Ken-
In your discussion of the methods of science, you mention that there are
four steps to the scientific process, the first of which was to observe.
By this construct, it appears to me that you are placing yourself firmly
in the camp of inductionists (a la Bacon), who believe in the notion of
"pre-suppositionless" observation, or that observation precedes and
begets theory. Unfortunately, this idea was refuted by Hume, who firmly
stated that observation in and of itself cannot lead to a new theory of
nature, nor can a new theory be justified (?proved?) by observation.
More likely you meant the proper order to be:
1. Hypothesis
2. Attempt to refute hypothesis through experiment (note, this is clearly
not observation in the absence of theory).
3. If hypothesis is disproved, then new hypothesis.
This is the philosophy of Sir Karl Popper.
But where did the first hypothesis come from? From observation? This was
essentially the question that Kant addressed, i.e. how are synthetic a
priori judgments possible?
But this is an immunology discussion group, not a philosophy discussion
group. The point I am trying to make is that the reductionist approach,
of which you seem to be a forceful advocate, ultimately fails because the
"observer" (in your case the molecular immunologist) has to be told by
the theorist which questions are important to answer. Let me illustrate
with a concrete example. The current molecular paradigm of self/nonself
discrimination (and so back to the origins of this thread) states that T
cells require two signals for activation: signal 1 is T cell receptor
ligation by antigen + MHC, and signal 2 is a "costimulatory" signal
mediated by the interaction of B7 on the APC and CD28 on the responding T
cell. There are two problems with this paradigm: 1) Control of the S/NS
discrimination is given to the APC (by its expression or not of B7), and
APCs cannot discriminate self from nonself; and 2) Activated B cells
express gobs of B7 (specifically B7-2) but either fail to activate or
induce tolerance in naive T cells.
What I am trying to say is that the current molecular explanation of the
central question of immunology, the self/nonself discrimination, is
intellectually bankrupt. Now as a developing immunologist, you have two
choices. You can go to the creators of such a paradigm (Ron Schwartz,
Peter Linsley, Lee Nadler to name a few) and ask them for a new theory.
Alternatively, you can go to the holists (Antonio Coutinho, Mel Cohn,
Polly Matzinger to name a few), apologize for insisting upon inductivism
and reductionism as the supreme methods of science, and ask for help.
Ephraim Fuchs
ejf at welchlink.welch.jhu.edu
P.S.: I am not angry. I hope you won't be either.
