The End Of Cancer

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Cancer is doomed. Just as the CIA has extended Castro’s lifespan to many times the natural half-life of a Latin American dictator, the FDA bureaucracy has protected and nurtured cancer from the biotech industry. But cancer’s time is running out. Soon malignancy, like polio and other obsolete diseases, will exist only in the despairing, forgotten residents of foreign-aid regimes. The question remains: will cancer be wiped out before you and your family die horribly, or after? Little details like this matter.

Biologists have known for decades that there are other mammal species that control cancer a thousand times better than our shorter-lived simian-derived bodies. Bowhead whales weigh 500 times as much as a human being, and live over twice as long. Bowhead cells have been grown and studied to a limited degree at the University of Southern Maine and other academic labs. But cells from the USM repository are not made available to commercial biotech companies, thanks to Endangered Species Act regulations. (It is OK for one arm of the US government to subsidize the rocket harpoons and outboard motors of the Inupiat who slaughter the ancient Bowheads, but to let evil commercial medical researchers derive benefit for mere human children from already-dead whales would be immoral, of course).

Looking at how Bowhead cells work (for instance, by using a protein-expression chip and comparing the expression patterns in the Bowhead to those of human cells) would make it too easy to cure cancer (and possibly less patentable… maybe The Krill Diet is all we need?). But even without helpful hints from our fellow mammals, the weak points of cancer cells are becoming known.

Why Cancer Exists

You exist as a sort of cellular economy. Your individual cells specialize and trade with each other; some process food, some fight viruses and bacteria, some become academic specialists (brain cells) and read articles on LewRockwell.com . The metabolic economic benefits of specialization allow you to maintain the billions of neurons that contain the relatively stable meme patterns that are “you”. Until one day, an error (actually, at least four errors) in just one cell’s DNA returns your system to the “nasty, brutish, and short” state of the war of all against all. Dividing uncontrollably, using resources while producing nothing, the criminal progeny of this one rogue cell can destroy the whole body.

Sometimes cells are subverted by outside agitators. Many viruses use cancer-causing factors to make infected cells divide uncontrollably. Sure, it eventually kills the host, but just as agricultural subsidies make Archer Daniels Midland bigger than non-subsidized companies while weakening the taxpayer host, cancer gives a genetic advantage to the virus. Removing these outside agitators (such as papilloma viruses) through vaccination is one approach to reducing cancer rates.

To prevent the overthrow of the body by rogue terrorist sleeper cells, most mammals (but not rodents… which is one of many reasons that mice are the worst possible cancer research animal) turn off the telomerase gene in their somatic cells. This allows the telomeres of body cells to shorten at each division. So, most cells can only divide a limited number of times, meaning that they cannot usually accumulate enough mutations to become malignant.

For example, "BJ fibroblast" human skin cells can divide about 90—100 times in cell culture before they senesce (stop dividing). But cancer cells that turn on their telomerase gene can go on to be fully "immortalized" and divide forever; telomerase-positive HeLa cancer cells have been growing in culture since the 1950s. Normal BJs and other normal body cells that have had telomerase added via retrovirus can also divide forever (or at least 400 times so far with no sign of slowing down, which is multiple human lifetimes’ worth).

For a cell to lose its respect for other cell’s property rights and go on to become the cellular equivalent of a politician, at least four to six genetic mutations have to occur. These mutations make cells cancerous, but they also make them different from normal cells, and are thus the Achilles’ heels of all cancers. The odds of any particular mutation are quite low, so each mutation must first occur in one cell, that precancerous cell must divide twenty times or so until the next mutation occurs within that mutated population, and so on. And so they use up all their TTAGGG repeats, their telomeres run out, and the cells flatten out and "senesce"… Unless before the cells senesce they turn their telomerase gene back on. 90% of malignant tumors have active telomerase.

Telomerase As A Target

The problem with most "cancer therapies" is that they use the baseball bat principle: hit the patient with a baseball bat, and maybe the impact will kill more of the cells that are dividing than those that aren’t. Radiation and conventional chemotherapy do kill more dividing cells, but cancer cells have already lost many of their error-checking systems. Thus they change and evolve to evade the baseball bat strategies.

Another problem with the baseball bat approach is that you NEED your cells to divide: immune system cells, gut cells, etc. Also, these therapies induce more DNA damage in normal dividing cells, producing fresh generations of future cancer cells. (Just as bombing of normal civil populations produces more terrorist recruits).

So the goal is to find targets that normal cells don’t use, or can do without for a while. Telomerase is such a target. It is especially vulnerable because of its tight regulation; even wildly growing cancer cells only have about three active telomerase molecules per cell.

Where is telomerase used in normal cells? Germline cells (sperm and egg-producing cells) obviously must have active telomerase; otherwise the whole human race would run out of telomere and senesce. Lab mice that have their telomerase gene knocked out of all their cells including the germline are normal for six generations, then senesce all at once. (Yeah, once we finally produce the bermouse in the lab, they’re going to kick our butts for what we’ve done to them.

When the night is done,
Their plan will be unfurled,
By the Dawning of the Sun,
They’ll take o-ver the…)

Stem cells turn telomerase on at a low level while they are producing new daughter cells; this is one reason that stem cells are suspected by some of being the progenitors of most cancer. But most normal cells don’t use telomerase at all (believe me, I’ve looked; I grew BJ fibroblasts in fetal serum for weeks trying to get them to switch on enough telomerase to pick up in a TRAP assay on 10,000 cells; no dice).

The good news is that telomerase-positive cancer cells stabilize their telomeres at short lengths, typically 3—7,000 base pairs. Once their telomerase is knocked out they will run out of telomere long before normal cells would; normal cells typically have 15—25,000 base pairs at birth. And cancer cells tend to have unstable genomes and a high casualty rate from errors during division. (This is why many cancer cells are vulnerable to caffeine; they can’t repair the DNA breaks induced by the toxic trimethylxanthine). Without active telomerase, many quick-dividing cancer cell lines are doomed to quick extinction.

Also good news is that according to cell-culture results, stem cells will survive telomerase suppression for the time that it takes to kill off the cancer, then rebuild their telomeres to their preset length when the telomerase inhibitor is removed.

So if we can use a drug to inactivate telomerase, we could kill off the cancer, then allow the stem- and germline cells to recover. This has already been done in a dish via a variety of methods. Geron Corporation has a variety of oligomers that bind to the RNA site of telomerase and inactivate it. There are also small-molecule telomerase inhibitors, which will probably prove to be more effective in reaching every tumor cell.

For a long time studies have shown that populations who drink green tea are less susceptible to cancer. A team of Japanese researchers elucidated one possible anti-cancer mechanism of green tea in 1998.1 It turns out that green tea, or rather the epigallocatechin gallate (EGCG) that it contains, is a telomerase inhibitor. When they treated cancer cell cultures with EGCG at levels found in heavy green tea drinkers, the cultures grew but the cells lost telomere length at each division. After a couple months of treatment, the cells ran out of telomere and stopped dividing. So it turns out that green tea might not just prevent cancers… maybe it has been curing some of them. But of course we want a stronger, more controllable effect. The Japanese group that demonstrated the anti-telomerase effect of green tea has since developed new synthetic molecules, based on EGCG, that inhibit telomerase more thoroughly and at lower doses.2

Other classes of telomerase inhibitor have been demonstrated, as have other telomere-affecting strategies. Soon (I mean next month soon; these screening systems already exist) robotic screens will be done to find more. Modern biology is depending more and more on Nature’s way of doing things: don’t try to think, just try every possible combination. Cells will be infected with a telomerase and a luciferase driven by the same promoter. Thousands of 96-well cell culture plates will be treated with hundreds of thousands of chemicals; those that switch off the glowing luciferase (and therefore also the telomerase) without killing the cells will be further investigated. The silicon-based march of knowledge far outclasses the limited DNA-change options of mere carbon-based cancers. Metastasis is irrelevant. Resistance is irrelevant. They will be assimilated.

An interesting byproduct of these robotic screens will be the discovery of better telomerase stimulators (the resveratrol in red wine is already known to activate telomerase in some cells). After cancer is eliminated, some people will live long enough to want telomerase temporarily activated to rejuvenate their cells’ capacity to divide.

The Limits Of Telomerase Inhibitors

Telomerase inhibitors can’t completely eliminate all cancers. A minority of cancers use an alternative pathway for lengthening telomeres, creatively named the ALT pathway (Alternative Telomere Lengthening). ALT uses the recombination mechanisms in the cell to lengthen short telomeres by matching them to long telomeres and duplicating the long telomere onto the short-telomere chromosome. ALT cells don’t grow quite as fast as telomerase-competent cancer cells, and it’s not clear whether they can be as effectively invasive. To exterminate ALT cells will require treatments based on other molecular differences between normal and ALT cells. These are starting to be elucidated; normal cells don’t need to recombine their telomeres when they divide, so molecular targets for inhibition of ALT should be identified soon.

The End Of Cancer, Or The End Of You

If telomerase inhibitors were a new kind of computer chip, they would have been on every Wal-Mart pharmacy shelf and selling for ten dollars a bottle by now. However, in the US it has been decided that only computers (sorry: "Silicon-Americans") may benefit from the free market. Technologies that enhance mere humans, like medicine, education, communication, transportation, etc. are kept firmly within the control of guilds and government. So before telomerase inhibitors get down to the level of your doctor, they will have to run the 19-year, $897 million regulatory gauntlet while it is decided which large pharmaceutical company will be granted a patent for something which probably came out of some pathetic starving Lebanese grad student’s work.

Meanwhile, if you or your child get most types of cancer you will die a slow, agonizing (but very profitable) death. You’ll be all: "Make it stop! Make it stoooop!" And the doctor will be all: "The DEA won’t let me give you too many pain drugs. You don’t want me to lose my license, do you?" And you’ll be all: "AHHHHH! AHHHH AUUUGH!" And so on, for several years of immeasurable pain. Sound good to you?

A New Paradigm: We Own Ourselves

The current paradigm (same as the ancient paradigm) is that all humans are owned by the State, who decides what chemicals may go into their food and medicines. This paradigm makes sense from the viewpoint of PETA (People for the Ethical Treatment of Animalcules), in that it keeps many pathogens and cancer lines off the endangered-species list. But unless you believe in the rights-to-live of viruses and trypanosomes, this sort of "humans-as-property" thinking is suicidal.

Even if you are a committed Socialist, it makes no sense to give the FDA power to suppress free speech about drug effects, or to keep the terminally ill from trying "unapproved" medications for incurable diseases. For anyone who believes in any form of human freedom, there can be no objection to allowing individuals to opt out from the FDA "protection" of pharmaceutical interests.

People are taught to fear free choice. They are told that their food will be poisoned and their medicines ineffective (maybe as bad as Vioxx? Or calcium-channel blockers? Or…) In the absence of an FDA with power to force the commercial use or disuse of any particular chemical, companies would struggle to produce the most effective medicine and the cleanest food, under the watchful eyes of numerous independent labs. Fraudulent or harmful drugs would be subject to lawsuit, and "but it’s FDA-approved" would no longer be any defense.

In a free system, life insurance companies, consumer magazines, and other competing interests would provide medical databases. Maybe even the AMA would become a force for "truth-in-medicine," as it was to some degree before the creation of the FDA. Under common law but free of arbitrary regulation, drug development would be as fast as computer development. Cancer would be extinct and human beings would finally, really, own their own bodies.

Cancer Delenda Est, Ergo FDA Delenda Est

Notes

  1. Naasani, I., Seimiya, H., and Tsuruo, T. Telomerase inhibition, telomere shortening and senescence of cancer cells by tea catechins. Biochem. Biophys. Res. Commun. 249: 391—396, 1998.
  2. Seimiya H et al. Telomere Shortening and Growth Inhibition of Human Cancer Cells by Novel Synthetic Telomerase Inhibitors MST-312, MST-295, and MST-199. Molecular Cancer Therapeutics, Vol. 1, 657—665, July 2002

Bill Walker [send him mail] works as a Research Associate in telomere biology at an undisclosed (thanks to legal threats from his tax-financed employer) location.

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