made in the first sentence had never been made before our first paper, in 1949, was published. I think that a reader of the paper by Scheinberg, Harris, and Spitzer would be given the idea, by the first sentence in their paper, that knowledge of the existence of sickle-cell-anemia-hemoglobin antedated our 1949 paper.

I am looking forward to seeing you in Cambridge next spring, when I come to give the Prather Lectures.

Sincerely yours,

Linus Pauling:W

cc: Dr. Itano