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Two weeks ago, New Scientist created a minor Web phenomenon when they published an article entitled Cheap, safe drug kills most cancers.  In the article, New Scientist reported the results of a University of Alberta-led study on the anti-cancer properties of the small molecule dichloroacetate.

The article's contents probably wouldn't have set off the firestorm that it did had it not contained the following two sentences:

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.

I'll try to explain the basics of cancer biology and why the community's reaction was, in my opinion, a gross over-reaction after the break.

First, some history of the phenomenon on Daily Kos.  After the New Scientist article was published, Randular wrote a diary, Potential cheap, safe cure for cancer: Will Big Pharma Allow It? that focused on the Two Sentences from before the break.  Randular wrote:

Again, if proven effective, will we ever see it in use in this country? Will patients have to take 'DCA tours' to Canada for treatment?

Within the comments a fervor (and some skepticism) developed that propelled the diary to the rec list, focusing on the meme that Big Bad Pharma would never allow such a drug to take hold in the US.  Some anonymous comments (you can follow the link back to the story if you want to find the authors):

I know that cancer is a complicated beast. But if this stuff works even a little bit, wouldn't it be worth a few million in research dollars? I'll wager those dollars will be spent... but in Canada or Sweden or Japan or somewhere that patients lives are actually valued.

The NIH is now nothing but a tool of Big Pharmas. They use taxpayer dollars to develop the meds the companies want, and then make sure only those companies have the right to bid for production.

I presume that DCA is an approved therapeutic agent for the metabolic uses; there isn't anything that would prevent a doctor from prescribing it at such--although I suppose there are some insurance plans that wouldn't cover it.

There has already been debate on the issues raised in the comments and in subsequent diaries, such as Hobbitfoot's excellent diary Cancer cures and the evil of false hope.

Before I give my input into these issues, let me give you some background information on myself.  I am a molecular biology graduate student (Ph.D.) in my first year.  I do not study cancer, but like all molecular biologists I am familiar with the basics.  So I am not an ultimate authority, but I do think I can provide context and a more informed point of view than your average Joe.

That said, let's get into the meat.

Cancer is largely a modern disease.  While juvenile cancers do occur (cancer is a top-3 killer until age 15), cancer really starts to wreak havoc as people get older -- older, in fact, than our historical life expectancy.  This is significant.  It means that the selective pressure for anti-cancerous genes has been very light until recently.  In plain English, this means that anti-cancer genes didn't confer much of an advantage to our ancestors because they died too young to use them, decreasing the frequency of these genes and resulting in the rather high susceptibility to cancer that we have today.

(As a side note: when one says "anti-cancer gene" in this context, it doesn't usually mean a new gene that a previous generation didn't have.  It mens a different version of a previously existing gene that tilts our cells away from cancer, such as a more active form of a DNA damage-fixing protein.)

Why is cancer a disease mainly of the elderly?  The reason for this gets to the root of what cancer is in the first place -- a loss of the normal control of proliferation of our cells.  Step back for a moment and compare yourself to a bacterium.  The goal of the bacterium is simply to divide as fast as possible and maintain as large a population as possible.  We, on the other hand, are multicellular animals.  Our cells have a carefully orchestrated pattern of dividing that maintains a relatively constant number of cells throughout our adult life.  There is relatively high turnover in the skin and intestines, but low turnover in the brain and heart.  But the important new word here is turnover -- cells aren't trying to multiply for the sake of multiplying.  They multiply to replace older or damaged cells.

This is a careful balance, mediated by a beautifully intricate signaling and control system.  For an example of what a "signaling and control" system means, consider when you cut yourself.  The physical process of cutting yourself rips apart cells that were once connected.  And, importantly, it rips apart the dense, fibrous material that sits between most of our cells -- the extracellular matrix.  When that material is ripped apart, it releases tiny little molecules that tell surrounding cells hey, we just had some trauma!  Fix us up!  And the surrounding cells are released from their normal restriction against cell proliferation in order to heal the wound.

In addition to pro-proliferative signals, there are also anti-proliferative signals, which can either be intracellular or extracellular in nature.  Because this is getting boring pretty quickly, I'll focus on arguably the most studied cancer pathway: the p53 pathway.

p53 is one of those fascinating proteins that has been the subject of an enormous amount of study since it was identified as a tumor-suppressing (anti-cancer) protein (originally it was thought to be oncogenic, but then we realized we had it backwards).  The short version of the story is that among p53's roles is its role in responding to DNA damage.  Say you're laying out at the beach, baking in the sun without enough sunblock on.  While you're warm and happy, the DNA in your skin cells is being steadily damaged (one kind of damage from UV is the formation of abnormal covalent bonds between thymines, the T in A, T, G, and C of DNA).  Unbeknownst to you, p53 has gone to work.  It has sensed the damage in the DNA and told the cell don't divide!  Your DNA's damaged!  The result is that you don't get skin cancer (or you do, if the damage overwhelms p53 or a cell happens to have a bad copy of p53).

(Another side note: DNA damage is primarily bad during division.  If damage is caught before division, the cell can often repair the DNA to its original state.  After the cell divides, any mutations that were caused by the damage are written in stone in one of the daughter cells)

But DNA isn't just damaged from the sun.  DNA damage also happens at a slow, steady rate from numerous sources.  And this damage builds up over time, because as I mentioned, once a mutation is passed on to a daughter cell, it's there forever.  This is why cancer is a disease primarily of the elderly.  As mutations accumulate, the chance that a cell will have a mutation that destroys the normal control of proliferation increases, and your chances of developing cancer increases.

Let's return to p53.  Its first role in responding to DNA damage is to halt cell division.  But if the damage is not repaired fast enough, the cell will actually commit suicide to save you, the host, from death from cancer.  This process is called apoptosis, and it is the focus of the New Scientist article.

The real title of the academic article being reported on was A Mitochondria-K+ Channel Axis Is Suppressed in Cancer and Its Normalization Promotes Apoptosis and Inhibits Cancer Growth.  To make another long story short, the apoptosis (cell suicide) pathway includes proteins that are embedded in the membrane of the mitochondria.  Apparently, when glycolysis overtakes energy production for the cell and the mitochondria turn off, this apoptotic pathway is inhibited.  And the study also suggests that dichloroacetate turns the mitochondria back on (by restoring the proper electrical balance of the mitochondrial membrane indirectly), restoring this part of the apoptotic pathway.  The result is a cell with damaged DNA that can suddenly kill itself as it is supposed to.

Now that you understand to some degree what the article is talking about, I'll just spit out some thoughts about why I think our reaction was overdone:

Remember that I said p53 is mutated in up to half of all cancers?  It is significant that this number isn't 100%.  The reason is because I've only mentioned a minuscule number of players in the massive beast that is cell cycle control and the apoptotic pathway.  Cancer is the result of multiple mutations acting in concert.  Between types of cancer, the genes that are mutated will differ.  Between the cells in a single cancerous growth, the genes that are mutated will differ.  Our understanding of exactly which genes are mutated and how often is largely limited to research targeting specific proteins of interest (like p53), rather than a more global understanding.  In fact, the Broad Institute of Harvard and MIT was recently awarded a $200M grant from the NHGRI (part of the NIH) to sequence cancer strains so that we might have a more global understanding of the roles of different mutations.

Now can you understand why scientists are so skeptical of cancer "cures"?  A treatment that attacks p53 (and probably also PDK2, the target of DCA) will only affect a subset of cancers, and might only affect a subset of cells in a single tumor.  In a tumor where only some cells are affected the remaining cells will, via natural selection, then dominate the cancer and make subsequent targeted treatment less effective.  This is why to this day the most common chemotherapies are basically clear-cutting drugs that attack all dividing cells, including the cells in your gut and your hair.  So while dichloroacetate may indeed be a potent anti-cancer treatment, I am personally very skeptical that it will turn out to be a cancer cure.  All that is required is one cancer cell to be immune to the effects of the DCA, and the surviving population will proliferate into a DCA-resistant cancer.

Just as important is the fact that no study with DCA has been carried out on humans.  While in vitro tests and animal models do provide information on the anti-cancer activity of a drug, it is absolutely not a guarantee that it will behave the same way in a human as it does in a mouse or a tube.  Thus, DCA simply is not a human cancer therapy at the moment, and it will not be until these human studies are carried out.  This is why the University of Alberta page on DCA says:

At this point, the University of Alberta, the Alberta Cancer Board and Capital Health do not condone or advise the use of dichloroacetate (DCA) in human beings for the treatment of cancer since no human beings have gone through clinical trials using DCA to treat cancer.

In addition, I'd like to vehemently squash the notion right out that the NIH is somehow in the pocket of Big Pharma to the degree that they would never fund a study into the efficacy of DCA.  This is simply not true, and to peddle in this falsehood makes us liberals look like tin-foil hat-wearing loons.  The NIH pays an enormous sum to study cancer every year, including studies into potential anti-cancer drugs.

As for the patent issue, drugs that have a well-established history can be patented as far as I know, but the patent covers specifically the use of the chemical for a novel purpose (such as cancer treatment).  This is why fluoxetine hydrochloride was patented for use against depression (and given the trade name Prozac) and separately patented for use against pre-menstrual dysphoric disorder (and given the trade name Sarafem).  Same drug, different name, different patent.  So while doctors could probably prescribe DCA off-label for cancer if it pans out (which at this point would be entirely unethical), there is some degree of patent protection that the discoverers could enjoy and could license to Big Pharma.  Of course, I am not a patent lawyer, so this information is just my understanding as a scientist.

As for the future, keep holding out hope for DCA, but do not expect it to be a cure for cancer, and don't believe that research on it is being suppressed.  If you want to help the scientists studying DCA's efficacy, you can make a donation to the University of Alberta and even specify on the second page that you'd like your money to go to "DCA - Cancer Research Fund".

And also remember that everything I've described in this diary is a scientific model.  It is not fact.  It is merely the story we have developed that best explains the large amount of data we have accumulated over the years.  Some aspects are virtually certain (such as the notion that p53 halts the cell at a cell division checkpoint) while others are higher-level abstractions (such as the idea of a mitochondrion turning "on" and "off" as if from a light switch).  So approach everything with an open, skeptical mind as all good scientists do.

p53 (blue) in complex with DNA (orange) (picture licensed under Creative Commons Attribution ShareAlike 2.5 and graciously taken from Thomas Splettstoesser here).

Originally posted to jforman on Sat Feb 03, 2007 at 08:37 AM PST.

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Comment Preferences

    •  thank you (2+ / 0-)

      for an extremely well written and interesting piece.

      I have no scientific background but find your work fascinating, because it sheds light on the machinery of life.
      For some time I have thought that perhaps breast and prostate cancers are increased by the hormones injected into factory farmed animals.
      Since estrogen supposedly is linked to breast cancer, would not the estrogens that increase the "yield" of factory farmed animals possibly adversely impact the people who consume this? Isn't estrogen an endocrine disruptor?
      Thanks, in advance, for letting me ask this since my college major was economics and political science decades ago and my question might be nonsensicle to a scientist.

       

      •  nonsensical, that is (0+ / 0-)
      •  Thank you for the question (5+ / 0-)

        And sorry for the delay.  In an amazing coincidence my Internet access at home dropped right after posting the diary, so I had to run back to the lab after taking a shower  :)

        Like I said before, I don't study cancer, so I can't give you a definitive answer.  But as I understand it estrogens behave as proliferative signals to some tissues.

        To understand why this would cause cancer, you need to understand that the cells that divide in our adult selves (such as cells in your ovary or colon) receive a mixture of pro-growth signals and anti-growth signals, and these signals are integrated in a complicated fashion to answer the question should I divide now?  A pro-growth signal may be a nutrient of some kind, telling the cell, for example, that there's enough food to sustain a cell division.

        So as I said, I think estrogens are proliferative signals to some tissues (i.e., they tilt the cell toward answering yes to the above question), such as, I'm guessing, tissues in the ovary or breast.  Anything that causes cells to divide faster than normal will increase the incidence of cancer.

        As a side node, estrogens are naturally-made chemicals made by our bodies.  Since cows are animals, too, they make estrogens as well.  If the estrogens that cows make are similar enough to our own, then they will attach to the estrogen receptors on our cells and activate them even though they are exogenous.

        Note that I have no idea whether or not the estrogens that may or may not be in milk actually do increase the rate of proliferation of the cells in our bodies.  I'm just giving an explanation for how the mechanism would work if this were the case.

        •  Breast Cancer (5+ / 0-)

          A mechanism observed in breast cancer for example, is that some cancer cells have a receptor protein on their surface which responds to estrogen.  These are called ER cells (estrogen-receptor positive).  So estrogen then will stimulate these cells continuously, and they will proliferate abnormally.

          So yes, estrogen can have a cancer-inducing effect, but it's dependent on a particular genetic signature which is seen in some breast cancers, but not all.

          As a result, some women will benefit from drugs that interfere with estrogen, which then blocks the stimulation of the cancer cells.

          •  Here's a pretty good resource on this topic (4+ / 0-)
            Recommended by:
            Athena, TiaRachel, eve, ChemGeek

            if anybody wants more information:

            http://www.cancer.gov/...

            I'm a little unclear as to whether ER+ really means "any estrogen receptor is present" as some web pages seem to say, or whether it actually means "estrogen receptor up-regulation".  Either way, though, the idea is pretty much the same.

            And I'd like to fix a mistake in my previous post.  Estrogen receptors are not cell surface proteins as I implied.  They are inside the cell.

          •  Our understanding of Estrogen Receptors (3+ / 0-)
            Recommended by:
            Athena, eve, goldberry

            is changing rapidly. It is now known that there are multiple forms of ER. Typically, these are thought to be "nuclear receptors" that bind to estrogen inside the cell and then move to the nucleus where they can alter the expression of different genes.

            There is accumulating evidence that there are some estrogen receptors located on the surface of the cell membrane. Their mechanism of action and their functional relationship to other ER forms is the focus of ongoing study.

            Very complex and very interesting.

            •  Thanks, A Question (1+ / 0-)
              Recommended by:
              ChemGeek

              Thanks for this clarification - as soon as I posted this, I rethought my "surface" characterization.  I had to rethink and remember that steroid receptors are usually nuclear, not surface.

              But a more precise question:

              Do you know if the ER-positive breast cancer cells might have ER on their surface as well as nuclear receptors?  

              •  Membrane-associated ER (0+ / 0-)

                My reading of the latest studies indicate that ER+ breast cancer cells have both ER that can be found localized in the nucleus and at the cell membrane. The bulk of the data indicate that the membrane-associated estrogen-responsive receptors are very similar to the "classic" ER. It is likely that forms of the classic ER can become associated with the membrane as part of its "traffic" through the cell.

                However, there are researchers who maintain that there are non-classical receptors at the membrane that can respond to hormones including estrogen. For example, a "G-protein coupled" receptor termed GPR30 may play a role in allowing rapid responses to estrogen signalling -- pathways which would not directly involve action in the nucleus or alteration of gene expression. However, much more careful work will need to be done to provide compelling evidence for the presence of this or other non-classical estrogen receptors.

                If you are so inclined, you can check out this reference:

                "Nature of functional estrogen receptors at the plasma membrane"
                Ali Pedram, Mahnaz Razandi and Ellis R. Levin
                Molecular Endocrinology   yr:2006 vol:20 iss:9 pg:1996-2009

                Keep in mind, it's just one opinion.

        •  thanks so much (0+ / 0-)

          and I'm looking forward to more diaries if and when you have time.
          That's one of the nice things about this site, people can share their expertise:))

      •  Depends (1+ / 0-)
        Recommended by:
        eve

        Some cancers are stimulated by hormones like estrogens, some aren't.  This is true of breast cancer, for example.  Some breast cancers are stimulated by estrogens, others aren't.  As jforman wrote above, there are many different causes of cancer and what might trigger cancer in one pathway, may not in another.  
        It's probably best to be cautious and not eat too much of anything.  But I wouldn't get too worried if I occasionally (like once a week or so) had factory bred animals for dinner.  

        -3.63, -4.46 "Choose something like a star to stay your mind on- and be staid"

        by goldberry on Sat Feb 03, 2007 at 10:58:01 AM PST

        [ Parent ]

        •  well I'm pretty much (0+ / 0-)

          a vegetarian anyway, lol
          But I won't buy factory bred animals on ethical grounds because their treatment of animals as I understand it is so inhumane.
          That said, it gives me some comfort when you say that because family members (and pretty much most people in this country) do on occasion eat from that source.

          (I am so appalled at the way factory farms treat animals that it would not be surprising that their methodology (which after all has "yield" not "nutrition" as its goal) is counterproductive to the well being of consumers of their meat.)

          I also suspect, but as a non-scientist obviously don't know, that the pesticide laden food fed to children may also trigger certain cancers or diseases.

          I'd love to see epidemiological studies along these lines as well as epidemiological studies on the tons of toxins spewed into our air by the petrochemical and coal industries.

          But I've taken this down a pathway that is far removed from the intent of the diary's author:))

          •  I confess to enjoying... (0+ / 0-)

            ... veal chops seasoned with porcini mushroom rub and grilled to a tender and delicious medium rare...
            It would be nice to know that the little buggers hadn't been force fed but I rarely think about it when it's in front of me on my plate.  
            Mea culpa.  

            -3.63, -4.46 "Choose something like a star to stay your mind on- and be staid"

            by goldberry on Sat Feb 03, 2007 at 12:08:30 PM PST

            [ Parent ]

            •  if you live in a part of the country (0+ / 0-)

              where there's a Whole Foods Store or a Wild Oats store (or even a local health food coop), you might want to drop by to check them out. Whole Foods is sells only meat that is free of hormones and antibiotics and is supposedly family farm raised.

              Whole Foods foundr John Mackey has funded (and is chairing I think) a foundation that is developing humane animal husbandry standards for the industry.

              (One thing that astonished me was to learn that factory farmed cattle are fed a tiny dose of arsenic about two weeks before they're slaughtered to increase their weight. I was told that by someone who grew up on a farm and talks to ranchers but I don't have solid evidence.)

              So for a variety of reasons starting with health, you might wish to look into this for yourself when you have a chance.

  •  Good explanation and illustration of complexity (3+ / 0-)

    Thanks for a well-written diary. I hope that DCA proves a useful weapon to add to the arsenal against cancer.

    On "Big Pharma", it is always worth remembering the power that capital brings - even if today it is being used benevolently, cynicism and oversight are not wasted (and I like my tin foil hat).

  •  excellent work (3+ / 0-)

    and a wonderful illustration of the strength of this community.

    really well done.

    I will permit no man to narrow and degrade my soul by making me hate him. - Booker T. Washington

    by jmonch on Sat Feb 03, 2007 at 09:02:32 AM PST

  •  Nice Diary well done (3+ / 0-)

    As a pharmacist I understand what you are saying. However it is evident that Big Pharma over the years is not interested in a cure per se. There is no money in a cure but there is a helluva lot of money in the treatment of a disease.

    •  This is false (2+ / 0-)
      Recommended by:
      Athena, TiaRachel

      There is plenty of money to be made for many different cancer treatments.  There is likely never going to be one cure.  There are many targets to go after and, therefore, absolutely no reason not to pursue every one of them.  
      Please don't make pharma to be more callous than it is.    Besides being false, it just doesn't make sense.  

      -3.63, -4.46 "Choose something like a star to stay your mind on- and be staid"

      by goldberry on Sat Feb 03, 2007 at 11:02:41 AM PST

      [ Parent ]

  •  Excellent work, thanks. (1+ / 0-)
    Recommended by:
    Snakes on a White House

    I'll add a "teaching" tag so plf515 will pick this up in his next "what are you teaching" agglomerative diary.

    That DCA thing (and the genetically engineered prion-free cows story) have motivated me to work on a "How to read science journalism for the general public" diary. I keep getting stuck on my general contempt for much of what passes as "science" "journalism" (yes, double air quotes there), which I don't want to come across as contempt for the readers. I think we could also use an explanation of the funding/drug development process, but one thing at a time...

    It's the Sausage Grinder of Snark: the Daily Show/Colbert Report spoiler (and chat) thread, Live at 11.

    by TiaRachel on Sat Feb 03, 2007 at 09:30:45 AM PST

  •  Very interesting - thanks. (1+ / 0-)
    Recommended by:
    Snakes on a White House
  •  Nice diary (2+ / 0-)

    I like your balanced approach to the 'latest and greatest cure for cancer'.  It certainly warrants further research, but let's avoid the usual hysteria that accompany these things.

    And your point about Pharma is right on.  It is most certainly not the obligation of pharmaceutical companies to test this drug since it is not something they developed or brought to market.  

    NIH or other governmental agencies are the ones who should pony up and provide the funding for research.  I'm sure that will happen if the preliminary, animal research is as promising as it seems.

    Got an issue, here's a tissue - Will & Grace

    by Flinch on Sat Feb 03, 2007 at 09:44:17 AM PST

  •  Are you familiar with the work being (1+ / 0-)
    Recommended by:
    Snakes on a White House

    done at Introgen and how their drugs work? I would be interested in how their drugs fit with the above.

    It does not require a majority to prevail, but rather an irate, tireless minority keen to set brush fires in people's minds - Samuel Adams

    by Overseas on Sat Feb 03, 2007 at 09:49:19 AM PST

    •  They seem to have a few drugs in the pipeline (3+ / 0-)

      did you have one in particular you wanted more information about?

      Since I'm here, I'll give a brief explanation of Advexin, which I found on their website.  It appears that Advexin is a gene therapy -- they literally put a normal p53 gene into a semi-crippled adenovirus and then infect you with that virus.  When the virus inserts its DNA in your cells, the p53 goes along for the ride.  If your cancer had a mutant p53, then the exogenous p53 can replace it with a good copy, which would do a good deal to halt the cancer.  Of course, getting the gene into every cancer cell must be difficult, so who knows the efficacy.  And gene therapies can sometimes cause cancer if the exogenous DNA inserts itself in the wrong place.  But I have no idea about the specifics of their system, so I can't give you more information than that.

      •  Good explanation (1+ / 0-)
        Recommended by:
        goldberry

        at base-level for the nonscientists out there. If you become frustrated with getting your doctorate, you might consider science journalism.

        And so far as it goes, how do we scientists convince people that "cancer" is not a single entity disease? Even those cancers of the breast are multitudinous, some are ER-positive, some lack p53; and once cells from the original tumor metastisize, they may look like some other cancer entirely (well, some markers will remain).

        •  We need to start a weekly series. (2+ / 0-)
          Recommended by:
          TiaRachel, ChemGeek

          The more Kossacks educate themselves, the better to make more infomred decisions.  I'd be willing to start a diary about how the drug industry works from target to drug but I would love to have help on a project like that.  

          -3.63, -4.46 "Choose something like a star to stay your mind on- and be staid"

          by goldberry on Sat Feb 03, 2007 at 11:05:31 AM PST

          [ Parent ]

          •  I have already (1+ / 0-)
            Recommended by:
            ChemGeek

            offered to help emptypockets with MSM science article reinterpretation, but I would be happy to help out, being unemployed right now. There ought to be a powwow of all the scientist-Kossacks to figure out how best to use our expertise to educate, inform and interest others outside of our (microscopic) worldviews.

            •  Great idea (2+ / 0-)
              Recommended by:
              TiaRachel, riverlover

              I think that you may find that there are quite a few pockets of Kossack scientific expertise that can be tapped. Although many of us are overwhelmed with our current research commitments, I bet that at any point in time there would be a healthy number who would be happy to help translate current studies in biomedicine for the general readership.
              I'm really appreciative of jforman for taking the time to go over the issues related to DCA more carefully. It takes a lot of effort to communicate these topics in a way that includes the complexities and nuances.

          •  If you ever get a project like this going, (0+ / 0-)
            let me know. I have a B.S. in Biology and sometimes I have to roll my eyes at all the NewAge woo on DKos.
      •  No, they are working on some really interesting (0+ / 0-)

        things. Advexin is due for approval soon and is more beneficial combined with Avastin, surgery or chemo. Some of the other drugs in their pipeline look even more promising.

        It does not require a majority to prevail, but rather an irate, tireless minority keen to set brush fires in people's minds - Samuel Adams

        by Overseas on Sat Feb 03, 2007 at 02:20:27 PM PST

        [ Parent ]

  •  Even in the US, one nation under Big Pharma... (0+ / 0-)

    ...there is promising research being done on the anti-cancer properties of compounds that could not possibly be patented. For example:

    An extract from common button mushrooms has promise against breast cancer.

    There is no way that a company could patent a drug made from the common button mushroom. However, the City of Hope is making it possible to pursue this research. There is another promising non-patentable compound in the spice Turmeric which might even hold out some hope for my husband. I am willing to lay money out (not much, we're broke) that scientists over there are looking at it seriously in spite of the non-patentability issue.

    I'm also willing to bet that there's stuff going on there with Dichloroacetate. When you are completely run as a charity, you have a lot of leeway on what you can do research on.

    I will post what I find out in a later, related diary.

    Thanks for kicking the science, jforman.

    Wes? HELL YES!!! Clark 2008! http://www.securingamerica.com/
    Medicare for All...it's doable! HR 676 NOW!!!

    by Snakes on a White House on Sat Feb 03, 2007 at 09:49:42 AM PST

    •  You'd be surprised ;-) (1+ / 0-)
      Recommended by:
      TiaRachel

      Most big pharma companies have "Natural Products" departments.  Botanists collect samples from around the world and researchers study these biologicals for potent drugs.  For example, taxol was originally isolated from the bark of a pacific yew tree.  Rapamycin, a transplant anti-rejection drug and the coating of many stents, was isolated from a fungus in the soil from Rapanui (Easter Island).  A cacer therapy was isolated from vinca plants.  Big Pharmas have databases and compound libraries that they can use to find the drug to fit the target.  It doesn't matter to us where the sucker comes from.  To us, it is just a representation of atoms and bonds.  After we find out what works, we find out how it works and then we try to make it work better.  Most biologicals need to be modified to be potent enough so you don't have to take massive quantities of it and risk serious side effects.
       

      -3.63, -4.46 "Choose something like a star to stay your mind on- and be staid"

      by goldberry on Sat Feb 03, 2007 at 11:14:50 AM PST

      [ Parent ]

  •  Thank you for this (4+ / 0-)
    Recommended by:
    TiaRachel, ChemGeek, cfk, Ellicatt

    well written and informative diary.  And while much of it went far over my head, I think I understand quite a bit of what you're saying.

    I was diagnosed fairly recently with a T-cell proliferative disorder that is malignant.  It took three years to get a diagnosis at all as it wouldn't fully show itself as a malignancy until a TCR gene realignment was done.  It's very slow growing at this point and my oncologist feels that it will eventually show itself in full form as lymphoma.  I'm receiving no treatment at this point as it is growing as slowly as it is.  If and when the time comes that it does accelerate the standard treatments of chemotherapy and radiation therapy are most commonly used and, from what I've read regarding lymphoma, only increases the patients lifespan by 3-5 years.  I'm hoping something more promising and less severe is developed and made available for too long.

    I can't tell you how little information is out there on proliferative disorders and understanding what is available, from a layperson's POV, is difficult to say the least.  Thank you for helping me to understand a little better how this "works" (for lack of a better word).

    "Ancora Imparo." ("I am still learning.") - Michelangelo, Age 87

    by Dreaming of Better Days on Sat Feb 03, 2007 at 09:51:34 AM PST

    •  Response (3+ / 0-)

      Sorry to hear about your news.  There are likely clinical investigations that could be of use to you as you and your doctors monitor your condition.  If you are not aware, here's a link to help you  identify clinical trials which would be studying new treatments for various cancers.  You can search by cancer type:

      http://www.cancer.gov/...

      •  Thank you, Athena. (0+ / 0-)

        I've been doing a bit of research myself, but as I said I have no background in medicine and what I've found is hard to understand, for me at least.  (I wish I had a decoder pin or something that would put it in a "language" I could understand more easily.)  I do know that the cancer center I go to offers stem cell treatment, however I don't know if this would even be an option for my type of cancer.

        I do know that chemotherapy and radiation are not options that I'm willing to take, for very personal reasons.  And so I keeping hoping for something with less side effects and a more promising outcome for where my malignancy seems to be going.  (Keeping my fingers crossed.)

        "Ancora Imparo." ("I am still learning.") - Michelangelo, Age 87

        by Dreaming of Better Days on Sat Feb 03, 2007 at 10:42:37 AM PST

        [ Parent ]

    •  Thank you (4+ / 0-)

      your comment alone made the diary worthwhile.

      There's a lot of cancer in my family (maybe I inherited a bad MutS homolog, who knows), so I also hope some progress is made soon.

    •  Some reassurance... (5+ / 0-)

      ... Although I don't know the nature of your malignancy, I can tell you that several companies are working on drugs that target lymphomas.  The thing about cancer treatment that I find interesting is that it is moving away from the "shock and awe" type drugs that just go marauding through the body killing every dividing cell in sight to more of a "special forces" kind of treatment that is more narrowly tailored to affect only a specific family of protein targets.  Gleevec is one example of how these treatments are changing.  
      jforman will probably tell you that our knowledge is changing at an explosive rate.  It's difficult to keep up with it in some respects.  What you learned in biology 30 years ago would look extrememly simplistic compared to today.  And while we are trying to keep up, we need to develop technology that will allow us to take advantage of that knowledge.  There's a bit of a lag time.  But I think there is room for optimism on the cancer front.  

      -3.63, -4.46 "Choose something like a star to stay your mind on- and be staid"

      by goldberry on Sat Feb 03, 2007 at 11:24:07 AM PST

      [ Parent ]

  •  Good, informative post (1+ / 0-)
    Recommended by:
    badger

    For additional thoughts on the need to take a step back and re-think the sound and fury on whether or not DCA is an anti-cancer wonder drug that is being ignored by big-pharma, people might take a look at this post over at ScienceBlogs:

    http://scienceblogs.com/...

    A warning though, the author (an oncologist) makes some dismissive comments about one or two bloggers who are generally held in high esteem here at DailyKos (i.e. Digby over at Hullabaloo).  As a scientist myself, I can understanding his frustration when lay people, who may not be real familiar with a topic make overbroad statements about said topic.

    •  Yeah, Digby's comments were unfortunate (1+ / 0-)
      Recommended by:
      TiaRachel

      She/he was really off the reservation.  She//he is usually so rational that it was quite depressing to read it.  But, I have faitht that Digby is intelligent and adaptable and will be a lttle less reflexive next time.  We chewed her/him out pretty good in the comments.  

      -3.63, -4.46 "Choose something like a star to stay your mind on- and be staid"

      by goldberry on Sat Feb 03, 2007 at 11:27:45 AM PST

      [ Parent ]

  •  DCA causes neurotoxicity (1+ / 0-)
    Recommended by:
    ChemGeek

    DCA has undergone clinical testing to treat lactic acidosis.  It was found that it causes peripheral neurotoxicity (NEUROLOGY 2006;66:324-330. Dichloroacetate causes toxic neuropathy in MELAS) http://www.neurology.org/...  You are correct that a use patent could be filed but only if it was filed before publication of the journal article.  I agree with your conclusions that DCA used without other therapeutics has little chance of making an impact on eliminating cancer.

    •  I thought (0+ / 0-)

      there was a one year lag in the US between when you release/report an invention publicly and when you need to file for the patent.  Is this not the case for drugs?

      •  Patents (0+ / 0-)

        I am not a lawyer but have worked in biotech.  You can file a provisional patent that outlines your invention and then a year later file the patent with supporting data.  Once you make a public declaration of your invention (therapeutic) you may not file a patent (I believe this would be called prior art).  That is why the provisional patent is very useful: when you get an idea file the provisional, then publish your paper, and then add the data to your patent.

        •  One more point (0+ / 0-)

          Building on your excellent discussion of the mechanism for DCA you could file a use patent pairing DCA with another existing therapeutic and that would constitute a novel use even if both had patents as individual therapeutics.

      •  Yes, One Year (0+ / 0-)

        Yes, U.S. law has a one-year grace period between public disclosure and patent filing.   But that only protects you against your own disclosure - if the "invention" is already known or disclosed elsewhere, you won't get a patent.

  •  This was great! More, more, more (0+ / 0-)

    I'm not a molecular biologist but I am forced to understand this stuff.  (I'm a molecular modeler)  The DCA story was very depressing.  Too many Kossacks have been conditioned to respond knee-jerk fashion whenever pharmacueticals are mentioned.  It's like ringing a bell and all the dogs salivate.  The most rational, clear headed thinkers (Digby, for example) start saying things only a wingnut would say whenever they hear the words Big Pharma.  
    For the record, I work for Big pharma and I can tell you that there is absolutely no truth to the notion that we would sit on a cure for cancer.  Looking for cancer cures, and other disease cures and treatments,  is what we do, 24/7/365. That doesn't mean we have an obligation to jump on every little piece of data.  Whether DCA works or not is immaterial.  I just don't think it would make a particularly good drug.  There is more to drug design that just shoving the stuff in the body.  Metabolism, transportation through the gut, efficacy, delivery mechanism and side effects are just some of the things that need to be considered.   Of course, that won't stop people from ordering it from some chemical catalog and taking it in large quantities in some desperate attempt to halt the progress of the disease.  I just hope no one dies from it.  

    -3.63, -4.46 "Choose something like a star to stay your mind on- and be staid"

    by goldberry on Sat Feb 03, 2007 at 10:52:58 AM PST

  •  Forest for the trees approach (0+ / 0-)

    If the drug has been around that long, it's side effects should be well documented. Therefor a patient should have the ability to try it rather than "standard" treatment for which the side effects are unfortunately well known. By the time you have diagnosed cancer, the cells are throughout your body, it's just a matter of whether it is an aggressive form or not.

  •  so what's you guy's take (0+ / 0-)

    on the HPV vaccine?

    It's my very lay understanding that there's a bunch of different forms of this virus, and only one can lead to cervical cancer.

    •  I'm ecstatic about the HPV vaccine (1+ / 0-)
      Recommended by:
      rgdurst

      I have a daughter, and I'm thrilled that this will be available to protect her as she becomes older. I was really impressed that the Republican governor of Texas just signed a bill mandating HPV vaccination for Texas school-girls. This was a great example of a politician listening to the advice of public health experts.

      As far as I remember, the data on human trials of the efficacy of HPV vaccine were extraordinarily clear-cut. Despite the fact that there are many types of HPV, and only some are associated with cancer, this vaccine was very effective at preventing cervical cancer.

      I would not hesitate for a moment to have my daughter vaccinated, and tend to be very tough to convince regarding health claims.

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