Gilbert Ling: A Great Pioneer

Some years ago, I was taking a physiology course. One chapter is cell physiology. A cell is a tiny battery. Its inside is negatively charged. Its outside is positively charged, mainly by sodium ions. The electric potential is maintained by the sodium pumps. These pumps keep pumping sodium ions across the cell membranes. I thought the way to maintain electric potential is very energy intensive. Is there a more efficient way? (More formally, I have questions about the Hodgkin Huxley theory. I feel a better understanding could unlock some mysteries in life.)

I searched the internet for an answer and came across the name of Gilbert Ling. He proposed an alternative theory. I browsed Ling’s 1962 book, A PHYSICAL THEORY OF THE LIVING STATE: THE ASSOCIATION-INDUCTION HYPOTHESIS.  His basic ideas are association and induction. I’ll explain them with two simple examples.

Na+ ion is smaller than K+ ion. One might think Na+ can move through a narrow channel but K+ couldn’t. But the reality is the opposite. Why? This is because Na+ ions, being smaller, have stronger electric attraction. More water molecules are attracted by, or associated with Na+ ions, than with K+ ions. As a result, the associated Na+ groups are larger than K+ groups. The channel that is open to K+ groups may be close to Na+ groups. In general, we cannot think water molecules, and other molecules, as free particles. We have to consider the association principle.  

The second idea is induction. Consider molecule CH3-COOH. This is acetic acid, or vinegar, the most common acid in our life. It is a weak acid. We don’t get burned drinking vinegar. Consider a similar molecule, CCl3-COOH. Both molecules have the same COOH, the acidic part. So CCl3-COOH must be a weak acid as well. No. It is a strong acid. Cl has much stronger pull to electrons than H. The atomic group CCl3 has a much stronger pull to electrons than CH3. As a result, CCl3-COOH is a much stronger acid than CH3-COOH. Atomic groups can act over a distance. This time, CCl3 or CH3 acts over COOH. The action over a distance is called induction. With domino effect, the distance can be very long. The concept of induction is also standard now.

I just finished reading the introduction. I guess Ling will propose induction as a way to transmit information over long distance. This is different from the standard Hodgkin Huxley model.

The whole semiconductor industry is based on PN junction. P means positive charge. N means negative charge. Similarly, all cells are tiny batteries, positive charged outside and negatively charged inside. I believe a clear understanding of cell membranes, as PN junctions for living systems, will greatly advance our understanding of life.

Gilbert Ling's idea was summarized by Gerard, Ling’s PhD advisor, in the preface of Ling’s 1962 book, A PHYSICAL THEORY OF THE LIVING STATE: the Association-Induction Hypothesis

Extensive experiments directed toward analysis of the metabolic events maintaining these potentials led to the conclusion that the frog sartorius muscle fiber retains a considerable membrane potential despite the blocking or suppression of all known metabolic processes. The potential and the asymmetric concentrations of ions inside and outside the muscle fiber with which the potential is associated must then be a static rather than a dynamic or flux type of equilibrium.

 Ions, Ling reasoned, distribute themselves between the protoplasm and the intercellular phases in accordance with a pre-existing standard free-energy difference established by the architecturally maintained pattern of fixed charges. The protein skeleton of the cytoplasm, with its ionic sites, would bind free ions; on thermodynamic grounds, potassium would be the more firmly associated cation. This was the heart of Ling's "Fixed-Charge Hypothesis." It led to many experiments, successfully performed, which indeed indicated that no pump or semipermeable membrane is required to maintain the ionic inequalities inside and outside the cell.

In the introduction part, Ling present the main ideas of his theory, association and induction. The first is association.

That is, in the living state, the system of protein, ions, and water must exist in close association. Thus, association between proteins and interacting particles is the critical difference between the behavior of proteins in dilute salt solutions as treated by the Linderstrom-Lang theory and the behavior of proteins, salt, and water in biological systems as described by the present theory. (xxix)

This idea is already mainstream. But it is not attributed to him. The second idea is induction.

Thus, the second major proposition of the present theory is that the primary function of the highly polarizable resonating chain is to provide a vehicle for the ready transmission of an inductive effect (see below) from one functional group to another. Through this inductive effect the various orders of arrangement of side chains may contribute to the specificity of proteins by adding a dimension beyond the mere summation of the isolated characteristics of all the constituent amino acids. This dimension gives each protein its identity as a distinct functional whole. To understand this, it is necessary to examine the nature of the inductive effect.

From organic chemistry we know that the effective charge carried by a polar group on an organic molecule may be varied by altering other chemical groupings in the molecule. For example, acetic acid, CH3COOH, is a weak acid, while trichloroacetic acid, Cl3CCOOH, the well-known protein denaturant, is a very strong acid. Yet both have the same functional COOH group. The substitution of the three hydrogen atoms for the more electronegative (having greater power to draw electrons toward themselves) chlorine atoms effectively diminishes the negative charge of the distant carboxyl group. This redistribution of electrons in the functional groups brings about a decrease in the electrostatic interaction energy between the negatively charged coo- groups and the positively charged H+ ion. The result is the conversion of a weak acid, which holds its proton tightly, to a strong acid, which holds its proton loosely. The mechanism that brings about this change is called the inductive effect. (xxxiii)

The inductive effect means that properties at one part of a molecule can affect the other parts of the molecule. Similarly, one molecule can affect neighboring molecules. This means that molecules may be highly structured in an electric field or other fields, such as magnetic field. All molecules are small batteries, with inside negatively charged and outside positively charged. This means that molecules around a cell, include water molecules around a cell, are highly structured. This property should be the core of our understanding about life. This is very much like PN junction is the core of our understanding about semiconductor.

All diodes and transistors are based on a thin layer called PN junction. So are all solar cells and light emitting diodes (LED). PN junction is what makes silicon works. For detailed mechanism of PN junction, please watch a YouTube video. Graphics and animations give very intuitive explanations on the working of PN junctions.

Properties at one part of a molecule can affect the other parts of the molecule. One molecule can affect neighboring molecules. This means that the change of property at one place can transit the change along a chain of molecules. Information can be transmitted through this association-induction principle. This provides an alternative theory to Hodgkin Huxley model.

For more updated discussion about Ling's theory, please refer to

The Fourth Phase of Water by Gerald Pollack

https://blog.creaders.net/u/10630/202204/432239.html