March 13, 1959

Mr. Richard 0. Boyer

Physicians News Service Incorporated
130 East 59th Street

New York 22, New York

Dear Mr. Boyer:
To yours of February 19th:

A considered reply to your penetrating questions could fill
several volumes but ! will try to touch on just a few points.
Barring some brilliant stroke of insight, we are probably many
years away from systematic, clinical application of the new know-
ledge of mechanisms of genetic transfer. The obvious point of
application would be to restore biochemical defects of genetic
origin and offhand it would seem to be a simpler proposition to
transplant whole cells and tissues from competent donors rather
than isolated genes. In the development cf transplantation technique
itself, however, genetic transfer is bound to play an important
role at least in the analytical stages and possibly in the actual
perfected technique of transplantation from one individual to another.
As you know, genetic individuality is reflected in a rather em-
barrassing way, as far as the surgeon is concerned, by virtue of
the Immunological rejection of foreign tissue by the normal host.
Experimental designs similar to those used in the study of micro-
organisms are bound to play an important role in the solution of
basic problems of transplantation. | suppose there is a remote
possibility that the transduction of genes may ultimately prove
to be as feasible or perhaps even more so than the transplantation
of whole, competent cells. It is important to polnt out, however,
that these phenomena have so far been detected only In micro-
organisms. and several laboratories are busily trying to extend
their application to the somatic cells of higher organisms.

Until we have learned how to influence the genetic constitution
of every single cell, it is doubtful whether transduction will
furnish a direct approach to cancer therapy,@since unmodified
cells would continue the progress of the disease. TWis may be an
open question for the future; meanwhile genetic anaylsis again may
be expected to be an indispensable part of the understanding of
the mechanism of cancer. The enclosed publications may he!p
bring out this point.
A great many constitutional diseases are beginning to be
understood as having at least some basis in a@ genetic defect
In enzyme production. Apart from such conditions as diabetes and
hypothyroidism, whose biochemical basis is perhaps more obvious,
there are many workers who are hopeful that mental disease may
be approachable from a similar standpoint. The most direct appli-
cation of this concept, of restoration of defect by actually
supplying the enzyme, may perhaps be found In Dr. Pauling's work.
As i understand you will be interviewing him, there may be little
point in my expanding this theme.

In brief, the clinical application of biochemical genetics
may, in part, have to wait upon the development of new techniques
of handling of somatic tissue cells with the same facility as is
now possible for micro-organisms. Meanwhile, biochemical genetics
has given a remarkable theoretical insight into a large number
of otherwise obscure conditions.

Yours sincerely,

Joshua Lederberg
Professor of Genetics