The design and the demise of cancer – Steven G. Ayre MD
I always thought a petard was some sort of medieval weapon – like one of those things with a big rounded blade and a smaller pointy thing sticking out of the other end, all mounted atop a longish wooden shaft. Spanish, I thought. Thus, to me, getting hoist by one’s own petard meant getting stuck in the butt with the pointy end while waving the thing around in the heat of battle. I recently had occasion to question the veracity of this particular concept, so I went to the books and actually looked it up.
Much to my surprise, I discovered that a petard was in fact a large and powerful explosive charge that one, or maybe two or more, would carry to the base of the wall surrounding the city they were besieging, and carefully lay it there. The idea was to have this explosive charge blow a significantly large hole in the city’s protective wall, through which hordes of one’s fellow besiegers – cleverly lying low in ditches and behind things safely far away from the large and powerful petard – could run screaming and yelling into the besieged city to do primitive things there. Returning for a moment to the base of that wall, once properly positioned, the petard would be lit, and immediately – a la Monty Python and the Holy Grail – all present would be loudly encouraged to
Knowing all of this now, the phenomenon of being “hoist by one’s own petard” conjures up for me the image of some poor fellow – who, not having fully comprehended the seriousness of the “Run away” message or perhaps, through no fault of his own, the victim of some faulty lightning fast fuse – flying face first through the air, rather quickly and on an upward trajectory, back arched, head and legs trailing, arms too, still clutching in one hand one of those Spanish petard things. (Letting go of old concepts is hard).
I go into this in such detail here mostly because it is fun, but more so because this idiom of being “hoist by one’s own petard” pertains directly to some scientific facts involving cancer cells, and a certain ingenious method of using these facts to treat these cancer cells to death. “Caught by the very device one had contrived to hurt another” goes the formal definition of the above idiom. By the following story I would like to illustrate just how precisely and practically this particular idiom applies here. This, to my understanding, is the story of the design and the demise of cancer.
This exciting story begins back in 1975 one particular day in July when I decided to pray for the cure for cancer. There is another whole story back of this which I may tell at another time. In any event, during that following month of August, amongst the two dozen or so weird and unorthodox cancer therapies which magically swam into my ken, there was this one I heard about from Mexico called “Cellular Therapy to Change the Biophysical Biochemical Constants of the Blood or Donatian Therapy.” This approach to the solution really held my attention because it was medical – drugs, hormones, needles & etc – rather than enemas, apricot pits, and calf liver juice. The innovator of this wonderful therapy – Donato Perez Garcia, Sr., M.D. – deserves, in my humble opinion, to receive the Nobel Prize for Medicine. And that too is a dramatic story for telling at another time.
Strange as it may sound at the outset, what this therapy is based on is an action of insulin to potentiate anticancer drug effects at the cellular level. Cancer treatment with this approach can be effected completely medically, without any surgery or radiation. Several decades of anecdotal evidence with this testify to something remarkable going on here. While my subsequent exposure to this thing led me to believe that it did in fact work, I didn’t feel quite the same about its name. I mean, even as an acronym it came out CTTCBBCBDT. Unwieldy to say the least. So, with the assent of my Mexican colleagues, I changed it to Insulin Potentiation Therapy, or IPT for short, and then got down to more substantial concerns.
I have always remembered from my medical ethics course way back when that if a physician were to discover something of value in his medical practice, it would be his duty and his responsibility to share such information with his colleagues. I always believed in that. I still do. The first few months after my discovery of IPT were taken up with sketching out my own ideas of how this insulin thing might work. I came up with some real oxoplasm here, and I now refer to this fondly as my “phlogiston” period. Thereafter I acknowledged that what was needed to free this medical innovation from the obscurity in which it had wallowed since its inception in 1932 was some really good science.
It bears mentioning here that, generally speaking, I had always had a somewhat jaundiced perspective towards science. Some of this is rooted in personal experience; some is simply intellectual disagreement. Next to “we think maybe it’s tuberculosis,” my least favorite phrase in the whole world is “properly designed, randomized, controlled clinical trials.” Metaphysically speaking (which is a language most physicians don’t speak much), research is really “me-search.” Quantum physics and the lot inform us that a much of what is observed scientifically is actually created by the observers themselves – like the ‘electrons are clouds – electrons are particles’ thing. To the scientific mind – our culture’s container for righteousness – these notions simply don’t fit in, and so they get ignored. Voicing opinions on such stuff in the context of our prevailing paradigm doesn’t get you a lot of golf dates. So, from the outset, I had my share of handicaps to pursuing this scientific quest. Like a lot of doctors, I had my own “know-it-all” stance.
As far as the dialogue about “medicine is an art” versus “medicine is a science” went, I was staunchly on the “art” side. The politically correct “scientific objectivity” left me feeling cold, wanting to express something crying to be. Scientific truth does have a certain coldness to it. This isn’t just my own sensitivity complaining; science comes from its own roots. Sir Francis Bacon was the father of the modern scientific method. His fundamental affirmation was that to find truth one had but to perform an infinite number of observations of natural phenomena, and the truth would then just as naturally tumble out. In spite of Bacon’s apparent reverence for the truths hidden within it bosom, his approach to nature itself speaks of something I think rather dysfunctional. Witness this other of his pronouncements: ”Nature must be placed on the rack, tortured, and forced to give her secrets to the scientists, put in constraint, made a slave, and controlled.” This is some attitude, and stuff like this is what created the hole in our ozone layer and my jaundiced perspective towards science and its necessities.
In a more jugular vein, history tells that Sir Francis met his demise early in the spring of 1629 via a bout of pneumonia whilst conducting a scientific experiment to see whether chickens might be preserved the longer by being stuffed with snow. History does not record whether the chickens were alive or dead at the time of their being enrolled in this particular trial. They probably were. There may be a natural justice in the possibility of his pneumonia having in fact been ornithosis. The revenge of the cold chickens.
But I digress. Science was the path to be followed, and – having here vent a modicum of personal spleen – I can say that this was the path I resolved to follow. Happily, some years ago, an accounting of things disclosed that science had in fact conducted something very close to Francis Bacon’s recommended ‘infinite number of observations of natural phenomena,’ and had managed to write all of these down and publish them in the peer-reviewed scientific medical literature. Thus truth was now a possibility. I started off by searching “insulin and cancer” and I found a ton of remarkable truths.
The abstract from my first really big find contained the following statement: “Insulin enhances the cytotoxic effect of methotrexate in MCF-7 human breast cancer cells in vitro by a factor of up to ten thousand.” There are no scientific citations in this piece. I will quote things, but I will not cite them. I have written plenty enough of those kinds of articles for those of strict scientific bent to peruse. So, if you must, go seek and ye shall find. This composition is mine, and it is intended for the enjoyment of myself, and for all those of my dear medical colleagues who may enjoy with me a little holiday from them other kinds of articles.
Hmmm, I mused. That seems relevant. I then read that many different cancers – breast, colon, lung, renal cell carcinoma, Hodgkins lymphoma – actually manufacture and secrete their own insulin, and that they also have have their own insulin receptors. Breast cancer cells are in fact reported to have six times more insulin receptors than normal somatic cells. This set-up makes for interactions called, respectively, “autocrine” for stimulation of a cell’s receptors by its own insulin secretion, or “paracrine” for stimulation of adjacent cells’ receptors.
Much of all the same things were reportedly true for insulin-like growth factor-I and its receptors in cancer cells. Here, however, the receptor concentration was reported to be ten times more than that on normal somatic cells. One other important point I found in my search of the voluminous literature is that there was a high degree of homology in the amino acid sequences of insulin receptors and IGF-I receptors, and that both of the ligands here could thus cross-react with the other’s receptor. Stating this more directly, insulin can and does very effectively cross-react with IGF-I receptors.
To my own growing understanding and subsequent conclusions, all of these reported findings appeared to be extremely relevant to the decades of anecdotal successes generated out of the work of Dr. Perez Garcia (and of his son and his grandson. Part of that other story). There was a fascinating correspondence between this molecular biology of cancer and what IPT was all about: insulin and its related compounds, and their receptors. For the cancer cells, all this made sense. Why should they go out and invent some totally odd-ball and mysterious bunch of biochemical mechanisms to procure their energy and to stimulate themselves to grow uncontrollably? Why not use what’s already available within the genetic code – made unblocked and expressible via something in the malignant process – residing within the nucleus of every cell in the human body? Why indeed? And now we know this, scientifically:
“This combination of insulin and IGF-I operates autonomously at the cellular level within the tumor, and this operation is free from any higher level of integrated control. The two work together in an autocrine or paracrine manner and in a complementary fashion, with IGF-I being the major anabolic hormone responsible for mediating messages about growth, while insulin regulates and provides the fuel for these processes.”
This passage articulates what has become conventional wisdom regarding the actual mechanisms of malignancy in solid tumors. Cancer is seen as operating through our own physiological mechanisms, dangerously removed from healthy integrated control, and that is how it kills. This is the design of cancer’s “device contrived to hurt another.” Following traditional allopathic reasoning, the strategy developed for hurting it back was to find ways of blocking these mechanisms. Unfortunately this didn’t work very well due to the fact that the specific receptors they wanted to block were so widely distributed on normal as well as on cancerous cells. They did succeed in developing some monoclonal antibodies – alpha-IR1 and alpha-IR3 – which could effectively block the insulin and IGF-I receptors, but could not be made to discriminate between normal and abnormal cells. At this point, the literature indicates further research on this line of investigation was abandoned. I did attempt to communicate to some of the authors involved about what I knew to be going on in the Mexican experience, but that was to no avail. I’ve learned to stop asking why.
Nonetheless, while these eminent scientists may have concluded that their work with insulin and IGF-I had all been to little avail in the war on cancer, I beg to differ. I cannot thank them enough for what they did. I was extremely fortunate in knowing what I knew, and equally fortunate in having access to finding out what they knew – so much of which so completely supported the things that I knew. I realized that success lay not in blocking these insulin-related mechanisms of cancer, but rather in stimulating them. Via a complex of interactions with IPT cancer gets hoist on its own petard; “caught by the very device one had contrived to hurt another.” This is something which could only be surmised by someone knowing what the Drs. Perez Garcia and I knew via our empirical exposure to the wonders of IPT.
Another remarkable discovery here was that, because of all the vital things I came to learn through my years of reviewing the scientific literature, I found the grace within to abandon by some degrees the jaundiced perspective I had held towards science. I have much gratitude and a great respect for the integrity and thoroughness of the people comprising our biomedical research community for the help they provided me and IPT – albeit inadvertently – through their comprehensive work in delineating the molecular biology of malignant neoplasia.
Now we have this scientifically accurate picture of cancer’s nasty mechanisms, and this picture connects cancer to what IPT is all about.
So what is IPT all about? Beginning at the beginning, imagine what would happen in a typical IPT treatment if a fasting non-diabetic individual with a diagnosis of breast cancer – and all those cancer cells just bristling with scads of insulin and IGF-I receptors – were to suddenly be given an intravenous dose of regular insulin? (Actually, we use Humalog). Well, you would probably say, the patient would become acutely hypoglycemic, go into convulsions, then lapse into a deep coma and die. And all their relatives would arrange to sue you with malice. Individually. Right?
Wrong. The Drs. Perez Garcia thought of all that. They are doctors and they know, as do we all, that hypoglycemia due to a surfeit of insulin – however or in whatever circumstance that surfeit of insulin got there – can be handled very nicely with Kool-Aid, Kraft caramels (I prefer the chocolate ones), or orange juice orally, or with a good sized bolus of 50% hypertonic glucose intravenously. The latter is a natural part of the IPT protocol. Over the sixty-odd years that IPT has been practiced, with thousands upon thousands of individual applications, there has never been any serious or unanticipated sequelae of this innovative therapeutic undertaking. This is a specialized practice of medicine, to be sure, yet one using little more than simple clinical skills and other common tools of our trade. And the practice of it is as safe as it is (purely anecdotally) effective.
What then really happens in the above scenario with insulin encountering that great abundance of insulin and IGF-I receptors on the cancer cell membranes? Well, it stimulates both sets of them – as well as these same receptors on normal cells. It is understood that insulin is a powerful hormone producing widespread changes and reactions throughout the whole body. Dealing with the “whole body” reaction first, about a half an hour after getting the insulin, one witnesses the arrival of the expected mild to moderate hypoglycemic response. At this time, the low dose chemotherapy is administered, followed by the 50% hypertonic glucose. This is added to 500 cc of saline that has been running in at a TKO rate, and the combination is now run in rapidly over the next fifteen minutes or so. And that’s it. The patient then rests under observation for about another hour, receiving additional oral fluids (12 ounces of Gatorade). Then they go home with a family member or friend. Humalog’s duration of action is only about two hours.
At the cellular level, the interaction of insulin with the insulin receptor alters cell membrane permeability allowing more of the administered drugs to go intracellularly. This particular effect will predominate in the cancer cells by virtue of their disproportionately higher concentration of insulin receptors. Ligand effect is a function of receptor concentration. This, plus the lowered doses of chemo used – typically a 75 to 90 percent dose reduction – accounts for the virtual absence of toxic side-effects seen with this therapy. I think this is one truly clever part of the whole IPT phenomenon. There are others. Insulin also cross-reacts with the IGF-I receptors. This causes a virtual doubling of the proportion of cancer cells in S-phase, rendering this greater proportion of the cancer cell population more susceptible to the cell-cycle phase-specific anticancer agents that are administered in the mix. More drug in cancer cells + more cancer cells susceptible to drug = more dead cancer cells. More clever stuff.
As to the question of the mechanisms of altered cell membrane permeability, this has not been completely elucidated as yet. My bet for the most likely cause is activation by insulin of delta-9 desaturase enzyme activity. As its name suggests, this promotes desaturation of membrane fatty acids, producing a species of lower-melting point compounds here resulting, at physiologic temperatures, in increased fluidity of the cell membranes and a corresponding increase in their permeability. Other possibilities for this membrane transport enhancement include big words like insulin-receptor mediated endocytosis, or glycosylation of drug molecules via adsorption with glucose with the resulting complexes being taken intracellularly via the insulin-activated glucose transport protein. Whatever. There are other hypotheses. Science, when it looks at this question, will create the answer. Meanwhile, “a rose by any other name…”
And this then is IPT – a new drug technology having complete reverse compatibility with existing medical hardware (drug companies) and software (doctors), and scientifically tied to the mechanisms of malignancy. And what does it provide? As stated above, more drug in cancer cells plus more cancer cells susceptible to drug equals more dead cancer cells. With repeated applications, you end up with nothing but dead cancer cells, and a viable host possibly in need of some deeper healing (which, again, is another story). Lowered doses of drugs equals no anticancer drug side effects. No radiation or surgery. Less hospitalization costs. Lowered costs to health care insurers. Gosh, what a wonderful story! What could possibly stand in the way of our looking at this and seeing if we couldn’t move ahead and make some of these much needed changes for the benefit of human beings everywhere?
The question about whether medicine in America is a science or an art is a moot point, because what medicine really is is a business. And business in America is about competition for money. You can get into some Hobbesian discussion about whether business operates through virtue or self-interest if you want, or you can get righteously horrified about this or that social wrong not being addressed by “them.” Great. Neither of these activities involves the exercise of any personal power. By indulging in them, you just give your power away. I have given a lot of thought to this, and I have arrived at this one firm conclusion: The only way to make progress against evil, be it real or simply perceived as such, is to make unremitting progress in the good.
There are a lot of good things. Sunrises. Loving and caring for others. Sunsets. Fast red cars. And Kraft chocolate caramels. And Insulin Potentiation Therapy. Clever molecular biological synergy. No magic bullet here, but rather a magic gun for shooting our conventional bullets more effectively. Another descriptive phrase for IPT is this literary gem from my first published article on this subject from back in 1986. (This is from the days before I learned about the IGF-I connection):
“Serendipitous would be the appropriate commentary on this “deus ex machina” phenomenon involving insulin and its receptors on cancer cell membranes – if in fact all these things are true. That very natural physiological mechanism through which nourishment and sustenance is brought into the deadly cancer cells would allow us, with our reasoned use of the hormone insulin, to more effectively poison just these same using our deadly anticancer drugs.” Yummy.
Insofar as IPT may be able to effect a medical cure for cancer, and thereby afford human beings the freedom from their fear and suffering so as to be the more able to effect inner healing of themselves, it is my considered judgment that this work is of some value. It may provide us comfort, and give us time. And the time we enjoy in life is our most valued commodity.
I remain intrigued by IPT and I still believe that it is the best cancer therapy around – either conventional or alternative. The mechanisms of IPT mesh perfectly with the mechanisms of malignancy. Insulin for and against cancer – its demise through its design: hoist by its own petard.