July 8, 1975

Dr. Egon Digzfalusy

Swedish Medical Research Council
Reproductive Endocrinology Research Unit
Karolinska Sjukhuset

Stockholm 60 SWEDEN

Dear Egon,

It was certainly a pleasant surprise to see you at the Wi0 restaurant.
I am sorry we did not have just a bit longer to chat together. I hope you
may have at least a few minutes while you are in Palo Alto if you in fact
receive this, before you are again on your way.

You asked me to put fown in writing some of the comments I passed to
you about the possibilities and some research needs with respect to passive
immunization against sperm,

The main point is that by anyone of a number of methods it is a very
reasonable prospect that some time in the next five or perhaps ten years
it will be possible to produce large quantities of specific human antibody
globulins. My own favorite candidate of technology for this purpose is DNA
insertion, and I have written a little piece about that which Tamm enclosing
with this letter, Perhaps you will have noticed the article by Stanley Cohen
in the current issue of Scientific American which gives a rather nice review
of the background of this whole story.

At any rate, the possible advent of such antibodies puts a new wrinkle
on the prospect for immnmnccontraception. I am sure that there have been a
number of people who would share my own concern about establishing active
auto-immunity as a mass technology in this particular field. But if we can
really get fairly cheap antibody protein, I think {ft does open up a somewhat
diffdrent approach although, of course, it is likely to be more costly to
provide the actual delivery of the material than a single active immunization.
Even in that context I think that there is likely to be better general
acceptability of the active approach if there has been wide experience with
passive immunization for that,

If you will just grant me the stipulation that such materials will be
available, then it is fairly obvious that there are a number of experiments
that should be done fairly soon. The most cogent, and I am not aware of any
report of it, would be to demonstrate the passive transfer of sterilizing
anti-sperm immunity from man to man. Since you should be able in favorable
cases to establish a diagnosis of autoagglutination as a way of monitoring
the effect, this of course will mean a much simpler experimental design than
a more complete demonstration of male sterilization. The information would

over

 

 
Dr. Egon Diszfalusy -2- 7/8/75

also be very important in enabling us to learn something about the dynamics
of secretion of the antibody or subsets of the antibodies of various types
into the seminal fluid. And I am sure you can use your imagination to look
into the question of various sources of such antibodies which may include
women as well as men and perhaps vice versa.

One point that I do not think anyone has considered is the potential
bearing of the rather prevelant autoimmunity that we already know about
on the distribution of blood for transfusion. I am not suggesting that this
is an urgent risk but I think that people should be at least aware of the |
possibility, and of course it does mean that the experiment that I am ,
advocating may already be being done as a byproduct of other clinical measures! |
And I certainly think somebody should look into the anti-sperm component of
the pooled gamma globulin which is used in a variety of prophylactic ways.

Since there is still a great deal of confusion about the distribution of
IGG versus IGA activity in these cases, I hope that you will be able to keep
a lookout for that!

The same principles might of course apply with respect to ant igonadotrophic
hormone activity by passive transfer. I do not know if you have seen very many
in human sera having that component.

I might mention to you that I am trying to get a number of people
interested in the actual (and that probably means commercial) development of
these ideas. So, it seems to me that it would be a very useful bench mark
to look for the production of a diagnosticealy valuable immunological reagent
before undertaking the very difficult steps involved in validating therapeutic
efficacy and safety.

I wonder if it would not be particularly useful to attempt to get a
clonal antispecific antibody preparation directed against the active site
of either LH or ICSH or whatever other candidate hormone you would like to
recommend! If you have any ideas about the most pressing needs in this
direction, I would be happy to hear then.

Along the same, if you can refer me to any literature on the more detailed

immunochemistry of the antibodies that have been studied so far in this general
arena, I would be most grateful to you. We have to try to find an antibody
whose active site is mostly located on a single chain, probably preferably
the light chain of the gamma globulin. I just do not know if anyone has carrted
studies of the specificity of these antibodies to that degree of refinement.
It just seemed to me that it would be important to first establish some ground=-
work with material that would be useful in a diagnostic sense before taking the
more courageous steps that would be involved in the development of therapeutic
preparations.

Sincerely yours,

Joshua Lederberg
Professor of Genetics
JL/rr

En 304, 2.