can’t see the forest

Dichloroacetate and the Iron Triangle

Posted in Canada, cancer, medicine, News, technology by Curtis on 2/23/07

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I’m a logical positivist, a philosophical materialist, a right empirical bastard all the way.

Nevertheless, sometimes I wonder. This morning, while working my way through a cup of coffee by hitting the ‘random article’ button on the Wikipedia sidebar, I consecutively stumbled into two articles—neither term had I heard of before, but they go together like peanut butter and jelly, like Batman and Robin, like big pharmaceuticals and the FDA. It’s just too serendipitous for passing by, and yet too isolated for empirical study.

Dichloroacetate (DCA for tired tongues and fingers) is a form of acetic acid (the stuff that makes vinegar so sour) that turned out not so great at curbing lactic acidosis, as intended, but looks to be an excellent weapon in any physician’s anti-cancer arsenal.

The unchecked development of cancer cells comes about because cancerous cells do not have functioning mitochondria. Mitochondria are cell organelles that play an important role in providing energy to individual cells. They are also key to the process of apoptosis, or “cell suicide,” through which abnormal cells can destroy themselves to prevent the passing of their defective genetic material. Since the mitochondria in cancerous cells do not function properly, this mechanism fails and thus cancer tends to spread.

A study by the University of Alberta published last month has shown that this simple, inexpensive chemical analogue of the essence of vinegar has the power to restore mitochondrial functions in the cancerous cells of test rats. Some of the researchers behind these tests described the findings as “astounding.” It had previously been thought that cancerous cells have only the jagged, twisted ruins of mitochondria; as it turns out, the mitochondria are only in deep sleep, and DCA looks to be Prince Charming.

The researchers believe that DCA treatment, while not without its risks, could be unprecedentedly effective at combatting cancers. They observed consistent tumor shrinkages in their trials, and it is believed that DCA treatment might have far less acute side effects than current chemotherapies.

The New Scientist reported:

It sounds almost too good to be true: a cheap and simple drug that kills almost all cancers by switching off their “immortality”. The drug, dichloroacetate (DCA), has already been used for years to treat rare metabolic disorders and so is known to be relatively safe.

It also has no patent, meaning it could be manufactured for a fraction of the cost of newly developed drugs.

Evangelos Michelakis of the University of Alberta in Edmonton, Canada, and his colleagues tested DCA on human cells cultured outside the body and found that it killed lung, breast and brain cancer cells, but not healthy cells. Tumours in rats deliberately infected with human cancer also shrank drastically when they were fed DCA-laced water for several weeks.

DCA attacks a unique feature of cancer cells: the fact that they make their energy throughout the main body of the cell, rather than in distinct organelles called mitochondria. This process, called glycolysis, is inefficient and uses up vast amounts of sugar.

Until now it had been assumed that cancer cells used glycolysis because their mitochondria were irreparably damaged. However, Michelakis’s experiments prove this is not the case, because DCA reawakened the mitochondria in cancer cells. The cells then withered and died (Cancer Cell, DOI: 10.1016/j.ccr.2006.10.020). . .

. . . The next step is to run clinical trials of DCA in people with cancer. These may have to be funded by charities, universities and governments: pharmaceutical companies are unlikely to pay because they can’t make money on unpatented medicines. The pay-off is that if DCA does work, it will be easy to manufacture and dirt cheap.

Let’s switch gears to geometry for a moment. “Iron triangle” is a term which originated from economic papers in the 1970s. The term describes the corruptly symbiotic relationship between Congress, special interest (read: pharmaceutical) lobbies, and regulatory bureaucracies (read: FDA.) Through the model of the iron triangle, kickbacks fly any which way along any which side of the triangle. The end result is that government agencies which are supposed to be watchdogs end up as allies of those they are supposed to be policing. It happens in defense contracting, and it sure as hell happens in healthcare. In fact, the simplicity and durability of the iron triangle underlie America’s failure to vigorously pursue such basic amenities as a public healthcare system.

And, so, while DCA is incredibly promising and unbelievably inexpensive, because it is a public domain chemical it is not likely to be nudged through FDA trials by the pharmaceutical giants that have the oomph! to get it done. Much like a presidential candidate in search of a constituency, a drug searching for a market needs principally, in this great land of freedom and opportunity, money. So far, the response from the mainstream media and from the medical community has been lukewarm at best.

But, as the above article hints, there are good, knowledgable, and generous people willing to do such unexciting chores while the pharmaceutical companies make the big bucks. Thanks again, Canada!


One Response

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  1. Harry Jay said, on 7/29/07 at 9:23 pm

    Many drugs appear to be promising in lab models, in vitro or in animals, but do not have the same response in humans. Conclusion have to be made in vivo (i.e. humans).

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