October 11, 1974

Dr. Francis Crick

NRC Laboratory of Molecular Biology
University Postgraduate Medical School
Hills R.oad, Cambridge CB2 2QH
England

Dear Francis:

   I am sorry to have delayed so long in answering your letter.  How-
ever, Sung-Hou Kim went to Korea to see his mother and I felt I could
not reply, especially in terms of drafting a letter for publication, without
consulting him.  In writing my previous long letter to you, I consulted
with him quite thoroughly so in a sense that letter came from both of
us.

   Your general criticism of our publication is unfounded.  It is not
true that Sung-Hou's interpretation was not sufficiently convincing for
us to have published it without the stimulus of the English work.  Prior
to the Madison meeting we had started, and his visit to M. I. T. then
was precisely for that purpose.  It is quite likely that we could have
been more rapid in publication if the two laboratories were not separated,
but that is not the issue.  Furthermore, it is not correct to say that if
we saw the advantages of the revision as early as April that we should
have then proceeded with publication.  As I described in the earlier
letter, some of the interactions were becoming definite in April, but
they were not all apparent and many were tentative.  It takes a long
ti.me to make sure that these interactions are correct since there were
many alternative tracings to be considered.  Sung-Hou found the partial
structure method of value here.  However, I learned in August from
Robertus that in April the h1RC workers had already established a number
of the tertiary interactions which are in their final paper.  The same
question can be raised.  Why did they wait until mid June to write up a
paper when they already knew of these relations in April?  The answer is
obvious.  The structure is large and complex and one has to make a
number of decisions. Even so, by June it was apparent that a' number of
these interpretations were still tentative as shown both in our paper and
in the MRC paper.

   Unfortunately~ the i.mpression I get from here is that you are either
not being given all of the facts or you are being misled.  You were given


Dr. Franci.s Crick

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October 11, 1974

incorrect facts about what went on at the Gordon Conference.  David Blow
had incorrect notes on the Steenbock Conference, which I have been
able to clear up by listening to the tape recording of the meeting.
Furthermore, if it is your impression that your colleagues gave a full
presentation of the structure at the Steenbock meeting, you are being
grossly mi.slctd again.  I have recently received a copy of the "New
Scientist" article which has caused me a great deal of distr,ess.  In it
the MRC group are quoted as having given a full account of their proposed
model a-t the Steenbock meeting.  This is very far from the truth.  The
tape transcript shows exactly what was disclosed, a slide of the wire model
`and an electron density map section.  The wire model was chiefly useful
in allowing me to point out to Jon Robertus that our revised D stem
looked similar to his.  However, as you know, one cannot see details
in a wire model slide.  In the discussion Robertus said that they have
defined a large number of tertiary interactions, but unfortunately he could
not show them now, but would be able to in "several weeks time. "
He described two of the four tertiary interactions which I had mentioned
in my talk and, in response to a question, added the third one.

   There are some points in your letter which I should comment on.
You mention uncertainty about our incorporation of A9 into the model
before the meeting.  I suspect this arises from the response which
Sung-Iiou made at the meeting to Jon Robertus' comments about the A9
interaction.  The tape transcript makes this clear.  In response to a
question about A9 being protected, Robertus said that this opened up
" Pandora' s box, " as A9 was involved in a "triple base with 12 and 22."
Sung-fIouls response to this, audible in the tape, was one of confusion
and incredulity.  I am sure that this was taken as evidence of the fact
that he had not known of this interaction.  In fact, A9 does not bind to
either 12 or to 22; but binds to residue 23.  Robertus had made an error
in describing the interaction and Sung-Hou was trying to understand
how he could possibly interpret that residue as interacting with both 12
and 22.  Some of Robertus' confusion may have stemmed from the fact
that there was an error in the diagram of the "Nature" paper which shows
a tertiary interaction bctwccn A9 with both 12 and 23.  In any case, if you
had doubts about this interaction, all you had to do was contact Struther Arnott
since he has it in his notes.

   My presentation was the first one of the first day of the meeting.
h!Iy comment,, q covered our research in more or less chronological order,
except at the beginning I stressed the special role of the constant bases.
Near the end of the talk I presented information about the chemical
modification studies and stressed the role of the constant bases in the
tertiary interactions.  I mentioned that we have a modified tracing with a
clifferent folding of the anticadon,  differ -cnt from that which we had described
earlier.


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0ct01:,er 11, 1974

   I am glad that you mentioned my junior colleagues in your letter
because I have been feeling very badly about them.  They attended a lecture
at Brandeis when Aaron was there in which Aaron more or less openly
suggested that we had purloined his interpretations, repeating the charges
which were in your and David's letters. This was told to me not only
by my junior colleagues who attended the lecture, but also by other
crystallographers in the audience.  He also had apparently told this
in private conversation to a number of individuals in this country
because when my colleagues went to a meeting of the American Crystal-
lograhic Association at the end of August, there was considerable
discussion there about the nature of these charges.  Both I and my
colleagues received telephone calls at that time from friends asking
what was going on, as knowledge of the charges in your's and David Blow's
letter seemed to bc widespread.  These unfounded charges have done
considerable damage to our reputation.  Now in the "New Scientist"
publication Aaron has developed a number of additional charges which
as you may imagine also distress my colleagues and myself.

   Let me cite a specific example which leads me to believe that you
are not completely informed about what was going on.  The point I wish
to raise stems from the statement in your first letter that we gave no
indication that we were planning to publish material based on what we
had said at the Steenbock meeting.  This is quite untrue, for not only
did your colleagues understand that we were publishing a paper, but they
acted in accordance with this.  Let me cite the following facts:

  Fact 1: The original version of the "Nature" paper, which R.obertus
sent us a preprint of on August 5 makes only passing reference to chemical
modification experiments, involving only residues 16, 1'7 and 20. This
was despite the fact that a large experimental effort had been Carrie B out
dealing with the study of the pyrimidine modifications of yeast tRNAp e.
The studies were completed well before the Steenbock meeting as Brian
Clark reported on them there.  I suspect that a general statement was not
made in the "Nature" paper because of residual uncertainty about the
interpretation of certain parts of the electron density map.

   Fact 2: During my presentation at the Stecnbock meeting, I laid
great emphasis on the chemical modification studies. I showed a s$ide
listing the purineG c that are unreactive and reactive for yeast tRNAP le
and also discussed the analogous studies of Chang on other tRNA's for
pyrimidine modifications.  It was clear that the slide which I showed
was prepared for publication and indeed it was an earlier version of


Dr. Francis Crick        Page Four

October 11, 1974

Figure 1 of ollr publicat.ion.  This was noted by your colleagues. I
made a statement, repeated twice, that we have a tertiary folding in
our model which accounts for the chemical modification data.

   Fact 3: Immediately after ihe Steenbock meeting your colleagues
prepared an unusual paper for the journal "Nucleic Acid Research" which
presents very little experimental data, but essentially says that the
model is entirely in agreement with chemical modification studies.  This
paper was prepared in a great rush and special pressure was put on the
Editors to publ.ish the paper quickly.  An Editor of this journal informed
me that the rule of the journal is that papers received and refereed by
the 2 1 st of the month go into the next month's issue.  Their paper was
received on the 2 8th of June and it appeared in about two weeks time.
In fact, it appeared in such a rush that a figure was included in it with
an incorrect twisting of the T@C loop.  They would never have rushed so
and published a paper with so little data except they knew we were to
publish.  Furthermore, nowheres in that paper is there any reference to
the fact that I had clearly stated at the Madison meeting that our molecular
m.odel agreed with the chemical modification data.  In addition, they
describe the T54-A58 interaction with more confidence than in the
"Nature" paper, and it was one of the tertiary interactions described
by me in my talk.

   Fact 4: When the "Nature" paper was revised some two weeks later,
a sentence was added saying that the model is in good accord with
chemical modification data.

  All of this occurred of course before my preprint arrived in
Cambridge and it is quite clear to an outsider that it was done in response
to my presentation at the Steenbock meeting.  In short, the interpretation
of their electron density map wa s not sufficiently convincing for them to
ha&`k%%road statement about chemical modification without the stimulus
of my presentation at the Steenbock meeting.  I rather suspect that you
know nothing about this, but the facts speak for themselves.  Under these
circumstances, do you think that a public statement from your colleagues
might be appropriate?

   Let me say how much I deeply resent this whole business.  Aaron
sent two junior colleagues to a meeting with instructions: They were
to say they had sent a manuscript in, but were not prepared to disclose
t.he contents except in a superficial fashi.on.  When we then joined in
this cat-and-mouse game of not telling all, a hue and cry arose from the
Ml~C,when we sent you our paper, with a large number of false charges
flying about.  The informnti.on on which these charges were leveled was


Dr. l?rancis Crick

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October 11, 1974

completely unreliable, based on inferences obtained in the context of
discussions at a meeting in which we adopted Aaron's ground rules,
i. e. , tell only a minimum of what you have been doing.  Aaron then
proceeded to publicize these initial charges without attempting to
verify them, and when these were shown to be false, he then proceeded
to invent new charges dealing with the interactions between Kim and
myself, again with no factual basis whatsoever.  On top of this, he
made false statements to the "New Scientist, " and again strongly implied
publicly that we had purloined his interpretations.  Minimal effort was
made by him or others at Cambridge to ascertain the factual basis of any
of these charges.  Having carried out a very complete public character
assassination of me and my colleagues, he poses as the injured party.

   The "New Scientist" is widely read here and several friends have
asked me about the charges it contains.  It seems to me that Aaron has
been leaking selective portions of our correspondence in such a way as to
cast me in a very bad light.  In view of this I do not see how we can make
a simple public statement along the lines suggested in David Blow's or
your letter without responding to the various charges aired in the "New
Scientist" article.  I have been in touch with the editors of "Science"
who have read the "New Scientist" piece, but they have informed me that
they are strongly disinclined to publish anything on this matter either
from me or the MRC.  So at the present time I am pondering what would
be an appropriate course of action.  I feel that Aaron has behaved very
badly in making a number of public charges both in lectures here and
in statements to the "New Scientist" and I am now debating whether a
lengthy and detailed reply to the "New Scientist" would be an appropriate
forum for setting the facts straight.

   On the scientific side I agree entirely with your comments concerning
the desirability  of proving the structure.  In the present state of our
analysis we regard many of the interactions as tentative as indicated in
our paper; however, judging from the description of the MRC fourier as
published in the "Nature" article, I believe there are some small, but
perhaps significant differences in the structures found in the monoclinic
and the orthorhombic forms.  However, this will only come out in the long
run with further work.

With best regards.

AR: edc

Alexander Rich