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Conspiracy Theory 101: Dichloroacetate, Cancer and Big Pharma

May 14, 2011

Twitter alerted me to a claim that “scientists find a simple cure for cancer, Big Pharma refuses to get involved because they can’t patent it”.  This claim stems from work at the University of Alberta (press release here), in which the drug dichloroacetate (DCA) was shown to reduce cancer cell growth in vitro and tumor size in rats fed with water containing DCA (75 mg/L; Bonnet et al., 2007).  Very interesting stuff, but what interests me is how this work has been “translated” into a conspiracy of silence by Big Pharma…

First, some basics.  There has been a great deal of research interest in DCA for as long as I can remember, because its effects are very precisely understood and its use in humans is safe.  It works by inhibiting pyruvate kinase, which in turn regulates the flux through pyruvate dehydrogenase (resulting in Acetyl-CoA production and entry to Krebs TCA cycle).  This is absolutely fundamental in cellular energetics because it is what determines the fate of carbohydrate (whether it is oxidised or not).  If carbohydrate is not oxidised pyruvate is reduced to lactate, a process which also produces a proton.  Hence the term “lactic acidosis”.  This process was central to the film “A Few Good Men”, where it received “One Really Bad Explanation” by Christopher Guest.  It wasn’t his script though, so he is forgiven.

Lactate is produced for a whole host of reasons, which would be much too hard to explain here.  However, by increasing flux through PDH, DCA has the effect of reducing lactate production.  It is thought that lactic acidosis is a key component of the development of tumors, and so reducing this and restoring mitochondrial function should reduce tumor growth.  It is thought that this is due to the secondary function of the mitochondria to initiate cell death.  Depending on which branch of physiology you work in, this might be considered their primary function!

To exercise physiologists, DCA has been of recent interest because we think that the control of oxygen uptake at the onset of exercise resides within the cells themselves (the metabolic inertia hypothesis).  This led to the idea that the so-called “oxygen deficit” was actually an “acetyl group deficit”, and that activating PDH through DCA would speed up the rate of increase in oxygen uptake as exercise commenced.  However, all experiments to date have provided negative results: DCA does reduce lactate concentration at the onset of exercise, but O2 uptake is unaffected (or, at least, not measurably affected).  Instead, it appears that the phosphorylcreatine shuttle is responsible for the metabolic inertia.  But I digress…

The post I was directed to via Twitter got just about every detail about the experiments and the function of glycolysis and mitochondria wrong.  DCA does not “turn off glycolysis”; this would actually be a very bad idea indeed.  Mitochondria are not cells but organelles (though I admit the distinction in the case of mitochondria is arguable), and DCA does not “trigger mitochondria” (see above).  Which leads me neatly to the point of this post: rather than focus on a positive message of scientific discovery (which the post very nearly achieves), it instead uses the lack of a patent for DCA as a means of highlighting the evils of Big Pharma.  Because they can’t patent it, so the theory goes, they cannot make money from it and therefore they won’t invest in this cancer treatment.  Just like they did with anti-retrovirals.  The evil pricks.

But, but, but: the study in question is a proof of concept, in cell lines and an animal model.  The deafening silence of Big Pharma is not insidious but perfectly understandable: the treatment of human cancers with DCA is not yet standard clinical practice, and DCA is cheap enough that experimental trials will not need Big Pharma involvement.  You might as well accuse FIAT of being evil because they are not manufacturing moon buggies by the container ship-load: there is no market yet!

I’m no fan of the pharmaceutical industry, as many of the very worst ethical and financial abuses in the life sciences can be laid at its door, but in this case I think we would be better off appreciating the pleasure of finding things out rather than dishing out a meaningless kicking.

More detail on the specifics/politics of this story can be found here.

Update: I neglected to mention in the above post that the notion that DCA can cure cancer is not supported by the data in the above study or in follow-up work.  The tumors may have been reduced, but they were not eliminated.  Moreover, subsequent studies in humans have not been designed to specifically evaluate DCA, as other treatments took place concurrently.  It therefore appears that DCA may be a useful addition to treatment, but a magic bullet it is not.

One Comment leave one →
  1. May 19, 2011 5:16 pm

    hah its conspiracy?

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