The Neal Deoul Story

  A. KEITH BREWER, Ph.D.
A.. Keith Brewer Science Library, 325 N. Central Ave., Richland Center, WI 53581

BACKGROUND

The isotope effect throws a very direct light on the mechanism of carcinogenesis. In this study it was shown that the ³⁹K/41_K ratio in ocean water down to 6000 ft was 14,20000 [9-11]. In normal matured cells, both plant and animal, the ratio varied from 14.25 to 14.21. Embryonic and cancer cells all gave a ratio of 14.35. In the case of all synthetic cells across which there was a potential gradient, the ratio was 14.35. From these values it will be seen that the ratio in normal living cells indicates that as many isotopes leave the cell as enter.

In the case of potassium for embryonic and cancer cells as well as synthetic type cells with all types of membranes even including liquid mercury films the observed isotope ratio was given by equation 1.

(³⁹K/41_K) o = (³⁹K/41_K) n (41 + m / 39 + m) ¹/₂ (1)

where n refers to the normal ratio, o to the observed ratio, and m is the associated mass for the ions.

All cations in solution are associated. The attached mass for Cs⁺ is 3 molecules of water, for Rb⁺ it is 5 molecules, for K⁺ is 7 molecules. For cations below potassium in the Electromotive Series all ions are highly associated. This is to be expected from their position in the Hoffmeister Series. In the case of Ca⁺⁺ the association is 30 molecules, while Na⁺ is 16. Equation (1) holds for all cations tested from H⁺to U⁺. The value of m however will vary when polar molecules are present in the solution. For example, K⁺ can also attach glucose. In contrast, Ca⁺⁺ can attach a wide variety of molecules; it is this cation that transports peroxides into the cell, as well as metabolic products out of the cell.

The results given in equation (1) are most significant in that they show that transport is dependent entirely upon the frequency with which the ions strike the membrane surface. It is not a matter of capillary action, but one on which the ion and its associated mass pass directly through the bonding space between molecules which comprise the membrane. That the associated molecules are not lost in this transport is due to the fact that the attraction between the molecules and the ion is far greater than their attraction by the material of the membrane.

In the case of potassium an exact similarity exists between embryonic and cancer cells. The isotope ratio indicates that the K⁺ ions are taken up by the most efficient process possible. The same held true for Cs⁺ and Rb⁺.

In contrast to the above, a vast difference exists for cations below potassium in the EMS. In the case of embryonic cells all cations tested obeyed equation (1). In the case of cancer cells cations below potassium were taken up sparingly, if at all. For example the amount of calcium in cancer cells is only about one percent of that in normal cells [18].

The above isotope effect for potassium which transports glucose into the cell, and for calcium which transports oxygen are most significant with respect to cancer. They mean that glucose can readily enter cancer cells but that oxygen cannot enter. This accounts for the anaerobic state of cancer cells pointed out by Warburg as early as 1925 [26].

The mechanism responsible for the similarity in the isotope effect for potassium and rubidium in cancer and embryonic cells and for their marked difference in case of calcium was investigated in some detail using mass spectrographic analyses, and also fluorescence and phosphorescence decay patterns.

The phosphorescence decay patterns were found to be peculiar to and specific for all cell types or parts thereof [12-15]. It should be mentioned that the decay spectra is due entirely to the light emitted from the energized double bonds. All double bonds are capable of being raised to the energized state. While the fluorescence spectra and the phosphorescence decay patterns are both specific for each double bond they can be influenced by adjacent strong polar radicals. Again, both can be completely depressed by molecules absorbed over the surface; thus morphine, as well as attached polycyclic type molecules, will completely depress the excitation of the P=O radicals which characterize all cell membrane surfaces.

It was observed that the membranes tested gave a phosphorescence decay pattern due almost entirely to the P=O radicals which are composed of phospholipids. These radicals are specifically oriented over each type of membrane. This is most significant from the point of view of membrane action, since the P=O radicals are moderately strong electron donors in the ground state and strong to powerful donors in the energized state. This is due to the fact that the ionization potentials, 1st to 5th, are appreciably higher for the 0 than the P atom. This means that the 4 bonding electron orbitals will be displaced nearer the 0 atom thus surrounding this atom with a pronounced negative field. The P atom is thus positive in nature.

The above results are most important with respect to membrane action. They show that the strong electron acceptors Cs⁺, Rb⁺, and K⁺ can be attracted into the membrane so that they will enter the negative potential gradient which exists across all living membranes. In contrast to these cations, the highly associated cations farther down in the EMS are not sufficiently strong electron acceptors to be drawn into this gradient except when the P=O radicals are in the energized state. This means that K⁺ cations which transport glucose into the cell can readily enter cancer cells, but that Ca⁺⁺ ions which transport oxygen into the cell cannot enter. In the normal cell the glucose, upon entering the cell, reacts with the oxygen in the cell and is burned to carbon dioxide and water with the liberation of heat. This heat in turn is absorbed on the membrane surface and raises the P=O radicals to an energized state which permits them to attach more Ca⁺⁺ ions. Thus it will be seen that the amount of oxygen entering the cell is determined by oxidation within the cell, primarily that of glucose. This action is responsible for the pH control mechanism of the cell which maintains a value near 7.35.

The reactivity of the double bond has been studied in some detail using both light absorption and electron impact. It was found that energy states of the order of those produced by metabolic processes were not reactive. In contrast, high energy states such as those that are induced by radioactivity. are very reactive. Intermediate energy states in the ultra violet range were not reactive. Intermediate energy states in the ultra violet range were not reactive by electron impact, but slightly with light quanta. Here however the reactivity increased with a high power of the energy intensity per unit area [16]. This suggests that the reactivity may be due to the multiple absorption of light quanta, thus raising the energy of the bond to the sum of the quanta absorbed (see Table 1).