Letter from John Burton Sanderson Haldane to Francis Crick
In this letter, Haldane, the population geneticist, evolutionary biologist, popularizer of science, and free-thinking intellectual,
raised astute questions about the effect of gene mutation on protein synthesis and the function of nonsense triplets, triplets
of nucleotides that do not code for proteins.
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1959-05-06 (May 6, 1959)
Haldane, John Burton Sanderson
Original Repository: Wellcome Library for the History and Understanding of Medicine. Francis Harry Compton Crick Papers
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Here are a few lines to congratulate you on your F.R.S. This title gives one a satisfactory feeling that one can be fairly
sure of getting a job if need be, and that someone besides old really thinks ones work has been good. I should be fascinated
to know what you are going to do next. Here everyone thinks they would like to do your sort of work, until I give our mathematicians
the problem. "How many amino-acids can you represent with sequences of a members chosen from b nucleotides, given that
all sequences of a beginning at the wrong place are nonsense?" Much more interesting to me on your "model", if
we define a unit mutation as the substitution of one purine or pyrimidine in a chain, what fraction of mutations will give
actual proteins? And what happens when you get a nonsense sequence of three? Does this mean the end of a peptide chain?
In other words do nonsense mutations break peptide chains? If so one can see at once why most mutations entail loss of function.
The work which I am getting started here is elementary biology which might perfectly well have been done by Darwin, but wasn't.
However it is exciting enough, and may give quite fantastic increases in crop yield. Nobody seems to know anything about
variation of organs in the same plant. In fact S.K. Roy finds that while the mean petal number (for example) may hardly change
in a season, the variance may double. However I suppose this is less up your street than the origin of life, in Penrose's