Presented by THE ROBERT CATHEY RESEARCH SOURCE http://www.europa.com/~rsc --------------------------------------------------------------------------- All rights reserved, R. S.Cathey, 1997. Partially corrected, updated 18 December 1997. This is a work in progress, for review, criticisms gladly accepted. References and bibliography will be added. rsc http://www.europa.com/~rsc/cancer/overvie1.txt (overview part 1). Biological methods are making great inroads in the field of cancer therapy. Immuno-enzymology (IE) is one of the most exciting. IE is not new. It had its inception in the work of John Beard, instructor of experimental embryology at Edinburgh University around the turn of the century. Around this same time Sergey Metalnikov developed the concept of the enzyme mediated function of immunity, and he is sometimes referred to as the father of the school of enzymatic immunity. A biographical essay on Metalnikov is in preparation for the RCRS web site. Beard proposed the first rational treatment of cancer using pancreatic enzymes or "ferments" derived from porcine or bovine pancreases. By the end of Beard's professional life, it had been well established that cancer (as well as several parasitic or pathogenically mediated diseases such as malaria and TB) responded to injections of trypsin and amylopsin (alpha-amylase or diastase). Early on several physicians mistakenly called this the "trypsin" treatment of cancer. But Beard always refuted such a concept, saying that amylase was not only equally important, but in the later stages, more important than trypsin. Trypsin alone in cancer treatment, (or sole use of proteases, proteolytic enzymes) can be a dangerous experiment. The result can be shock and death, with symptoms similar to eclampsia. Beard deduced that cancer was an anomalous manifestation of ordinary pregnancy trophoblast, acting outside its normal canalization in time and place. The primary role of trophoblasts in pregnancy is the establishment of the zygote in the uterus, and subsequent differentiation into the entire placental interface, but maintaining their primitive, proliferative, invasive and metastatic character in the two outermost layers of tissue in direct contact with the mother's tissues. In examining the erosiveness and invasivity of cancer cells Beard recognised a startling similarity with normal tropohblast which also possess invasivity and ability to metastasize. The invasive or "malignant" phase is called the cytotrophoblast, at one time sometimes referred to as the cytotrophoderm, the fundemental constituent of the chorion. Within this lies the amnion. With time, the cytotrophoblast differentiates into a benign, non-dividing form called syncytial trophoblast or plasmotrophoblast. This is the steroid phase, sometimes called the "second pituitary", one function of which is to maintain the highly swollen, vascularized tissues of the uterine mucosa that holds the placenta. It became clear to Ernst Krebs in later research on Beard's hypothesis that the syncytial phase is a defensive response to action by the maternal pancreatic enzymes, and not a "regression" of cytotrophoblast. It is a linearly evolved attribute of cytotrophoblast when exposed to the degradative action of pancreatic and other enzymes. Syncytial trophoblast actually hybridizes or merges with the surrounding tissues, advancing by means of cellular fusion. For this reason this phase displays multinucleated indistinct masses rather than discrete cellular accretions. Beard knew that in the course of normal pregnancy, the maternal pancreas acts at full tilt in an attempt to control the proliferation of the cytotrophoblasts. But these trophoblasts have a very effective defensive system, consisting in diffusing glycoproteins and sugars that act as enzyme inhibitors which protect against the pancreatic and other enzymes which would degrade these trophoblast. It was by means of histological examinations of successive stages of embryonic development made it clear to Beard that something caused cytotrophoblast to undergo a dramatic change around the 8th week of pregnancy. It later became clear to Beard that this alteration coincided with with the completion of the digestive system in the fetus, and the activation of the fetal pancreas. Thus in the 8th week of pregnancy, the real difficulty of the gestating mother begins, as she begins to experience morning sickness. Beard reasoned that morning sickness or pre-eclampsia was a result of the lack of a specific enzyme in the fetal secretions. For the fetus produces proteases, but not the glycogen degrading enzyme amylase. And thus the carbohydrate (glyco-) part of the trophoblast glyco-proteins were not adequately broken down into their smallest units. This in turn put a strain on the kidneys, and stressed the capacities of the maternal pancreas, with subsequent nausea, pain in the lower back, and low energy, high arterial tension, albuminuria, etc. This is pre-eclampsia and can lead to eclampsia resulting in spasm, delerium, coma and death. Beard deduced the lack of amylase was responsible and it's supplementation was essential in preventing this. It followed that if cancer was trophoblast, then these same symptoms would occur in enzyme therapy utilizing trypsin (or any proteolytic enzyme) alone. Thus Beard instituted the addition of amylase (amylopsin) to this therapy, and doctors utilizing this new protocol reported cessation of the bad symptoms. Later it was found that the best results followed when amylase was applied in quantities at least double over that of trypsin. On such grounds as the foregoing it can be asserted that this was the first rational treatment of cancer, because it was recognised cancer was trophoblast and must respond just as pregnancy trophoblast responds to the functions of the maternal and fetal pancreatic enzymes. It was a brilliant sequence of reasoning on Beard's part, and he gave up a safe, prosaic career as an ordinary anatomist and embryologist to extend and perfect his findings. It was due in part to his brilliance as a keen observer in biological studies that made this possible. Today we know with far greater precision the composition of the substance of cancer glycoproteins, hormones, steroids, etc. We even know the particular sites in the chromosome which are involved in the trophoblastic process. Although Beard's solution was rational, his protocols were almost entirely empirical, lacking as he did any information characterising the chief hormone of the trophoblast/cancer cell. However, here again his findings presaged future knowledge. For example, Beard found that amylase ideally must be in excess of protease in degrading the cancer/trophoblast by two to three times. We know now that carbohydrate forms roughly 36% of the hormone hCG, or human chorionic gonadotropin. The cancer metabolic process is biased towards the fermentation of sugar. For every protein molecule in human chorionic gonadotropin, there are 12 sialic acid side chains, a particularly stubborn sugar, that renders the carbohydrate moiety highly electro-negative, thereby repelling the approaches of the white blood cells which also carry a negative charge. Every cancer expresses the same glycoproteins, the same immunological "M.O." for avoiding attack by the white blood cells, the same hormones and steroids of trophoblast in its normal function. Even the many different and rare types of cancer express, in metastatic phases, this hormone hCG is found, either diffusing or bound to the membranes. In the diffusing phase this hormone can be used as a biomarker to determine cancer in very early stages. In some cancers, the hybridization with the site of origin masks the purely cytotrophoblastic features when viewed under a microscope, but the glycoproteins, hormones or steroids are consistently found. The sialylated glycoproteins are a constant phenotypical feature, in both the metastatic and steroidal phases. Hormones only found in pregnancy trophoblast are found in cancer, and not found in other normal cells. As Dr. Krebs was fond of saying, two things equal to the same thing are equal to each other. Dr. Krebs and his associates catalogued over 300 points of identity shared between trophoblast and cancer and not shared by other cells in the life cycle. His work on this will be published in the near future. In the 1940s, Dr. Ernst T. Krebs, Sr., M.D., his son, E.T.Krebs, Jr., Dr. Clifford Bartlett, Howard Beard (no relation to John Beard), Charles Gurchot and others were involved in researching Beard's thesis. In a comparatively short time their own laboratory experiments and the studies of independant research by other investigators tests affirmed that Beard was right. In 1949, Krebs and Bartlett wrote a paper on the pregnancy toxemias and the role of the pancreas and trophoblast in these disorders. The following year, the Krebses and H.H.Beard published their paper The Unitarian or Trophoblastic Thesis of Cancer, in the Medical Record, New York, which is showcased on our web site. In ensuing years, Dr. Krebs and son investigated co-enzymes, and the possibility that cancer as such is a vitamin deficiency disease. Because they had worked with natural plant extracts and enzymes earlier, when they saw definite intermittent action of these enzymes on cancer, they felt that further research to determine the active agents was warranted. This began due to reports by several writers of cancer-free populations amongst indigenous cultures, particularly the Hunzakuts of Northern Pakistan. They knew that they ate huge quantities of apricots, but they felt nothing in the fruit would have much pharmacological action to account for this freedom from cancer. Later they learned these Hunzakuts also ate the seeds, and apricot seeds had been investigated by the elder Krebs years earlier. They had worked with apricot seed extracts. The reasons for this has it's history in lab work done by the Senior Krebs, looking at wood alcohol evolution in "moonshine" being sold during the prohibition years. As an inveterate experimentalist, Dr. Krebs investigated all natural plant extracts for any medicinal usefulness. Before this Dr. Krebs had found the extracts of Leptotaneia, an herb used by native Americans for fever, was effective in his treatment of dread influenza during the 1918 outbreak. As was more common in those days for MDs, Dr. Krebs had graduated in pharmacology, and this type of investigation was not so specialized as it is now. A glance at any Materia Medica for this period shows that 80 to 90% of the medicinal formulations are herbal. So this wasn't a foray into "snake-oil", but serious pharmacological research. The information that apricot seeds were heavily relied upon by the Hunzakuts thus re-stimulated looking at their earlier apricot seed extracts which had showed some intermittent action in cancer, with the result of the realization that it was not the enzyme content of the seed that probably played the active role, but the cyanophoric glycosides. This was due primarilly because Dr. Bartlett recognised some of the bad side-effects of their extracts as similar to cyanide toxicity. When the extract was purified of certain activating enzymes and purified it was again tested on their lab animals and found to be non-toxic. Later, a patent was applied for a process of producing a metabolite form of this compound for clinical use, and named Laetrile. (LAE-vo-mandeloniTRILE-beta-glucuronoside). At first it was only known to have definite effect on several experimental animals. It took several years and actual clinical testing around the world before a model was proposed rationalizing the utility of Laetrile in the prevention as well as the treatment of cancer, when it received the suggested name of vitamin B-17. (The natural form is actually a precursor, and so is sometimes referred to as pro-vitamin B-17). A vitamin is a co-enzyme. The definition of a coenzyme or vitamin is an organic molecule that must be loosely associated with an enzyme in order for the enzyme to function optimally. We know that the pancreatic and other enzymes are reliant upon several essential co-factors and co-enzymes. For example, trypsin is dependant upon chromium for it's normal function. Correspondingly, in the presence of certain inhibitors found in the serum, trypsin must be acted upon by Hydrogen cyanide to become active once again. On this basis, we feel, the nitrilosides may be defined as vitamins or co-enzymes, for they carry into the serum in harmless form a metabolizable molecule whose function extends enzyme life and accelerates it's catalytic or hydrolytic action. As noted, if biologically active chromium (GTF or glucose tolerance factor) is deficient in the cancer patient, the effectiveness of trypsin is correspondingly diminished. In experiments in which trypsin was dialysed from a trypsin solution, trypsin was reduced to a mere 5% of "normal". Of course what we define as "normal" for trypsin cannot be accurately judged until we realize it's optimal activity. Early in this century it was observed that by addition of HCN proteolysis can be accelerated, and breakdown of proteins furthered by up to 300%. This is not a sometime fortuitous benefit, but will consistently occur by persistent intake of cyanophoric glycosides. Thus it's utility is essential for optimal action. This will occur in all animals, and so can be termed an essential cofactor, specifically a vitamin. Any factor that gives these enzymes their optimal conformation or in aiding in oxidation-reduction processes, must be viewed as co-factors, and the hydrogen cyanide (HCN) component of B-17 and metabolites thereof play a role as protease enzyme re-activators. The serine enzymes like trypsin or chymotrypsin may be inhibited or denatured by various means derived either from the environment such as by heavy metals, organophosphates from pesticides, or by serpins from parasites, cancer cells or by stubborn substrates. Plant derived proteases which are inhibited are also reactivated by HCN as well as by various other factors in the body, like glutathione, cysteine or even hydrogen sulfide. Interestingly, chloroform also serves as an enzyme re-activator, which may account for some of the early surgical successes in their attempt to remove cancerous tumours. In this case the anaesthetist may have played a more important role than realized. The essentiality of B-17 is not based solely on the incidence of cancer, which is merely the most severe expression of a deficiency related to pancreatic function, but B-17 probably also plays a role in several other problems, which we will not delineate exhaustively here, except to mention a few: *anemia, *chronic fatigue, *hypoproteinemia, *several immunologic insufficiencies indirectly a result of a deficiency of vitamin B-17, especially those in which proteases are involved that might be strongly inhibited in it's absence. *pain of rheumatoid arthritis, (through action of benzoic acid derived from the benzaldehyde moiety of amygdalin) *B-12 deficiency (through the nitrile moiety of B-17 conjugated to hydrocobalamin or pro-B-12 into cyanocobalamin), *dyspepsia, *parasitism, (Krebs noted that several sexual parasites such as t.mansoni, would be susceptible to the action of HCN through a deficiency of rhodanese based on the similar nature of their glycoprotein to hCG, which depresses rhodanese.) *high blood pressure, *flatulence, through the anti-bactercidal action of HCN and benzaldehyde in the lower intestine, *NO depletion-related disorders, including flacidity or erection-difficulty. Some Natural Sources for vitamin B-17 (nitriloside) All fruits seeds, except citrus Apple seeds Apricot kernel Peach kernel Pear seeds Plum etc. Nectarine (the flesh), Huckleberry, Elderberry, Blackberry, Strawberry (wild), Raspberry, black Current, Manioc (cassava), Papaya Lima beans (cooked) & sprouts, Mung bean sprouts, Garbonzo (chickpeas), Vicia fava (Italian broad bean), Lentils (all beans should be cooked or sprouted due to their content of tryptic-inhibitors). Some forms of garden peas Buckwheat, Barley, Millet, Flax seed Wheat grass, Johnson Grass, Bermuda Grass, etc. Alfalfa sprouts, chia sprouts, mustard sprouts, buckwheat, lentil, all sprouts are very rich in B-17 and other nutrients More extensive information can be found on the web site listed at the beginning of the article, as well as in the signature below. (For example: file http://www.europa.com/~rsc/cancer/013097.txt and others) Feel free to direct inquiries to: --------------------------------------------------------------------------- The ROBERT CATHEY RESEARCH SOURCE. All pages Copyright © 1996 R.S.Cathey, except where specified otherwise.