"Fathers" and "sons" of theories in cell physiology: the
membrane theory
Vladimir V. Matveev1 and Denys N. Wheatley2
1Laboratory of Cell Physiology, Institute of
Cytology, Russian Academy of Sciences,
Tikhoretsky Ave 4, St. Petersburg 194064, Russia and
2BioMedES, Leggat House, Keithhall, Inverurie, Aberdeen AB51 0LX, UK
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Abstract. The last 50 years in the history of life sciences are
remarkable for a new important feature that looks as a great threat for their
future. A profound specialization dominating in quickly developing fields of
science causes a crisis of the scientific method. The essence of the method is a
unity of two elements, the experimental data and the theory that explains them.
To us, "fathers" of science, classically, were the creators of new ideas and
theories. They were the true experts of their own theories. It is only they who
have the right to say: "I am the theory". In other words, they were carriers of
theories, of the theoretical knowledge. The fathers provided the necessary
logical integrity to their theories, since theories in biology have still to be
based on strict mathematical proofs. It is not true for sons. As a result of
massive specialization, modern experts operate in very confined close spaces.
They formulate particular rules far from the level of theory. The main theories
of science are known to them only at the textbook level. Nowadays, nobody can
say: "I am the theory". With whom, then is it possible to discuss today on a
broader theoretical level? How can a classical theory - for example, the
membrane one - be changed or even disproved under these conditions? How can the
"sons" with their narrow education catch sight of membrane theory defects? As a
result, "global" theories have few critics and control. Due to specialization,
we have lost the ability to work at the experimental level of biology within the
correct or appropriate theoretical context. The scientific method in its classic
form is now being rapidly eroded. A good case can be made for "Membrane Theory",
to which we will largely refer throughout this article.
Introduction. At present, it is commonly accepted that the most
characteristic feature of the modern science is its marked specialization. Even
researchers studying similar cellular structures – for instance, channels – live
now in parallel worlds: those who study Na-channels do not see too much sense in
communicating with those who study Cachannels, and even less with those who
study channels for organic molecules. Of course, expanding specialization is not
merely a sensation or individual observations. We see everywhere objective
evidence of degradation of sciences into individual "earldoms" whose autonomous
status is constantly being enhanced. The most evident proof in favor of this is
a rise in the number of co-authors on publication, reaching in some cases up to
several hundred names. Also the number of specialized journals and conferences
is steadily increasing. The mean length of formulations of the essence of
discoveries, for which Nobel Prizes are awarded, increases, while the number of
"discoveries" decreases and their significance can only be correctly evaluated
by an increasingly narrow circle of specialists. The decrease of significance of
investigations on the background of a steady rise of the number of publications
means that expenditure on science increases, while their actual yield decreases.
But whereas economic consequences of the specialization are widely discussed,
the intellectual problems that beset modern science still escape proper
attention.
The danger has descended through "Scientific Method" itself. Theories of a
general biological character were accepted many decades ago, and nowadays, due
to the specialization, there are no scientists who master these theories so well
as those who could be rightfully considered their bearers. As a result, the
profound generalizations of the past seem to be beyond the natural process of
renovation, and indeed beyond criticism. If competing theories appear under
these conditions, their significance and advantages over classical knowledge
will not be properly evaluated - fantastic and worrying as this might seem.
There has appeared or can appear the situation where scientists mastering the
most modern methods of investigations at the molecular level are guided in their
work by obsolete or even erroneous concepts of the general character that they
inherited from the classicism epoch. The theories of the past, instead of
being always under scrutiny, have turned into the dogmas incompatible with the
spirit of the scientific method. The extra layers of present day
specialization are a menace, which may lead to the loss of the integrity of
scientific knowledge.
Scientific method in an epoch of specialization. In the opinion
of Popper (10), the structure of the scientific method seems to be as follows: i)
identification of problem (for instance, failure of a previous theory); ii)
proposal of a new solution (i.e. of a new theory); iii) deduction of verifiable
conclusion, predictions from this theory; iv) choice of the most suitable theory
among the competing ones. Let us consider the effect of the process of
progressing specialization in science on functioning of the scientific method as
the main instrument of scientific investigation.
The overwhelmed number of authors writing about scientific method find the most
illustrative examples of its application in history of science – e.g. failure of
Ptolemaeus’ theory, establishment of Copernicus’ system, the appearance of
Newton’s classical physics, Einstein, etc. But let us imagine for a while a
fantastic case: in the XIX century, after the 300-year long development of
Newton’s mechanics, the degree of specialization in physics reached such limits
that scientists appeared who were experts in only one of Newton’s laws, poorly
understanding the rest of his laws. In this case, physics, like modern biology,
would have been disintegrated into many semiindependent "earldoms" and "states".
Now let us pose the following questions: would it be possible in this case for
Einstein and his theory to appear? In such a scientific community, who
could have appreciated his theory and made a realistic choice between classical
mechanics and the relativity theory? The answer is obvious: the appearance of
Einstein would have been impossible and nobody could have evaluated his theory,
as both the former and the latter necessitate understanding of physics as a
whole and such integral knowledge has to be realized in some single
head. The role of the personality-creator can neither be substituted by a
council of experts, nor by a conference, nor even an international congress. The
history of science contains no example of some discovery being made by a
symposium, rather than by an individual person or personality. Hence, we contend
that only personality can reliably provide knowledge with integrity and logical
orderliness. From all the above-said, the unanimous conclusion follows: the
scientific method exists only until it, from the first to the last point, can be
placed and operated in somebody’s head. Under conditions that there is one
expert responsible for mastering only of the first Newton’s law, while the other
one, only of the second law, the scientific methods ceases to operate or even
exist, and becomes a myth.
Mythology starts at the time that one mind ceases to encompass the whole subject
area under study, after it has been revised refined and generalized as far as
possible. To preserve scientific method in a working state, the area of
investigation inevitably starts disintegrating, and is doing this precisely as
much as necessary for the intellect of one person to be able to operate with it
as with a logically closed construction. Whereas from the beginning of the 19th
century to the 1960’s, the subject of investigation had been the cell, beginning
from the 1970’s the uninterrupted process of specialization led the cellular
theory beyond the limits of competence of an individual specialist. This border
is remarkable; it shows the attempts to present a generalized concept of
fundamental cell properties (1,4,5,6,9,12,13). The last change of the commonly
accepted paradigm in the modern history of cell physiology is connected with the
names of Boyle and Conway (1) and Hodgkin (5) through their versions of membrane
theory, of Dean (2) with his hypothesis of sodium pump, and of Skou (11) with
his suggestion that it is Na, K-activated ATPase that is indeed the sodium pump.
Since then, no such massive attempts at theoretical generalization of our
knowledge of the cell have already been made, as their volume seemed to exceed
significantly the possibilities of the intellect compass of the individual
scientist. Let us consider the situation by the specific example of the
competing theories.
Two competing theories in cell physiology. Whatever aspect of
cell activity you try to explain, your consideration will include concepts of i)
how some substances penetrate the cell easily, while others have more
difficulty, and still others may not not penetrate the membrane at all (the
property of semi-permeability); ii) why substances, for instance, K+
and Na+ ions, are distributed non-uniformly between the cell and the
medium: some are more abundant in the cell than in the medium, while others, on
the contrary, are more abundant in the medium than in the cell (the property of
selectivity); iii) by what means the cell generates electrical potential, and
iv) how the cell manages to maintain osmotic equilibrium with the medium
(osmotic properties). All other ideas about the cell, including those at the
molecular level, depend on how you explain these properties. For this reason,
the above properties have to be considered fundamental.
There are two approaches to explaining these properties. The first is the
membrane theory – the commonly accepted, dominating theory of our time.
Everybody who is interested in biology faces it from the school bench and keeps
acquaintance with it in university courses, whereas to scientists this is not a
theory, but rather the style of thinking. In other words, whereas the "fathers"
of the membrane theory retained a (little bit of the) uncertainty in their
thinking, their sons have accepted it absolutely without doubts as the truth in
their scientific inheritance.
According to the membrane theory, all four fundamental cell properties are
explained by properties of the membrane that separates the cell content from the
environment. With such an approach, cell physiology is reduced in fact to the
physiology of a film no thicker than 100 Å. From the point of view of the
theory, the cell content can be considered as a simple watery solution of
cellular components, this solution not differing theoretically from a mixed
solution of organic and inorganic components in a test tube. This theory does
not need a cytomatrix as a theoretical parameter; it needs none of the
properties of the cytoplasm and nucleus, but the only necessary ability of the
cell contents to "swim" in the solution. Common sense should suggest that at
least the minimal doubts that the single plasma membrane alone, with its mass
accounting for a thousandth fraction of the whole cell mass is capable of
regulating ion composition of the intracellular medium on a scale exceeding a
million times its own volume.
Another point of doubt is the existence of a strange exception. If the membrane
"theory" is a theory in the same meaning as this word is used in physics (i.e.
from a logical, integral system from which deductions can be made), it should
follow that any asymmetrical distribution of a substance between the
cell and medium is a result of activity of a necessary special system of
activated transport located in the superficial membrane. However, this
attractive theory does not operate. Oxygen turns out to be concentrated in
erythrocyte not because it is pumped into the cell by a special pump, but
because it is concentrated due to adsorption by hemoglobin. There is no oxygen
pump. If so, let us ask a simple question: can it be that nature used the
adsorption mechanism only once? The negative answer to this question provides a
different approach to explain the fundamental properties of the cell – the
Association-Induction Hypothesis (AIH).
Unlike membrane theory, the AIH has only one author –
Gilbert Ling (6,8). He
believes that the case with oxygen is not an exception, but reflects the general
rule: sorption (or its absence) on intracellular structures can play an
important role in highly asymmetric distribution of substances between the cell
and environment. All four fundamental cell properties are eventually explained
by sorptional processes in the cytoplasm and nucleus. The plasma membrane and
other cell membranes also are involved in the regulated process of
sorption/desorption. Also of importance is that the AIH needs the
cytomatrix as an organized structure. For this reason, as well as for other
reasons, this theory considers the cytoplasm not as "bullion", but as an
organized structured system that includes, among other things, cell water which
is so often ignored or assumed in other concepts. Essential defects of the AIH
are the absence of its own interpretation of the structures that the membrane
theory calls channels, carriers, and pumps. This depresses the further
development of the AIH and weakens its attraction in eyes of the scientific
community. But this lack of development hinges on the fact that this alternative
concept has received negligible funding.
"Sick" science. One can become convinced that there has been a
seachange in modern science, which has acquired an essentially different quality
from what it had 50-60 years ago, at the period of foundation of the membrane
theory and of its competitor, the AIH. With respect to fundamental cell
properties, it seems that nowadays the 1st and 4th elements of the scientific
method have stopped operating. As a result of specialization, many researchers
have left such a level of understanding of cell physiology by immersing
themselves in the abyss of the endless diversity of details. The scientists are
occupied, for example, in studying molecular or even submolecular structure of
some channel, meanwhile their knowledge of membrane theory, of which these
channels are components, remains at the level of an undergraduate university
course. With the horizon as narrow as the lumen of the channel, identification
of problems becomes minimal. It is evident that without the first step, the
necessity of the fourth one does not even appear. Meanwhile the choice
between competing theories is a much more difficult task than merely recognition
of the existence of the problem. Thus, the scientific method keeps operating,
but its remit or frame for the individual becomes increasingly narrower, and
dwell at the feet of molecular detail with little or no integration. In the
grander theoretical scale of living processes, scientific method has all but
ceased. Afew who do extol new encompassing ideas generally find themselves
ignored because the army of modern day scientists are too busy with their
details to take notice, and the new ideas are debated by too small of faction of
the scientific community to appeal to grant giving bodies, who seldom give funds
to pursue theoretical work in life sciences. Some rectification, however, may be
afoot, as new institutes such as the Bauer Center at Harvard, desperately try to
reverse the tide, and meet the problem of finding people who can think in more
general terms that are required for the synthesis needed in formulating "general
theories", to continue the analogy with Physics. The greatest problem is that we
do not have any theories in Biology that match up to those of classical and
modern physics, possibly with the exception of the theory of natural selection.
One piece of evidence in favor of this contention is that there are no
monographs in the literature that would explain the fundamental cell properties
from consecutive theoretical positions. And whereas we can still say about the
fathers (the Newtons) of the membrane theory, nothing remains to be said about
its sons (the Einsteins). Instead of large generalizations from the fathers of
science, we have a large circle of reviews about either biopotentials
or problems of semi-permeability or osmotic cell properties, but these problems
are never considered together in the single work form positions of a
logically closed theoretical approach. But even these limited plans of
analytical work are too large for the present time. In most cases, the authors
prefer considering only isolated aspects of the problem. Further
evidence for degradation of the scientist’s horizon is conversion of cell
physiology into molecular physiology or physiology of the living
molecule. The cell as the whole has become a history. The specialists who
graduate from universities know reasonably well the operation of only some part
of the cell, and the more limited the sphere of competence of a specialist, the
more greatly appreciated such a specialist is. Such terms as "protoplasm" and
"cytoplasm" are used increasingly seldom. Papers have already begun to appear in
which the even the term "cell" is absent. That is why "sons of science" came
into being over the last two decades.
The AIH looks interesting, as its theoretical construction reminds us of a
classical physical theory, in which numerous consequences are logically deduced
from several initial postulates. In this sense, this is an attractive theory.
Logic and integrity of this theory allows one to bring to a single denominator
quite diverse factors that otherwise seem to have nothing in common. The logic
of this theory becomes the instrument that allows conceptualization of the whole
from parts and creates prerequisites for the larger view of the problem; from
this, molecules are arranged into a structure, and structures into a cell.
It is much easier to master a logically harmonious theory. Such theory can
easily become an instrument of thinking of one individual who will raise the
scientific method above the Brownian movement of molecules and will provide some
foundation for new theoretical generalizations. In the AIH, it certainly can be
traced the structure of the "Greek approach" to the construction of a theory, as
opposed to the "Babylonian" tradition. The Greek method was to construct theory
on the basis of axioms, while the Babylonian method was a theory representing a
complex of individual examples (3).
The evidence for the AIH fruitfulness is that its logic has brought about
non-standard experimental approaches, posing interesting experimental tasks. The
AIH potential is also indicated by Ling’s monographs, in which the author
considers both foundations of the theory and its applications to explain various
physiological mechanisms at the level of cell and of individual structures. The
theoretical integrity of the AIH reveals hidden defects of the membrane theory
(7). With all the supposed successes of the membrane theory, it is misguided
if not wrong to lose a critical attitude to it. The blind faith in its
truthfulness can only lead to accumulation of methodological and theoretical
mistakes, which in the long run will reduce efficiency and progress of science.
It is always important to remember that there are no theories that would not
have to face the awkward little fact that contradict them (10).
We also see the painful symptom in that the available experimental evidence in
favor of the AIH is ignored by the scientific community. There are
neither checks, nor arguments against it, nor analysis of the theoretical AIH
non-justifiability. Meanwhile, we are dealing with publications of Ling and
other independent authors in prestigious scientific journals. Ignoring the issue
itself destroys scientific method and destroys science as an instrument of
obtaining reliable knowledge. It would be much more useful for the scientist to
know two idioms, that of the membrane theory and that of the AIH. If experiments
had been carried out taking into account the methodological requirements of both
concepts, the appearance (phantom) of truth would not be threatening science.
The play would have been fair, and if so, then let the stronger win. But to whom
will come the idea of studying these metalanguages of cell physiology, if
general attention is completely paid to details and the horizon of thought is
measured in nanometers?
Conceptual hallucinations. The bearers of hypotheses and
theories always were the vanguards of science, its real creators; however, the
sphere of their competence is constantly narrowing at the epoch of
specialization. Narrow specialists also become limited people. The generation of
scientists with a large circle of theoretical interests abandoned science long
ago. Nowadays, even Nobel Laureates are specialists of a narrow profile. Similar
specialists also are reviewers determining standards of the modern scientific
literature. An important question arises: who at our time is able to appreciate
the completeness of the correspondence to facts relating to the membrane theory
that formed half a century ago? Who can make a choice between the membrane
theory and the AIH, or any other competing theory?
The answer to all these questions is that nowadays there is nobody to make such
choice. For as long as several decades, the sons of science have come to believe
in the infallibility of their fathers and cast no doubts on the membrane theory,
at least because they do not master it. This belief that contradicts the spirit
of science, which accepts nothing by just taking on trust, will inevitably lead
with time to conversion of the membrane theory into "conceptual hallucination".
And this could be true not only for the membrane theory. Any large
generalization of the past and present, with time, could become the
hallucinatory, as science becomes fractionated into more and more minutely
focused areas of investigation. Einsteins of the cosmic scale are replaced by
einsteins of nanostructures. And as the intellectual narrowness continues to
deepen, the number of hallucinations will rise. The attitude towards scientific
method will be that it is a myth.
Acknowledgment. We thank Dr. Leonid Pevzner for his help
throughout the preparation of this article.
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