Albert Szent-Györgyi

Electronic Biology and Cancer

Publisher Summary This chapter discusses electronic biology and cancer. Electrons, in molecules, are paired and tend to go from one molecule to the other pairwise. Therefore, bivalent acceptors, which can take up two electrons, would always take over two electrons, even if the two go over one by one. The transfer of an electron pair to oxygen is called oxidation, burning. This transfer of an electron pair leaves a smaller but still well-balanced molecule behind. The situation would be different if the acceptor is monovalent, that is, can take up but one electron. Taking one electron means that both molecules, the one that accepted the single electron and the one that donated it, become reactive free radicals. The transfer of a single electron from one molecule to another is charge transfer that was hitherto looked upon by most biologists as a rare event, an oddity, an item of Natures own curiosity shop. The oxygen molecule, O = O, consists of two O atoms linked together by a double bond. Therefore, oxygen, as such, could not transform the protein into free radicals.

Cancer Therapy: A Possible New Approach

Two substances, one promoting growth (promine) of ascites tumors in mice and the other inhibiting it (retine) have both been found in several tissues, namely, thymus, aorta, muscle, and tendon. In spite of similar solubilities in the solvents used for their extraction, the substances could be roughly separated. The value of the ratio between these substances in the same tissue may be significant.

On the nature of the cross-striation of body muscle.

Abstract After the removal of globular proteins, solvents used for extraction of myosin remove from glycerol-pretreated body muscle a considerable amount of protein other than myosin, the quantity of which is sufficient to account for the differences in refraction between the A and I bands.

Bioelectronics and cancer.

The appearance of oxygen on our globe induced profound changes in the nature of living systems which started to differentiate and build complex structures with complex functions. Oxidation was added to fermentation and unbridled proliferation was subjected to regulation. Fermentation demanded no structure, being the result of the action of a series of single molecules. Oxidation, with its electron flow, demanded structure and electronic mobility. To produce meaningful structures and complex functions the action of the single molecules had to be integrated. The question is: how could oxygen bring about these transformations?These changes are not limited to the distant past because in every division the cell has to revert, to some extent, to the undifferentiated, fermentative, proliferative state of ist earlier anaerobic period. After having completed its division, it has to find its way back to its oxidative resting state. If this road of return is deranged the cell has to go on dividing as it does in cancer. By elucidating the details of these processes we can hope to be able to control them. We can control only what we understand (Bernal).That oxygen can induce profound changes in cell life can be demonstrated even in the acute experiment. L. Pasteur showed that fermentation is inhibited by the admission of oxygen (“Pasteur Reaction”), and H. G. Crabtree demonstrated the opposite effect. The intimate relation of cancer and oxygen was made evident by H. Goldblatt and G. Cameron who provoked malignant transformation in their tissue culture by periodically limiting their oxygen supply.O. Warburg attributed the changes, induced by O2, to a wealth of energy it produced. Undoubtedly, without a new and rich source of energy these changes could not have occurred. Energy made them possible, but energy offers no mechanism. The chemical mechanism underlying these transformations will be the main topic of this paper and it will be shown that charge transfer is one of the central biological reactions. A biologist trying to understand life without electronic mobility is comparable to a Martian trying to understand our civilization without knowing about electricity.This paper will chiefly be concerned with principles. The chemical methods employed will be discussed in a subsequent paper by Dr. L. Egyud.

Changes in cell surface charge and transmembrane potential accompanying neoplastic transformation of rat kidney cells

Free flow electrophoresis measurements have been used to determine the surface charge density of normal rat kidney (NRK) cells and a clone of NRK, designated as 6m2, that exhibit a transformed phenotype at 33 degrees C and a non-transformed phenotype at 39 degrees C. A clone of 6m2, designated 54-5A4, which is transformed at both 33 degrees C and 39 degrees C was also studied. A surface charge density of -1.42 microC/cm2 was obtained for the NRK and non-transformed 6m2 cells at 39 degrees C, whereas at 33 degrees C values of -1.85 and -1.78 microC/cm2 were determined for the transformed 6m2 and 54-5A4 cells, respectively. It was found that 72% of the increased charge that appeared on the transformed 6m2 cells compared with the non-transformed 6m2 cells was RNAase sensitive. The time-dependent decrease in surface charge that accompanied the shift of the 6m2 cells from their transformed to non-transformed state was found to mirror the increase in transmembrane potential previously reported using a fluorescent dye technique, and was also comparable to the reported temporal changes in their morphology and virally-coded protein content.

The series elastic component in muscle

Abstract Electron microscopic pictures of the muscle show that the protofibrils of the cross striated muscle are built alternatingly of contractile and elastic segments. The division lies in histological dimensions. In its middle every sarcomer contains such an elastic segment.

The action of iodide on oxidative phosphorylation

Abstract When iodide replaces chloride it suppresses oxidative phosphorylation in rat mitochondria. The results are discussed.

The Living State

As biologists we can contribute to quantum chemistry only by clearing up the mechanism of some of the biological processes, thereby opening the way to their quantum chemical analysis. We have tried to do this by isolating and identifying the central catalysts of those processes. One of us (A.S.-G.) studied biological oxidations first in the plants that turn dark on exposure to air such as potatoes, apples and pears. He found the central catalyst of these oxidations to be a catechol derivative that oxidized to o-diquinol which forms dark complexes with protein. After this, he turned to the oxidation of plants that do not turn dark and identified two catalysts, one of which was ascorbic acid, the other succinic acid. His third problem was the generation of motion, the function of muscle. This study led to the discovery of a new protein, which he discovered with I. Banga at the University of Szeged, Hungary. They called it “actin” because it made the inactive myosin act to contract. This discovery has an unu...

PERSPECTIVES FOR THE BIOFLAVONOIDS

In presenting the final paper in this monograph, I feel I ought to sum up what has been said and give account of where we are and whither we are going. Many interesting observations have been presented, and Doctor Martin has given us a most lucid review of the diverse actions of flavonoids. To complete this list, I should like to mention Doctor J. Kramar’s paper, given last year a t the International Physiological Congress a t Montreal, Canada, which suggested that flavonoids have a part even in the hormonal balance influencing the relations of cortisone and the somatotropic pituitary hormone. Taking everything together, there can be little doubt that flavonoids are not only useful therapeutic agents in conditions of capillary fragility, but have many diverse actions in the animal body. Such anactivityposes an intriguing problem. My long-standirg acquaintance with living matter has taught me to look upon it as a mechanism which, in its precision, greatly surpasses the finest Swiss watch. Capillary fragility means that this mechanism is out of order, and the idea of rectifying it with a decoction of orange peel seems to me like repairing a Swiss watch by driving a nail into it. In my eyes, there is but one living matter on this globe. However different their shapes, colors, and complexities, all living systems are but leaves of the same old tree of life and are based on the same common basic principles. There is no real difference between cabbages and kings. So, if the king’s capillaries do not work well, possibly because one of their constituents is missing, and you can put these capillaries right again by an extract of the cabbage, then this means that you have set one precision mechanism right by taking out an identical screw from another similar precision mechanism, and the good fit only shows the close relation, the essential identity, of the two systems. This picture resolves the contradiction, but involves an assumption for which there is no conclusive evidence; namely, that flavonoids are normal constituents of both animal and vegetable systems. Our whole outlook on the action of flavonoids depends on this question whether they are normal constituents of the animal cell. If they are, then we can suppose them to decrease capillary fragility because they replace a missing normal substance which the animal body itself was unable to produce. In this case, the flavonoids conform to the definition of a vitamin. However, if they are not normal constituents of the animal body, then we have to abandon the idea of a vitamin, and are faced simply with some accidental drug action which cannot claim a deeper biological interest. Perhaps this division of substances into “vitamins” and “drugs” is too rigid and there is something between. There is no doubt that our body is dependent on an outside supply for the classical vitamins under any condition. But there also may be vital substances which our body can produce under normal condi-

Electron spin resonance studies of the interaction of oxidoreductases with 2,6-dimethoxy-p-quinone and semiquinone

Previous electron spin resonance studies have demonstrated that the decay of ascorbyl plus semiquinone radicals, produced in an aqueous mixture of ascorbate and 2,6-dimethoxy-p-quinone, is accelerated by ascites cells. This effect was concluded to involve a sulfhydryl-containing NAD(P)H-enzyme, and work on cultured cell lines showed that on neoplastic transformation the activity against the radicals was increased. We show here that at least three disulfide-oxidoreductases are able to quench the radicals in a similar way to that of viable cells. Glutathione reductase (EC 1.6.4.2) in the presence of NADPH and oxidised glutathione, and dihydrolipoamide dehydrogenase (EC 1.8.1.4) with NADH and lipoamide, are found to accelerate the radical decay by reducing the quinone or semiquinone. DT-diaphorase (EC 1.6.99.2) in the presence of NAD(P)H can also achieve this by reducing the quinone directly. Lipoamide dehydrogenase and glutathione reductase are also capable of reducing nitroxide spin labels, a finding considered of relevance to the reported reduction of such spin labels by neuroblastoma cells.