Cell Physiology Myths?

[Guest guest]

As promised, here is some more information on Dr Gilbert Ling's

Association-Induction Hypothesis, this time drawn from a recent book review:

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Book Review

Townsend Letter for Doctors and Patients Aug/Sept 2002

Life at the Cell and Below-Cell Level: The Hidden History of a Fundamental

Revolution in Biology

by Gilbert Ling, PhD

[Excerpts given ...]

.......The paradigm used is that for each disease there is one and only one

corresponding microorganism, whereas, since at least 1892, biologists have

recognized that change of internal bodily environment produces change in form

and function of most invading microorganisms!

It is reasonable to assume that an accurate picture of how the cell functions

would also lead to knowledge of how cancer can ought and won. Several

inaccurate models of the living cell are repeated in virtually every

scientific paper, leading in many cases, of course, to inadequate conclusions

regarding the meaning of the funded research. Clearly, if it can be shown

that the model upon which the normal day-to-day, operation of a cell is based

on non-existent energy, then the cancer research, and in fact, all biological

research, is defective.

This brings us to a fundamental discovery about life at its basic structural

and functional level, basic research that has stood the test of a half

century of laboratory research, and has been all but ignored in clinical

research and practice.

Dr. Gilbert N Ling's Life at the Cell & Below-Cell Level reflects extremely

important laboratory discoveries on the nature of the human cell, and its

relationship to disease and methodical selection of appropriate drugs for

those diseases.

A Long-Standing False Biological Model

One such model, the sodium-potassium membrane pump (in unifacial cells or

cells with a single uniform cell membrane like muscle or nerve) is wholly

false, according to Dr. Ling's outstanding research .

The currently taught model of a unifacial cell - such as a nerve or muscle

cell - would have us believe that these cells have a microscopically thin

covering (plasma membrane) filled with lipids and proteins, with marvelous

small structures such as " gates " and " pumps " that allow certain charged ions

or other particle: (e.g., potassium ion, K+ or sodium ion, Na+) in and out of

the cell, with a cell interior composed of free water. Furthermore, it is the

" fixed charge " of either Na+ or K+ (outside or inside the cell) on the cell

membrane, that, when the gates open or close, cause an " action potential. "

These pumps, it is said, operate at the expense of energy stored in

high-energy-phosphate bonds of ATP and other organic phosphates. This theory

requires continual energy expenditure to maintain an uneven balance between

K+ inside the cell membrane, and Na+ outside the cell membrane.

The cellular Membrane-Pump theory - developed to explain the low level of Na+

in cells such as muscle cells, nerve cells, and erythrocytes - was a general

theory attempting to deal with all solutes in living cells. According to

Ling, " The Na pump theory has never attempted to offer more than an ad hoc,

patchwork theory dealing with one solute, Na+. "

Here is what Ling says regarding the cellular Membrane-Pump theory:

" The membrane theory's apparent strength in simplicity is also its fatal

weakness. When Nasonov, Aizenberg and Kamnev demonstrated that the cell

membrane is in fact permeable to sucrose and galactose, the paradigm of cells

as membrane-enclosed dilute solution faced grave difficulties.

" In the crisis thus created, the sodium pump was installed. However, one

(sodium) pump is not enough. To keep the cell afloat, an ever-lengthening

list of pumps has been introduced. Yet the sodium pump at the cell membrane

alone would require at least 15 to 30 times the total energy available to the

cell - under rigorously controlled conditions and with the assumption that

the cell needs no energy at all beyond pumping sodium (pg. 235) The disproof

of the sodium pump hypothesis on the basis of energy considerations relied on

the employment of two tools: the radioactive tracer technology and the

Gerard-Graham-Ling capillary microelectrode. " (pg. 237)

No one, says Ling, has yet given even a rough estimate of just how many pumps

are required to keep afloat the cellular Membrane-Pump theory of " unifacial "

cellular functions. Them simply is no Maxwellian demon that can sustain it.

The famous scientist of history, Maxwell, described a small demon that could

sit inside a tube of flowing fluid, and separate out hot from cold molecules

without adding additional energy. Ling's studies clearly show that an

energy-free Maxwell demon must prevail for the Membrane-Pump model to work

for cellular membranes.

(On the other hand, " bifacial " cells such as epithelial, frog skin,

intestinal mucosa, kidney tubules, etc. have two different types of

membranes. Active transport of Na+ and other solutes across bifacial cells is

not disputed.) Ling's exceptional and patient basic laboratory work clearly

demonstrates insufficient energy for them to exist an actual sodium/potassium

pump in a given cell, not to mention the total energy required for hundreds

of other special pumps often postulated for that same cell.

And here is what Ling says about the resting and action potentials:

" As for the action potential, the basis for a nerve or muscle impulse,

laboratory experiments show that the insides of nerve and muscle cells are

not dilute solutions containing free ions and water, as once believed. A

membrane potential does not seem to exist in the real world, living or

non-living (pg. 265). The membrane potential - as currently defined by most

scientists - using the demonstrably incorrect model of the Membrane-Pump

hypothesis simply doesn't exist. "

Dr. Ling produces additional laboratory evidence to support his claim in this

and in his earlier book, " A Revolution in the Physiology of the Living Cell "

(Krieger Publishing Company, Malabar, Florida, USA, 1992).

Benefits of Ling's Discoveries

But there are many other basic scientific discoveries nicely laid out in Dr.

Ling's Life at the Cell and Below-Cell Level that will lead the reader to two

profound conclusions:

1. The membrane-pump hypothesis is dead;

2. A new cellular paradigm is due, one that Ling has titled the

" Association-Induction " hypothesis.

After reading this marvelously communicative book, one will wonder how the

stumbling block of the Membrane-Pump Hypothesis has lasted so long. Perhaps

the fact that the originator of the Membrane-Pump Hypothesis received the

Nobel Prize for an imaginative construction, non-experimentally derived,

contributed to its unwarranted an pervasive longevity.

Changing from the defective Membrane-Pump Hypothesis to Ling's

Association-Induction Hypothesis:

1. has already brought into existence the Magnetic Resonance Imaging MRI)

device;

2. laid the groundwork for a true science of drug selection, as opposed to

present-day trial and error;

3. demonstrates that biological axioms need laboratory proof based on

evidence and logic;

4. presents a unifying theory of life at the cell and cell level

Scope of the Book

Life at the Cell and Below-Cell Level contains 17 chapters, including five

devoted to Ling's Association-Induction Hypothesis, an outline of the entire

history of cell and subcellular life science, 72 text figures, 6 tables, an

appendix a list of abbreviations, over 550 references, an author index: and a

subject index, a " super glossary " containing over 900 scientific names,

technical terms and basic concepts, and an " Answers to Readers Queries " that

explains how best to read the book and make use of the " Super Glossary. "

While some knowledge of biology, physics and chemistry is useful, the " Super

Glossary " provides detailed background information, thus insuring that the

reader can understand without outside help.

Most health professionals, having had some smattering of chemistry, physics

and math, pride themselves on their " scientific " background. Very well!

Read this book! All doctors and other health professionals should read this

book!

It is also written for science-oriented, career-seeking students; dedicated

biology teachers; medical-pharmaceutical researchers; physics, mathematics or

chemistry teachers, and sophisticated, adventuresome readers who are

unsatisfied with what they have read about our most precious possession -

life itself!

Dr. Ling's Association-Induction Hypothesis (AI) was first presented in 1962.

A decade before, in 1952, he published Ling's Fixed Charge Hypothesis (LFCH),

and in 1965 his Polarized Multilayer theory (already incorporated within the

AI Hypothesis). These hypotheses, and their experimental confirmation

worldwide over the last half-century, cause us to reflect when we realize

that the scientific community, by-and-large, has ignored these hypotheses and

the confirmatory research . The current paradigm has been disproved, time and

again, yet hangs on like an albatross around the neck of science.

Ling's AI Hypothesis has been consistently confirmed, yet is ignored. This

book is long overdue, and every student of biology, medicine and history (not

to mention the " scientifically " oriented health professional) owes it to

themselves - and to the future - to mad how this situation was allowed to

occur - as Ling also captures the history of cellular biology in extremely

clear prose.

What Others Have Said

Nobel Laureate C.N. Yang (Institute for Advanced Studies, Princeton, NJ,

April 12, 1961), speaking of Ling's A Revolution in the Physiology of the

Living Cell, said, " At a time when we look forward to the merging of the

physical and biological sciences, this is a most stimulating book,

distinguished by a bold and inquisitive attitude on the one hand, and careful

experimental methods on the other. "

Nobel Laureate Albert Szent-Gyorgyi (MBL, Woods Hole, Jan 16, 1962) said,

" Dr Ling is one of the most inventive biochemists I have ever met. "

Describing Ling's latest book, Life at the Cell and Below-Cell Level - a

further development of A Revolution in the Physiology of the Living Cell -

others have said: " The work is genuinely revolutionary. The thesis is full of

penetrating insights in the inner workings of the cell, offering a dramatic

alternative to the 'conventional wisdom' of current views. Ling de

demonstrates that many textbook axioms of cell function are incompatible with

evidence and logic, and goes on to produce a richly detailed construct that

shows promise of being largely correct. It is both a fascinating read and a

monumental contribution to science. " (Prof. Gerald H. Pollack, University of

Washington, Seattle, Washington)

" Gilbert Ling's new book arrives in perhaps the last hour to provide the true

historical aspect of the search for understanding of the living cell .... a

compact description of all the elements of the Association-Induction

hypothesis with only the most compelling experimental supports behind each

component embedded in an extensive (and to our best knowledge, fully

complete) historical background in such a way that, despite its scientific

authenticity, the volume appears as highly colourful and enjoyable to read. "

(Assist. Prof. Tamas Henics, Department of Microbiology and Immunology,

University of Pecks, Pecks, Hungary; Intercell, Vienna, Austria.)

" Dr. Ling's work is sophisticated and essential. This book will guide its

readers to the new era of genuine biology. " (Dr. Hirohisa Tamagawa, Gifu

University, Gifu, Japan.)

We believe that Gilbert Ling, PhD through his lifetime of inspired research

projects demonstrates that present day physiology teaching on the cell's

functioning is in error and thus leads to faulty medical paradigms resulting

in slow or no progress in disease resolution. Ling's keen insight

demonstrates how the cell does function, thereby producing numerous formerly

undiscerned phenomena which, when searched for, are found and lead to new and

wonderful medical discoveries, such as the Magnetic Resonance Imaging (MRI)

procedures.

This is an outstanding book, marking Dr. Ling's lifetime achieve achievements

in discovering the true biochemical basis for life itself - a remarkable

achievement more than deserving of a Nobel Prize.

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Dr Mel C Siff

Denver, USA

http://groups.yahoo.com/group/Supertraining/

[Guest guest]

There is no doubt that Dr. Ling has more credentials than Chek or the like,

however I find his approach to be the same. A general rule I have for

greatness is that if you have to tell everybody how great you are, you

probably aren't that great, while if everyone else tells you how great you

are then there may be substance to it. Dr. Ling, through his books and

websites, is trying to tell me how great he is, and on face value I do not

buy it any more than Chek or .

I have not read the book, and hopefully at some point will get the chance

to, although it may not be any time soon. In the website and postings I

have read so far, he still has not given me a stitch of evidence for his

theories, merely some interesting experimental observations that could have

numerous explanations. There is no doubt that early theories of cells

being bags of water and ions is wrong. Cells are highly organized,

compartmentalized and internally social intities. The proteins in a cell

are closely packed into working units to function for whatever purpose they

were designed. Originally it was thought that the cell's internal melieu

was like jello, a mix of proteins and water. In reality it seems that the

proteins are not " solubilized " at all and diffusional studies indicate that

flux through the cell behaves much as it would be predicted through

water. Therefore, in this sense Ling is right on. As well, he is correct

in stating that our understanding of what passes through membranes, and

how, is not terribly clear. We have transporters and channels for almost

every lipophobic molecule out there, but it does not explain molecular flow

across the membrane 100%. That could mean that there are other mechanisms

not yet explored or there are transporters/channels that have not yet been

discovered. The story of aquaporins is an example of this. Where Dr. Ling

falls out of my graces is when he refutes the role of membrane pumps and

channels as being fiction.

As I said I haven't read the book, but here are some of my thoughts:

1/ The work of Nernst and Goldman/Hodgkin/Huxley has created models for

predicting membrane potentials and cell permeabilities. In essence, if you

change the relative ionic concentrations inside and outside of the cell,

the membrane potential will change predictably. This model has been

experimentally applied thousands of times. Is this all conjecture and

artifact?

2/ If action potentials and change in membrane potentials does not happen,

why do we have ECGs, EMGs, EEGs, and why can we record action potentials

with electrodes and measure changes in membrane potential with voltage

sensitive dyes? Why do we have almost 100 different genes encoding voltage

gated ion channels?

3/ I have not recently done the calculations, but the actual localized

change in ion concentration necessary to evoke an action potential is very

small and would not require huge amounts of resources to remove. As well,

channels work in both directions and there are non-energy requiring methods

of exchanging ions. However, the Na/K pump is the key to the function of

all of these.

4/ If the cell maintains its internal environment independent of channels

and pumps why is it that most cells bathed in a hypotonic solution

explode? Why is it that we can change this outcome with the expression of

different channels and pumps?

5/ Why is it that if we have the same channels and pumps expressed in

unifacial and bifacial cells, they would only have a physiological role in

bifacial cells? Seems like a big waste to me.

Those are some thoughts for now.

P.S. Cancer is a disease of age in that mutations accumulate over time to

effect a cancerous outcome. Unfortunately some children are born with the

genetic defects in place and the smallest promoter influence will allow it

to proceed. If cancer rates are truly rising then we should look at this

younger population only and compare the rates. I haven't done this but

suspect there has been little change. I also suspect that mortality rates

are much lower in this group thanks to new treaments. Childhood leukemia

is an excellent example of this.

Trevor Cottrell

Kingston, ON