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Correspondence

Letter from Linus Pauling to Ma Hai-teh. February 7, 1974.
Pauling writes to discuss the history of his research on oxypolygelatin. In so doing, Pauling describes a number of the blood plasma substitute's properties and likewise suggests possible uses of and approaches to large-scale manufacture of oxypolygelatin in China.

Transcript

February 7, 1974

Dr. Ma Hai-teh

Peking

China

Dear Dr. Ma:

My wife and I enjoyed very much our evening with you and Rewi Alley. We are grateful to you for having invited us. I swish that we had had more time, and could have discussed many more subjects.

Perhaps we shall be able to make another visit to the People's Republic of China. If you come to the United States at any time, I hope that you will consider visiting us, and seeing our new Institute of Orthomolecular Medicine, of which I am the director.

I enclose the published paper on Oxypolygelatin, which I mentioned to you. I have also copies of the rather long final report on our work, but I have not been able to find them. When I find a copy, I shall send it to you. I do not think that it is necessary, in order for work to be started in China, because the paper itself gives detailed enough instructions about the preparation and properties oft he substance to permit work to be started. The preparations that we used, so that the conditions probably would have to be changed somewhat to get the best product.

The work on Oxypolygelatin began when I had the idea that the properties of gelatin as a plasma extender would be improved if the long thin gelatin molecules could be tied together into rosettes, in order to keep the molecules from escaping through the pores in the glomerular filter into the dilate urine. Also gelatin is non-antigenic, whereas other proteins are anti-genic. We carried out some preliminary studies in which we coupled gelatin onto bovine serum albumen with gelatin, and obtain a nonantigenic product. Soon, however, we decided simply to couple the gelatin molecules to one another, and, of several bifunctional reagents that we tried, glyoxal seemed to be the best. Coupling the gelatin molecules together in this way gives a three-dimensional network. We tried several oxydizing agents to break up this network into rosettes, and decided that hydrogen peroxide was the best. Moreover, hydrogen peroxide apparently converts from amide groups into carboxylate ions, so that the resulting Oxypolygelatin has about the same isoelectric point as a serum albumen. Because the rosettes are roughly spherical in shape, they do not escape through the glomerular pores so easily as gelatin molecules, and accordingly the retention time in the body is greater than for gelatin with the same viscosity as Oxypolygelatin.

The preparations that we made remain liquid at ordinary room temperature, and can be infused into a vein without heating.

A great advantage of our treatment is that the final step of autoclaving with hydrogen peroxide destroys pyrogens. None of the preparations of Oxypolygelatin that we have made contained pyrogens. This is a great advantage, because ordinary gelatin solutions have to be made with great care to exclude pyrogens. A paper about the destruction of pyrogens was published by two of the people in our laboratory: It is listed as the first reference in the paper on Oxypolygelatin.

Oxypolygelatin is very cheap. I myself feel strongly that it should be given a very extensive trial as a plasma extender. I have several bottles of Oxypolygelatin that are over 25 years old. They still look clear - a clear amber color - and I think are probably still satisfactory for use.

The preparation contains a range of molecular weights and sizes. This is largely for this reason that the Committee on Blood Substitutes of the U.S. National Reserach Council did not approve it for general human use, but only for experimental studies. I tried to get one of the pharmaceutical houses interested in it, but was not successful, except that one firm (Baxter Laboratories) manufactured it for veterinary use. It can, of course, be used for animals other than humans.

We made preparations using either bone gelatin or pigskin gelatin. The gelatin should, of course, be prepared with care. You have a large supply of pigskin gelatin available in China, and I suppose also that glyoxal and hydrogen peroxide are easily available.

I would be glad to come again to Peking (with my wife), if I could be of help in getting the manufacture of Oxypolygelatin started. I may mention that Dr. Arthur Cherkin is a member of the board of trustees of the Institute of Orthomolecular Medicine. When he was a director of research for Baxter Laboratories, he supervised the manufacture of Oxypolygelatin on a moderately large scale. I think that if you were seriously interested in investigating this preparation it might be worth while to invite him to come to Peking, also.

I must point out, however, that the manufacture of the preparation is reasonably simple, and that the biochemical and pharmaceutical people in China could, without doubt, make satisfactory preparations on the basis of the information given in our published paper.

I may mention that from the standpoint of nutrition the Oxypolygelatin would be improved by adding some of the essential amino acids. the aromatic amino acids are missing from gelatin.

One investigation that I had hoped to carry out is the study of the products of hydroloysis of Oxypolygelatin, with the use of an amino-acid analytical instrument. These instruments were not available 25 years ago, and we were not able to carry out such a study at that time. The composition of some of the amino acids might well be changed by the interaction with glyoxal and hydrogen peroxide. Our studies show that toxic substances apparently are not produced, but it would be worth while to carry out a scientific study of the material.

I think that I told you I heard a rumor, 15 or 20 years ago, that Oxypolygelatin was being manufactured in China. Probably there was no basis for this rumor.

I hope that you can interest the biochemists and pharmacologists in investigating Oxypolygelatin. I may point out that no special apparatus or equipment is needed.

Sincerely,

LP:dm

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