Brenner here reported progress in his research with acridine mutants--mutants produced by chemicals of the acridine family,
such as proflavine, which are chemically similar to the bases of DNA. Acridines slip in and out between the bases of one
chain of the DNA molecule, leading to the insertion or deletion of a base on the complementary strand, thereby causing a mutation.
Research with acridine mutants led Brenner, Crick, and their collaborators to conclude later in 1961 that the genetic code
was to be read three bases at a time from a fixed starting point. This research involved the use of suppressors, also discussed
by Brenner, which are second mutations, at a different site on the DNA chain, that mask the expression of a first mutation.
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4 (1,074,560 Bytes)
1961-07-27 (July 27, 1961)
Original Repository: Wellcome Library for the History and Understanding of Medicine. Francis Harry Compton Crick Papers
I have just sent off another letter to you about the Alice paper and must say here, off the record, that I have been extremely
angry about it; however, I have not said anything about it. Lab news:
I have just had a session with Leslie and am not too happy about the mapping of suppressors. The order seems to jump about
quite a bit. In order to try and sort this out a little more effectively, I have got her to to make double mutants of suppressors
of the same generation. The first one that looks as though this is successful is FC1FC7. This should be like a deletion and
help to locate the others. She is also busy testing what I call the "spin" of suppressors that map at the same site.
This should be known by the end of next week and is an important experiment; to test whether suppressors of opposite spin
can nevertheless occupy the same site. Richard is busy with minute suppressors, which should generate another set of mutants.
I have been helping him with how to do the experiments. I am very impressed by his initiative and I think he is bright.
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Muriel has isolated 150 A gamma mutants. We confirm that there are very few rIII mutants: the main aim is not to throw away
the high teverters [?] which may be very hot for suppressors. We are looking for one in the B1-B4 region since this is no
[sic] well worked out. Also, whatever rIII we have found I shall try and get mapped without K selection: they may well be
at the ends of cistrons. This should be quite exciting. I think we should also look at Acridine mutants at the other end of
the cistron B to see whether there is a similar pattern of suppressors. This will come in good time.
We have a student working here and I have got him to isolate 20 r mutants from each mottled plaque induced from r plus with
EMS to see if they are all the same. He can do this for photodynamic and hydrazine mutagenens [sic] as well. Everything will
be steadily pushed on.
(iii) My work:
At the moment I am concentrating on lambda preparing the lambda dg. I have induced clear mutants with acridines in lambda
which, incidentally is not inhibited by acridine dyes.
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(i) the ribonuclease producing strain arrived from Japan but I haven't done anything with it yet. Am waiting for subtilis
strains from Josh: the strain I have is very poorly transformable. Also somebody has a transducing phage for subtilis -- I
have written for this as well.
(ii) We propose doing the r plus/rII protein experiment next week having got the Oxord [?] electropharesis to work. I am most
(v) Jim's work has not got much further. I do not believe that they have any evidence for specific peptides but they are
The boys came back with the following story from Strasbourg. Paul Berg has purified the RNA synthetase and finds that if he
takes the coli incorporating system adds DNA and the enzyme, protein synthesis goes on for hours. He gets the same effect
if he makes the RNA first, then adds particles. But if he tries to isolate the RNA and add it, he gets no effect at all. I
think our approach would be in trying to make the messenger in situ
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with the enzyme. Perhaps we can start this when have people come.
You may care to know that Hildegarde Louefron [?] has now delayed her coming here until January which should ease space considerably.
Lots of love to you all; we are inundated by American visitors