Ld gyn’ -
THE WALTER & ELIZA HALL INSTITUTE OF MEDICAL RESEARCH (C

Department of Experimental Medicine, Clinical Research Unit,
University of Melbourne The Royal Melbourne Hospital

Director:
SIR MACFARLANE BURNET, O.M., F.R.S.

28th February, 1962.

Professor Joshua Lederberg,

Dept. of Genetics,

Stanford University School of Medicine,
PALO ALTO, CALIFORNIA.

Dear Josh,

Thank you very much for your note and
enclosures. . I have passed the invoices dealing with
the microscope on to Mr. Hughes, and no doubt you have
received a cheque by now. Might I say once again how
grateful I am to you for saving our lives in this regard.
We all heaved a deep sigh of relief when the microscope
came.

, Unfortunately the two excellent references
to the chaining phenomenon arrived a little bit too late
for inclusion, in my Stanford papers, but:they certainly
will come in handy later on. Thank you*'very much for
that too.

. I was very excited to see that you have
moved seriously into the area of mental retardation,
though I am a little skeptical about the ‘experimental
approach which you have outlined. I realize that this
type of Captain Cook work has to be done sometime, but
I doubt whether the country chartered would be as fertile
as Australia, even. But as you suggest, it is getting
the right sort of people interested in the area, and
getting some work going along these lines that is the
important thing. It matters little whether the research
project one-year after its start has already deviated
sflong the way from the line indicated.

I am now fairly certain about my dates

in America in June. On present plans, I'11l be arriving
in San Francisco on the evening of June 6th, and will be
staying in the Bay area till the evening of llth or the
morning of the 12th. The temptation to see all of you
again when the Paris invitation came proved too much for
me. I was delighted to hear that you will be back from
Japan by that time.

Address: C/o ROYAL MELBOURNE HOSPITAL POST OFFICE. MELBOURNE, AUSTRALIA. TELEPHONE: FJ 9177
You will be interested to hear that we
now find that the precursor of plasma cells in a primar
response to bacterial antigens is also a primitive
lymphocyte, in fact the primary response seems to be
merely a scaled down version of the secondary response.
The crucial difference in cellular proliferation between
the primary and the secondary responses appears to be a
maturation arrest of the blast cells between the second
and the fourth day after antigen injection. In the
secondary response, the cells started differentiating
into plasma blasts and plasma cells virtually from time
zero, whereas in the primary response, they appear to
start multiplying almost without lag, but remain quite
primitive for the first 3 days, and the first sign of
antibody production by gingle cells is on the 4th day.
If one extrapolates the proliferation curves back to
the time of antigen injection, one gets the impression
that too many cells are proliferating and eventually
differentiating for any straight forward clonal
selection approach. I know that unknown questions of
nett emigration of cells into the node are a qualifying
factor here. On the other hand, we are thinking more
and more along the lines of the primitive lymphocyte as
a "mother" qr "nurse" cell rather than as a "memory "ctl.
The possibility that the information is being tranemitted
from another cell type is still prominent in our minds.

Before these alternatives. can be tackled
experimentally, we need a tremendous amount of background
information about the behaviour of RNA in antibody
forming cells and their ancestore, which with the
collaboration of Gordon Ada we are just beginning to get.
Eventually direct transfers of RNA derived from a cell
with one competence into another cell with another or
no competence should be possible.

Please give our fondest love to Ester.
Lyn won't be able to make it with me this time, but is
already agitating very actively for another swing und
the world in 1964. We'll see}?

As ever,