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
