* Unanswered Questions - Response *

Margaret Fowler 101722.35 at CompuServe.COM
Tue Jun 11 18:05:34 EST 1996

1. Discourtesy, assumptions of ignorance, and emotive remarks are no
substitute for measured argument and evidence. Each of these quest-
ions highlights a contradiction *within* current views; for example,
    (a) everyone agrees that intracellular movements can be seen by
low power light microscopy in living cells, yet most people also
believe that there is a cytoskeleton, which would not permit such
    (b) most people believe in the Second Law of Thermodynamics, yet
in subcellular fractionation they change the entropy of their systems
(homogenise and centrifuge), and assume that this does not change the
free energy, which drives all the biochemical reactions they are
studying, and at the same time, they have refused for fifty years to
do the necessary control experiments to find out by how much;
    (c) most people would agree that the laws of solid geometry must
be obeyed, while in their electron micrographs - as opposed to their
diagrams - they do not see a random selection of orientations, includ-
ing oblique views of cell membranes, nuclear membranes, myelin
lamellae, synapses, nuclear pores, etc.

2. In my publications cited, and in about 120 other full-length
papers, I have shown, in detail, with evidence:
    (a) That one can not yet derive conclusions from subcellular
fractionation about the chemistry of organelles, which are relevant
to their original states in the intact, living organisms;
    (b) That the following structures do not exist in the living
cells: endoplasmic reticula, Golgi bodies, lysosomes, nuclear pores,
mitochondrial cristae, the cytoskeleton, actin filaments and synapt-
ic knobs, either because they would not permit the evident intra-
cellular movements, or because they disobey the laws of solid
geometry. Transmembrane molecules and receptors can not be seen on
the cell membranes by transmission electron microscopy, although
sequencing shows them to be 2-3 times the diameter of the cell
membrane, which *can* be seen by electron microscopy;
    (c) That in the central nervous system, the only cells are
neurons and microglia; astrocytes and oligodendrocytes do not exist
in the whole intact mammalian nervous system;
    (d) The chemical transmission hypothesis contains many untested
and untestable hypotheses, and was worked out for neuromuscular
junctions; it has been assumed to be relevant to synapses - especial-
ly since the latter term has been extended from its original meaning
(nerve-nerve connections) to include neuromuscular junctions (nerve-
muscle connections).

3. I have always suggested alternative and testable hypotheses, not
open to the criticisms of current views, for example, how to local-
ise biochemical activities without disruption of tissue, the struc-
ture of the living cell, the cellular structure of the central
nervous system, the passage of excitability from one neuron to
another, etc, etc.

4. The fundamental questions I must raise with the Internet
cytologists are:
    'By what criteria are questions improper?'
    'Do all academics have a duty to address the difficulties and
apparent contradictions of their own views?'
    'Do they believe that progress can be made without examining
their own views?'
    'Would they disagree that a good academic should answer all
these questions in the affirmative?'

5. It seems to me to be absolutely essential that any experimental
project to list as many as possible of the assumptions inherent in:-
    (a) the use of the experimental procedures;
    (b) the processing of raw data into the results to be published;
    (c) the interpretation of the results in the light of previous
theories and new ones being generated.

It is simply not good enough to support one's case with other
peoples' findings without examining the validity of the findings
cited. One is responsible not only for the interpretation of one's
own results but also for the validity of experiments or interpreta-
tions of other authors whose results one uses to interpret one's own
findings. The validity of an experiment depends upon the warrantab-
ility of *every* statistically potentially significant assumption,
both those recognised and those not recognised or ignored. Like a
chain, its overall strength depends upon its weakest link. The
validity and value of an experiment in pursuit of truth depends upon
the warrantability of the weakest assumption. Indeed, *any* wrong
assumption, whose error would make a significant difference to the
result of an experiment, renders the whole experiment invalid. Of
course, it becomes worse if the assumptions are testable but have
never been tested, or are untestable. An assumption does not dis-
appear just because research workers singly or collectively do not
recognise it, or do not wish to do so.

6. I wish to repeat that I am prepared to enter into personal
dialogue with anyone about any of these questions, and I have dealt
with each of them in *detail* in my publications. I have answered
the Internet responses received so far.

7. We are  talking here about intellectual integrity, and not about
promotion, grant applications, casuistry, verbal acrobatics, scoring
points, theology or dogma - at least, I hope we are!

Hillman, H.  *Certainty and Uncertainty in Biochemical Techniques*
(1972), Surrey University Press, Henley-on-Thames, U.K.

Hillman, H. & Sartory, P.  *The Living Cell* (1980), Packard
Publishing, Chichester.

Hillman, H.  *The Cellular Structure of the Mammalian Nervous System*
(1986), MTP Press, Lancaster.

Hillman, H.  *The Case for New Paradigms in Cell Biology and
Neurobiology* (1991),  Mellen Press, Lampeter.

Dr Harold Hillman
Unity Laboratory of Applied Neurobiology,
76 Epsom Road,
Fax:  UK 1483 31110
Telephone:  UK 1483 568332

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