June 8, 1959
London

Dear Joe:

_ Esther and I are now on the last leg of our trip and
should be home just about the time you cet this. All the
best luck to you in your new laboratories]

The symposia we've attended have been quite instructive,
especially the one at Royawnont on cellular inmmity of which
I am enclosing the gbstr,cts. It is hard to escape the feeling,
which I know you already share, that immunology is in for a new
era of importance in medicine, and with this a new challenge to
the phamaceeatical industry. I would urge you to be especially
attentive to this field to be ready to exploit its developments
at the earliest moment. The most important step, not yet quite
achieved, « be the artificial cultivation of Munctionally active
*immunocytes’-- cells of the lymphoid system involved in antibody
production.

The linea of development I can foresee include:

1. Agents which interfere with the primary immme response,
as well as with its terminal effects. We have already discussed
sereening for such agents from microbial broths; there would also
be the further possibility of ‘substitutional chenothersapeutic'
methods. To the systens for screening for the terminal effects we
have also alreaity discussed, I might add now the inhibition of

antibody extotoxicity (ef. Gorer) on leukemia cells,. which may or
may not be equivalent to compiement fixation a:d imnune lysis of
RDC. Milescher's system of the inhibition of clot retraction through

the effect of Ag-Ab complexes on platelets may also be quite promising
as an in vitro method.

 

&. Production of specific antibodies through in vitro culture
of clones of (hunan?) immunocytes. This stiil needs somé important
advances in technique.

5. A revival of serotherapy in which the gntibody-specific frag-

ment of antibody is isolated to avoid the gatigeniol ty of the globulin
carrier. This is based on the work of Porter and others (Nature

1958-— full reference in my article on genes and antibodies) on the
aplitting by papain of rabbit AX Ab globulins into a common antigenic
fragment aud a differential fragment, not antigenic, having the
specific combining ability of the Ab. It is not yet know whether

the Abefragnent has any protective value in infection: if it does

it may be the basie of a revival of serum therapy, and I strongly
recomend you look into this.
As a temporary expedient, someone ought to inquire whether
serum sickness, brought about by sensitization to, say, rabbit
antibody globulin, could be mitigated by the injection of ti-
globulin antibodies from other species. A human anti-rabbitglobulin
serum might be the ideal reagent, but expensive, The argument would
be that an excess of circulating antibody should facilitate the
clearance of the offending antigen, the persistence of which is
a troublesome feature in serum sickness. I haven't taxa had the
chance to review any literature in this; field.

Y vA ——_—
(AS ever

Joshua Lederberg

P.S. I Left out one of the most exciting prospects — See
Lawrence's abstract (and a symposium he edited, 1959, Hypersensitive
States, Hoeber—Harper publ.) You might market the antibody~
producing microsomes to transplant direct to recipients, as a
substitute for potentially dangerous vaccines,