BARRY C. SMITH

GENERAL DIRECTOR

THE COMMONWEALTH FUND

           41 EAST 57T" STREET

             NEW YORK

BARBARA S. QUIN

ASSISTANT DIRECTOR

DIVISION OF PUBLICATIONS
  GRAHAM R.TAYLOR
     DIRECTOR

GEODES SMITH

ASSISTANT DIRECTOR

ELLEN THAYER

ASSOCIATE

ROGER A.CRANE

DlSTRlBUTlON MANAGER

January 10, 1940

Dear Doctor Heidelberger:

Mulling over the sort of thing that we talked

of the other day, I have come on a question which I
realize has been in the back of my mind for some time
but which I wasnft bright enough to get into the con-
verssltion with you.

Isnft it true that information as to the pre-

sence of antibodies in the living host and deductions
as to their significance are based wholly upon cir-
culating, free antibodies? And if so, how does one
know that the deductions are not distorted by uncer-
tainty as to the physiological significance of circu-
lating, free antibociy? What is the relation of circu-
lating,' free antibody to the antibody which conceivably
has alresdy done its work? Is it just a safety factor,
a physiological overflow, or what? Would this account
for the late rise of antibody titer in recovery from
acute infection, slnd should one postulate a period before
antibody becomes demonstrable when it bay nevertheless
be effectively reacting with antigen in the blood  stream
or conceivably within cells? When one measures potential
resistance in terms of antibody titer, is one really
measuring the physiological vagaries of one organism as
compared with another in its capacity to produce an ex-
cess of a needed substance? Are there any instances in
which one can recover hnd demonstrhte not free antibody
but the product of an antigen-antibody reaction - I mean,
of course, in vivo?

    Probably I'm greatly
which doesnft exist, but if
straight very quickly. With

Dr. Michael Heidelberger
College of Physicians

and Surgeons
620 West 168th Street
New York, N. Y.

GS EZ?

exaggersting a difficulty
so I'm sure you can set me
many thanks, as always, I am

Yours sJncerely,