SYNTEX CALIFORNEA

P.O. BOX 5129 -
STANFORD, CALIFORNIA ~

August 17, 1960

Br. Erast Sorkin
State Serum inst! tute

Copenhagen S$, Denmark

Dear Ernst:

Thank you for your letter of August 9th. | would like to be able to answer
your questions about Syntex more decisively but It Is difficult for me to speak
for the Company and i can only give you ay own Impressions of It from the outside.

As to the overall direction of the Company, this at least ought to be no
great concern. {It is certainiy true thet there were many changes in the earlier
days of its development but at the present time Syntex Is a publically owned
corporation whose stock is listed on the American Stock Exchange and the shares
of which are quite widely distributed. This means, In practice, that the present
management could only be displaced by the most unexpected and sinister events and,
particularly In view of the great success of the present corporate policy, | do
not belleve that there should be any cause for concern in this direction. As to
the stability of the program, | believe you are quite right to bring up the point.
My own considered view Is that on s five-year besis at least, there should be no
cause for concern. The directors are very well aware of the long term requirements
before basic research can be translated even in pert Into practical and useful!
developments. in fact, whet is unique about the present ventura, Is the dedication
to @ long-term point of view on the part of the company and it is In hopes of
setting @ rather unique pattern in pharmaceutical research thet | have been
interested In the effilitetion myself. Realistically, If after the first five
years of work, the Institute hed done nothing that could even point to the
possibility of a pharmaceutical development, | can visualize that the directors
might begin to wonder about the wisdom of their commitment. However, even In
this event, {| belleve that the institute would heve obvious value to Syntex --
from the standpoint of Its overal! prestige and, In addition, by merely having
some intelligent people doing plonesring research work who might instill some
genera! Interest In the overall Syntex program. Since the whole strength of
the Company has depended upon its research, | cannot concelve of any fundamental
retreat from a besic research policy but f might have to admit with you that
there would be some risk of @ dampening of enthusiasm over a long period of time.
However, the time Interval thet would be appropriate for this discussion would
be, in my opinion, five years and not one. If the experiment falled from the
standpoint of ultimate pharmaceutical productivity, | would visualize thet the
fnstitute might be converted into a self-sustaining, non-profit foundation, of
which there are already many examples and which would have no difficulty in.
obtaining continued support if it Indeed had already established the basic facilities
for doing its research work. | do not seriously envisage that this would heppen,
but | mention It as an Indication of the kind of security that Is avallable
against the calculeble risks. By and large, | can honestly recommend to you that
these particular Issues should be no cause for concern on your part. There are,
of course, other questions that | Imagine you will be considering very seriously.
Or. Sorkin, cont. 2

The matters of budget and facilities, etc. should not be so difficult to decide and
will doubtless be the subject of further correspondence, particularly If you Indicate
shat your Interest Is sustained.

Perhaps most important Is whether you ere sympathetic to the basic premises
‘of the intended organization. in the long run, will work in the flelds and at the
level In which you are Interested justify the Company's continued support? Can this
be accomplished without unduly distracting you from your own basic scientific
objectives? if i did not belleve in the possibility of @ reasoned affirmative
answer, | would not heve proposed the arrengement In the first place. Mowever,
what the answer actually should be is something you wil! ultimately have to work
our for yourself. What | heve In mind Is thet In the course of your basic work, and
to some extent in consequence of it, possibilities of useful applications will present
themselves. it will be your own responsiblilty to evaluete these possibilities and
to arrange the means to bring them to frultion. This would imply that over the
course of time a considerable supporting staff should be developed at the Institute
in order to follow through on these conceptions. Fortunetely, the contract with
Lilly also provides access to their very large scale facilities for routine screening
In a number of areas and this should greatly relieve the burden of testing that
might otherwise be encumbent on the Syntex laboratory. in any position, not least
in the University, there ere many obligations to the Institution besides one's own
research -- for example, teaching and sdministration. { would visuelize that In the
fInstitute your responsibilities towards ultimate application would be the equivalent
of these other tasks In a university position.

You asked ebout your colleagues -- a very important question. The Initial
research group, 6% you must already know, would consist of five investigators
(hopefully including yourself). Of these, two are already chosen at the present
time: Boris Rotman and John Zderic. Rotman Is an accomplished blochemist and
microbiologist. His main Interests at the Institute would be the mechanism by which
nucleic ecids enter bacteria and other cells. This is, of course, a problem of very
great interest to us in connection with ONA transfer and genetic transformations.
Zderic is an organic chemist from Syntex Laboratories in Mexico who Is switching
flelds now from steroids to nucleotides. All i can sey of him is that Djerass!
thinks very highly of him as a chemist. in addition, Zderic would furnish the
aduinistration liason between the Institute and Syntex Corporation. The other two
positions are not yet filled. One has been offered to Or. W. E. Rezzell who has
Spent some yeers with Khorana at British Columbia and is still there at the present
time. His malin interest is In the organic chemistry end blochemistry of poly-
nucleotides -- you will see examples of his work In the JBC for August, 1959 and
JACS 79, 1002, 1957. He Is particularly Interested In methods for sequence
analysis of DHA and in the preparation of synthetic polynucleotides.

§ hope this discussion can help answer some of your questions and please
write me ageln if ft can further clarify any of these or other tssues.

You remarked about Szilerd's papers on antibody formation. He presents a
rather formalistic model, perheps over-eleboretely, which | cannot teke too
serlously. Fitting it Into my own approach to the problem, he seems to be suggest-
Ing that each cell of the antibody- forming series contains al! the Information
necessary to produce any conceivable sntibody. Me has then given a somewhat
detailed analysis of the way In which the kinetics of antibody synthesis could be
erranged so thet it would follow an on-off pattern. { have no quarrel with the
latter pert of this, although | am not sure of the necessity of worrying about
this espect of the problem at the present time. { am not even as optimistic as
Szilard Is In ilmiting the variety of potential antibodies to the point of comfort
in assigning @ separate preformed genetic determinant In each cell for each antibody.
On the other hand, | think the idea of looking for a generalized repressor -- which
Or. Sorkin, cont. 3
Is not Szitard's, he is thinking of specific ones -- is not at all a bad one and [it

would be Important to have the datum as to whether or not such repressive effects
actually exist. Your answer to this is presumably no.

Trusting t will hear further from you, es ever

doshue Lederberg
Ji/jh