As the work progressed it was deemed advisable to obtain data on the curative action of molar peroxides and their unsaturated precursors. For an investigation of this importance the best talent available was necessary. The American research institutions were examined carefully and found wanting. Europe was likewise scanned until Professor Joseph Maisin was selected as the best prepared for a task of this type. Cancer was induced in many hundreds of mice and rats by the usual carcinogens and tumor transplants and treated with the peroxides of formaldehyde and formic acid and with unsaturated substances prepared at the time of their use. These latter substances were pre-peroxides by virtue of their high double bond content. The tables appended show the results of their use. These observations were made at Louvain in between 1934-35.
The protective action was found on further investigation to be due to the free radicals formed by the dehydrogenating action of the Carbonyl groups present in the dehydrated unsaturated bodies and the free radicals formed in the peroxides which gave rise to peroxide free radicals. A comparison with the highly efficient curative action of the Reagent used in the Bandeen Experiments, (pages 30-35) bears this conclusion out since in the latter experiments the very highest Carbonyl ability to dehydrogenate was provided whereas in the Louvain Experiments no attempt was made to boost any activity at all. Nevertheless the latter experiments show that it is impossible to prepare molar peroxides sufficiently clear of free radicals to serve for pure biological tests. The speed with which free radicals are formed by light and by simple rubbing of the dry crystals also shows this trend. This is one of the basic provisions of nature for the continuance of life on our planet.
Protective Action of Diformaldehyde Peroxide
The mice received applications of Benzene solution; 1/200
Benzopyrene three times each week. The peroxide was injected, 1
cc. solution 1/20,000, on the 35th and 65th days.
SPECIFIC EFFECTS OF THE CARCINOGEN, VIRAL AND CHEMICAL
To account for the Pre-growth Symptoms and Changes would take much experimental work. However, we have a few clinical facts that are so evident that there need be no doubt. One is that the reticulo-endothelial system weakens and atrophies just previous to the appearance of the tumor, and before it goes truly malignant. This happens in natural and in chemically induced cancer as well as in virus produced cancer. The fatigue and the final atrophy of the protective cells of the liver, spleen and lymph glands must result in abnormal products which are atrophy producing. The carcinogen, be it chemical or viral, must be legated with these products as a chemically integrated complex, and wherever such products are carried they must have their effects. Embryos developing under such circumstances must be defective, and adult tissues will undergo the changes that give the picture of cachexia as an end result. But preliminary thereto, there must be functional injuries such as were described in part in the text, — the bone marrow function, the nervous system function, the skin function and what not. In fact every tissue is subject to the action of such poison in varying degrees. Thus a differential diagnosis may be based on the chemical status of the lymph glands even before a tumor is recognized.
Our Postulate provides for the polymerization of the carcinogenic toxin as it develops to the cancer producing stage, and this provision is based upon the chemical and clinical circumstances that stare one straight in the face. Atrophy precedes neoplasia. If one answers that the neoplasia is a reaction to the atrophy stimulus as hay fever is to the pollen stimulus, one must still offer a mechanism for the reaction. The simplest mechanism that could be involved is that the toxin produces both changes, and this mechanism we have already explained as due to a block in energy production and transfer. Recovery from the states caused by the carcinogenic agent, be it viral or chemical, is therefore a satisfactory support to our contention, since this same agency accomplishes the corrections in all such states as atrophy, pre-growth toxic state, cachexia, and tumefactions.
The best proof of the correctness or practicability of any postulate in medicine is doubtless the curative value of its application. So to check up on the correctness of our Thesis on the atomic bondings and electronic dispositions responsible for the integration of the pathogen with the host cell’s functional mechanism, we developed an additional step for demonstrating the presence of the double bond that activates the production of the free radical in the pathogen, which makes the pathogenic addition. Likewise the double bond that activates the condensation of the pathogen’s amine group with the Carbonyl of the host cell can be demonstrated. As we showed, these additions depend upon anoxia.
By starting out with the contribution of an atom of hydrogen from the Reagent to one pole of this double bond or of any other double bond in the pathogen whose exposure and high polarity invites the addition, a free radical is produced at the other pole of the bond which simultaneously adds to the free radical formed in the Reagent when its hydrogen atom was lost to the pathogen. By synthesis, the hydrogen atom concerned was made most active by receiving electrons from the double bond system with which its position was conjugated, and the free radical left in the Reagent that adds to the other pole, brings to the pathogen a moiety that is a great electron donor and hence invites ready oxidation (dehydrogenation) even by the weaker of the tissues’ oxidation agents. Thus the integrated pathogen is left at the mercy of the ordinary tissue reagents that can accomplish its progressive oxidation away from the host cell’s functional mechanism leaving its FCG activated by conjugation with a Carbonyl group, the advantage of which we explained earlier.
The first step then is a reduction, which opens the way for the burning of the pathogen off from the host cell by ordinary cellular dehydrogenators. The advantage of this means of attack is quite evident, and our next edition will report the clinical results. These have been most gratifying so far. In fact, hog cholera and dog distemper, which required different Reagents, are both quickly cured in the highest percentage on the one Reagent discussed here.