The following science paper was written for the Cancer Cure Foundation by Roger Cathey. A less technical document is also available.
Trophoblasts: On the Cause of Birth And Its Relationship to Cancer Regression
[Note: In the following, footnotes are represented as letters within brackets, and endnotes as numbers within brackets.]
Abstract: Cancer has long been recognized to share histological and behavioral characteristics with pregnancy trophoblasts. Modern methods have proven biochemical and genetic characteristics are shared between cancer and pregnancy trophoblasts. Cellular or cytotrophoblasts are the source cells for the entire placenta and are the first differentiated tissue that forms after sperm and egg unite to form the zygote. Cellular trophoblasts are invasive, eroding, and metastasizing cells, which mediate the parasitization of the mother's uterus with a new life form which grows concomittantly and distinctly alongside the placental process. The relationship between placenta and fetus represents a unique process in terms of tissue and organ development: an extra-somatic tissue, an organ, is developed with transient functions that forms no part of the somatic complement of tissues and organs, and whose growth and development is unrestricted by intrinsic factors, that is, factors within the trophoblasts themselves. It is proposed that factors extrinsic to the trophoblasts themselves eventually cause these trophoblasts to surrender their grasp on the uterine tissues, and the fetus itself. Furthermore, that these extrinsic factors are principally hydrolytic enzymes secreted by the maternal and fetal systems, and secondarily immunological factors. This degradation and cellular destruction of the trophoblasts that comprise the interface between placenta and uterus initiates a sequence of events which eventually culminate in the birth of the baby. It is believed that these same mechanisms may be pertinent to the regression or destruction of cancer cells as well, since there is a fundamental genetic identity between cancers of all types and from all origins and pregnancy trophoblasts. Thus the cause of birth and the control of wandering trophoblasts in pregnancy may provide insight to the control and possible rational therapeusis of cancer.
Key words: trophoblast, hCG, biomarkers, enzymes, hydrolysis, immune augmentation, hybridization, catalysis, degradation, inhibitors, proto-oncogenes, tumor-necrosis-factor (A glossary is appended).
Early histologists and embryologists conceived of trophoblasts primarily as a mediating tissue responsible for passing nutrients to the fetus. This is the basis of the name given these cells by Ambrosius Arnold Willem Hubrecht in 1888: from trophe: nourishment, and blastos: germ. The first embryologist to strongly suggest that cancer and trophoblast may be one and the same was John Beard  in 1902. However, it was beyond the experimental and analytical techniques of his time to isolate any genetic proof of an identity between placental trophoblast and cancers. The Krebses  compiled an extensive list of hundreds of functions and products expressed or shared exclusively between cancer and trophoblast but not by body or somatic tissues [a]. In the 1940s Howard Beard [b] and others developed more sensitive techniques similar to those used for detecting pregnancy, focusing on hCG, which they found in all cancer sera [c] to varying degrees. Anti-body, sedimentation and agglutinization tests also were developed that could work in cancer serum analyses, such as those developed by Navarro . HH Beard also found that the glycoprotein hCG was an effective enzyme inhibitor .
In 1995, a crucial work by Acevedo et al. provided the first quantitative genetic analysis that proved that hCG-holo (see glossary), or it's subunits were always found as a perfusing and/or membrane bound expressions in all cancers, regardless of type or origin. They also demonstrated that the transcriptional RNA resulting in this glycoprotein could be detected upon analysis. Numerous other researchers have confirmed these findings by performing corroborative genetic and biochemical analyses of cancers of all types and from all sources (pathological samples or clonal cultures). Furthermore, yet other studies have demonstrated expression by cancer cells of other hormones of pregnancy trophoblasts, trophoblastic or placental enzymes, and other products or gene activity [7,8,9,10,11,12], none of which are expressed by somatic cells. A simple search of Medline with just two terms: trophoblast and cancer will return some 50 pages of 20 citations per page, and the number of studies and observations is always increasing. Not by any means focusing exclusively on gestational cancers. Collectively, these studies and especially because of the genetic motifs they have revealed compel the conclusion that cancers of all types, regardless of origin are trophoblastic.
Amongst the immediate questions that arise are: 1) what causes the spontaneous degradation of the placental trophoblasts which represents, in its culmination, the commencement of birth of the fetus? and, 2) are the same mechanisms applicable towards the regression and control and remission of various cancers?
This paper examines these questions and proposes that the cause of birth and the regression of cancer may be
A) mediated not by intrinsic genetic programs (within the trophoblast), but by extrinsic, "epigenetic" factors akin to an immunologic processes.
B) that these anti-malignant processes consist primarily in enzymatic digestion after enzyme inhibition is overcome.
C) that the enzyme expression effecting these changes is primarily a combined assault from the pancreases of both mother and fetus, therefore making the pancreas a component of the immune system, and
D) that the normal cellular immune components of the maternal system are potentiated by this prior maternal-fetal pancreatic enzymatic attack.
Identity of Trophoblast and Cancer systems, Shared transcription products of Trophoblast and Cancer
Amongst a much longer list of biochemical properties shared by both cancer and trophoblast may be listed these: hCG: human chorionic gonadotropin with 2 subunits: alpha and beta. hC-GnRH: human chorionic gonadotrophin releasing hormone. hPL: human placental lactogen, or human chorionic somatomammotrophin (hCS). hCT: Human chorionic thryotrophin. hCCT: human chorionic corticotrophin. hC-TRH: human chorionic thryotrophin releasing hormone. Enzymes shared by Trophoblast and Cancer: CAP: Cystine aminopeptidase (oxytocinase). HSAP: Heat-stable alkaline phosphatase. DO: Diamine oxidase (histaminase).
Proteins whose function is unknown, and all of which appear to be expressions of the syncytio-trophoblasts and cancers: SP1 or PSBetaG: Pregnancy Specific Beta1-Glycoprotein, a syncytio-trophoblast transcript product (Schwangershafts protein 1) (Bischoff, 1980) PAPP-A and B: Pregnancy Associated Plasma Proteins A, B, etc. PP5: Placental protein 5.
These are all products not found in the non-pregnant adult except in association with cancer, and thereby may be used as "biomarkers" for the detection of cancers of various types. While not all cancers have the same degree of expression of any of these products into the plasma (or sera) at detectable levels, and there is currently no single infallible test for all cancers, hCG has by far the widest and most persistent occurrence, and most easily detected. A new test for detecting the antigenic proteins, the Anti-Malignin Antibody Serum test (AMAS) may enable easy early recognition of the malignant horizon as it detects the underlying trophoblastic proteins. As will become evident further on, enzymatic therapy will potentiate this test. By combining various pregnancy-standardized analyses, we believe a positive diagnosis can be arrived at long in advance of current techniques that do not take into account the trophoblast/cancer motif. These have the advantage of being non-invasive and non-toxic.
Immune avoidance or invisibility is a defining characteristic of both cancer and the placenta. In pregnancy the trophoblast expresses proteins and enzymes that are antithetic to those hormones and enzymes that mediate the monthly cycle. This causes a preservation of the swollen tissues of the uterus. Digestion and sloughing off of these tissues is mediated by proteolytic enzymes, thus those protein products whose function is unknown from trophoblast may act as proteolytic enzyme inhibitors.
On the basis of immunologic invisibility and ultimate rejection of trophoblast (the placenta)--and by default the fetus to which it is mutually associated--pregnancy has been termed both an allograft and homograft[d] (Hertig, 1964). It is a temporary graft and in its duration there is continuous immune suppression , just as there must be in any successful allograft . At some point, however, the rejection process is successful. Thus the birth of the individual and the associated processes of the placenta represent, essentially, an immunological rejection of the blood dependent phase of the fetal "parasite" [e]. The immuno-privilege of trophoblasts has been postulated on various foundations , but the exact cause of birth has never been established to everyone's satisfaction.
Joseph Needham developed an exhaustive bibliography and data base on pregnancy, the placenta, and the various theories on development as well as the cause of birth, including John Beard's. Beard's contention devolved upon the commencement of the function of the fetal pancreas whose enzymes could freely circulate into the placenta and therefore act as a principal cause of birth by means of digestion of the placental trophoblast. Beard based his inference on the coincidence of 1) the completion of the formation of the fetal digestive tract, 2) onset of fetal pancreatic function and 3) the sudden onset of morning sickness by the mother as well as the first signs of the degradation of the placental trophoblasts. He inferred therefore that pancreatic proteinases represented the antithetic principles causing the loss of interface with the uterine tissues. Beard later defined this as the ultimate biochemical test for malignancy: reactivity to pancreatic trypsin and amylase (Beard, 1907).
The majority of opinion states that the basis of immuno-privilege of trohoblast depends on the membrane bound glycoproteins or hCG. The membrane coat of the cancer cell is characterized as a glyco-protein. This means it is composed of a protein part and a carbohydrate part. The carbohydrate is composed of a variety of different sugars. To the main sugars are appended side-chain sugars consisting of a particular type that can carry an electrochemical charge. These are the sialic acid side chains. For this reason the coating is sometimes referred to as a sialomucinous coat. These sialic acids render the coating electronegative in charge, which also happens to be the same charge as that on the white blood cells. Furthermore, these sugars and their sialic acid side chains, cover and mask the protein part which is embedded in the cell surface. Since antibodies are specific to proteins, the cancer cell escapes detection and resists attack [f]. This hormone is also a powerful enzyme inhibitor, and is found throughout the blood-stream. Therefore, for there to be antigenicity, this coat and the diffusing hormone that acts as the "mote" around the tumor or placenta must be overcome. This is a problem, since there is often a limit to the ability of the body to produce enzymes in sufficient quantity.
A review of the literature shows that much of the speculation on the topic of the expulsion of the fetus and his or her associated processes consisting of the chorion and amnion or the placenta has focused primarily, and we think correctly, on immunologic principles. However, the concept of immunologic function can be restated to accommodate a Beardian[g] perspective that is closer to the Metalnikov-Metchnikovh definitions. This in turn will provide a basis of understanding the role of enzyme digestion as another way of viewing the term: "antibiotic."
Proteo- and glyco-lysis as the basis of General Immunity
When a foreign, or antigenic protein or non-genome-translated product enters the blood stream by some means, the first action taken by the body is enzymatic attack or activation of hydrolytic enzymes...enzymes of digestion. These enzymes are, principally amylase, lysozyme, chymase and other proteases. Since these are acting outside the digestive tract, Metchnikov described the process as 'parenteral digestion', that is, along side the digestive tract.
It was Flemming who first delineated the cellular enzyme lysozyme, when after dropping some effluvia from his nose on a petri dish, it was later observed to have digested the cultures growing thereon. The principle modality of protection of the germs and molds was described by Metchnikov and Metalnikov as a special carbohydrate coating, a mucin or waxy coat that prevented both dehydration and repulsed the like-charged white blood cells of the contact or cellular immune system.
This modality of resistance by means of a carbohydrate coating is also common to cancer cells. The membrane bound glycoprotein hCG consists, as noted above, of two parts: a protein part (moiety) and a carbohydrate (glyco-) part. Since white blood cells are designed to recognize foreign proteins, and the proteins of the trophoblast are masked, or covered by the carbohydrate moiety, it is evident that this coating must be stripped away.
Amylase is a pancreatic enzyme that is found in the plasma of normal adults and especially high in pregnancy. It is secreted in the mouth, by the pancreas and liver, and a similar form is found in the white blood cells. It digests carbohydrates and glycogen. It is believed that through action of this carbohydrate digesting enzyme (or similar ones) the antigenic proteins that have been expressed by the maternal-paternal hybrid tissue of the placenta are unmasked. This constitutes potentiation of the immune system against it. (See for a graphic depiction of the role of the sialic acids on the hormone hCG and the action of amylase on potentiation of the action of trypsin).
Once these proteins are unmasked, the circulating plasma proteases may attack the peptide linkages to which they are specific, and to which they had little or no access prior to the amylase enzyme action[i]. It is then that the contact immune cells, the killer T cells, the Helper cells, and other components of the specific immune system are activated, and this constitutes the rejection process in full force. Nevertheless, it requires 9 months of continuous action to consummate this superiority, and obviously in some cases this threshold is not reached. What transpires then is an "intractable syncytium", or retained trophoblast with the concomitant possibility of the most malignant form of cancer known: chorion-epithelioma[j] Since the resolution of the trophoblast is not self induced, and its normal activity cannot but be invasive, erosive, metastatic and antagonistic to the uterine tissues, its control can never be intrinsic, but extrinsic, and such an eventuality as chorionepithelioma must follow when the defensive forces are not total and absolute in their eradicating functions.
Thus, by enzymatic digestion ... parenteral digestion ...we have true anti-biotic action not based however on enzyme inhibition. This approach will work when it comes to virus, protozoa or germs as well as it does with trophoblast [k]. In so-far-as the alternative interpretation, wherein anti-biotic is based on enzyme inhibition, it would appear that it does not take place in man or beast to any appreciable extent, or as an accident of consumption of bacteriophage, or intentional use of marketed mold produced antibiotics.
Evolutionarily speaking, the body could not depend on the tactic of enzyme inhibition, that is, inhibition of the enzymes required for synthesis of parts of the invading organism because of the possibility of also acting on similar or identical enzymes required for the human host. Many millions of different enzymes can be synthesized that will synthesize the same cell coats, but the components of the cell coats are always bound to be suitable substrates to the regularly occurring enzymes of the host. Thus an enzyme like trypsin that attacks linkages of two amino-acids in a sequence will always find utility, and there will not be regular resistance. The body does regularly inhibit its own enzymes. The cancer cell also inhibits enzymes: the attacking enzymes of the body. HCG occupies the enzymes to such an extent they are slowed from completely deshielding the cell coat...long enough for the cell to synthesize replacement components.
Concentration of enzyme is therefore essential for success, and this is provided by the combined action of fetal and maternal enzymes, and in cancer therapy, supplementation of enzymes from food and synthesized sources.
Besides enzyme concentration, there is also the possibility that cofactors can be brought in that reactivate the inhibited enzymes. Hydrogen cyanide has been observed to have a unique accelerating and life-extending effect on the protein-digesting enzymes of papayap, and tests done by the author of this paper indicate that it also accelerates digestion of carbohydrates by amylase. Having the ability to reactivate these enzymes repetitively and thereby recycle them into the tumor milieu makes HCN-bearing compounds potent anti-cancer adjuncts. In addition, the HCN is directly toxic to cancer cells during their aerobic phase, while being relatively non-toxic to normal cells due to the absence in cancer cells of an enzyme that detoxifies HCN into thiocyanate. This HCN detoxifying enzyme (rhodanese) is present in the normal cell. It has been shown that hCG inhibits this enzyme, therefore it is logical that cancer cells which rely on hCG production for defense cannot also support rhodanese. From this researchers have taken nitrilosides or cyanophoric glycosides found in many seeds and vegetables to be an important dietary factor for enzyme functionality because they carry HCN in a harmless form. On these grounds, it has even been proposed that nitrilosides answer to the description of a vitamin, since in their absence susceptibility to proliferating trophoblasts is many times greater, and the simple observation that where ever nitrilosides are ingested in higher amounts cancer incidence also is much lower or entirely absent. However that may be, it may simply fit into a new category of nutritional science that may be termed adjunctive-catalytic factors. If vitamins are co-enzymes, and metals cofactors, these simple molecules could be termed colytic factors. Other molecules in this category could be gluthione, dimethyl sulfoxide (DMSO), ethylene disulphonate, thiocyanate (a by-product of HCN detoxification), nitric oxide, glyoxilide. It is interesting to note that sulphur bearing compounds seem especially to have this potential, and it is possible that the special potential of HCN may be in the entire cycle of detoxification with consequent evolution of thiocyanate, which is also known to accelerate proteolysis. However, studies done early in this century showed that in regards to its effect on enzyme reactivation, it seems more to do with the lability of hydrogen or the ease of exchange of the hydrogen between the enzyme and the cyanide radical than to the cyanide radical itself.
The tumor or placenta responds to enzyme attack by producing multiple nuclei both by cellular fusion, and nuclear division, for the sake of greater transcription to replace the continuously digested cell coats at the limb of the placenta or the cancer tumor. In addition to multiplication of nuclei, it appears that by means of desmosomes or gated channels that this form of trophoblast may take on characteristics of the cells with which they fuse that are entirely normal until such hybridization. At this point it may be that we see the appearance of odd numbers of genes, pleuripoidy, anuploidy, etc. as if the syncytial phase -- which we might term the defensive and relatively benign, or non-metastatic phase of "trophoblastism" -- takes selected components or gene-sectors and multiplies them. This is the source of the seemingly unlimited variety of cancers that exist. It is also this hybridized component that perhaps forms the most difficult aspect of healing from cancer. For how can the body differentiate between a normal cell and one having both components in one? Since hCG forms part of the makeup of both the pure trophoblast and the hybridized cells, it may be that this is the one defining characteristic that determines body-knowledge that this tissue is active, and the enzymes that can attack this have some feedback mechanism to insure activation and proliferation to clear them out.
If the forces that induced this syncytial/hybrid phase should fall back, this phase may return to an actively dividing phase, but now with the hybridized characters picked up during its syncytial, plasmodial phase. This characteristic of cancer cells to show relentlessly the characteristics of their site of origin actually represents their site of conversion from the highly malignant, and metastatic or cytotrophoblast phase, to the less malignant, but hybridizing phase (syncytiotrophoblast). Thus the metastatic cell found in the lung that appears to be a prostatic cell, indicates two possibilities: 1. A somatic prostate cell has by some means been induced to totipotency, and activated the trophoblastic alleles along with its characteristic, or limited potency; 2. A totipotent cell has undergone direct differentiation into trophoblast somewhere in the body by means of sufficient activating factors[l]. This pure trophoblastic source cell has metastasized, then at some implantation site, has undergone enzymatic attack, with consequent differentiation to the syncytial phase, wherein hybridization may take place. Then a period of battle: enzyme-inhibition/digestion takes place. If the body wins, the cancer is erased. If the cancer cell wins, we have a metastatic recurrence, and the cell shows the characteristic of the first entrenchment site, not truly and necessarily the origin of the first cancer cell.[m]
Assuming some probity to this postulate, the metastatic characteristic, which is constant, represents already that the body can conquer this cell in it's most vicious---although most rarely seen---phase.
In cancer, this trophoblastic invasion, as opposed to the pregnancy type, is an "auto-graft", or autologous evolution of trophoblast. This poses in contrast to pregnancy, a more dangerous condition, since the criterion for antigenicity is absent as such: the entire genetic code of the trophoblast is derived from the individual (except where caused by a parasitic or viral insertion as activator). It would have to be by another criterion that the body attacks this cell, or sees it as "not self" than a genetic variation. Beard postulated it was simply because this cell is a suitable substrate for digestion, and that its suitability was related to stereochemistry[n]. It should be pointed out, that in actual allografting, or transplantation, the incidence of cancer amongst these individuals is about 8 times greater or more frequent. And usually takes the form of lymphomas, a wandering cell with properties already very similar to cancer cells (Norman, 1999).
Onset of Fetal pancreatic function and the appearance of anti-trophoblastic action: Implications of Therapeutic anecdotes for mechanisms of the cause of birth
We could derive the mechanisms of the cause of birth for realization of similar modes to the resolution of cancer. Fortunately, experimentation instigated by Beard obviates the need to recapitulate such a model theoretically. Believing it was the onset of function of the fetal pancreas that marked the beginning of the end of the placental trophoblast, it was logical for him to instigate the attempt to insert such enzymes into the cancer environs. The observations made by physicians utilizing these enzymes, once properly prepared, did conform to a general outline provided by the process of pregnancy and birth itself.
Complications of pregnancy and protease therapy in cancer:
Beard worked with Italian physicians in the year 1905-6 and found that patients undergoing enzyme injections of a proteolytic type alone were experiencing symptoms identical to "eclampsia"(pre-eclampsia). Beard realized that the fetal pancreas did not secrete amylase, and that in pregnancy the problems of morning sickness and eclampsia only begin after onset of fetal function. The fetus does not need amylase until after weaning, when his or her foods incorporate complex carbohydrates. When Beard suggested they add amylase, the bad effects disappeared.
Clinical Experience using Enzymes for Chronic, metabolic Diseases
Clinical Experiences using pancreatic and plant enzymes for cancer has a continuously developing resume of success. A compendium developed by Klaschka details the development of the use of enzymes for other diseases that evolved into a program for cancer. The unifying basis of trophoblast as cancer by means of Beard's insights was rediscovered later by these experimental approaches, but Beard's approach represents the first rational treatment for cancer. It is evident now that it can enable a wide variety of rational approaches through recognition of trophoblastic mechanisms involved in all cancers.
In the mutual and exclusively shared properties between cancer and pregnancy trophoblasts, as distinct from normal somatic cells, a simple axiom comes into definition: two things equal to a third thing are equal to each other. In a historical context, we may ascribe the multitudes of different cancers that have been delineated as the description of a universe of hybridized trophoblast and somatic tissues. The criterion of malignancy can be derived from the purest form of trophoblast that acts outside its normal constraints: chorionepithelioma. All other forms of cancer that may arise would represent a diminishing grade of malignancy. Furthermore, all other cancers would represent a model of the site of origin or the first implantation site. The actual mechanisms of origin of that first cancer cell are not understood, but we may suspect that any stem cell can give rise to the trophoblast with far greater ease than a specialized cell. If a specialized cell gives rise to trophoblast, then that will determine the hybridized characteristics. If an undetermined stem cell gives rise to a trophoblast cell, then it may land anywhere and implant itself. Thenceforth, the metastatic cell line represents the character of that cancer and it will not change.