Montrose T. Burrows

The Action of Mineral Oil per Os on the Organism.

Leitch 1 has shown that mineral oils applied repeatedly to the skin of animals induce cancer. It is known that these same oils are responsible for cancers in man. This is well illustrated by the studies of the so-called “mule spinners cancer” and the prevalence of cancers of the skin among the workers of the paraffin mines of Scotland. Several paraffin cancers have also been described in America and in other parts of Europe. 1 Our studies have shown that many animal and vegetable oils 2 , 3 are not absorbed when introduced under the skin of animals, but produce lesions quite identical to those produced by various mineral oils and tar. 4 , 5 Our analyses of cancer have shown that it is directly the result of the removal of the excess of the ergusia (fat soluble vitamins) from local areas of the tissues. 6 Such a removal of this lipoid substance or substances leads to a disappearance of the blood vessels, a crowding of the cells and stagnation sufficient for their independent growth. Mineral oils, tars, and especially the animal and vegetable oils and fats, which are largely free from fat soluble vitamins, when introduced into the tissues, induce cancer and crowd the cells in that they are able to dissolve and remove the fat soluble vitamins from adjacent areas of the tissues. 7 Since pastries and manufactured vitamin-free fats are common articles of diet of Europeans and Americans, and since cancer of the stomach is very prevalent in these parts of the world, and not so common in many other parts 8 , 9 it became of interest to investigate these fats and oils as a possible cause of cancers of the gastrointestinal tract. Mineral oils, when ingested, pass directly through the entire length of the gastrointestinal tract.

The reserve energy of actively growing embryonic tissues

In 1902 Fletcher 1 showed that the sartorius muscle of a frog will give a maximum contraction when stimulated every five minutes over a period of two hours in an atmosphere of pure nitrogen. In an atmosphere of oxygen, the same muscle will contract for a much longer time and the fatigue developing in an atmosphere of nitrogen may be removed by placing the muscle again in an atmosphere of oxygen. If differentiated muscle has sufficient reserve energy to allow it to contract for a period without oxygen, the question arises, will not the same reserve be found in an actively growing tissue. In a previous article in 1917 2 the author described a method which allows one to study quantitatively the effect of various concentrations of oxygen on the growth of cells in vitro. In that paper the main point studied was the relative effect of pure oxygen and various dilutions of oxygen in nitrogen on the rate and extent of the growth. The tissues used were fragments of heart muscle and other tissue of chick-embryo of various ages. These experiments showed that the growth was practically the same in an atmosphere containing 8 per cent. of oxygen as in one containing a much larger proportion of this gas or in a pure oxygen atmosphere. A low concentration of oxygen beyond which no growth of cells will take place was also recorded. But as stated this was not accurately determined. There were certain discrepencies in the method of measurements and as must be stated here the tissues used for determining this point were fragments of the heart of 15, 16, and 18 day old chick-embryos. In the present experiments, these objections to the technic used as outlined in the previous paper have been removed and tissues from embryos of various ages have been tested.

Studies to determine the biological significance of the vitamins.

Earlier authors have fully appreciated that conditions other than food and oxygen are necessary for an active growth of cells in the body. This fact is well exemplified in the work of Morgan 1 on the regeneration of the legs of salamanders. Morgan noted that the legs of these animals regenerate as rapidly in starved as in well fed animals. I have sought these other conditions by means of the tissue culture, and find they are a crowding of the cells and stagnation. Single isolated cells or small groups of cells will not grow in a drop of plasma. For these cells to grow they must be crowded with other cells to form a compact mass of considerable size, and be placed in a small amount of stagnant medium so that the loss of soluble materials from the mass is reduced to a minimum. In the presence of oxygen the cells in such a mass begin to grow after a given latent period. 2 In analyzing these factors of cell crowding, stagnation, oxygen and latent period more carefully, I have further found that they signify that growth depends on the accumulation of a certain concentration of an oxydative product of these cells. This product can be readily extracted with salt solution, and when added in a certain concentration to a drop of plasma it will stimulate growth in isolated cells placed in the mixture. In lower concentrations (S2) it stimulates these cells to migrate and store proteins and fats. Only in certain high concentrations (S3) can the cells digest these proteins and fats and grow. In all higher concentrations (S4) it leads to the digestion of the protoplasm of the cells themselves.

Studies on the metabolism of cells in vitro. The toxicity of dipeptids for embryonic chicken cells

In a previous paper 1 we have shown that peptone prepared from the yolk of egg is non-toxic for growing chicken cells even when added in considerable concentration to the medium. Egg yolk digested to the point of crystallizing out an a-amino acid is toxic. We tested a large number of a-amino acids and have found that all are toxic for the cells. In low dilution they stimulate the contraction of heart muscle fragments but did not affect the growth. In higher dilution they inhibit the growth of cells completely and killed. Having established this fact it became of interest to study the effect of dipeptids in a similar manner. Leucyl-glycin and carnosin have been tested. The leucyl-glycin was a synthetic product. The carnosin was obtained from muscle. It was prepared by Dr. D. W. Wilson. Both of these substances are toxic in large doses. Their toxicity is not as marked, however, as is that of the α-amino acids. The leucylglycin is more toxic than the carnosin. During the course of these experiments we prepared and tested peptones prepared from beef. These were found not to affect in any way the growth of the cells.

Further Studies of the Effect of Graded Doses of X-rays on Animals Fed on Various Dietaries, with a Note on the Effect of Dietary in the Treatment of Patients with X-Rays

IN previous papers (1) (2) (3) we have described studies of the effect of small repeated and larger repeated doses of X-rays on rats. In these earlier experiments we studied the effect of doses ranging between 10 milliampere minutes2 (13 e-units) and 50 milliampere minutes (68 e-units) given twice a week to rats fed on a balanced dietary and other rats fed on diets deficient in Vitamins A and B, respectively. In these experiments we showed that doses of 13 e-units given twice a week protect for a considerable time rats fed on a diet deficient in Vitamin B, while they have little effect on rats fed on a diet deficient in Vitamin A. Larger doses of 34 and 68 e-units, respectively, given twice a week, protect for a considerable time not only rats fed on a diet deficient in Vitamin B, but also those fed on a diet deficient in Vitamin A. Previous observations on X-rays have shown that they may cause changes in the ionization of atoms; such changes may cause either synthesis in one case or a breakdown of molecu...

Clinical and Experimental Observations Relative to the Etiology of Cancer

I WISH to describe in this paper some recent experiences in the treatment of carcinomas of the breast, skin, and lip in cases in which these lesions have been studied and treated as the direct result of some local, followed by some general, deterioration of the organism. In a former paper before this Society, and elsewhere, it has been pointed out that one of the striking differences between malignant tissues and normal tissues is the deficiency of the fat-soluble growth-promoting vitamins in the former tissues. In other studies with the tissue culture it has been shown that differentiation is associated with the accumulation of certain lipoid substances in the tissues. With the accumulation of these lipoid substances within the cells and the intercellular substances the ability of these cells to grow in a plasma culture decreases proportionately. If means are provided for the removal of these lipoid substances, growth then intervenes readily in these same differentiated cells. Careful feeding experiments...

The Chemical and Biological Changes Induced by X-rays in Body Tissues1

THE object of a series of experiments which we have been carrying on during the last several years has been to throw light on the general biological action of X-rays. While much work has been done on the immediate effects of these rays on cells of various kinds, little has been learned about the chemical effects induced by them in the organism. One striking fact that has been the outcome of the general studies of X-rays and which promises an eventual solution of this problem when more has been learned about cellular growth in the organism and cancer, is that X-rays are not only able to destroy cancer cells, but may induce cancer. Another equally important fact is that growing cells are more sensitive to these rays than the more differentiated tissue. In the light of these various facts it has become evident, therefore, that X-rays will be understood only when we understand cancer, and every advance in the knowledge of cancer must throw further light upon the nature of the action of these rays. As early as...

The Effect of Vitamin Feeding on the Growth of Cancer.

Cramer 1 states that the removal of one or the other of the vitamins from the diet of animals with transplanted and growing tumors has little or no effect on the growth of the tumors. The animal alone suffers from the deficiency. We have noted a similar result excepting when very large doses of vitamin B are given in a diet deficient in vitamin A. Rats inoculated with the Jensen sarcoma were used for these experiments. Rats given very large doses of vitamin B in a diet deficient in vitamin A suffered a marked anemia with a rapid disappearance of the tumor in a few cases and an early death of the rats in most cases. Tumors in two men broke down with this diet much the same as with X-rays. The tumors were lip cancers metastasizing to the neck. These patients also suffered marked anemia and it was necessary to stop the treatment after a short time, not only on account of the anemia, but because of a developing parenchymatous nephritis. Quite different from the animals, men with malignant tumors have responded more readily to small changes in the vitamin A content of the diet. A man with a melanoma arising from a birthmark on his head and a large mass of metastases on one side of his neck, recovered from his cachexia and anemia completely after six weeks, and worked hard during the next four months, maintaining his nutrition and suffering no extension of his tumor. The diet he received contained a large amount of vitamin A and a moderate amount of vitamin B. He left us at this time and a competent diagnostician thought the tumor was not malignant on account of the patients good physical condition. He removed the tumor with eventual disaster.

Further Notes on the Relation of Nutrition to the Development of Cancer.

In previous papers 1 we had shown that malignant tissue differs from the normal tissues of the body in that it contains no demonstrable or very little of the growth promoting fat soluble vitamins. We had also shown that many of the so-called cancer producing substances and forces, such as coal tar, other lipoid solvents, x-rays, radium, other lights and heat act directly to dissolve or otherwise remove these fat soluble vitamins from the tissues. While these studies were interesting in that they indicated that cancer may be nothing more than the result of the removal of the fat soluble vitamins from a tissue, it seemed quite unlikely that a lipoid solvent, no matter how often applied to a tissue, could remove sufficient of the vitamin to induce cancer. When a solvent is brought into contact with a medium it removes only a certain fraction of the dissolved substances from the medium. That the local action of coal tar is not alone responsible for coal tar cancer has been indicated further by the fact that all animals painted with coal tar do not develop the disease while cancers have been known to develop in man years after a single injection of paraffin or a single dose of x-rays. There seems also to be little evidence to show that the appearance of cancer in man is related directly to the extent or severity of a previously existing local lesion. In fact, many patients carry definite precancerous lesions for years without any evidence of malignant degeneration. All these facts indicate, therefore, that factors other than the local lesion must be responsible for the malignant changes. To throw light on the possible nature of these other factors it has become of interest to study more carefully the action of coal tar and x-rays on animals fed a normal dietary and animals fed varying quantities of both vitamin B and the fat soluble vitamins.

The Action of X-Rays on the Organism.

X-rays can produce cancer as well as destroy it. The action of X-rays, therefore, will be understood only when we have first understood the mechanism of growth in tissue cells. One of us had shown 1 that the protoplasm is a colloidal fluid substance which reacts differently according to its immediate state of aggregation. The state of its aggregation is regulated by a substance or substances which is formed by the cells. This substance or substances has been called the archusia (S). In low concentrations (S1) the archusia has no effect. In medium concentration (S2) it causes the cells to migrate, to coagulate extracellular proteins, engorge themselves with proteins and fat particles, or to function. In high concentrations (S3) the cell digests these proteins and fats, absorbs water, grows and divides by mitoses. In all higher concentrations (S4) it causes the cells to disintegrate or suffer self-digestion. In the growth of the cell protein synthesis is not the only essential reaction, but the cell must also acquire or form a lipoid substance, the ergusia. This substance is essential for maintaining the structure of protoplasm. It is an active coagulant of protein. It is liberated by the cells in an (S2) concentration of the archusia. It is the active agent in the specific absorption of water and other substances necessary for growth, and the surface tension lowering substance necessary for the migration of the cells. The ergusia in excess in the tissue inhibits growth, as any substance, formed in any incomplete reaction, inhibits the reaction. It is also liberated by cells when they disintegrate as the result of a high concentration (S4) of the archusia. 2