This blog will elucidate the mechanism of cancer and show why only a full understanding of genomic reactions can result in complete and definitive cures. I developed this theory about 20 years ago. I now publish it because in that time I haven’t seen anything quite the same and I hope that it might encourage someone to test the idea experimentally.
Twenty years ago I heard of a woman biologist who placed cancer cells in an embryo and found that the cancer cells went back to normal. This theory is an attempt to explain that finding. I call it the Cell Recognition Theory. All comments and questions would be welcome.
One billion years ago there was a unicellular organism that underwent a mitotic division but rather than separate completely, the two cells decided to stick together and call themselves multi-cellular. This held some advantage. Perhaps it did nothing more than create a heavier organism that remained sessile thereby saving energy by allowing food to come to it. To ensure evolutionary success with this new plan, the two cells had to make sure that the stickiness that kept them together was unique to them and only them; otherwise, they could stick to foreign cells that might be predatory (with luck, a symbiotic relationship might occur but such an association is rare).
Just as these two daughter cells stuck together by recognizing one another, additional daughter cells decided to hang together. Diversification of function was present from the start; the daughter cells took on specialized duties and this gave rise to tissues. As soon as tissues came onto the scene, evolution introduced vector qualities with organisms needing to maintain top/bottom, inside/outside, left/right, over/under, through/around and other spatial relationships. Not to do so—to have a hodgepodge, homogeneous group of cells is not advantageous because communication, locomotion, and sharing of resources would be slow and inefficient. Also, if you want to build a more complex organism with novel structures, you have to create parts with unique form and function. Form is very important and, as such, it is precisely orchestrated.
Structures like blood vessels may appear to have a random distribution but limits are placed on how they spread throughout the tissues (e.g., capillaries cannot associate with each other). Blood cells, although motile are derived from stem cells that remain in one place all their lives. Moles seem to be randomly dispersed but note that they have a predilection for skin and on many people moles prefer to inhabit the right side of the face somewhere on that crease that forms between the nose and corner of the mouth. Some dogs have a more precise mole placement. Of course, we also readily see that a certain son has his father’s ears or a certain daughter has her Grandmother’s hands.
In order to ensure proper form or tissue formation, a cell has to recognize its neighbor and stick to its neighbor(s). When cells first began their multi-cellular existence they had to stick to their own kind; otherwise, multi-cellular organism A might associate with multi-cellular organism B and there would be no way to package all the relevant DNA in one place. In order for evolution to work efficiently, the DNA for an organism must be in one place. Symbiotic organisms regardless of how intimate the relationship may be, always remain separate species—tissues are never mixed. Today, tissues still need to be free of extraneous cells for maximum efficiency.
How does a cell lose this stickiness that is so important and why does it turn into cancer? A cell begins it’s journey into the cancerous state when it stops recognizing its neighbor. On the surface of every cell are substances that stick to or recognize other cells—we’ll call it the R factor (R for recognition). Either something in the environment degraded the R factor or it stopped showing up on the cell’s surface because the cell’s DNA no longer made it (the DNA may actually have started making a different R factor). The culprits that start cancer are well know but they all either degrade the original R factor or degrade the DNA so that the appropriate R factor is no longer made. The causes include chemical pollutants and/or radiation pollutants and/or repeated physical trauma and/or viruses. If the cell loses contact with its original neighbors then it does not know where it is. Not knowing where it is, it cannot continue to exist—it must either die, get killed, or find the right R factor to use.
The first option, to die, readily happens after the cell divides for a certain number of times (Heyflick limit—predetermined by the length of a chromosomal structure called a telomere). The second option, to be killed, also happens routinely when the aberrent cell is recognized by the killer cells of the immune system.
The third option, to find the right R factor to use, is attempted by the cell but the only R factor it can come up with is embryonic R factor. Before the cell reached adulthood, it had used embryonic R factors; now, after losing the ability to express its adult R factor, it has no choice but to try the embryonic markers. A cell goes through many guises before ending up in its final role; indeed, we have all seen pictures of our human gill slits while in our mother’s womb—we, thankfully or not, lose them just as we begin to lose our tail. These structures are ghosts of their former selves and this reflects a move towards greater efficiency in the embryologic process, but the conservancy of form is still manifest millions of years after they were first employed.
With each embryologic change, the cell utilizes a different set of R factors. To re-use stickies like you might re-use a crayon color because no adjacent area has that same color would probably be disastrous for the multi-cellular organism; for example, if cell A were to express an R factor whose complement was being expressed by cell M, it might stick to cell M instead of the better and intended neighbor, cell Q.
At the very least, we know that embryonic R factors are different than those in the adult because when the adult body is fully developed (fetal stage), the body has to tell its immune cells to disable those immune components that might mount an attack on the body’s own tissues—in essence, telling them, don’t recognize adult R factors. Later in life, this is used to advantage when immune killer cells attack what they consider to be foreign cells because the killer cells have never seen embryonic R factors before.
In a sad twist, some cancer cells evade the immune cells by repeatedly changing their R factor. Parasites also evade detection this way. In a happy twist, the expression of these R factors by non-stem cells may result in the priming of immune cells so that immune cells can “get a jump on” future cancers of that type. This may explain why low dose radiation, which, statistically, is more likely to affect a non-stem cell, seems to protect against cancer of the stem cell.
Why doesn’t the stem cell self-destruct? At the top of the biological priorities is the perpetuation of life. No mechanism for termination has ever been developed that has purposely destroyed life—cells that do self-destruct arise from stem cells that remain immortal, and senescence is failure to repair and maintain rather than willful destruction. Killer cells do so because they believe they are attacking something foreign. The stem cell is by nature immortal. Unlike the clones that it produces, the stem cell cannot kill itself and must rely on re-establishing recognition of its neighbors.
It may seem advantageous for cells, after becoming adults, not to ever show embryonic R factor again; however, the cell is simply using a mechanism that has been found to be very useful—particularly in embryonic life. If the cell needs to stay alive why doesn’t it just sit there? Why not disable embryonic R factors forever?
The answer lies in a second important biological principle: the cell must also perform some function useful to the organism or species. In a multi-cellular organism that function is enabled only when the cell is sure of its location and the only way it can be sure of that is by recognizing its neighbors. Before the cell can show function, it must know where it is (a liver should produce enzymes only in the liver and a kidney cell must produce urine only in the kidney). [It may be that the R factor is physically tied to the nucleus of the cell and disables it from any further developmental activity for as long as suitable contact is maintained. Losing contact activates parts of the genome that had already played their role and had been disabled.]
So what will the cell gain by expressing embryonic R factors? Of primary consideration in the adult cell is the priming of immune killer cells. The embryo, on the other hand, has no immune cells of its own and is merely trying to re-establish contact with any cell possible. The embryo cycles through the entire repertoire in its original cell line then, failing that, it reverts to earlier and earlier cell lines. The argument that an adult is not an embryo and should, therefore, not display embryonic R factors, is not a valid one for every adult cell is merely an embryonic one in a state of arrested development. It is arrested until a mutation adds another R factor to its program. This phenomenon may be at work in cancers with a strong hereditary component. In other words, some cancers may be just evolution at work.
Remember that experiment mentioned at the start of this paper—about the cancer cells placed in an embryo? The cancer cells went back to normal because the embryo provided the kind of R factors that the cancer cells were seeking. There is a component to cancer that we have not mentioned; cancer cells arising from stem cells in an adult organism are in serious trouble because all its neighbors are expressing adult stickies. The cancer cell puts out embryonic R factors but to no avail. Finally, in a desperate move, it tries to find a suitable match in some other place, and it is at this point that a metastatic cancer comes into being.
This colonizing of distant tissue is detrimental to normal cells because it robs them of resources and interferes with their functions. The site of metastasis is only selected because the R factors being expressed at that location happen to be “similar enough” to what the cancer cells are trying to find. [The mechanism whereby one sticky R factor attaches to another probably involves reactions similar to that of an antibody and its antigen.]
The ideal treatment would consist of providing embryonic R factors to the cancer cell. Harvest every embryonic R factor for a given cell line and make them available to the cancer cells. They may have to be attached to some inert substrate but maybe not. This same embryonic R factor could be used to sensitize the immune system into combating the cancer cells or used to create monoclonal antibodies against cancer cells. When the genome is finally deciphered, a pancreatic cancer cell may be coaxed into thinking it is a more benign connective tissue cell.
Although a cancer cure may be had through any number of fortuitous discoveries, the most precise solution requires complete knowledge of the genome at least as far as R factors are concerned. This theory may be wrong but I have come across no data that disproves it; albeit, caveat emptor, I have not actively worked as a biologist in 15 years and there may indeed be data that refutes it.
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