REC’D JUN 22 1964
Woods Hole, Mass., June 18 1964
Dear Dr. Pauling :
I much regretted not to be able to wish you good bye as I left Caltech. I was unaware of your plans to go to your ranch
and therefore missed you. But I was happy to be able to think and am now happy to say : A bientôt !
After the meetings at Cold spring Harbor we spent a few quiet days here in Woods Hole with my father-in-law and are about
to leave for France. I used these days largely to put in shape the manuscript on the paleogenetics of hemoglobins (the talk
I have in Bruges) of which I left a copy with you.
In this manuscript and in my presentation I gave our table 1 from “Horizons in Biochemistry” (the approximate time of
derivation of different hemoglobin chains from there common ancestor) with slightly revised figures. The order of magnitude
of time elapsed between two evolutionarily effective mutations still was 10 Million years. I then proceeded to examine the
rate of evolution of cytochrome c and to compare it with the rate of evolution of hemoglobin. I found the two rates to differ
only slightly. You may not have at hand the figure that relates to these matters, and I am therefore including another copy
This type of quantitative treatment of the data was criticized at the Bruges meetings by several participants, notably
by Ingram, who felt that the uncertainties are still to [sic] great to warrant any quantitative statement in relation to the
common ancestors of polypeptide chains.
I was not very impressed with these criticisms. I am however much impressed now to discover that my own paper…implicitly
contained a strong criticism of the above treatment of the data. One of the three main sections of the paper is devoted to
putting forward and defending the hypothesis that a high degree of morphological similarity between organisms is accompanied
by a high degree or similarity of most polypeptides. This is thought to apply not only to contemporary organisms that have
changed little in appearance during a given evolutionary span. The most widespread opinion is just opposite. It is thought
that two morphologically similar organisms, if separated by many millions of years of evolutionary time, are probably biochemically
If the proposed hypothesis is correct, it follows that if we compare homologous polypeptide chains from two contemporary
forms whereof one is placed low, the other one high on the evolutionary scale, say man and a fish, one of the chains will
have undergone a great many changes in amino acid sequence since the time of the common chain-ancestor, the other chain (that
of the fish) relatively few. In comparison with their common ancestor, a contemporary fish indeed has changed morphologically
much less than man. In such a case, the procedure of halving the number of differences between the two polypeptide chains,
in order to arrive at an approximate figure of the number of evolutionarily effective substitutions that occurred in each
line of descent, is no more valid.
Consequently it cannot be considered that the graph with the data on cytochrome c represents “the” rate of evolution
of cytochrome c. The graph may still have a certain interest: but since it compares man with all other forms, the error introduced
by an inequality in the amount of evolutionary change that occurred in each pair of lines of descent since the time of the
common ancestor will be the greater, the more distant on the evolutionary scale the other organism is from man. In relation
to the human line of descent the apparent rate of evolution of cytochrome will be an underestimate, and with respect to the
other line of descent, an overestimate. Perhaps it is possible to devise a factor of correction that would take into account
the vertical distance on the evolutionary scale, as known from all available evidence, or any two organisms that are being
It seems to me that our table in “Horizons of Biochemistry” is not critically affected by this discussion, for the following
reasons : we used the differences between the horse and human alphachains of hemoglobin as the basis for all other calculations.
It may be that the rate of evolution in both the human race and the equine line of descent, since their common point of origin,
has not been drastically different. – Moreover we used the figure obtained by the comparison of the sequences of human and
equine hemoglobin to calculate the time of common origin of chains, not as they occur in very different animals, but as they
occur within one and the same animal. Although the rates of evolution of the different homologous chains found in man alone
– the alpha, beta, gamma, delta plus the recently discovered epsilon chain – may even here differ significantly, the chances
appear good that this difference in rate of evolution is not too great at least in the case of the two “adult” major component
chains, the alpha chain and the beta chain.
I am writing to ask you whether you would like to give me your opinion in relation to these matters. I intend to introduce
into my manuscript a discussion along the lines indicated in this letter. But since this discussion is directly related to
our “Szent Györgi – paper”, it occurred to me that, in case you would wish to express your ideas on the subject, I might remove
this whole chapter from my “Bruges – paper” and reserve it for our “Rutgers – paper”. Either procedure would be fine with
Unfortunately my “Bruges”-manuscript is overdue, and I shall have to finish it within the next few days. My address is
the following :
Laboratoire de Physico-Chimie Colloldale, Route de Mende, Montpellier, Hérault.
Jane and I are sending you and Mrs. Pauling our affectionate greetings.
P.S. At Cold Spring Harbor a number of people referred to matters that are treated in our article published in the book
dedicated to Oparin. People refer to Itano, because he also has described possible consequences of isosemantic substitutions
(not so called by him) and has sent a preprint of his paper to numerous investigators. Our paper is ignored, because it has
been published in russian [sic] in a russian [sic] book. You once told me that “Evolutionary and Industrial Biochemistry”
might be re-edited in English. Do you know what the chances of such an event are? If the_y are low, could our article conceivably
be reprinted in English in some american [sic] periodical ?
Handwritten: I’m sorry, I can’t find the figure I meant to include. It must be in a bunk that we shipped over to France directly.