Pollack's
recently published book (Pollack, 2001) cannot be correctly understood if it is
taken out of the context from the scientific ideas first introduced by
Gilbert
Ling in his Association-Induction Hypothesis (AI hypothesis: Ling, 1962, 1984,
1992, 2001) and other closely-related writings (Nasonov,
1962; Ernst, 1963; Troshin, 1966), because not only
does it deal largely with AI hypothesis, but it is presented as a relatively
random collection of fragments. Both the uniqueness of the AI hypothesis as the
first unifying physicochemical theory of life, and the fact that it has stood
40 years of world-wide criticism are not even briefly mentioned. As a result,
one could easily be misled into believing that it is Pollack rather than Ling
who had introduced this unifying theory of cell function. The possibility of
doing harm by an unbalanced presentation of the material is going to be greatly
exacerbated by the lack of familiarity of most biologists with the AI
hypothesis.
For nearly
a century, two opposing approaches to an understanding of the physiological
properties of the living cell have co-existed. They are the 'conventional'
membrane theory and the 'heretical' bulk phase theories. Depending on which one
of these approaches you adopt, your view of the life of a cell will differ
profoundly. Following the first approach, many major attributes of a living
cell reflect properties of a specialized submicroscopically
thin cell membrane and its attached appendages. Following the second approach,
as for example spelt out in detail in Ling's AI Hypothesis (Ling, 2001), the
same fundamental features of a cell reflect the properties and behaviour of a water-ion-protein complex maintained at a
high (negative) energy and low entropy state, irrespective of where this
complex is located. It can be on the surface of a cell or in the depth of
cytoplasm. Pollack presents a thesis built on the second approach, and broadly
speaking reiterates Ling's fundamental concepts explicitly or implicitly in a
cool and superficial way.
Let us
consider from several different angles whether the ideas presented in Pollack's
book are truly his own and new, and ask how they compare in soundness and
veracity with the corresponding original ideas in the AI hypothesis, which are
not specifically mentioned.
1. Phase transitions
These are
at the basis of a unifying theory of cell function. Pollack seems unaware of
two relevant facts. First, 'phase transitions are essentially cooperative
phenomena...' (Domb and Green, 1972). Thus phase and
cooperative transitions are essentially the same
thing. Second, Ling's AI hypothesis includes the unifying notion that cell
functions in general involve cooperative transitions between resting and active
state. Regrettably, Pollack makes no mention of these prior deliberations,
which suggests that his phase transition theory is just another name for the
idea that Ling introduced decades ago (Ling, 1962).
2. The polarized
multilayer (PM) theory of cell water
The PM theory of cell water and what it stands for are not
mentioned in Pollack's book, an omission that will create confusion. Troshin, in the latest (English) version of his book
'Problems of Cell Permeability' (1966), wrote: 'in my opinion... all the water
in the protoplasm is somehow organized (''bound'').' However, neither Troshin nor anyone else had offered a molecular mechanism
of cell water organization until Ling (1965) proffered the first molecular
theory of cell water referred to as the polarized multilayer theory of cell
water. By not mentioning Ling's prior theory by name and what it stands for,
and by filling the pages with picture after picture of water existing in
polarized multilayers, Pollack risks misleading us into the false belief that
it was Troshin, Szent-Györgi,
or even Pollack himself, that first introduced the PM theory and what it stands
for.
Furthermore,
the PM theory is not just a theory of long-range water ordering. It is that,
and much more. The PM theory
represents also the first mechanistic theory of how cells can keep Na+
and sucrose levels low without the postulating a sodium and other pumps.
Ling (1993)
further developed his theory of solute exclusion to such a level of
sophistication that, from solute distribution data, one can determine precisely
what is the excess water-to-water interaction in frog muscle cell water (i.e.
126 cal/mole). By not mentioning the PM theory by name and what it stands for,
that part of the PM theory which is so important to cell physiology is placed
outside the reach for no good reason.
3. The seat of
multilayer water polarization-orientation
Pollack
claimed that the seats of water polarization in living cells are the
side-chains carrying net electric charges on the surfaces of cell proteins. In
doing so, he ignores the vast amount of experimental evidence collected over
many years by Ling and his coworkers, pointing to the fact that it is the
exposed backbone -NH-CO- which is the primary seat of
polarization and orientation of cell water. Parenthetically, Figure 5.2 in
Pollack has been redrawn from an original figure of Ling's, which contains, in
addition to what is reproduced in Figure 5.2 two highly informative insets. The
graphs presented in these omitted insets demonstrate that it is the exposed
backbone -NH-CO-grouping and not charged groups on the surface of native
proteins that polarize and orient water in multilayers.
4. Gels in lieu of protoplasm
Pollack
wrote: 'the concept of a gel-like cytoplasm turned out to be replete with
power. It accounts for the characteristic partitioning of ions between the
inside and outside of the call... It also explains the cell's electric
potential. . . Thus the gel-like character of the cytoplasm account for the
basic feature of cell biophysics.' This is an astonishingly sweeping statement
from a scientist whose expertise lies in muscle contraction and not in ion
partitioning and cell electric potentials. But Pollack is apparently so
convinced of the critical role of gel that he even includes the word in the
title of his book.
Equally
astonishing is the fact that throughout the book, the word protoplasm is not mentioned once. Thus Pollack is implicitly, if
not explicitly, suggesting that all living matter is not made of protoplasm but
of gels. But there is no reason given for this casual dismissal of such an
age-old concept that all the bulk phase cell physiologists almost to a person
believes in. And they include Ling, but apparently not Pollack.
However,
contrary to Pollack's protestation, gel
is not difficult to define. A gel is a pliable solid and like all other solids,
it does not flow. A sol is a liquid, and like all other liquids, a sol flows.
With this basic distinction in mind, one sees clearly that gel cannot be a
substitute for protoplasm-because protoplasm can exist both in the gel form and
in the sol form. Thus, whereas myoplasm and axoplasm are gels, the protoplasm
(endoplasm) of Nitella cells can be
poured out of a cut end of the cell (Kuroda, 1964). Protoplasm in the
pseudopodium of an Amoeba even goes through cycles of sol-gel transformation as
the organism migrates (Taylor and Condeelis, 1979).
Nor does
the existence in a gel state endow a substance with what Pollack calls 'characteristic
partitioning' of ions. In an extensive study of model systems, Ling and his
coworkers (Ling et al., 1980; Ling
and Ochsenfeld, 1983) have shown that solid gels may
show little or no exclusion proprieties of Na+ salts and sucrose. In
contrast, solutions (or sols) containing various oxygen carrying linear
polymers like polyvinylpyrrolidone strongly exclude
Na+ salts and sucrose. The next paragraph presents evidence that
being a gel has little to do with the basic mechanism underlying the creation of
a resting potential, as Pollack contends.
5. Seat of the
generation of the resting potential
Generation
of a resting potential is attributed by Pollack to surplus electric charges
inside the bulk of a gel. There are good reasons for rejecting this notion;
first, such a theory violates the basic law of the macroscopic electroneutrality. Second, Inoue et al., (1973) and Ueda et al.
(1974) have shown that if a microelectrode is inserted into an isolated droplet
of Nitella protoplasm, an internal
negative resting potential of 70-90 mV can be measured across the droplet
surface. Furthermore, an action potential can be elicited by the application of
an electric pulse (Inoue et al.,
1973). This protoplasmic droplet is not a gel, but decidedly a sol.
Pollack suggests
in his book that excess electric charges of one sign or the other inside the
gels give rise to what is known as the resting potential of living cells.
Again, this statement is made by ignoring an enormous volume of work by many
investigators, including Ling, whose PhD thesis was on this very same subject.
The results of their extensive studies showed that the seat of the resting
potential is a microscopically thin surface layer of the cell carrying
negatively charged beta- and gamma-carboxyl groups and
the ions they preferentially adsorb.
So we might
ask, are there any completely good and accurate aspects in Pollack's book? The
answer is yes; indeed many. Pollack's lampooning the big sodium channel and
small potassium channel is one. His effort at demolishing the so-called single
channel currents is another. Not the least is his strong recommendation as 'a
compelling read' Ling's 'Debunking the alleged resurrection of the sodium pump
hypothesis' (1997). For this
article alone shows, purely on energy grounds, how the membrane pump theory
ought to have been retired 40 years ago. But there are still other reasons for
retiring the membrane pumps including the following:
(1) Closed
sacs of perfectly healthy giant squid axon membrane furnished with ATP and other
requisite components do not pump Na+/K+ against
concentration gradients. Thus, this preparation, ideal for verifying the
central postulates of the membrane theory, has not justified the hopes assigned
to it.
(2) Cells
without functional cell membranes and (postulated) pumps continue to
selectively accumulate K+ and exclude Na+.
The crucial
question arises as to why the majority of life-scientists have so utterly
failed to come to grip with one incisive fact after another against the
membrane pump theory for so long? The answer is very complex. But one of them
is the fragmentation of cell physiology. The big picture is not in the focus of
more and more scientists engaged in the pursuit of smaller and smaller
subjects, with all the inevitable shortcomings of fragmentation.
In support
of this fragmentation idea is the striking difference between the number of major books on cell physiology published by the
subscribers to the bulk phase theories compared with subscribers to the
membrane pump theory. From the supporters of the bulk phase theories, one can
count the first book by Nasonov (founder of the then
Leningrad Institute of Cytology), called 'Local Reactions of Protoplasm and
Gradual Excitation' (1962), another book by Nasonov's
pupil and successor, Troshin, a former director of
the Institute of Cytology, which dealt with the 'Problems of Cell Permeability'
(1966), four books by Ling (1962, 1984, 1992 and 2001), and finally Pollack
(2001), which is a total of seven. And now what of the number
of books from the supporters of the membrane theory? The result of a
similar search gives a figure of zero.
It seems
that the supporters of the membrane theory cannot write books covering the
broad overall subject of cell physiology-perhaps because the fragmented pieces
of cell physiology seen from that perspective are hard to be put together as a
coherent piece. Anyone attempting to do this will inescapably have to confront
the list of devastating evidence against the basic membrane pump theory
including those cited above.
SUMMARY
In my best judgement, Pollack (2001) does not add much valid knowledge
beyond or different from Ling's AI Hypothesis. If anything, it might even
detract from it. That said, I must also add that its shortcomings
notwithstanding, I can still recommend Pollack's book for several reasons. In a
world of the education and research of basic biology stacked from floor to
ceiling with the membrane pumps and phospholipid bilayers,
any book from the camp of the bulk phase theories of cell physiology is like
water in a scorched desert, even if this water is not pure water, but water
contaminated by errors of omission and commission. This is my major reason for
recommending Pollack's book. Then there are some lesser reasons for my
recommending Pollack's book.
Ling has
spent his entire life single-mindedly testing and developing his unifying
physicochemical theory of life. By this time, few of his once large entourage
of students have survived the persecution (real or
threatened) for their dissenting views. The publication of Pollack's book shows
that it is still possible for those with courage and dedication to continue the
life of a dissenting scientist from received wisdom, and which still make a
very real contribution to Science.
Then there
is a third reason for recommending Pollack's book. As years pass, Ling's own
adventure into the inner working of the living cell has taken him deeper and
deeper, and inevitably farther and farther away from the younger generation of
scientists who will eventually inherit one day all that is truthful and valid,
which is plentiful in Ling's work. For them, correct or incorrect, Pollack's
more light-hearted four-colored approach may serve the role of a
chocolate-coated introduction to Ling's more serious book, from which the more
seriously minded must seek and glean more definitive answers. However, I need
to state my conditions for recommending Pollack approach.
To begin
with, if you have only casual interest in cell physiology and look for some
relatively lighthearted entertaining reading to begin with, by all means buy a
copy of the book, read it and take what you will from it. For the more
serious-minded cell physiologists, the condition for my recommendation is that
you must get hold of a copy of Ling's latest book (2001): 'Life at the Cell and Below-Cell Level. The Hidden History of a
Fundamental Revolution in Biology' which offers the most effective
antidotes to some of the more serious errors in Pollack's expose. Thus armed,
you will be protected from the lasting harm of the errors of commission and
omission I mentioned in Pollack treatise.
We ought to
be reminded at this stage of the words of Max Planck: 'New theories do not
necessarily prevail; they simply survive as old ideas fade away.'
REFERENCES
Domb C, Green
MS (Eds), 1972. Phase
Transitions and Critical Phenomena, Vol. 1. New York, Academic Press. ix
Ernst E,
1963. Biophysics of
Striated Muscles. Budapest, Publishing House
of the Hungarian
Academy of Sciences.
Inoue I, Ueda T, Kabatake Y, 1973. Structure of excitable membranes
formed on the surface of protoplasmic drops isolated from Nitella. I.
Conformation of surface membrane determined from the refractive index and from
enzyme actions. Biochim Biophys Acta 298: 653-663.
Kuroda K,
1964. In: Allen RD, Kamiya N, eds. Primitive Motile Systems in Cell Biology.
New
York, Academic Press. 31-44.
Ling GN,
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A Physical Theory of the
Living State: The
Association-Induction Hypothesis. New York-London, Blaisdell Publ. Co.
Ling GN,
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The physical state of water in living cell and model
systems. Ann NY Acad Sci 125: 401-417.
Ling GN, Walton
C, Bersinger TJ, 1980. Properties of polymer-oriented
water to exclude Na+, sugar, amino acids and other solutes normally excluded
from living cells. Physiol Chem Phys 12:
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Ling GN, Ochsenfeld MM, 1983. Studies on the
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In Search of the
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A Revolution in
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Ling GN,
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Ling GN,
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hypothesis. Physiol Chem Phys and Med
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Life at the Cell
and Below-Cell Level. The Hidden History of a Fundamental Revolution in Biology. New York, Pacific Press. (Ling's new book
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110
Marcus Drive, Melville, NY, USA 11747 or
http://www.pacificpressnewyork.com
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Nasonov
DN, 1962.
Local Reactions of Protoplasm and Gradual Excitation. Published for the
National Science Foundation, Washington, by the Israel Program for Scientific
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contractility in amoeboid cells. Int Rev Cytol 56: 57-144.
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Problems of Cell Permeability.
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