In which my words will be misinterpreted as "proof" that I am a "pharma shill"

Hey, the Geiers are trying to patent their Lupron protocol for the bogus treatment of autism. Why can't the DCA protocol for cancer be patented? Hell, it doesn't even have to be proven to work - it just has to be novel.

Off topic, but congrats on hitting 1,000,000 served!

I might also add that a PubMed search for "efficacy xenograft" reveals over 2,000 publications, a great many with experimental agents showing efficacy similar to or better than DCA.

The truth is that there are hundreds, if not thousands, of compounds competing for investment dollars of pockets big enough to develop these agents. Hence, many agents, inexpensive and not so, fall by the wayside because of cost barriers and competition with other worthy drug candidates.

Targeting the Warburg effect in cancer is a pretty cool idea that I'd like to see tested comprehensively, but there is just a hell of a lot of competition out there, with most decisions made by business/marketing folks, not always the docs and scientists.

4. Lastly, there was nothing stopping the investigator from patenting the idea of using DCA to treat cancer. I know someone who is doing just that for a use of a drug that's FDA-approved for treating something totally unrelated to cancer.

Exactly. Just because the compound can be synthesized cheaply doesn't mean the drug has to be sold or dispensed for next to nothing. The use in human patent will make it attractive to drug companies just like several other antineoplastic agents that are dirt cheap to make.

Nitrogen mustard is still used to treat certain cancers and it's pretty simple and cheap to make.

When you see a ridiculous title from some who should know better, you should consider that it might just be a joke...

At this point, whenever I hear anyone use the phrase 'Big X', I mentally substitute "the devil". There is never a loss of meaning.

Anti-stroke drugs are another example of drugs that have shown promise in in vitro experiments and in animal models yet, were unsuccessful in human clinical trials. In regard to the involvement of energy metabolism in a disastrous disease such as cancer, your readers might be interested to know that there is evidence that the mecahnism of other diseases, notwithstanding their genetic basis, involves altered energy metabolism (Alzheimer's disease and Parkinsonism, to name two).

Orac,
When I read this newspaper story, I immediately wondered what was stopping physicians from prescribing this med off-label to their cancer patients. Since the safety is already known, is there anything stopping them? Besides the fact that they would only obtain anecdotal evidence on way or another, I guess.

Orac -- you, of course, are familiar with CRISP, the online search application for information on NIH-funded research, but it may be new to some of your readers. I note that NCI is funding 171 studies related to mitochondria and cancer; this is hardly an overlooked area! Interestingly, the only specific mentions of dichloroacetate in all of NIH are environmental health studies looking into the mechanisms of its toxicity. No; it is not "harmless" in the broadest sense.
Bottom line: NCI is very interested in studies of mitochondrial activity in cancer, and it looks like dichloroacetate is wide open -- so PIs, start your engines!

If DCA anti-cancer action is mainly via its ability to activate a dormant mitochondrial K+ channel, then, there are other compounds more specific and less toxic than DCA that can do the same. It would be interesting and probably important to compare DCA anti-cancer activity to one or more of these compounds to find out about their efficacy and toxicity.

I was wondering why he was going private sector for funding when there are public funds available for these tests. At least, I thought there were. I'm at the University of Calgary and we hear all the time about our cancer research centre, but never really in the context of a private donor.

Maybe I just don't understand how medical testing works re: funding, but if something is promising and has press, the Alberta government will be all over it to fund as it makes them look rather good.

And this might be urban university legend only, but I was under the impression that certain sections of the university could not have corporate sponsorship, so that might also contribute to it.

I guess my mind just doesn't jump to "conspiracy!" fast enough.

ORAC:

thx for doing such an extensive review of the claims being made for DCA. Hopefully it'll get some play over there.

All this cost/profit talk has me thinking about the whole process again. I've seen quotes of hundreds of millions of dollars to get a new drug to market and I don't doubt them. My question is, is there anything we can do to make this better? We talk endlessly about the patent process and the number of patients and whether we're providing enough profit incentive to get the research done. What can we do on the other side, though? If we could lower the cost in the first place, we wouldn't have to do worry nearly about generating huge potential revenues through patents or large numbers of patients. The revenue bar to jump over and into the black would just be a lot lower. I want to make it profitable to find a cure for a rare but terrible disease, and it would be really nice if that profitability could come from a less expensive R&D cycle than from insanely high prices for an already unlucky few.

I'm really not familiar with the drug R&D industry at all, so I can't make any suggestions. Is there a way to (safely) change regulations? Can we do more to subsidize research? We subsidize domestic energy and food production in the name of national security. How do those subsidies compare to government support for homegrown pharmaceutical research? Anybody have any thoughts (he asks, knowing full well that he'll probably be buried in answers)?

Guide to conspiracy theories regarding Big Pharma (or the US government or some other powerful 'bad guy') and Disease X:

1. Big Pharma suppresses the cure for Disease X because there is no money in it for them.

2. There is no Disease X; Big Pharma just wants us to think that there is because there is money in it for them.

3. There is a Disease X, but Big Pharma can't cure it; we'd never get it in the first place if we would just (eat raw foods, see a chiropractor etc).

4. Big Pharma created Disease X, either a) as a side effect of its 'cure' for Disease Y or b) deliberately, because it wants to make more money.

If Ray thought of 'Big Pharma' instead of 'Stay-Puft Marshmallow Man' in Ghostbusters, what would they have had to fight?

The kneejerk backlash against pharma companies really irritates me. But then I would say that wouldn't I. The pharma companies have had a huge impact on quality of life, as well as length of life. Just off the top of my head, antidepressants, bisphosphonates, antiepileptics and antiparkinsonism drug have had massive impacts. I could go on and on.

Yes, 'Big Pharma' is a bit naughty from time to time. They introduce isomers that have no benefit over the parent compound (compare esomeprazole with omeprazole), and they play about with dosage forms: Tritace (ramipril) caps were withdrawn a few months before the patent ran out and tabs introduced, the same with Flomax (tamsulosin). They bring out modified release preparations that have no advantage over standard products: Cardura (doxazosin) and Cardura XL. But part of my job is to guide doctors through this maze and advise them on the most cost effective choice.

Colugo, conspiracy theory 2 does has a ring of truth to it. Of course the condition actually exists, but once a new drug is approved for it the marketing and education machines go into overdrive - I got stacks of information on restless legs syndrome from GSK once Mirapexin was approved for it.Theory 4 also has a ring of truth: corticosteroid induced osteoporosis and gastric ulceration anyone? 1 and 3 are total bollocks though.

I hope I'm on record as solidly rejecting any and all conspiracy theories claiming that pharmaceutical companies have suppressed or are suppressing new discoveries in order to protect their profits.
With that out of the way, let me gently suggest that there is a reason people find such theories plausible: it's because pharmaceutical company executives behave like unprincipled scum. From the Wall Street Journal, 03 Jan. 2007, we have an article titled "Inside Abbott's Tactics to Protect AIDS Drug." Here's an excerpt:

At one point the executives debated removing Norvir pills from the U.S. market and selling the medicine only in a liquid formulation that one executive admitted tasted like vomit. The taste would discourage use of Norvir and competitors' drugs, the executives reasoned, and Abbott could claim it needed Norvir pills for a humanitarian effort in Africa. Another proposal was to stop selling Norvir altogether.

(Chart showing US sales of Kaletra climbing from $20M in 2000 to $400M in 2005, with $500M projected for 2006)

A third proposal carried the day: quintupling the price of Norvir. One internal document warned the move would make Abbott look like a "big, bad, greedy pharmaceutical company." But the executives expected a Norvir price hike would help Kaletra sales, and they bet any controversy would eventually die down.
They were right. Kaletra sales in the U.S. rose 10% over the next two years. Some objected that the price hike made it harder for patients who needed drug combinations pairing Norvir with non-Abbott pills to get their medicine. After an initial burst, the criticism faded, partly because Abbott exempted government health plans and AIDS drug-assistance programs from the Norvir price increase.

Anyone else think there's more than Norvir that tastes like vomit here?

This is the central contradiction in the existing system for drug R&D. On the one hand, Abbott executives see sick people as a resource to be exploited by any means, fair or foul. On the other hand, without Kaletra, Norvir and the rest of the pharmacopeia, there are a lot of living people who would be dead.

Just for clarification, does DCA stand for 'dichloroacetic acid', or for 'dichloroacetate', implying that it is in a salt form, or perhaps an ester of the acid?

Troublesome Frog,

Well, we could stop doing so much of that pesky safety and efficacy testing. Don't hold your breath for that, though. The current push is in the other direction. Recent criticism of the FDA says it should be doing even more to ensure that rare but serious side effects are detected before approval.

But never fear, there's an easy solution. One that doesn't compromise safety or efficacy testing at all. We just need to get better at predicting which drugs are worth testing in the first place.

Right now, a drug that enters Phase 1 testing has something like a 10% chance of being approved. Bump that up to 30% or 50% and drugs will get a lot cheaper.

By the way, if you figure out how to do that, please PLEASE let me in on the secret. Your net worth will probably make Gates look middle class.

Humor aside, I don't know what else we can do. No doubt there are some other changes that would have modest benefits (although which changes is hotly debated). But for dramatic improvements, we either need to decrease the cost of getting a successful drug approved, or decrease the amount of money spent on unsuccessful ones. IMO, of course.

Points well taken. I may have been a bit hyperbolic in the title and content of my post (Will Cancer Panacea Go Unfunded?), but from the information from the NewScientist.com article, DCA did sound rather promising. Regardless, thank you for your comments and your post. It's easy to read something that reinforces preconceptions and jump to conclusions. I am not a doctor or a scientist, nor am I intimately familiar with the process of testing and bringing medications to market. From the content of the article DCA didn't sound as though it was going to be a profitable venture, and as such may well have been ignored by the pharmaceutical industry. You have informed me that I may have been incorrect on this count. I did however state that I believed that DCA would receive public funding, and if it is promising it certainly should.

That said, my point was not to make DCA out as a surefire cure for Cancer, nor was it to raise expectations of some miracle drug. Rather, it was to highlight some of the problems that exist today in the development and distribution of useful and important drugs, and to point out that profit motives for big corporations is not always a positive force.

I will admit that I am rather reflexively distrustful of big corporations, not because I think they're inherently evil, but because they are largely amoral constructs, whose purpose is not to serve the public good, but rather to generate profit. This is certainly not all bad; we know that corporations help drive the economic engine of the US and provide both goods and services for public consumption. But they do not make decisions based on what is good for the nation or the world at large, instead they make decisions to make money and please their shareholders. In the case of pharmaceuticals this can have some negative consequences, including unprofitable drugs being ignored, drugs being rushed to market before adequate testing has taken place, or drugs being priced at too high a level for people who need them to afford them.

Finally, while I am not wholeheartedly opposed to alternative medicine, I am by no means an "altie." I place a great deal of importance on the development and distribution of medications which will serve the public. It is for this reason that the article on DCA caught my attention in the first place.

Renee, they are the same.

Lucas McCarty: "If Ray thought of 'Big Pharma' instead of 'Stay-Puft Marshmallow Man' in Ghostbusters, what would they have had to fight?"

The familiar 'fat cat'?
http://www.newstarget.com/019956.html

As much as I enjoy making fun of conspiracy theorists, I have to admit that there are small elements of truth to some of the recycled chestnuts I listed, as UK Community Pharmacist points out.

When you see a ridiculous title from some who should know better, you should consider that it might just be a joke...

It sure didn't sound like a joke to me, Ezra. Look at what your first words were after your ridiculous title "Objectively Pro-cancer":

Digby lights on the sort of story that makes my blood boil:

So the title's a "joke" but you're outraged enough to say that the story "makes your blood boil"? Sorry, I don't buy it. You said something stupid, and I called you on it. Just admit it. We all screw up every now and then and put our foots in our mouths, so to speak.

Two points:

1) It's possible to criticize our current drug development system without indulging in conspiracy theories. I thought Matt XIV, a commenter on my post, really nailed the problem: "This is a major blindspot of the incentive structure of the patent/FDA approval system. If you can't patent the compound, it is often impossible to make a profit on it after the expenses of clinical trials. DCA as a compound may be cheap, but DCA as a drug is expensive, because it isn't considered a legit drug until it goes through clinical trials, which aren't cheap whether the money is recouped by charging monopoly prices for the finished product or collected via taxation." I don't expect pharm companies to fund drugs that aren't lucrative or potentially profitable. However, unless the system is fixed, promising treatments (like DCA) will end up being ignored because they are too cheap. That seems nonsensical. We shouldn't make it more difficult to fund clinical trials for less expensive medicine.

2) It's possible to talk about possible cancer drugs that seem promising in rodents without engaging in a celebration of "woo," as you like to call it. As I noted in my blog post, "Chances are, of course, that DCA won't turn out be a miracle cure. (This isn't the first anti-cancer drug to look great in the lab, and it won't be the last.)" If you want to have a serious discussion about the state of research and drug development then I suggest you stop labeling all who disagree with you as conspiracy mongers who peddle false hope.

Thanks for doing this post. I've had something very similar in the works for a few days now, but Movable Type troubles behind the scenes have kept me from posting.

As someone who has been earning a living doing oncology drug discovery, I can tell you that this is a very interesting idea - and is nothing more than that until it gets into humans. Which, as you point out, it most certainly can, considering it's already used in humans for other indications. More when I can get it onto my site!

Thanks for posting a very interesting and informative article! I don't think "Big Pharma" "suppresses" cures, but the disconnect between the social benefit produced by cheap treatments, vaccines, etc., in the form of reduced mortality and morbidity, reductions in lost economic productivity, etc., and the relatively low levels of profit derived from their sale proves that we cannot rely exclusively on the private market to develop new treatment and therapy strategies.

Jonah:

Three points (because when you're as long-winded as Orac always is, two is never enough):

1. I didn't once use the word "woo" in this post. I did, however, point out that some of the bloggers ranting against "big pharma" on this on this were clearly exhibiting magical thinking that is bordering on altie-like, if not already there, Read the specific posts that I linked to (particularly Digby and akaoni) if you don't believe me. I stand by my characterization. And, no, I am not labeling "all who disagree" as "conspiracy mongers peddling false hope" and tried to be specific in picking my targets, restricting my "insolence" to some egregious examples of specific bloggers who are guilty of that. In addition, my comments were so vociferous because I really believe this sort of thing is harmful. Again, I stand by everything I wrote in this post.

2. You were pointedly not one of the bloggers mentioned as demonstrating that magical thinking, although I did take you to task in the comments of your own blog for repeating the half-accurate factoid that it would take "hundreds of million" dollars to test this drug in humans. At the risk of irking you again, though, it is hard not to remind you that you did entitle your post "When promising cures are ignored" (emphasis mine), not "When promising drugs are ignored." Whether that was just sloppy on your part or done in order to tweak, it did catch my attention. In any case, DCA is almost certainly not a "cure" and is certainly not being ignored; it's getting more attention at the moment than just about any anticancer compound I can think of. In any case, I only mentioned that I had learned of the story through you (and some readers) at the very beginning of my post in order to send a little traffic over to a fellow ScienceBlogger. You seem to have taken this a bit more personally than is warranted.

3. Nowhere did I say that it isn't possible to talk about promising cancer drugs that work in rodents without engaging in a "celebration of woo" (a term, again, that I did not use in my post or in either of the two comments that I left on your blog). In fact, my main objection to the sort of spin being put on the DCA story by the Kos diarist, Digby, et al is that it is unproductive and muddies up the very discussion you want to have about problems getting pharmaceutical companies interested in drugs that aren't patented and therefore have little profit potential. In short, it generates a lot of heat and no light. Quoth I:

I'm not in any way saying that it isn't a problem that drug companies show little or no interest in potentially promising new compounds that they can't patent. It can be a problem, just as "orphan" drugs often don't make it to market because there aren't enough patients who could benefit from the them to make it profitable for drug companies to invest in developing and marketing them.

See? I acknowledge that it there is a problem with the incentive structure for developing new drugs. And here's me explaining why the blogosphere's take on this story irritated me so much:

What irritates me about the hysteria some bloggers are whipping up over this is that it is at its heart basically paranoid conspiracy mongering, and the reason this story has any legs at all is because people are inherently distrustful of big pharma. There are some good reasons for this and many reasons that boil down to little more than an inherent distrust of big corporations.

[...]

What is most pernicious about the conspiracy-mongering stories being spread about DCA is that it builds false hope. People with cancer hear about this drug, and they think there's an amazing cure out there that's being withheld from them because of the greed of big pharma. That's a very distorted version of the true situation.

[...]

Yes, it's very easy and satisfying to take this promising preliminary study and build from it a conspiracy theory of evil big pharma "keeping cures from the people." It's just not very accurate and it adds too much heat and noise to the debate over the real shortcomings in our system of developing new drugs that make drug companies reluctant to pursue research on drugs that show promise but little profit potential.

I realize that I may be a tad on the blunt side sometimes, but I think you're over-reacting.

Derek:

Thanks for chiming in. It's good to hear from someone actually in the business. (I'm in academia.)

"Read the specific posts that I linked to (particularly Digby and akaoni) if you don't believe me. I stand by my characterization."

Orac, I can't agree with you here , particularly on your slagging off of Ezra.

Proving a drug's safety and efficacy takes $$$. Not as much as the numbers the pharma industry throws around (which come from two academics at Tufts: basically, they're are economic costs [i.e. including expected return on investment] counting in discovery overhead and failures, not accounting costs for one specific drug). A pharma company CFO is *required* by fiduciary duty to get a return on capital for their shareholders. They can't get the requireed return on investment. It isn't a question of individual morality of the CEO or CFO or any conspiracy here.

Now, it's not out of the question the non-patentability could be worked around given that a pharma company, with smart medicinal chemists like Derek, could derivatize DCA to both improve it and make it patentable (a methyl group here, a phenyl group there, and soon you're talking real money). Or a synergistic patentable co-formulation could be found, analogous to the augmentin antibiotic.

But there is a structural problem with developing non-patentable molecules as drugs, and with developing drugs for diseases with small patient pools ('orphan drug' incentives aren't sufficient). A possible solution might be to have a non-profit fund the drug, or have the government have [smaller] firms bid on a contract to develop the drug, using CRO's for the clinical trials and relying on the generic drug makers to pick it up once it went through Phase III. We do have potential policy levers to solve this problem (although the DHHS's experience sponsoring vaccine development in Project BioShield doesn't give one hope on its effective execution.)

Orac, you write: Lastly, there was nothing stopping the investigator from patenting the idea of using DCA to treat cancer. I know someone who is doing just that for a use of a drug that's FDA-approved for treating something totally unrelated to cancer.

I'm confused by this, and would like you to expand on it... My understanding of the patent system is that you can patent an inventions, but you can't patent an "idea". To give an example from the high-tech world, if you have a patent on an algorithm, you can't restrict people from describing that algorithm, but you can stop them from selling computer software that uses that algorithm with a license from you.

So how is a patent on the "idea of using DCA to treat cancer" supposed to work? As long as it's legal to sell DCA without a license from a patent holder, and it's legal for doctors to prescribe it, how can a patent holder get royalties when a doctor prescribes DCA for a patient with cancer?

What I can imagine is getting a patent on a particular treatment that has DCA as part of the treatment... Maybe the researcher finds that you need to use it with a different drug to be safe and effective, and patents the combination. If one then takes this combination through clinical trials, only the combination would be available by prescription, and the inventors would be assured of their royalties.

But my understanding of the patent system is that treating new conditions with old drugs is not protectable with a patent. Am I wrong on this?

The researchers did, in fact, file a 'use' patent:
more on DCA

Today there are thousands of pets dying from CANCER! Let's try DCA on them in the hope that they may live. This could speed up the approval process for human trials.

Bill Oldknow, I agree. That's actually the reason I'm browsing these sites to get a fuller picture of the efficacy of this DCA treatment for possibly my dog suffering from cancer. DCA seems like a safe treatment as an alternative to chemotherapy.

However, I'm going to try to find out more. This blog doesn't explain much with vague unscientific negatives such as the following statements:

- "However, remember the saying: "If it sounds too good to be true, it probably is." Well, it probably is in the case of DCA."

- "They are not miracle cures, and I'd be willing to bet that DCA isn't, either."

What role does "probably" or "bet[ting]" play in an objective blog? None whatsoever, unless the article is biased. It's really deceptive to claim to be a science blog ... However, as a reader, I do appreciate the effort in providing an alternative perspective, even if it is biased, as it provides me another data point.

As for the defense of pharmaceutical corporations ... I have personally stayed away from all forms of drugs for the last decade or so with no ill effects. I think it is more than possible to avoid these drugs if a healthy lifestyle is substituted. These pharma drugs are for profit NOT necessarily for health since there are inexpensive, safer alternatives available. These pharma drugs are probabilistic ventures into our health; seems like more a risk than its worth. However, it probably provides a job support structure for all those NIH research applicants out there and provides an appearance of validity for the pharmaceutical corporations.

Arun,

Give me a break. You cherry picked two statements from a very long post and then dismissed them as "not scientific." In actuality I explained exactly why caution is warranted, after summarizing the results of the reported research and how DCA is thought to function and correcting misinformation that's being spread about how much it would cost to do the next clinical trial necessary to demonstrate DCA's efficacy. Long is the list of drugs that seemed to be almost miraculous cancer cures in mice but failed in humans. It is possible that DCA may be just as miraculous as it's being billed as. However, based on my experience doing cancer research and studying antiangiogenic compounds, I tell you that it's far more likely than not that it is no miracle cure.

As for your comment that big pharma "provides a job support structure for all those NIH research applicants out there and provides an appearance of validity for the pharmaceutical corporations," well, that's exactly the sort of conspiracy-mongering I was talking about in my post. By the way, perhaps you could "educate" me as to the "inexpensive, safer alternatives available" to treat cancer. DCA may turn out to be just such a thing, but I'm unaware of any cheap "alternatives" that are as efficacious as the combinations of surgery, chemotherapy, and radiation. I (and pretty much every doctor that deals with cancer) wish there were such "alternatives." In any case, here's your chance to shine and teach us all a lesson.

Peter K, I checked the official U.S. patent office website, the For Dummies website, and other websites for more information and found out that the U.S. has 3 basic patent types: utility, design and plant. The most common kind and the kind which I think applies to drugs is the utility patent. SCOTUS has also, apparently, extended patents in other ways, to include other (non-plant) living organisms.

I couldn't find any information, even on Canada's patent website, on "use patents." Perhaps they're known by a different name or perhaps it's because searching with "use" returns a million unrelated results.

Could someone in the know clarify this? Also, like Alex R questioned, how could something like this be enforced regardless of jurisdiction beyond perhaps advertising? FYI, I think the "no ideas" thing only applies to copyrights, not patents.

I have a Google Alerts set for DCA and this is the best and most complete series of blog posts that I have seen.

In the face of hopig for miracles, it is important to be realistic in ones expectations.

I am not sure what patents they might or might not have. None are evident at http://patents1.ic.gc.ca/intro-e.html

I was curious about one thing. I have seen DCA refered to as Sodium Dichloroacete also. Is this the same as what is refered to in the article or is it a variation?

Phil

Would like to point out the chemotherapeutic drug DFMO which acts as a depressor of the ODC enzyme,which has a key role in the Synthesis process of Polyamine molecules.
The drug showed very promising results at the the in vitro stage but did poorly at the human experimental stage. big disappointment.

I would also like to suggest that you write a post about the polyamines molecules. this important molecules receive little if any exposure to the public eye(though I'm sure most of the public couldn't care less).

It's pretty easy to believe that money is more important than human lives to many powerful entities.

If we pretended for a moment that we lived in a world without Cancer and AIDS, the money that would be lost would certainly be in the billions, a number that would be out of touch with the average individual.

The sad part is that while no cures have been found that I know of, there are scientists that have created much better treatments than chemotherapy with exponentially higher success rates, keeping cancer in remission while giving a better quality of life - and you'll never hear about these treatments.

There have been doctors and scientists in jail under claims of fraud and violating various FDA laws - families destroyed and lives lost - according to law and a justice system that doesn't care if the treatment "works", only if it was processed or sold according to rules set up by the FDA.

What if these treatments were natural and couldn't be patented by a drug company?

Truth is stranger than fiction.

Peter and Nathan,

A "use" patent loosely refers to a utility patent with claims drawn either to a new use for a compound (e.g., "Use of DCA for curing cancer.")or to a method employing the compound (e.g., "A method of curing cancer comprising administering a therapeutically effective dose of DCA."). Generally, using a new compound in an old method may be patentable. You may not have found teh applications because patent applications are not published until 18 months after they were filed.

Mike stated: The sad part is that while no cures have been found that I know of, there are scientists that have created much better treatments than chemotherapy with exponentially higher success rates, keeping cancer in remission while giving a better quality of life - and you'll never hear about these treatments.

So, do you have any references where I can find documentation of the exponentially higher success rates for these treatments?

The sad part is that while no cures have been found that I know of, there are scientists that have created much better treatments than chemotherapy with exponentially higher success rates, keeping cancer in remission while giving a better quality of life - and you'll never hear about these treatments.

Do tell.

I agree with tonyl: Educate us about these treatments with "exponentially higher success rates." Oh, and intravenous vitamin C doesn't count, nor does Laetrile; neither has an "exponentially higher success rate" in treating cancer. In fact, neither of them does much of anything against cancer.

Re the type of patent called by the name 'utility' -

This is the legal term for what is commonly called a 'use' patent. There are 3 main things which must be satisfied for a use patent to be granted:

1. The item/substance/thing must have some practical application, and have been reduced to practice, that is shown by some testing to be useful in this application.*

2. It must be a novel idea, that is a new idea to use the thing/substance/item for this practical application.

3. The novel idea to use the item/substance/thing in this practical application must be unobvious to one skilled in the art of that particular field.

Which means, in this case of DCA, that this substance has the practical application of treating cancer, that it has been shown by some testing that it has utility in treating cancer (even if it's in vitro), that using this substance to treat cancer is a new idea, and that it would be unobvious to persons in fields like medical/pharmaceutical research that this substance would/could be useful in treating cancer.

Patent-wise, it doesn't matter that DCA is a substance that's been around a long time, that it's an organic acid that probably has use in organic synthesis, etc.

If there had already been any scientific papers out there by prior researchers who have worked with DCA and shown that it does/might have some cancer-fighting properties, than this would keep the Alberta researchers from being able to file for a US patent. And now that the Alberta researchers have announced publicly that DCA has promise as a cancer drug, this would keep a pharmaceutical company from being able to patent this substance for treating cancer.

If the Alberta researchers had checked to see that there were no prior publications or public presentations on DCA and cancer, then they could have filed a patent application (it can take 1-3 years for the actual patent to be granted). Only after the application could they have gone public with their findings. As it is, the cat is out of the bag, so to speak.

*You cannot patent a new, practical application of a thing/item/substance without showing by some sort of testing that it has practical value. A person can't just say, "I'm sure that DCA can fight cancer in vitro. Now I'm going to file for a patent!" The patent office will ask for proof (i.e., tests of some sort) that DCA actually has a negative effect on cancer cells.

Getting a patent is not the same as getting FDA approval to market a drug for a particular illness/condition. The patent office does not require clinical trials. However, without getting FDA approval, the drug company can't sell the drug. What patents do is protect a company from having their competitors sell the same substance/item/thing for the specified practical use, for a specified number of years.

In those blogs and stories on DCA, DCA is referred to as a drug well tested and used as a therapy for other (unspecified as fas as I've seen) conditions. Is this true?

If so, what's to stop me from getting this from my doctor regardless of trials or patents? How would a patent for a drug already in use for other condition(s) be applied to its use for cancer(s)?

Thanks.

The sad part is that while no cures have been found that I know of, there are scientists that have created much better treatments than chemotherapy with exponentially higher success rates, keeping cancer in remission while giving a better quality of life - and you'll never hear about these treatments.

Kevin Trudeau, ladies and gentlemen. He'll be on your 2 a.m. informercial all week. Be sure to buy two copies of "Natural Crap That Doctors Don't Know About Because It's Bogus" and receive a free membership to his equally bogus "Natural Crap" website.

There have been doctors and scientists in jail under claims of fraud and violating various FDA laws - families destroyed and lives lost - according to law and a justice system that doesn't care if the treatment "works", only if it was processed or sold according to rules set up by the FDA.

Kevin, let me make this clear. People who got busted by the FDA for selling bogus cancer drugs were busted because their drugs were bogus. If the Hoxsey therapy or laetrile actually worked on cancer, the drug companies would've found a way to make money off it. But they don't work, so they can't. You don't get to violate the law because you think your magic drug works, and you don't get to circumvent the standard of care in medicine because it's keeping you from your profitable work.

Why do you even bother arguing with him? As much as he concerned,you may very well be a part of the conspiracy :P

Isn't it possible to develop this using an open/free source approach?

Like in Linux, Oscar (the car) or Free Beer, for instance.

This looks like the patent (application):

http://www.wipo.int/pctdb/en/ia.jsp?IA=CA2006/000548

Its presumed "toxicity is predicated mainly on data obtained in inbred rodent strains administered DCA at doses thousands of times higher than those to which humans are usually exposed" (http://www.ehponline.org/members/1998/Suppl-4/989-994stacpoole/stacpool…

Off label use is a tricky thing. There needs to be some kind of general consensus before it would be commonly used for something it is not approved for.

Pharmaceutical marketers seek out early adopters when they launch a new drug. These are usually Key Opinion Leaders (KOLs) who set the trail for others to follow. Without that push and pull, the early adopters need to take the lead themselves.

In a case like this, it will usually follow the publication of (case) studies that show benefit. It could also be that some KOLs starting using it and word of mouth spreads. Lord knows that there are likely enough people who would be willing to take a chance.

The thought in the back of the minds of those who follow would be that if ever brought to task, they could point to some body of understanding that would remove at least some of their liability should an adverse event occur.

Renee, thank you for the response. Are you a lawyer? I ask not out of insult, but because issues like this tend to be complicated (in terms of understanding all the specific precedent--not just word of law) and generalized descriptions don't help much without the guidance of an expert who knows how it really applies in a specific case. I am curious to see such a patent is/would be even valid in the first place, but mostly I'm curious about the enforcement aspect (ala off-label use).

I tried asking in one particular forum with lawyers, but they didn't seem to know much about it. I'm too lazy, but someone could perhaps try asking on lawyers.com.

The main thing about this that makes me doubt the patentability is that it would seem virtually impossible to enforce (and IIRC continued enforcement is a criteria to keep a patent valid), so even if the courts would uphold it initially, it would crumble if they didn't do anything to thwart violations.

Phil Monk--I don't know about Canada, but in the U.S. a doctor is not legally required to have any kind of consensus to prescribe for an off label use. The only regulation I know of in this regard is that the pharmaceutical company can't advertise/endorse a new use without FDA approval.

This is why I can't conceive of how it would be enforced, especially because a doctor doesn't even need to specify on the prescription what it's being used to treat.

So what does prevent a U.S. doctor from simply prescribing it off-label?

Hugs and cinnamon buns,
Nathan

Orac,

I appreciated your comments on the DCA paper, and I understand your skepticism, but there is no reason for including these unscientific statements in an otherwise informative article. Maybe you have to deal with crackpots on a daily basis, but I still don't agree with dismissing an idea without full understanding (I consider that unscientific). Personally, I don't care about all the false miracle drug cases out there; but I do care about DCA since it seems scientifically plausible.

As for my statement regarding safer alternatives, it is not for cancer (that's too late). It's regarding the obvious alternative of leading a healthy lifestyle. I feel there's far more emphasis on curing rather than prevention, and I believe that has more to do with profit. For me it seems obvious. Long time ago, I used to conduct microbiology research as an undergrad on the natural mechanisms of fever, but apparently this area wasn't very well funded because it doesn't provide an incentive to the profitable industry or to NIH. I ended up switching my major to physics which I found to be far more objective.

It's ridiculous how NIH is driven by industry. Other government agencies suffer from the same problem, so it's not just NIH. Far too often do I hear people either selling their own research or disparaging other people's research; it seems like a big marketing game ... maybe I'm wrong ... I doubt it.

Jumping Jesus on a pogo stick!

"Dismissing the idea without understanding it"? I read the article and thought the science as highly interesting--and said so! That's hardly "dismissing" the work in the paper. I merely put things in context and pointed out that DCA was not a cure and probably won't do nearly as well in humans. That's hardly "unscientific," given the relatively low rate of drugs that work in mice and work as well in humans. That's hardly "unscientific" or "unskeptical."

What I was "dismissing" was the misinformation and conspiracy-mongering, and I explained exactly why I considered it such. As for whether there is insufficient emphasis on prevention over cure, that is mostly irrelevant to the discussion of this particular drug, which is intended as a treatment/cure.

Off label use is the same in Canada as it is in the US.

But how does Dr. Joseph Average use DCA? At what dose? For how long; only as long as the chemo, or should it continue after the chemo; or only after the chemo ends? Should it be used daily or pulsed? One could go on ad infinitum.

The point is that there needs to be understanding among the average treatment community on how to use it based upon the experiences of the leaders of the community.

It's totally off-topic, but as a former PET researcher, I just had one point of clarification based on your comment:

"Indeed, increased glucose metabolism resulting in increased avidity in taking up glucose is the entire basis of positron emission tomography (PET scans)."

I have to disagree. The basis of PET is the labeling of interesting compounds with positron emitters and the ability to measure accurately, in 2 or 3D, the source of the photons emitted from a positron annihilation event.

The connection between glucose metabolism and glucose uptake is, indeed, the basis of 18-Fluorine-2-Deoxyglucose (FDG) pet imaging of glucose metabolism and can delineate high-metabolism cancerous areas. I believe that 15-O water can also be useful as it maps blood flood and shows highly vascularized tumors (c.f. that part about angiogenesis and tumors).

So yes, PET is interesting for cancer studies, but it has uses way beyond cancer (e.g. dopamine D2 ligands such as 11C-raclopride) and its "basis" is certainly not metabolic imaging, even if that was the first application. Its basis is some fairly simply underlying radiochemistry and computer algorithms that make it work.

Keep fighting for the truth!

Alright, alright, I should have said the "basis for the ability of PET scanning to detect cancer" or something like that. ;-)

Anonimouse,

I don't know much about Kevin Troudeau - I only know those things that myself and my family have experienced first hand.

Why is it so easy to believe that companies profit from war and destruction but so hard to believe that people are kept from being as well as they could be for others' financial benefit?

Why is it so easy to believe that companies profit from war and destruction but so hard to believe that people are kept from being as well as they could be for others' financial benefit?

Because businessmen are quite smart; keeping secrets like that are HARD. Much harder than you seem to think. Other corporations, other large businesses, other smaller businesses can put pieces together and figure it out.

And from the other end, it's usually more expensive to keep such things secret (at the level they need to be in order to to keep the conspiracy effective) and generally isn't worth the problem.

In the US you can patent an invention for up to a year after it has been publicly divulged. This is not true in the rest of the world, with possibly a very few exceptions (Phillipines?).

Why is it so easy to believe that companies profit from war and destruction but so hard to believe that people are kept from being as well as they could be for others' financial benefit?

Maybe because I have a much easier time understanding how a Halliburton executive could keep his son out of Iraq than how a Pfizer executive could keep his daughter from getting cancer.

Remember that there are lots of non-Big-Pharma major economic players who would seriously benefit from a major reduction in the cost of medical care. Their collective economic clout greatly exceeds that of Big Pharma. A good conspiracy theory doesn't require most of its wealth-mad participants to act against their own economic interests.

It's the insurance companies who are paying those high prices for drugs. The billion dollar organizations have enough clout to get testing done. They could fund it themselves.

Just think of how DCA could, if it turns out to be what we all hope it is, reduce medical costs and keep people alive longer so they'll pay medical premiums longer. This is a potential windfall for the insurers that they will not let go by.

1) Read the book "The Hidden Story Of cancer by Brian Peskin, 2006.

2) Big Pharma is good and bad. Now if they would stop making some "bandaid" drugs and get down to the root cause of the problem they'll find that they can't change it because the root problem is in our poor food supply and in the 50,000+ chemicals created that pollute us.

3) Many answers are simple but sometimes the eggheads can't help but trip over their IQs looking for their brilliance in a solution.

4) Big Media won't tell all the news because big media gets a ton of money from BP. Here's an equation that is used 1,000s of times a day. M=PIC...Money = Power, Influence and Control.

5) Health is big money and to keep the big money flowing it just makes sense to keep as many people popping pills on a monthly basis as possible. And if you need more revenue, one tactic is to change the "healthy range" of whatever so you can increase the population that "needs" to take your bandaid drug. Statins (which are proven to be close to useless) comes to mind...hmmm...me thinks its time to change the "healthy range" again 'cause my coffers need a fill'n.

Health should always come before money.

"But it hasn't been tested human", LOL!

Its already used on humans for other things! There is no reason to not start testing...

Why is it so easy to believe that companies profit from war and destruction but so hard to believe that people are kept from being as well as they could be for others' financial benefit?

Ah, the "big conspiracy" theory.

The reason that can't work is simple - too many people would have to be involved. Public health agencies, government regulatory bodies, medical professionals and big Pharma would all have to be working in relative concert. And historically, all four of entities are too busy beating up on each other to pull something like that off.

It's far easier to pull a string here and there to move a cushy government contract to the "right" vendor than it is to systematically keep people unhealthy.

1) Read the book "The Hidden Story Of cancer by Brian Peskin, 2006.

Is he related to Kevin Trudeau? Maybe you should get together with Mike and form a woo comedy team. ("one of these homeopathic remedies is not like the other, not like the other...")

2) Big Pharma is good and bad. Now if they would stop making some "bandaid" drugs and get down to the root cause of the problem they'll find that they can't change it because the root problem is in our poor food supply and in the 50,000+ chemicals created that pollute us.

Yeah, because our food supply a hundred years ago was so much better - you know, before refigeration and a clear understanding of bacterial contamination. Next you'll tell me that the Hunzas live to be 200 years old or other such nonsense.

3) Many answers are simple but sometimes the eggheads can't help but trip over their IQs looking for their brilliance in a solution.

The answer isn't simple. Reductionist thinking like yours wants to MAKE it simple so you, excuse me, Brian, can easily sell books and diet plans.

4) Big Media won't tell all the news because big media gets a ton of money from BP. Here's an equation that is used 1,000s of times a day. M=PIC...Money = Power, Influence and Control.

Yeah, because Big Media really backed off the Vioxx story. Big Tobacco used to throw tons of money at Big Media as well - however I remember the tobacco controversy was covered pretty regularly. What a horribly, stupid argument.

5) Health is big money and to keep the big money flowing it just makes sense to keep as many people popping pills on a monthly basis as possible. And if you need more revenue, one tactic is to change the "healthy range" of whatever so you can increase the population that "needs" to take your bandaid drug. Statins (which are proven to be close to useless) comes to mind...hmmm...me thinks its time to change the "healthy range" again 'cause my coffers need a fill'n.

Perhaps there's a germ of truth in that. But in other cases, there's statistical evidence that shows that additional subgroups of people ARE helped by those drugs.

If you think DCA is a magic cancer cure, you might be disabused by searching for 'DCA neurotoxicity'.

According to this paper, "Dichloroacetic acid (DCA) is commonly found in drinking water as a by-product of chlorination disinfection. It is a known neurotoxicant in rats, dogs, and humans."

So the same people screaming that DCA is being ignored by Big Pharma are probably the same that are screaming about toxins in drinking water.

Their suspicions may not be grounded in this particular case (i.e. DCA may not be the silver bullet that could cure cancer) however general distrust of the medical and pharmaceutical industries that underlies these suspicions has very solid grounds: receiving institutionalized medical care as currently practiced subjects one to risks of infection and medical error that are huge, with studies suggesting that 40,000 - 90,000 people in the U.S. die (and many times that number are seriously debilitated) due to side effects of drugs and preventable medical errors. Look into 'iatrogenic disorders'. Here is a wikipedia article based on reports in IOM and JAMA, two peer-reviewed medical journals.

I never get why people think the onus is on "Big Pharma" to pay for clinical trials for such "they can't make any profit on them" drugs.

Although it might be true that "Big Pharma" isn't funding such trials (or at least, for the sake of argument, suppose it is), it's equally true that the people complaining about it aren't paying either. That is, they're just as much to blame. There's nothing stoppping them from raising money for the testing, either.

This kind of discussion frequently makes me laugh. Orac, thanks for attempting to bring some critical examination to the hysteria.

I've worked in pharmaceuticals in various jobs since 1981, and from what I've seen people have no idea how complicated it is to bring a new drug to the market. I have seen industry articles on pharmacoeconomics (which, by the way, are included in many or most applications for drug approval). One that particularly struck me was a study reporting that line extensions (new doses or other modifications to existing drugs) were noticeably more profitable than new drugs.

There are many parties worthy of blame in our system of bringing drugs to market, but I'd like to suggest you devote some thought to a couple of them.

First, the Waxman-hatch act that essentially created the generic drug industry. Why is this? Because it gives a fixed period of time in which profits can be made from a new drug. Most people don't understand what is actually involved here. What this act permits is the filing of an ANDA (abbreviated new drug application) that references the safety and clinical efficacy data from the original product.

In college they call that plagiarism and kick you out. In the entertainment industry, the RIAA or MPAA comes after you. For perspective, consider that the current life of a copyright has been extended to almost 100 years. Is Mickey Mouse worth more to our culture than an effective safe drug? Our current laws say so. The relatively short patent life of drugs simply amplifies the effect of corporate greed.

Another culprit that escapes attention is the public. Yes, I mean all of us. Most especially, our elected representatives who are given plenty of attention and news coverage when the criticize the FDA. Whoops, where did that come from? Quite frankly, I'd estimate that half of the cost of getting a new drug to market is regulatory. Worse, the ongoing regulatory cost of keeping a drug on the market is probably higher than fifty percent. There's not enough room here to detail what it takes to keep a drug on the market. If you're curious, research what DDMAC is. (Hint, it's a division of the FDA)

Wait a minute, what do public and government criticism of the FDA have to do with regulatory costs? Why, each public flogging of the FDA over some real or imagined failure gets translated into tighter restrictions on all drug manufacturers whether they need it or not. That's right, remember the Tylenol scare a few years back? It wasn't just the OTC drugs that wound up with safety seals.

Unlike most corporate manufacturing environments, FDA regulated industries really are on a tight leash. While firms that have established good reputations might get somewhat relaxed treatment, it's only by being even more restrictive internally. Why is this? Remember with a fixed time window in which to harvest profits from a new drug, even a week's delay in drug approval is worth millions. Most corporations abhor risks, and risks are frequently mitigated by throwing money at them. After all, it's just another cost factor.

Someone previously asked me if I'm a patent lawyer. I'm not; I'm an industrial chemist, but I've been involved in patent issues with some of the chemicals I've worked with, so that's where my limited knowledge of patents come from. ( Please be advised of my limits!)
That being said, I'd like to use an example of a drug called Neurontin (generic name is gabapentin), and how it's history shows the interplay between patents and FDA approvals. This drug is now made by Pfizer, who bought Warner Lambert, the originator of Neurontin.
The first patent for gabapentin was issue to Warner Lambert in 1978 or so, and it claimed it could be used to treat epilepsy. This is original medical condition that won FDA-approval for Warner Lambert around 1993. However, over the years, Warner Lambert had also been patenting gabapentin for other conditions, using a variety of evidence such as:
1. US patent 5,084,479 - "Novel methods for treating neurodegenerative diseases" (Parkinson's, ALS, etc). Claims based on studies on rat brain neurons.

2. US patent 5,025,035 - "Method of treating depression" Claims based on case reports of patients, while taking gabapentin for epilepsy, felt less depressed.

3. US patent 5,510,381 - "Method of treatment of mania and bipolar disorder."
For this one, I've quoted the following claim made by Warner Lambert:
"In studies of epilepsy, gabapentin has been noted to reduce anger and irritability, enhance concentration, and improve decision-making abilities. These effects will be beneficial in the symptomatic treatment of patients suffering from mania who exhibit irritability, distractibility, and poor judgement. This is a novel use for gabapentin which would not be obvious to a medical practitioner of ordinary skill." I've got to say, this is a real stretch. (to read the text of the patents, go to the US patent quick search page, and type in the above patent numbers : http://patft.uspto.gov/netahtml/PTO/search-bool.html )

The above illustrate that a company does not need solid clinical evidence to claim a drug is a treatment for a medical condition; there just needs to be some evidence. On the other hand, a company must provide a great deal of evidence from clinical trials to get FDA approval to market a drug; these trials cost a great deal in money and time.

Gabapentin, under the brand name Neurontin, was approved by the FDA to treat epilepsy in ~1993, after Warner Lambert showed through clinical trials that it did indeed work to treat this condition. Over the years, however, Warner Lambert also decided to expand their marketing of the drug, claiming it could treat depression, bipolar disorder and ALS (and more), conditions for which the drug was not approved, but for which Warner Lambert held the patents.

Warner Lamber, now Pfizer, got in a lot of trouble for this. The company was fined $430 million for the fraudulent marketing. See "fda.gov/fdac/features/2004/404_wl.html".

What I'm trying to show is that for a company to successfully sell a drug for a condition, they must have both FDA approval to treat that condition with the drug, and the company must have a patent that claims the drug is a treatment for that condition. The latter is necessary to keep other companies from also marketing the drug for that same condition. And this is why it's a big problem once a patent for a successful drug expires. At that point, other companies can legally market the drug for its FDA-approved condition(s).

With respect to DCA - right now it is not FDA-approved to treat any condition, which is why you can't go to a retail or hospital pharmacy, and get it. It is in clinical trials to treat a rare disorder that causes lactic acid buildup; if you google for 'clinical trials dichloracetate', the trials will come up. Please note, one of the trials had to be discontinued because DCA caused nerve damage (neuropathy) in most of the patients who took it.

To Joe above - What's wrong with safety seals? Today I opened a new jar of McCormack's Grillmates barbeque spice. It had an outer plastic seal, and an inner paper seal. I doubt this has seriously burdened the McCormack spice company.

Renee

There is nothing wrong with safety seals per-se. The point I was making is that most packaged prescription drugs never leave the pharmacy. What exactly are we being protected from? The safety benefit is marginal, while the cost is significant. Unlike meat tenderizer, the volumes on prescription medications tends to be a bit smaller, so the cost of the equipment, training, materials, etc. is spread out across fewer units.

My general point about regulatory overhead is that it increases the cost of products without any real assessment of the cost versus benefit.

You might find this example more enlightening. At a previous employer, we filed an ANDA for an oral solution product. One of the significant points about the formulation was that it was completely non-aqueous. The formulation (can't discuss specifics) used a liquid similar to sorbitol for the vehicle. When the review letter came from the FDA, it asked why we did not include a pH test for release.

On the one hand, this is completely absurd. On the other hand, arguing with the reviewer could easily have delayed approval, which could have ruined the economic viability of the product. Faced with this dilemma, what would you do?

The root of this problem is similar to the safety seals problem. The FDA does not appear to exercise critical thinking before asking questions...they follow a checklist. Unfortunately, the economics of our product delivery system mean that is difficult to argue about stupid questions.

Hope that more or less answered your question.

What's the big deal about doing a pH test? It takes a minute. You do it with something called a pH meter, an instrument that's been around since the 1930's.

I used to work for a detergent company, studying dishwashing detergents. We had to moniter the pH, because these solutions come in contact with the skin. Anything above pH 8 or so could be a problem, since above that value, the detergent could start to hydrolyze skin proteins. We did the pH readings on the concentrated detergent as sold, and dissolved in water, as would be used in a sink full of water.

I'm not clear about your reference to using something like sorbitol to make the oral solution you mention above. Sorbitol is a solid sugar, melting point 98-100 degrees C. If you were using a sugar like sorbitol, than you would have had to dissolve it first in water, to use it as the vehicle for your new drug. Instead, do you mean that you were using glycerol? That is not a sugar, though it is a liquid.

Doing a pH test, even for a non-aqueous solution, is not so far-fetched. An oral solution will first come in contact with saliva, then the contents of your stomach, both of which are aqueous. The oral non-aqueous solution will become diluted and dissolved in water, and then in contact with mucous membranes upon ingestion. I can see why the FDA would require a pH test, probably done on a diluted aqueous solution of your oral medication.

Informative retort to all the hype - I enjoyed being lifted up by the original article to the very moment of being thrown back down to the ground with your blog :)

I sometimes wonder if the whole world revolves around Snopes half the time and am thankful that there are people such as yourself that go to a lot of trouble to dispel certain hyped up rubbish :)

...Anyone thought to call the U in Alberta to get more of the straight scoop...? Might save a lot of typing. There are people just DYING to know...

Renee

Don't need to get too out of hand for this. A pH test for initial release and long-term stability testing has nothing to do what what happens when you take the drug. This is a purely abstract physical property test.

Sorry I got distracted and said sorbitol. I did a little more digging. I meant polyethylene glycol, which is not a solid, and is not dissolved in water. There is absolutely no water in this product.

Stop and think. What is the definition of a pH measurement, and how does a pH probe actually work? Is a pH measurement with a standard electrode even valid for a non-aqueous solution? (Try this yourself, go get a jug of antifreeze and read the pH. You say you're an industrial chemist, I think you should know better than this.)

Now, the meter will certainly give you a reading. Does this number actually mean something? Further, how do you establish valid measurement limits on a meaningless measurement? Most importantly, how often will you have to recall a product (increasing the overall cost of the product line) based on nonsense? That's the point here.

Product specifications are supposed to support ongoing product quality. If the measurement does not do this, it is no longer a quality tool but a bureaucratic checklist item.

It is the extended implications of seemingly simple decisions that can spiral out of control and raise the cost of manufacturing a product without providing any real benefit to product quality. I guess I've lived with the industry long enough that it seems obvious, but it probably is not.

Every test and every specification increase the cost of the product to the manufacturer and the consumer. Specifications must be met by each new batch of product, and must be met over the shelf life of the product. Roughly 10% of the commercial product batches are tested on long-term stability. If the specifications are not met during the life of the product, the product must be recalled. If this happens often enough, it opens questions on whether the product should be allowed to remain on the market.

Does this sound like a trivial issue? That's why it's hard to explain why drugs cost so much. These kinds of issues are present throughout the entire process from development to market.

Don't get me wrong, I'm not trying to blame the FDA for all the industry's problems. The industry is one large example of the law of unintended consequences. The FDA is trying to do it's job. The industry is trying to sell a profitable, ethical, quality product. The public simultaneously wants perfect products but balks at perfect product prices. Congress tries to juggle the interests of the public and the industry that makes significant contributions to their campaigns.

Me, I just work here.

Thanks for the extra information, Renee. From information I got from a new lawyer (not an expert in patents, but still) I gather that one condition is that you need to repeatedly "renew" the patent for a new use to be valid (Neurontin was given as an example--patented in the 70s). And of course, as Renee mentioned, DCA wasn't FDA approved for general use to begin with, so it's enforceable.

As for the bottle safety measures, it is silly and probably started with the whole Tylneol/poison killer. Bottles should be protected if they're OTC, of course, but given the security measures "behind the counter" for prescription drug, what's the point?

Ok, I understand now, since one of the liquid forms of polyethylene glycol was used as the base for the drug. You are right, measuring the pH would be meaningless. Dare I ask, how was this pH issue resolved?

In case anyone's wondering, there's a fair amount of regulation of the chemical industry. Instead of having one large federal agency like the FDA to deal with, we've got a multitude of federal, state and local agencies to reckon with, some of whom have competing interests with each other. There have been projects I've worked on where we've had to contend simultaneously with the air pollution division of the EPA and the new chemicals division of the EPA (neither of which coordinate their efforts together), each of the air quality districts of Los Angeles, San Francisco and the San Joaquin valley, U.S. Customs, the Dept. of Transportation, and OSHA. Each of which could either levy fines or prohibit the sale or shipment of any of our products. And during the project, fines were indeed levied, and sales temporarily prohibited. All of these issues are magnified when trying to work with a new chemical, even if it's no more hazardous than older ones in the same class.

We've had a small development program dropped because one of our German suppliers could not figure out how to ship us a new chemical, since they would have had to deal with the German equivalent of the EPA, German Customs, the German and American Depts. of Transportation shipping rules, the shipper's shipping rules (probably DHL), US Customs, and the US EPA.

All for a chemical that was no more hazardous than polyethylene glycol.

This discussion has veered quite a ways from DCA and cancer.

May I just say that Autism Diva blogged the New Scientist article on January 27th without going all "Big Pharma hates us" or "Whoopee! a cure for cancer at last!"? :-) she also blogged "A cure for all cancers" parasitic woo queen, Hulda Clark (no relation).
http://autismdiva.blogspot.com/2007/01/cancer-depression-parasitesautis…

Thanks for all the additional info on DCA. It sure sounds wonderful. I hope it turns out to work on lots of human cancers.

I'll be honest. This article just makes you look like a sad bitter competitor in the race to make cancer drugs.

Your four points say NOTHING about the possibilities of the drug. In fact you even point it out in the first paragraph. How can you tell people not to jump to conclusions when you yourself have already done so by taking the negative?

Get over yourself, realise that you don't know everything, and if you had ANY experience in the treatment of cancers you'd know full well that some hope for cancer patients is better than little or none. People having positive mental health is a big benefit in cancer treatment - false hopes occur in ANY CASE when many of the current therapy treatments fail, and with horrible side-effects.

I find your assumptions and conclusions baseless, and even more so than the article because at least the article bases itself on a "could be" stance, rather than your blog that attempts to already disprove something not even in testing.

Also, your indifference to big pharma companies and the way they manipulate markets is almost laughable. There is not a single company that isn't share market driven, and thus at the mercy of their shareholders & board to produce results - no matter the costs. There are a massive number of recent examples of this within the US, and many other countries. I think you need to take a bit of a more careful view toward these types of companies, since they are simply economically driven, not morally or ethically driven, and many assumptions people are making about many of the larger ones couldn't be any more accurate.

You aren't god.. you don't know everything, so don't pretend to. Support all the great number of 'possibles' out there - one day, you might need one of them.

Meh -

Did you read the article? Or did you just read the title and make a lot of assumptions? Your charecterization is truly stunning - one of the reasons for this article is to cut through the bullshit, to get to the legitamate discussion of the problems with our system of drug developement. Hysterics are not going to help change things - rational, accurate depictions of the situation are essential to fixing the problems.

It is the same with people who refuse to discuss anything other than mandated single payer, as the solution to our health care crisis. All that bullshit rhetoric accomplishes is preventing solitions that will actually provide the increasing millions of Americans, with access to care.

Many of us would rather find solutions to the problems. Whining like a small child does not accomplish this. Hysterical exageration does not solve the problem. Only when we cut through this bullshit, can we begin to solve the problems.

Get over yourself, realise that you don't know everything, and if you had ANY experience in the treatment of cancers you'd know full well that some hope for cancer patients is better than little or none. People having positive mental health is a big benefit in cancer treatment - false hopes occur in ANY CASE when many of the current therapy treatments fail, and with horrible side-effects.

Uh, Meh, read these.

I do treat cancer patients. I'm a cancer surgeon. And while I agree that hope is important to cancer patients, you're wrong about false hope. False hope is what leads patients to exhaust their bank accounts going to Tijuana to visit quacks instead of making the most of what time they have left. False hope is what leads some patients to forego effective conventional therapy in favor of quackery until it is too late. False hope leads patients, when they hear the overblown hype about DCA, to become enraged because they think that a cure for their cancer is being withheld from them.

As for my saying "nothing" about the possibilities of DCA, well, I can't help but put it bluntly here: That's a load of crap. My point was simply that it's a promising drug (which is true) but that. compared to a lot of promising compounds that come along it's not that different and it's almost certainly not the miraculous "cure for cancer" that some in the blogosphere are claiming. I certainly hope that DCA turns out to be a potent new tool in our armamentarium of cancer chemotherapy, but I have no illusion that it's a "cure," mainly because we in the biz have been down this road before, as I explained in this post. Many compounds show promise in cell culture and animal studies and fail utterly in human trials, far more than the number that ultimately prove efficacious.

I am reminded of a story I heard years ago about some promising treatment for AIDS that "cured" the virus in test tubes.

The commentator or scientist finished the report by saying that we should remember that gasoline also kills the virus in a test tube (but that did not make it a promising treatment).

The promise is that this is not some far off compound in phase I studies that may or may not work, either because of lack of efficacy or because of side effects.

One would assume that there will be enough off-label use in this case so that some indication of its effectiveness, or lack thereof, will soon percolate to the surface.

Some drugs are commonly used because they offer benefit to 1 patients vs 99 who do not show any (statitically) significant benefit.

Even If it only helps a little bit, for a small group of patients, it is help nonetheless, especially for those who it will likely be tried on first.

If is does not, then at least it seems to have renewed some interest into a different way in treating cancer (Warburg's Principle), which in of itself, is a benefit. This is a complex disease that needs to be attacked on as many fronts as possible.

In terms of it being a platform for making money, there are many many generic companies out there who make considerable amounts of money selling commodity products faced with umpteen competitors.

Meh:

People having positive mental health is a big benefit in cancer treatment

Anybody who has had a friend or loved one fall victim to cancer wants to believe in the importance of "positive mental attitude." When there is so little we can do to help, we want to believe that we are accomplishing something material by offering emotional support.

Emotional support from family and friends can help when a patient is trying to find the courage to persevere through the unpleasant side effects of chemo- or radiotherapy. But hard evidence that "positive mental health" is a big benefit when it comes to prognosis is hard to come by. See, e.g. http://www.bmj.com/cgi/reprint/325/7372/1066. And the risk of offering hope associated with untested treatments is that it may lead people to abandon well-established treatment modalities in favor of ones that are less effective.

Once one has seen a few of these compounds that are miracle cures in cell culture or experimental animal tumor models come and go, it is hard to avoid developing a somewhat jaded perspective on the big cure that is always just around the corner.

One thing that hardly anybody who thinks that the drug companies are withholding or neglecting cancer cures ever bothers to think about is just how ubiquitous cancer is. Above a certain age, pretty much everybody has experienced some kind of cancer-related personal tragedy, and that includes the people managing the pharmaceutical companies and those working in the labs. So while a business must necessarily keep an eye on the bottom line (and if you've followed the business news, you know that pharmaceutical companies have not been doing so well for quite some time), I think that there are very few companies that would be able to resist the lure of a compound that might really make a big difference in cancer therapy. Besides, if you did have such a miracle drug, even if it wasn't patentable, perhaps you could figure out how it works and produce an even better variant that is patentable.

1. This drug has only been tested in cell culture and rats. Yes, the results were promising there, but that does not--I repeat, does not-- mean the results will translate to humans. In fact, most likely, they will not.

Hey I Have an Idea.

How about let me have some and I will test it on myself.
How about I can't EF-ing wait for this stupidity called big pharma, the fda and the codex. (word of mouth could solve all that beauracracy)

Worse yet, tell me how to make it, and how to use it. A regular HOW-TO DCA or DCA for Dummies. Yeah Yeah, I hear something about toxicity. Teach me not to do that, I'll be fine. It'll be on me, if I screw up, I pay the price.

Hey, now that I solved this dilema, (actually not) in 60 seconds.

How about everyone stop the bickering, back-stabbing, boasting, and lawyer /doctor and patent crapping and work on a cure for West Nile Virus. I see the god damned HORSES have a vaccine. Still not a DAMNED THING for humans. I'm ready to break into a vetranery hospital. Do you know how painful WNV is?!

DO YOU!? ARGHHHH!

Okay, now imagine, having BOTH WNV and Cancer and NO MEDICAL, NO INCOME, NO DOCTOR.

Oh that's right, you have maid service.

Okay where's the Purchase 50mg DCA button?!
Or the manditory WNV school vacinations?!

Here's an idea Invisible Death: Click on the link for the Cancer Cell paper right there in the paragraph that comes after the first block quote. Right down on a piece a paper the authors' names and the institution listed.

Then get a piece of paper and write them with your dosage questions and where the stuff can be bought. You might also want to volunteer as their first human subject.

There will be no need to place blame anywhere if funding is secured, we will just wait for the results. I must admit that I do not, with all the information that is generated via technology today, believe that big pharma is interested in anything but profits. There are many drugs that were shown effective, (Hydrazine Sulfate), to name one, where shady trials and misinformation was generated by the powers that be. Why did they test synthetic vitamin E instead of natural Vitamin E? I hate to believe what appears to be true in the case against big pharma because it undermines everything we have placed our faith and trust in. Even though we don't all have a PHD, we are mostly intellegent and full of common sense. The fact remains that if green beans end up curing cancer than I guess there will never be a cure. If the people who represent these companies, making trillions per year on our various sicknesses, are not as intent on keeping us sick as it appears, than test it all. I'm sure that if treating cancer patients everyday, watching this degrading inhumane desease take the life out of one more person with such suffering, was how I made my living then I would be sqeptical too, and with good reason, BUT WE CANNOT GIVE UP, we cannot stop hoping. So test all the promising treatments, Its not as if the scientist at the University of Alberta is a "quack", he is well recognized and trusted, and so the testing should move foreward. I shall be forewarding my installment to the University for the testing to proceed, and if it proves unsuccessful, then we wait for the next one. Polio would never have been cured if we believed that the possibilities were hopeless. People are not as weak as you assume, we don't just sit and hold our breath and believe without merit. That is why we have any trust at all for big pharma, because deep down we just want informed answers, and relied on the research that they put foreward. The outrage with DCA is that it's inability to get funding, makes us renege the trust we so innocently placed in the hands of those corporate giants. If they back away from this research, than the Canadian Cancer Society better step up to the plate. Where's Bill Gates when you need him, I'm sure he could afford to waste a million dollars. Bottom line for me is this, because of the undignified horrible months spent fighting, winning, or losing the battle with this desease, the pain, the weight loss watching someone you love just waste away,it is immperitive that every avenue is travelled down. We can deal with it if it is not the wonder drug, what we can't deal with is that the circumstances surrounding this drug and it's lack of patentability might keep it from being tested properly. Any person currently taking a form of cancer treatment has hope, at least in the beginning, to hope is to be human otherwise we wouldn't even bother with treatment. It isn't mindless hope it is just hope. Sometimes a cure is found.

Denise Julien wrote "Where's Bill Gates when you need him, I'm sure he could afford to waste a million dollars."

If you want to help decide how Mr. Gates disposes of his charitable funds then apply for employment here:
http://www.gatesfoundation.org/AboutUs/WorkingWithUs/Jobs/

Oh, actually the "outrage" with DCA are those who are jumping the gun thinking that some testing on rats is all you need to approve a drug, especially a drug that has some problems with toxicity. The "outrage" are those who want to ignore any and all safety concerns.

Y'know, with all these drugs which work so well on rats and mice, if my pet *rat* gets cancer, it's pretty much curable, right?

First, thanks for all the very informative posts! I've been reading like a madman for the last few months since I first read about DCA in the paper.

The dilemma I have with DCA is the apparent contradiction.
First, it appears that it has been used (successfully at the right dosages http://www.ncbinlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&lis…
http://www.epa.gov/iris/subst/0654.htm ) for lactic acidosis for many years.

Second, it has been shown at the U of A to have anti cancer properties on test animals

Yet, a cancer patient who has been told by their doctors that there are no available conventional treatments, that chemotherapy at best will extend their life by one month with wicked side effects and that the patient's only real option is palliative care, when that patient asks about DCA they are told that, 'it is not an approved treatment for cancer but, we will make you comfortable while you die'.

Naively, could we not offer the above patient a second option to, 'make them comfortable while they die and offer them DCA at the aforementioned safe dosage?'.

I know, it's crazy talk, I mean we'd be wasting $2 per day in chemicals! Alternatively could some chemist out there reply with the recipe or url for an oral dose (preferably cherry flavoured)?

Kam - you cribbed that from the Anti-Med/CancerWooShillers(tm) phrasebook, didn't you?

anonimouse - alas no, it is my own crazy rambling. I believe 100% in our doctors, our health care system, their ethics and the scientific approach. I have met wonderful caring people in the medical profession and in our hospital system, but when they give up, must the patient also?

I'm definitely not anti-med and hate the predators that are preying on the helpless with their snake oil, but when you're told that there is no hope, that the medical profession can do no more, I say wheel out the experimental cart and let's start mixing our own! What's the worst that could happen, it kills you? And if we stick to the heretofore mentioned safe dosage, what's the worst that can happen? Well actually nothing will happen, but that will kill you also!

PS> if cherry flavoured is a problem, banana or grape are fine!

Kam, the worst that can happen is that it makes one's passing more painful and difficult. At least clinical trials can record this and prevent others from following the same route. They also help determine the doses that work, the doses that cause severe side effects, and where the overlap begins. Just because you have the right drug doesn't mean that you have the right dose, or even the right dosing schedule.

I can see that I am very late coming to this thread, but let me say my peice.

"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."

This is very wrong, and does point to a fatal flaw. The brain has its own immune system, the Glia, which is made up of Astrocytes and microglia. They are both able to combat infections by chemical warfare, in doing so theyr release a lot of nitric oxide (NO). Now NO inhibits mitochondrial respiration, and so these cells have a robust anaerobic glycolytic pathway in operation. Indeed, you can make these (clutured) cells hypoxic for up to an hour and they survive reperfusion very well.
If you give a patient a drug that attacks the glycolitic pathway, then the brains inflamitary immune resposen is going to be compromised.
The idea of compromising the glias glycolitic pathway, by one way or another, MAY Possibly actually underlay some diseases, I thank the Blog for this post as it has given me an idea.

How will we know if we never try? Saying that it may not translate to humans simply isn't a good enough excuse. Big pharma won't pay for its trials - no patent, there is no money to be made. Delusion is your problem if you really think that pharmy companies aren't thinking (even on the surface) of their pockets.

Straw man argument. I never said we shouldn't try it in humans. Do try some reading comprehension sometime before spouting off.

What I was saying is that hyping DCA before it has been proven efficacious in humans is harmful because it very well may not work. At the very least, we do not know what doses to use against cancer (they may very well be higher than for the metabolic conditions DCA is used to treat) or what cancers it will and won't work against, nor will we know how long to treat.

That's what clinical trials are for.

If you click on some of the later links in my list of followup posts, you'll see that unscrupulous "entrepreneurs" are actually selling the stuff to desperate cancer patients to self-medicate without the supervision of an oncologist.

Interesting, but you get a bit incoherent when you start talking about alleged conspiracies.

"Conspiracy" is a easy strawman to knock down, but it's a fact that drug companies, like any corporation, are trying to make money, and they are not going to waste money testing unpatentable treatments (and good luck trying to patent the "idea" of treating cancer with DCA and selling it to them; that's exactly the sort of legal dodge that will either end up in court with the horrible publicity of dying cancer patients on TV demanding to know why they're being screwed, or people just using DCA on their own and daring Pfizer or whoever to sue dying cancer patients for doing it without paying them for the privilege).

Now, to be clear, I'm not blaming Pharma for the problem. This is just the way capitalism works, and I have little common ground with the nutters at Dkos on that issue. But that doesn't mean we can't do better. I'd like to see something like an X Prize for cancer, where capitalism and competition are harnessed and put to good use. I would also like to see terminal cancer patients given better opportunity to try novel treatments; even if they don't work, at least their death helps prove that, and thus has some greater meaning.

"What I was saying is that hyping DCA before it has been proven efficacious in humans is harmful because it very well may not work."

Well, of course it may not work; in fact, it probably won't, but that's been true of every cancer drug ever tested.

"you'll see that unscrupulous "entrepreneurs" are actually selling the stuff to desperate cancer patients to self-medicate without the supervision of an oncologist."

Horrors! Dying people practicing medicine on themselves without the benefit of an overpaid bureaucratized cartel! Next they'll be asking for the right to vote, or carry guns. Where will the madness end??

Just wanted to wrap up my thread, my Mom was diagnosed in January and was dead mid March. I guess her quality of life didn't suffer, nothing was tried, nothing was learned, except maybe for another data point for the mortality stats. The good news is the status quo was maintained, the system withstood another desperate family. Take a decade to study DCA, debate endlessly if you want, most of us are only eager for a cure when we desperatly need one.