DIVISION OF   BIOCHEMISTRY

DEPARTMENT    0 F    BIOLOGY

MASSACHUSETTS INSTITUTE OF TECHNOLOGY

                                    CAMBRIDGE 39.   MASSACHUSETTS

March 15, 1960

Dr. F. H. C. Crick, F.R.S.
M.R.C. Unit for Molecular Biology
Cavendish Laboratory
Cambridge, England

Dear Francis:

     You will be interested to hear that the P-lactoglobulins
are at last being fingerprinted, successfully.  We have a visitor
this month, Robert Townend, from Timasheff's laboratory in
Philadelphia, who is mainly interested in the fascinating associ-
ation properties of these proteins.  Of course the work is still
in its preliminary stages, but I am writing to tell you about
it because you were always so insistent that it should be done.

     Two different methods of splitting the disulphide bridges
eventually lead to beautiful fingerprints and ionograms. It
appears that the protein is made up of two identical subunits
of 18,000; I think the X-rays-showed that to be likely.  An acidic
trypticle of the P-A (fast) protein disappears and is replaced
by two new trypticles in (3-B.  These are relatively faster and
slower.  Since there is supposed to be a charge difference of
two per 36,000 this looks like a neutral to lysine change. If
all goes well, the precise change but not the sequences, should
be known soon.  It is very nice to have this sort of thing
happening out side the hemoglobins, though I gather that Chris
.Anf.insen has a definite peptide change for one of George's
phage lysozyme mutants.

     Mike Naughton has been busy separating human hemoglobin
chains for his sequence work.  He is currently developing a
new method for finding the sequence of trypticles in a chain,
which looks very promising indeed.  Tony is making progress with
hemoglobin AZ.  All his four peptide changes are in the delta
chain (Val-His-Leu-...).  He is now quite sure that the first
glutamic acid of peptide A-T-26 is replaced by alanine. I
don-tt know whether he will have time to do the sequences of
all four, before submitting his thesis in England this next


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March 15, 1960

Dr. Crick:

autumn.  If all goes well, he plans to spend a couple of
months in Italy collecting thalassemia blood samples, before
returning to MIT for a year as instructor.  He has been a
great success here with everybody.  I think a year's teaching
experience will be useful to him.  We are pressing on with the
survey of normal hemoglobins and a search for non-electro-
phoretic mutations in thalassemia samples.  So far, no news.
Baglioni, from Cavalli-Sforza, who is doing this,is also
s&udying a person with four hemoglobins, AGCX, where X is
?? o

     I am busy on soluble RNA, yeast, where I enjoy greatly
working with Ed Herbert.  Most of my time has been spent on
tooling up on the preparation and doing base compositions,
particularly the nucleoside and the 3'05' diphosphate end
groups (roughly 1:70) and pseudo uridylic acid (nearly 4). I
would like to try Geoffrey Brown's separation of specific
RNA's and then do degradative studies - a modest aim! Am I
right in thinking that you have left this problem?  It is quite
fun to learn nucleic acid chemistry.  On the whole, I find
MIT enjoyable and stimulating, as well as hectic.

     It :would be very nice to hear what you and Sidney
are doing.  We were all excited to see Max and John's papers
in Nature.  When will you be in the U. S.?

    Best wishes to you and Odile, also to Max, John,
Sidney, Mary, Leslie, etc.

Yours,

VMI/dd

v -r
V. M. Ingram