Crick here reported on ongoing genetic work in his and Sydney Brenner's laboratory, work designed to complete the elucidation
of the genetic code by identifying the codons in the transfer RNA for each amino acid (here, methionine) that bind to the
complementary codon on the messenger RNA template, and by identifying those so-called nonsense triplets that do not code for
any amino acid. Hydroxylamine is a chemical that is structurally analogous to the DNA bases, and when supplied in the food
of the microorganisms used in genetic experiments (the research discussed by Crick focused on the much-studied rII gene of
the bacteriophage T4), could be substituted for the regular base during gene replication, producing a mutation in the gene.
Holley, who was to win a share of the Nobel Prize in Physiology or Medicine in 1968, obtained the first sequence of a nucleic
acid, the seventy-seven nucleotide-long strand of alanine tRNA of yeast.
Number of Image Pages:
2 (170,432 Bytes)
1966-11-30 (November 30, 1966)
Holley, Robert W.
Original Repository: Wellcome Library for the History and Understanding of Medicine. Francis Harry Compton Crick Papers
I'm sorry not to reply more promptly to your letter but it has been difficult for me to make up my mind. I should like
to come to the Gordon Conference but on the other hand I promised my wife that we would have our holiday in June this year.
After turning it over in my mind I feel that I ought to stick to this. What finally decided me was the realization of how
many people in our laboratory would like to come to this year's meeting.
As you probably know Fred Sanger now spends all his time on RNA sequence work. One of his younger colleagues has almost completed
the sequence of the 53 RNA from E. coli. In addition a group of our own people have started on the two methionine tRNA's,
and have got some way with the minor tyrosine tRNA which is altered in certain su+ strains. Recently Howard Goodman has shown
that the alteration is, as we expected, to the anti-codon, the GUA of the su- becoming CUA in the su+ (amber) strain. A preliminary
enquiry showed that probably nine people from the laboratory would like to come to the Gordon Conference!
I quite realize that you may not be able to fit in so many. May I suggest that you correspond direct with Fred Sanger and
John Smith about who should be invited? (Sydney Brenner won't be able to come) They can give you a fuller and more detailed
picture than I have of the work actually in progress here. It was really very nice of you to ask me to organize Thursday
evening, but I hope my absence will be compensated by the presence of some of the people who do the actual work.
The only other news is that we now have excellent evidence from our rII genetic work that UGA is a nonsense triplet. (We can
turn it into ochre - UAA - with hydroxylamine) Strictly our evidence shows that it is "unacceptable" but I have little
doubt that is nonsense, and not, for example, cysteine. What it actually does is a mystery. It may chain terminate but wobble
would suggest that there should be no tRNA for it. (Of course wobble may be wrong about this.) We don't think it can be
(by itself) a punctuation mark for the RNA polymerase because it is no longer nonsense if we phase-shift it.
I'm so glad you've been enjoying La Jolla. I shall be with you in February and look forward to lots of interesting