CALIFORNIA INSTITUTE OF TECHNOLOGY
PASADENA

GATES AND CRELLIN LABORATORIES OF CHEMISTRY December 35 1958

Professor Joshua Lederberg
Department of Medical Genetics
School of Medicine

The University of Wisconsin
Madison 6

Wisconsin

Dear Professor Lederberg:

Thank you for the supplement and reprint. I found the material very
interesting.

Sorry I don't have more to contribute at present than the resumé of
speculations published a couple of years agoe However, in view of additional
indirect experimental evidence and more thought, I still think the original
ideas are logical and suggest experimental approaches to the problem of
antibody synthesise In our early findings the possible significance of
the presence of RNA with most of the fragmented antigen material was not
considered. However, when others began to obtain data and to theorize on
the role of RNA in protein synthesis I began to think about the significance
of the RNA-antigen complexe One possible objection at that time was that
our RNA had a molecular weight of about 30,000-50,000 ("soluble" RNA) and
most other workers were thinking of protein synthesis in terms of insoluble
or microsomal RNA. It is now becoming obvious that this soluble RNA does
play an important role in polypeptide formation.

I cannot help but believe that antibody formation depends upon the pre-
sence of a small fragment of foreign material (either exogenous or endogenous).
The presence of extracellular antibody will depend on analytical methods as
well as subtle equilibrium reactions between antigen and antibody within the
cell.

The formation of antibody forming clones can of course be explained by
"mutation", but it can also be explained by the fragmentation-template idea.
For example, the number of fragments or even molecules of antigen retained
by each liver cell is quite large (Int. Arch. Allergy 12:70-88 (1958)). When
a cell divides there is also a division in the number of antigen particles.
However, there is only a definite number of such particles and hence one
observes small groups of cells in immune lymph tissue which are producing
antibody. It is cf interest, that from Al Coons work, one ean conclude that
the secondary response in immunization, which stimulates clone formation,
is the result of either destruction of the initial cell or stimulation of
division. I believe that destruction may take place due to a hypersensitive
reaction and that antigen fragments are released and picked up by adjacent

 
page 2

Professor Joshua Lederberg December 3, 1958

cellse ‘Your studies might answer this question if you use a soluble antigen
capable of inducing a secondary response. I cannot explain at present why
a single cell or clone (Coon's data also suggests this) forms only a single
type of antibody. I would have to determine whether more than one antigen
particle could enter any given cell.

Contrary to your apparent aporehension of my skepticism, I seek only
the truth, and hope my ideas may help, or at least contribute to, some
aspect of the probleme I hope that I have the opportunity of informally
diseussing this further with you, either at Stanford or the California
Institute of Technology, when you get settled on the west coast.

Congratulations on the Nobel Prize and with very best regards.

Sincerely
CMa be a
DHG:me Dan H. Campbell

Professor of Immunochemistry