Respectful Insolence

Given all the verbiage (see the link list below) about dichloroacetate (DCA) that I’ve spewed into the blogosphere decrying the hijacking of a promising cancer therapy by conspiracy-mongers (it’s the cancer cure “big pharma” is keeping from you because they can’t make money on it) and opportunistic entrepreneurs like Jim Tassanno preying on the desperation of terminally ill cancer patients, I had thought that I would be taking a break on the topic for a while. But wouldn’t you know it? My blogging colleague Abel at Terra Sigillata unearthed another fascinating article on the effects of this unsupervised and unregulated self-experimentation and how they may be endangering patients. Here‘s what the article says Dr. Evangelos Michelakis, the researcher who first reported the promising results of DCA against various rat cancer models:

Media reports that DCA won’t get developed because drug companies can’t patent the molecules (this fact has been used in DCA fundraising by U of A) caused outrage from patients. There were also claims that DCA can be cheaply and easily made from components purchased from chemical suppliers (partly true) and that it has no side-effects (false). DCA has long been used to treat rare metabolic disorders in children but is known to cause peripheral neuropathy in adults.

Despite the dangers, Californian biologist-cum-huckster Jim Tassano has started selling DCA on a website called BuyDCA.com. Although the site says it’s only for veterinary use, a sister site, TheDCAsite.com, openly promotes its use in humans. “He’s a pest exterminator with a biology degree who’s hired a chemist and is profiting from desperate people,” fumed Dr Michelakis in the Edmonton Sun. “He is bypassing every regulatory principle that exists to ensure pharmaceuticals are safe and selling hope for money. It’s horribly unethical.”

Mr Tassano, who sells DCA for 90 cents a gram, denies he’s in it for the money, saying he got involved because he wanted to save his terminally ill ballroom dance instructor’s life.

TheDCAsite.com features a message board where patients recount their experiences taking DCA (sadly, most have been negative — see “A physician’s DCA experiment” below). “That’s the worst nightmare in medicine, to start making judgments on whether a drug is good or bad based on what any patient will post on a blog,” said Dr Michelakis in the Edmonton Journal. “This is the death of medicine and organized research as we know it.”

As Abel puts it:

It’s amazing to be reminded that the original Cancer Cell paper from the Michelakis team didn’t even contain the word “dichloroacetate” in the title – the focus was on the concept of altering mitochondrial energetics in cancer. DCA was used as a tool at very, very high concentrations (0.5 mM in cell culture) to inhibit an enzyme called pyruvate dehydrogenase kinase (PDK2), an effect that was also duplicated using small interfering RNA against the enzyme’s mRNA. The net result was the increase in the expression of a mitochondrial plasma membrane potassium channel (Kv1.5) whose action pushes cancer cells toward programmed cell death, or apoptosis. DCA only shrinks tumors in animals and is by no means a “cure.”

Actually, although Abel is right on when it comes to describing the mechanism, I would quibble slightly with the characterization of “tumor shrinkage,” a characterization that has been hyped up in the press and contributed to the concept of this drug as some sort of “miracle cure.” As I pointed out, in most of the experiments, DCA exhibited what we in the cancer research biz call tumor growth delay. What this means is that tumors in treated rats were considerably smaller at the end of the experiment than they were in the controls but that they did not necessarily stop growing. Rather, they just grew considerably more slowly. For example, in the “prevention” experiments, where DCA was administered from the beginning, the tumors continued to grow, albeit slowly, while in the “treatment” experiments, tumors either stopped growing but did not regress or demonstrated modest shrinkage. It’s quite possible that higher doses would have resulted in much more impressive tumor shrinkage, and the results of the experiments were impressive for the first in vivo test of a new drug, but DCA was by no means a cure, even in animals.

In any case, I remain of the mind that hypesters like Jim Tassano, although he seems to think that he’s doing good, are in fact not only putting patients at risk, but putting the very clinical trials necessary to demonstrate the utility of DCA against cancer at risk. Thanks to Jim Tassano, idiots like DaveScot egging him on, and the general Kevin Trudeau-style “cure for cancer that ‘they’ don’t want you to know about” blogospheric meltdown, the taint of quackery has descended upon a new chemotherapeutic drug (and, indeed, a new overall approach to treating cancer in general) that is promising and the study of which could utimately yield a whole new class of anticancer drugs.

ADDENDUM: Walnut has posted his critique on Daily Kos as well.

All Orac posts on DCA:

  1. In which my words will be misinterpreted as “proof” that I am a “pharma shill”
  2. Will donations fund dichloroacetate (DCA) clinical trials?
  3. Too fast to label others as “conspiracy-mongers”?
  4. Dichloroacetate: One more time…
  5. Laying the cluestick on DaveScot over dichloroacetate (DCA) and cancer
  6. A couple of more cluesticks on dichloroacetate (DCA) and cancer
  7. Where to buy dichloroacetate (DCA)? Dichloroacetate suppliers, even?
  8. An uninformative “experiment” on dichloroacetate
  9. Slumming around The DCA Site (TheDCASite.com), appalled at what I’m finding
  10. Slumming around The DCA Site (TheDCASite.com), the finale (for now)
  11. It’s nice to be noticed
  12. The deadly deviousness of the cancer cell, or how dichloroacetate (DCA) might fail
  13. The dichloroacetate (DCA) self-medication phenomenon hits the mainstream media
  14. Dichloroacetate (DCA) and cancer: Magical thinking versus Tumor Biology 101
  15. Checking in with The DCA Site
  16. Dichloroacetate and The DCA Site: A low bar for “success”
  17. Dichloroacetate (DCA): A scientist’s worst nightmare?
  18. Dichloroacetate and The DCA Site: A low bar for “success” (part 2)
  19. “Clinical research” on dichloroacetate by TheDCASite.com: A travesty of science
  20. A family practitioner and epidemiologist are prescribing dichloracetate (DCA) in Canada
  21. An “arrogant medico” makes one last comment on dichloroacetate (DCA)

Posts by fellow ScienceBlogger Abel Pharmboy:

  1. The dichloroacetate (DCA) cancer kerfuffle
  2. Where to buy dichloroacetate…
  3. Local look at dichloroacetate (DCA) hysteria
  4. Edmonton pharmacist asked to stop selling dichloroacetate (DCA)
  5. Four days, four dichloroacetate (DCA) newspaper articles
  6. Perversion of good science
  7. CBC’s ‘The Current’ on dichloroacetate (DCA)

Comments

  1. #1 Abel Pharmboy
    April 24, 2007

    Indeed, my verbiage was not as precise as had intended; perhaps I fell prey to reading “tumor shrinkage” hundreds of times in the lay press. I have just looked over the Cancer Cell paper again, especially the prevention expts. You are indeed correct to correct me: the effect of DCA is to delay the growth of the A549 tumors. The tumors still grew while the animals were given DCA, they just grew at a slower rate as compared with untreated control animals. As you have pointed out elsewhere, had the experiment been carried out past 12 weeks the DCA-treated tumors would still have grown large enough to kill the animals.

  2. #2 Jeb, FCD
    April 24, 2007

    Why hasn’t Tassano been arrested, or charged with anything?

  3. #3 Joe
    April 24, 2007

    @ Jeb,

    I have noticed a few people appending “FCD” to their signatures. What does it mean?

  4. #4 Coin
    April 24, 2007

    Abel Pharmboy wrote:

    It’s amazing to be reminded that the original Cancer Cell paper from the Michelakis team didn’t even contain the word “dichloroacetate” in the title – the focus was on the concept of altering mitochondrial energetics in cancer. DCA was used as a tool at very, very high concentrations (0.5 mM in cell culture) to inhibit an enzyme called pyruvate dehydrogenase kinase (PDK2), an effect that was also duplicated using small interfering RNA against the enzyme’s mRNA.

    I hadn’t clearly been aware of this. If it turns out that the Michelakis’ team’s conclusion that mitochondrial energetics can be used to treat cancer is a good one, but it unfortunately turns out that DCA itself is not suitible for medical use against cancer in humans, is it possible that some other method of, for example, suppressing PDK2– like the interfering RNA mentioned– could be developed into a medicine in its place?

    Also:

    Orac wrote:

    DCA exhibited what we in the cancer research biz call tumor growth delay. What this means is that tumors in treated rats were considerably smaller at the end of the experiment than they were in the controls but that they did not necessarily stop growing. Rather, they just grew considerably more slowly.

    Excuse me if this is a dumb question, but do such “growth delaying” effects also have the effect of preventing a single tumor from metastasizing?

  5. #5 Blake Stacey, OM, FCD
    April 24, 2007

    Joe:

    “FCD” stands for Friends of Charles Darwin.

  6. #6 Robster, FCD
    April 24, 2007

    FCD: Friend of Charles Darwin

    I’ve been in for a while, but never added it to my signiture.

  7. #7 steppen wolf
    April 28, 2007

    Hi to all,

    The FDA is already investigating the illegal use of DCA: http://www.healthtalk.ca/content/view/100/9/
    However, I could not find any more news on their website.