Original Repository: Oregon State University. Library. Ava Helen and Linus Pauling Papers
Reproduced with permission of the Ava Helen and Linus Pauling Papers. Oregon State University Library.
Medical Subject Headings (MeSH):
Equipment and Supplies
The Molecular Basis of Disease
To: Dr. J. F. Catchpool
From: Linus Pauling
Date: 17 June 1960
Subject: Research program for the summer
In accordance with our discussion on Saturday, I propose that your principal job this summer be the construction of an apparatus
for making heat capacity measurements.
In addition, I suggest that you start some experiments on oxygen utilization by brain tissue, resembling those carried out
Mr. John Clauser, the young man from Maryland about whom I talked with you, will arrive in Pasadena on 17 June, and will come
to the laboratory on 20 June. I have asked him to come to see Mrs. Harris, who will turn him over to you. He is to start work
on that day. Mrs. Harris might have him fill out the employment form. He is to work full time -- a forty-hour week -- and
to receive the standard stipend given to freshmen students in the California Institute of Technology. He will become a freshman
student in October. He is interested in electronics, and should be a useful assistant to you.
Professor Albert Tyler in the Biology Division has offered to lend us some apparatus for use in the respiration experiments.
The apparatus that he will lend us includes a water bath, a shaker, and half dozen Warburg tubes. You will probably have to
make some special Warburg tubes for the experiments involving an electric current, in order that the electrodes can be attached.
These tubes can be made to fit onto the regular Warburg manometers. You might want to talk with Professor Tyler before I get
back, 23 June. He can tell you something about the operation of the apparatus. You may have made use of this technique already
at some time.
I suggest that a repetition of one or two of McIlwain's experiments be carried out, with metallic electrodes (silver or
gold plated platinum), in order to see if you can check his curves. Then the same thing should be done with calomel electrodes.
You can find in one of the volumes of techniques of physical chemistry how calomel electrodes are made. The calomel is made
by precipitation of mercurous ion with chloride ion, followed by thorough washing.
I am interested in the question of how an electric current could increase respiration of brain tissue. I think that a reasonable
possibility is that the respiration rate is determined by the concentration of some substances in the tissue, which may become
exhausted, and that these substances have electric charges, so that the electric current pulls them from the region of the
solution where they are not being used up into the place where they are being used up, thus increasing their effective concentration.
You may remember that I mentioned the other day that the anticonvulsants such as trimethadione might be operating in part
at least by changing the electrode potential of the electrodes. It might be worthwhile to check on this by a simple experiment,
consisting in putting silver electrodes in a solution of sodium chloride, measuring the current as a function of applied voltage,
at, say, 60 cycles, and then repeating the experiment with trimethadione present in the solution. In each case the relation
between current and applied voltage should be a curve with a foot at somewhere around one or two volts. The trimethadione
might shift the foot by changing the overvoltage at the electrodes. This is an experiment that does not involve brain tissue
at all. If McIlwain had made his setup in such a way that he recorded the current flowing as well as the applied potential
difference between the electrodes, he could have learned much more than he did.
The operation of the Warburg apparatus requires some care, and it is time consuming to carry out a large number of experiments.
I suggest that your plan for the summer be to get a series of experiments along these lines set up, for Mr. Clauser to carry
out when he doesn't have other jobs to do, but that you use him to the maximum extent possible in connection with the
construction of the heat capacity apparatus, and put him on the Warburg studies only when he is not needed for the other job.
Dictated by Professor Pauling
Signed in his absence: jh
P.S. In carrying out the Warburg studies, I think that you would find it worthwhile to measure the current as a function of
applied voltage for a sodium chloride solution, first with metallic electrodes and then with calomel electrodes. For calomel
electrodes, of course, the current would simply be proportional to the applied voltage. With metallic electrodes there would
be a foot on the curve, followed by a linear section. If you add trimethadione or other substances to the sodium chloride,
no effect of the added substances should be found on the conductivity with calomel electrodes, but a change in the foot might
be observed with metallic electrodes. This may be the explanation of McIlwain's observations.
Dr. Shaw has suggested that in your work on brain tissue it would be worthwhile to compare the effect of trimethadione with
that of other substances that are related to it in chemical structure, such as creatinine. You might want to ask Dr. Shaw
for his recommendations, when you reach that point in the experimental work.