Dichloroacetate (DCA) and cancer: Déjà vu all over again

I think we need an urgent research about the four PDK isoenzymes: which Laboratory or University is doing that? "We hypothesized that DCA may have differential effects on hypoxic versus normoxic colorectal cancer cells, and found that while some cell lines are refractory to DCAâs effects, most colorectal cancer cells examined actually displayed enhanced survival under hypoxic conditions in the presence of DCA. Consistent with this, DCA treated xenografts showed no anti-tumor effect but instead there was enhanced growth of treated tumors. Our findings suggest that DCA may have differential effects on cancer cell survival depending on the regional microenvironment within treated tumors, which may complicate its usefulness as an adjuvant anti-cancer therapy." (Sodium dichloroacetate (DCA) reduces apoptosis in colorectal tumor hypoxia, http://www.sciencedirect.com/science/article/pii/S030438351000251X ).
"Thus, although DCA inhibits growth of a variety of cancer cells, the effect and the underlying mechanisms seem to be cell-type dependent. A likely explanation for these differential effects could be the difference in expression of the PDK isoenzymes in the cancer cells examined. Dichloroacetate is a non-specific inhibitor of PDK (Whitehouse and Randle, 1973), and has a different Ki for each of the four PDK isoenzymes (Bowker-Kinley et al, 1998). In addition, the four PDK isoenzymes are known to be differentially expressed in various tissues. Thus, there is a need to develop inhibitors to the individual PDK isoenzymes that should allow cancer cell-type-specific metabolic manipulation." (Dichloroacetate induces apoptosis and cell-cycle arrest in colorectal cancer cells. , http://www.nature.com/bjc/journal/v102/n12/full/6605701a.html )

Question(?) If someone's going to die 'anyway' from the leading cause of death (cancer), then why not use DCA? I agree that avoiding 'Quackery' is a good thing in general, but it appears that medical ego's might be interferring with saving a life (?)

If something is useless [for the purpose, in this case curing cancer] and has any unpleasant effects, that's a reason not to use it. If something is useless and takes any time to use, that's a reason not to use it. If something is useless and costs any money, that's a reason not to use it. The promoters of DCA claim "hey, it's cheap," but "cheap" doesn't equal free, and why not spend the money on a chocolate bar instead?

I was recently informed that a member of my particular sport (a Canadian teammate) was diagnosed with a fairly aggressive form of Cancer & despite a variety of treatments, had progressed beyond the point of medical help.

Unfortunately, his family is now heading down the path of Homeopathy & intends to raise tens of thousands of dollars for these "treatments." I was extremely angry when I heard this, because we know those treatments aren't going to help & I know that money could be better spent being put in a trust fund for his children......that's exactly how a treatment like this hurts - because it is people spending money they don't have, for a treatment that isn't going to help them.

The problem I have with "what have you got to lose?" thinking shows that a person isn't giving thought about what they could lose. Even with a terminal case of cancer, there's still quality time that could be spent in quality time with the family, doing things you always wanted to, but could never find the time, saying your goodbyes, and arranging your final affairs.

False hope given by untested quackery eats up that precious time and drains money that could be left to the survivors. Dangerous forms of quackery can even shorten that time. Vultures feeding on desperation can cheat families out of everything they have. Quacks encourage rash desperation by speaking as if you don't have anything to lose. They don't want to you think, scrutinize, and develop genuine trust, they want you to feel cornered so that you'll jump when they tell you, no matter how crazy it seems.

Everyone is eventually going to die, and sometimes we simply can't delay death any longer. But for those who want to go down fighting every inch of the way, the rational response is to volunteer for scientific, clinical trials. Scientists test hypotheses based on plausibility, and clinical trials are designed to eliminate self-deception. Scientists want their test protocols to survive scrutiny so that doctors can be confident if they write a prescription.

Orac,

Thanks for your critical analysis of DCA. As a father of a 6 year old girl with neuroblastoma, high risk, stage 4, I understand a bit more about DCA.

What disturbs me the most about the state of affair in oncology is the lack of empathy from clinicians all over the world. Bottom line is, we (my daughter) are desperate and we want to live.

Yes there are quack cures everywhere. The reason for the existence of quackeries is due to the fact that cancer is not understood and there are no cures. If it was understood, if there were better than brutal and medieval therapies, perhaps you would not see desperate acts from the patients and those who are all too happy to take advantage of the dying.

Let me put it in another way; there are no quack cures for Polio!

Instead, I see too often physicians (Oncologists), who are too happy to shoot down questionable therapies, but less than capable of offering even just a bit of hope, let alone palatable therapy.

Would you not classify the use of Cyclophosphamide (a derivative of mustard gas) questionable? Is this the best we can do?

Physicians, please heal us!

Personally, I see the quack promoters as nothing more than distasteful opportunists. The real issue IMHO, is the failure on the part of the physicians to do better!

Yes, cancer is a hard hard disease. But human kind has overcome insurmountable challenges in many areas; It's time that you the physicians, tackle this challenge... better.

Sincerely,

Kirby

@kirby - our best wishes to you and your daughter.

There are thousands, if not tens of thousands of researchers diligently working on new treatments for combatting Cancer. If it was easy, we would certainly have a cure by now, but when battling a very complex disease, with multiple different types and reactions, it isn't going to be easy. Researchers like Orac are trying, and will continue to try - unlike the quacks who promise nothing but false hope.

"thousands of researchers diligently working on new treatments for combatting Cancer": no doubt about that, but the question is: why by the discovery of DCA for cancer, by 2007, by more than 5 years no clinical trials are executed around the World? DCA discovery is based on scientific processes and procedures, not on promises of false hopes. Of course that must be verified and this we'd like to be done.
To underline the importance of research about cancer metabolism, that involves also the DCA, I add a link to James D. Watson (Nobel Prize) article on NYT: "we may have to turn our main research focus away from decoding the genetic instructions behind cancer and toward understanding the chemical reactions within cancer cells." (http://www.nytimes.com/2009/08/06/opinion/06watson.html?pagewanted=all) and to Science (http://sciencecareers.sciencemag.org/career_magazine/previous_issues/ar…) .

Huh, very interesting. I had not heard of this "miracle drug" but I am very glad there are blogs like this available to sort through the information overload for laypeople. Good example of the knowledge vs. certainity quandry from a few days ago too.

Has it really been three years since the original DCA kerfuffle?
How time flies...

It's good to see Dave is still around! *waves*

Great review Orac!

Cluesticking it to Dave Scott...a bonus.

Thanks, nice to be able to read a good cautious summary of the latest re DCA.

Great post Orac! I'd actually missed the latest news about DCA...your post was the first to bring it to my attention.

Works very nicely as an introduction to clinical trials for cancer too.

Very interesting post. Thank you for taking the time to explain the science for us. I come for the Insolence, but love when I get to learn something new while doing so.

Fascinating science.

Wasn't DaveScot the moderator over at Dumbski's blog who used to trash negative posts? A sort of AoA for creationists.

Wow, I never knew DaveScot read my blog.

Didn't mean to put pressure on you but thank you for writing this summary and evaluation. Your analysis means much more than mine because of your own experiences as a researcher, surgeon, and clinical trials investigator.

I share guarded enthusiasm about DCA and other approaches to target aerobic glycolysis. My concern remains that DCA products of unknown quality will continue to be sold which may either contain other highly-toxic side reaction products (such as the aforementioned trichloroacetic acid) or no DCA at all as seen in the recent guilty plea of a Canadian internet marketer in Arizona. In fact, I am concerned that the promise of DCA may be compromised by some tragedy that involves a highly-toxic, bad batch of DCA sold to consumers.

Readers should also keep in mind that the five patients in this study were very carefully selected and monitored extremely closely for complications or side effects. This magnitude of oversight should not be underestimated by those seeking to use DCA in the absence of regulatory approval.

And believe me, if DCA pans out there will be no shortage of pharmaceutical companies willing to sponsor the compound for development and approval. There are several compounds in the public domain that have been sponsored, approved, and granted marketing exclusivity - take a look at what Reckitt-Benckiser did with the ancient, off-patent natural product guaifenisin, now generating millions as Mucinex®.

As halogenated acetic acids are a byproduct of chlorination of drinking water, you'd expect some level of DCA in drinking water where chlorination is practiced. Some European countries (e.g. Denmark) don't chlorinate their drinking water, so you could see if there's any difference in rates of the specific cancers supposedly affected by DCA between countries practicing chlorination and those not using chlorination.

Although concentrations of DCA in drinking water would probably be way below therapeutic levels, though.

In case any is interested in biochemistry (ugh!) I wrote up a little description of Regulating Pyruvate Dehydrogenase.

By the logic of the "big pharma" -hatin crowd, Bayer won't produce aspirin because it's off-patent.

If recycled bovine feces proved to have curative properties the pharma cos would produce it. Of course, the supplement cos would produce "all natural" BS, produced without any quantitative or qualitative controls.

Nice post. I think the cautious approach can be illustrated, as well, by looking at the early history of AIDS drugs. People with AIDS were clamoring for approval of drugs to treat their condition. FDA caved to public pressure and fast-tracked an early incarnation of AZT, IIRC. Once individuals started using it, the true risks came out and everyone realized that the drug was almost as bad as the disease, depending on the case. The AIDS advocacy groups issued statements saying that they may have been a bit over zealous and that the FDA had been correct in promoting a more cautious approach.

Similarly, there were quite a number of people promoting thalidomide as a treatment for nausea in pregnant women. However, the FDA stepped in and prevented its marketing in the U.S., after investigator Frances Oldham Kelsey refused approval, saying that more study was required. Imagine if Dr. Kelsey had not stopped its approval.

The FDA faces a very difficult balancing act. They must ensure that the products that reach the market do so with as little unnecessary obstruction and difficulty as possible, while at the same time ensuring that those products are safe and effective for the populations that will eventually use them.

I want to think about the "Big Pharma won't approve it because it can't be patented" nonsense. Now, aside from the fact that if it is promising, the NIH would have no problem supporting studies with it, so that nonsense is already moot. But more importantly, I look at the graph Orac showed and think, well, that's good, but could it be made better?

So what Big Pharma CAN do is to look into the mechanism of how DCA works (assuming it does) and build upon it. For example, instead of dichloroacetate, what about a di-thiolate? Mercapto-groups have a lot of the same properties as chlorine, but some differences that may or may not be beneficial.

Pharmaceutical industry knows a heck of a lot about the effect of structure on drug activity. DCA works by a little different mechanism than most current approaches, but that's great. It gives designers room to make modifications.

So despite the hype of DCA, it's not a "wonder drug" that is going to cure everyone's brain cancer, although it could certainly help. However, from a cancer drug perspective, the most important thing about DCA is that it provides a scaffold upon which to develop even better products. And THOSE are absolutely going to be patentable.

I'm not a drug chemist by any means, but if no-one is looking into a thioketal version, I'd be very surprised.

It IS a great article, but I think only the last bit hits davescot's real problem; namely, why we can't charge in and use DCA. Indeed he doubts the utility of proper scientific trials as compared to anecdotal private use. It's a failure to grasp the need for and function of the scientific method which isn't terribly surprising given his context. Davescot doesn't really understand how to answer "how do you know?" I'm not sure he even understands why you should ask that question.

Isn't it interesting that there is no conspiracy and DCA is getting the trials it deserves? Where is "big pharma" that should be suppressing the stuff?

Then, if it ever gets through as a safe and working drug, who wants to bet that "big pharma" will produce and sell it? Hell, if it makes through trials and they don't want to make money on it, then I want to make the money!...
;-)

Sock Puppet--

If you're looking at the United States, note that we don't have a national policy on chlorinating drinking water. We have a large number of separate water systems, run by different people (with probably insufficient supervision of, and rules for, all of them, because that's a federal-level pollution problem), with side orders of private wells and even cisterns.

My water was chlorinated for part of the time I lived in New Haven, Conn. (I'm guessing this is because high levels of something dangerous were found, but it's been 25 years and I don't remember.)

The water I get now, in New York City, has chlorine, fluoride, "food-grade phosphoric acid," and some sodium hydroxide, but that's added early enough in the system that the water doesn't taste chlorinated to me: it sits in a series of reservoirs before reaching the user. (In New Haven, we would take tap water and put it in a pot or pitcher to let the chlorine escape before we drank it.)

I would wonder whether the rates of those cancers varied between people who drink all or mostly tap water, and people who are drinking bottled water (which may not be so treated) and/or juice. (Soda probably counts as tap water for these purposes, because it's generally bottled locally using local water.)

But, as you say, the levels probably aren't clinically significant even if DCA is as helpful as they're suggesting.

It's kind of funny that I wasn't really all that encouraged by dca until somebody like you had a look at it. after my mom was diagnosed with gbm, the dcasite people gave me the heebie-jeebies. i'll see if she is a candidate for the next wave of trials i guess. we might need to chose between this and an avastin-before-recurrence trial. What would you recommend?

Great analysis.

I am confused, though, as to why the trial wasn't done using an antiangiogenic drug in combination with DCA? Cutting off the glucose supply in parallel with Warburg inhibition should work much better then combining it with an alkylating agent such as TMZ.

First heard of DCA in early 2007 and read your early criticism of it. Appreciated your thoughts then and now. I was interested then because I had just had 12" of colon removed due to colon cancer, 10/06. No chemo since my oncologist thought I had beaten it, stage 1/2. Stayed interested in DCA because my Dad had prostate cancer. I received a sample of DCA and it lay around while my Dad died of his cancer, I having failed to convince my siblings or myself that we should try DCA on my Dad.

Not so last April when I was diagnosed with metastatic colon cancer in lung and Hylar regions both confirmed by biopsy. Asked my primary doctor if I should try it and received an emphatic no. My oncologist suggested that the tumors were very aggressive having no evidence only four months before. I said I wanted a second opinion which took place in September. In the interim I took DCA and thinking that I would be on chemo in July asked my primary doctor to authorize another CT scan and admitting to DCA use. That CT scan showed a 35% reduction in tumor size. The next CT scan another "significant" reduction according to my second opinion oncologist. And over the last year I have had no change at all in tumor size in 4 CT scans. I am now increasing my dose of DCA to that which caused reductions early on.

Also looking at clinical trials I can join so am being seen my more oncologist. My primary oncologist, while not giving any credit to what I am doing, suggest that as long as my tumors are not growing she agrees with my decision not to start standard chemo.

I have no symptoms and feel fine. Have peripheral neuropathy that is under control.

Keep up the criticism. I am not advocating that anyone do what I have done. But there is the other side of this story. We who self medicate are often facing a death sentence that can sharply focus our attention.

My doctors all gave me 6 to 12 months to live without chemo and I think they thought my time was actually shorter. As it is I am in great shape and alive at a year.

I find myself surprisingly crediting DCA for this.

And you may be right; no one's arguing that it can't possibly be effective. The problem is that the unscrupulous marketing by those in a rush to sell is making it difficult to study the drug, which would benefit more than just you. You're doing better, which is great! Now we need to get everybody else doing better, and it's going to take science to know the bestt way to do that. (Note also that you may be lucky. Some people are. My aunt had a nasty case of ovarian cancer. They gave her months. She lived 14 years, suffering several relapses, before it finally finished her off. She was astonishingly lucky, and got written up in medical journals; I think samples were also saved for study, and maybe they'll reveal something useful someday, but most likely she was just exceptionally lucky.)

There is a flip side, too: some people are exceptionally unlucky. Hodgkin's lymphoma has a 95% cure rate with chemo. There was a woman in my home town who recently ended up in the other 5%. Despite early detection and aggressive treatment, she still died. Very tragic case, but fortunately not typical.

Rob:

Hang in there, man. Sorry to hear about your trials thus far.

I think you present a lovely paradox to the likes of davescot, though. You are precisely the sort of person whose anecdote he wants to champion over science, yet you advocate proper scientific, skeptical study of DCA.

The only inconsistent point I can see is your decision to actually use DCA, but I can understand your circumstances affecting your decision. Was it, then, a "what have I got to lose?" choice on your part? Did you discount the unknown risks based on the drug's history of on-label use? Ultimately, what I'm getting at is that despite being one likely to support the scientific/skeptical position, you chose to use DCA anyway. Could you elaborate on why? I do not ask that judgementally, and I think I partly understand based on your comment, but I'd like to hear more.

Excellent and interesting post. Minor FYI, the images in your post are MRI (T1 postcontrast) not CT. For accuracy's sake.

@terrasig

That was the first time I'd ever seen your blog. A few years ago I set a "google alert" for dichloroacetate and whatever hit the intertubes (about one article a month for most of the past 30 months) I glanced at. There was a flurry of activity last week and your blog was mentioned in one of the alerts.

@all

There's a big bit of missing fact in this story that shoots down any complaints of unscrupulous sellers of DCA or lack of purity. Pharmaceutical grade DCA has been manufactured by a large chemical supply house for at least a couple of decades. It's inexpensive even from them. Early on in the DCA kerfluffle the FDA ordered the big US supplier to not sell the compound to anyone who didn't have FDA approval to receive it. It's also not costly to have a compounding pharmacist whip some up if you have a doctor's prescription for it in hand. So, until the nanny state stepped in, there was an inexpensive safe supply of the stuff.

Second point, after 3 years of nanny-state-approved clinical testing that no one is willing to throw any serious money behind we know exactly jack diddly squat more now than we did in 2007 as a result of a few dozen people self-medicating and reporting results on a blog. It was already quite evident that DCA was effective against some cancers and not others, had positive results in some people and no results in others, how well it was tolerated and in what doses, some things that worked well along with it to regulate body pH so the drug was more efficacious, and things of that nature.

My biggest objection isn't that clinical trials don't yield more reliable results (albeit slowly and at great cost) but rather that a heretofore uncontrolled chemical that anybody could buy was quickly forced off the open market to prevent ostensibly free adults in a free country from making their own decision about whether to use it. I generally object when the government tells any adult what they may or may not ingest. And this isn't like heroin or cocaine. No one was using it to get high nor was there any risk of addiction. And this isn't like it was healthy productive citizens taking it either. These were people who were dying of cancer and for most of them they'd already been told they'd exhausted all other available treatment options and should go home, get their affairs in order, and die.

Nanny Orac evidently thinks his way should be the only way. Nice of him to make that decision for everyone else. What on earth would we all do without him and his ilk to dictate what we can and cannot do to try to rid our own bodies of cancer.

@orac

I thought you might mention what was likely a strong factor in choosing a brain cancer for the phase 1 clinical trial. DCA is a small molecule that readily crosses the blood brain barrier - a barrier which blocks a large fraction of alternative chemical treatments.

I also question how you managed to moan about there only being 5 patients in the trial without mentioning why that might be. The inconvenient truth of that matter is that Michelakis was fund-limited and got some significant fraction of the paltry $1.5M for the trial from private individuals. Michelakis almost literally got funded by holding a tin cup on a street corner asking passersby for spare change. One might reasonably ask why such a promising drug isn't getting more funding per year than a typical surgeon declares as personal income to the IRS every year.

To Rob, I wish you all the best in your health. Good luck.

As a counter antidote, I have a patient who was diagnosed with metastatic colon cancer to the liver and lungs about 5 years ago. He's still alive and doing reasonably well, though he had to finally have his tumor resected which led to a colostomy. He also has peripheral neuropathy from his chemo, but he still fishes, hangs out with his dog, and spends time with his family. That's all he really wants in life.

If DCA helps glioblastoma or metastatic colon cancer, GREAT. However, it requires study and time and patience.

I overheard someone in the lunch room saying something about how "they had discovered that oxygen kills cancer. Cancer cells can't survive with oxygen around." Or, something to that effect. I wondered if it was her interpretation of the news of this study.

I didn't try to dig for more information because we weren't even sitting at the same table.

But, it gives a clue how study results can get distorted by the time the news gets passed around in the general public.

Todd - are you thinking of suramine? I seem to recall that being used very early on in AIDS patients.

And of course there's always the possibility that DCA will be useful against something that isn't cancer. How many "cancer treating" drugs eventually became useful for something that wasn't cancer? (Thalidomide is the only one I can think of that was supposed to treat something else that became useful for cancer. And leprosy, although that's pretty rare here.)

@dedicated lurker

Possibly, though I'm pretty sure it was AZT at high doses. I believe the story of the approval of the drug was recounted in the book Protecting America's Health: The FDA, Business, and One Hundred Years of Regulation, by Philip Hilts. Good book, by the way. Interesting insight into the good and bad history of the FDA and drug regulation in the U.S.

@jaranath

Rob doesn't present any paradox to me. He was fortunate enough to have a source of DCA, used it, and is glad of it. I'm not at all sure at this point he'd be willing to take the freedom of choice he exercised away from others in similar situations. Cautioning against making the same choice is one thing. Taking away that choice is a different thing.

Rob also makes a great point that he'd still want to participate in a clinical trial if he could get into one. That speaks against the hypothesis that if experimental drugs were available to private individuals outside clinical trial settings then that would somehow ruin the trials. That said, I'm not sure Rob thought it through all the way. He might not want to participate in a DCA trial when he has even odds of being in a control group which is unknowingly getting a placebo instead.

I'll concede the point that experimental drugs on the free market would present a problem for clinical trials to anyone who is willing to concede that clinical trials essentially rely on legalized extortion to get their participants. If the experimental drugs were available outside the trial setting there would undoubtedly be a lot of people who would choose to not risk being in the placebo group and self-medicate instead.

On the other hand the DCA situation isn't typical. Experimental drugs are seldom as inexpensive and ubiquitous as DCA which, as one other poster pointed out, is present in all chlorinated drinking water (fyi: ostensibly in concentration too small to have any positive or negative health concerns) and heretofore was more of an undesirable side-product of industrial chemistry than anything else.

Given my libertarian support for allowing adults to make their own decisions about their own bodies and opposition to nanny-state policies which restrict such freedoms I'm still of the position that the clinical trial process is what needs to find a way to adapt to the loss of extortion as a means to enroll participants.

Somehow the human race managed to thrive when there were no authoritarian controls over what drugs a person could choose to take. Caveat emptor ruled the day and Darwin took care of those who ignored the warning. The thing of it is, as I mentioned in a previous comment, it isn't like experimental drugs such as DCA are heroin or crack cocaine which threaten to turn healthy productive citizens into dope addicts. The only threat DCA entails is a threat to the extortionary practice of clinical trial enrollment and/or threaten lucrative markets for very expensive chemotherapeutic alternatives which may or may not be more effective and may or may not have far worse side effects. The bottom line I guess is DCA threatens the status quo.

DaveScot--

Are you really advocating that we should deregulate meds and let the sellers lie, with the death penalty (or at least sterility) for those who guess wrong or believe liars? (And Darwin never did much to the vendors of contaminated or useless pills, or even those who sold things that were actively harmful when used as directed: at most, they lost money while their victims died.)

"Darwin will take care of it" does not convince me that I want to take, or encourage my loved ones to take, random chemicals that someone claims will be good for me. I can die without paying for nostrums, if it comes to that.

Fascinating. I had forgotten how incoherent your logic could be, davescot, let alone how poor your reading comprehension was.  Read Rob's comment again. He advocates the scientific study you scorn, and he does not advocate others follow his example. That's a paradox for you, unless you choose to pretend he doesn't hold those positions.

As for the rest of your comment, you're underscoring my earlier point. You don't understand how to answer "how do you know?" and you don't really understand the need to ask that question. Instead, you incoherently defend libertarianism and crusade against nonexistent causes.  Clinical trials "need to find a way to adapt to the loss of extortion as a means to enroll participants?" Wow. The purpose of clinical trials is not to enroll paricipants, sir. You ought to know what the purpose is, but as I've said, it's clearly something you don't understand.

DaveScot does have a remarkable ability to be precisely wrong on every single point. Most folks would be occasionally right by accident.

Anyone who wants DCA now can get it, safely and inexpensively. You can even get it (perfectly legally) under a doctor's supervision, since there is no legal bar to off-label prescriptions.

We now know quite a bit more than we did in 2007 -- precisely because careful clinical studies were conducted. Self-medication and non-reporting did exactly jack diddly squat for the state of our knowledge.

Substantial effort and funding have been, and continue to be, directed toward studies of DCA and cancer. NIH funded at least five just this year. Look it up.

FDA doesn't jail anyone who chooses to take DCA for any reason. FDA does stop folks like Tassano from making unsupported claims about drugs, and from distributing them without controls. That's what has DaveScot so worked up. Just the image of DaveScot spitting the dummy over one more intrusion of the nanny state tickles me so that I have to consider it one more benefit of the Pure Food and Drug Act.

@ DaveScot 30

"it isn't like experimental drugs such as DCA are heroin or crack cocaine which threaten to turn healthy productive citizens into dope addicts."

Just a simple question: without a proper clinical trial, how do you know this? How do you know that DCA does not have any annoying side-effect on the population you propose to give it?

@ JRE

exactly.

Seb30:

Because he wants it to be so.

The real killer is that he doesn't understand why it matters, even though he may be right about DCA's utility.

@ Jaranath 36

Oh, I was suspecting as much. I just wanted to hear it directly from him.
Or maybe an answer like: "because we know it from past experience" -to which we could answer "you mean precedent clinical trials?"

He also completly bypass the fact that, with self-medication, there is a heavy bias toward successful stories. Peoples who suffer harm or even die while automedicating have a good chance of being overlooked, since you will need someone else to know and report that the patient was taking some drugs by himself/herself. There is a good chance we will not know which drug was implicated, and a even greater chance we will not know which dose was taken, how often, and with which other drugs. A toxicology analysis could give some answers, but incomplete ones, and we need to know there are drugs to look for.
All issues a correctly designed "nanny" clinical trial will address.

"Somehow the human race managed to thrive when there were no authoritarian controls over what drugs a person could choose to take. Caveat emptor ruled the day and Darwin took care of those who ignored the warning."

Wow. Just wow.

Back in the late 70's Holroyde and Reichard did a lot of work on anaerobic tumor metabolism and the Cori Cycle activation in patients with cancer cachexia. I got to watch from the sidelines, and it was interesting to note that colon cancer with massive liver metastases seemed to be a very anaerobic tumor burden with very active Cori cycle. Watching this kind of patient receive TPN and go into lactic acidosis was frightening and yet intriguing.

One might also remember that hydrazine was approached as an intervention, based in part on this kind of research, and we all know how THAT turned out.

As far as Phase I-II clinical trials and Glioblastoma m. go, my one patient with inoperable GM who had long-term survival was treated in a ten patient trial of activated killer cells injected into the tumor. The other patients didn't fare so well, and his cure was abandoned after this "unsuccessful trial." 10% response isn't much, but there are plenty of treatment regimens out there only marginally better than that.

Conversely, I saw some clinical trial data published out of MSU in the late 80's pushing the use of cisplatin for all manner of solid tumors presented with what might kindly be termed mislabeled CT scans (before and after reversed).

My points? Well, you need more than one study to determine if a treatment is really effective, and many more to find the safest and most effective way to use a treatment. Single success in a treatment does not mean it will translate into a broadly successful regimen, and any one particular study may be strained but what I'll call investigator bias.

DaveScot is perhaps well meaning, but his approach is not only incompatible with science, it is destructive to science and good medicine, and potentially harmful to many. Like certain highly elected officials and their policies.

It's funny that Dave is singing praises for caveat emptor, when life spans are getting longer because its opposite: vende emptor has been practiced thanks to organizations like the FDA.

Personally, I see caveat emptor as subversive to capitalism: It sets up an environment of distrust between consumers and manufacturers, which discourages spending. It discourages short-sighted companies from performing "unprofitable" safety trials and other product improvements, leading to stagnation. And with medicine, it leads to shorter-lived consumers. Generally, it's a good thing for a company if your customers live long enough to demonstrate brand loyalty.

I look back to America in the early 1900's the way I look at today's third world countries.

Caveat venditor, emptor is buyer.

Just google: Bob Becks electronic pulser

DaveScot is the best!

@Vicki

No, I'm not advocating deregulation of everything. I'm saying that DCA was deregulated and should have remained that way.

In 2006, Joe the Plumber could have purchased pharmaceutical grade DCA from a chemical supply house on the west coast for a about a dollar per gram by the kilogram. In 2007 when Michelakis published his findings showing DCA melted human tumors placed in lab rats like butter on a hot plate. There's more backstory to that about how Michelakis was unable to secure any funding for further research because DCA couldn't be protected by a patent. He actually discovered its cancer killing capacity a few years earlier and kept it under his hat while he tried to secure a patent and research funding. He secured a patent but it was on the process of using DCA to treat cancer rather than a patent on the compound itself. His patent was widely construed by big pharma as being so weak as to be unenforceable so it was "Thanks but no thanks" from them. Failing that he finally went ahead and let the world know what he found by publishing a paper in peer-reviewed cancer journal.

Very quickly after he published, people like Joe the Plumber who'd been read a death sentence by their oncologists started ordering pharmaceutical grade DCA from said chemical supply company. As soon as the FDA got wind of people self-medicating with a heretofore unrestricted chemical compound they stepped in and ordered said chemical supply company to not sell DCA to anyone who wasn't registered with the FDA for receiving it.

Now if DCA had already been restricted before its potential for reducing malignant tumors with comparatively few and no unmanageable side effects was discovered I wouldn't be carping about it. The thing is that DCA had been well characterized for dosage (at quite higher levels and for continual use over periods lasting for years) and side effects for many years in treating lactic acidosis. It wasn't like it was some new and potentially dangerous chemical to be putting a gram of it into your orange juice with breakfast for a few months. Reversible peripheral neuropathy was the only notable observed side effect - your hands start to tingle if ingest enough of it for long enough and they stop tingling when you stop ingesting it. The dosages are length of use were much greater for treating lactic acidosis. Those receiving it were all young children because lactic acidosis otherwise kills them before they grow up.

So, I'm certainly not advocating removing restrictions on everything under the sun nor am I advocating no regulations on quality control in substances sold for human consumption. DCA was as unrestricted as aspirin before people wanted to self-medicate with it. I'm certainly not saying that we should abandon the manufacturing controls that ensure when you buy a bottle of Bayer at the grocery store you're getting pure aspirin rather than something that could be laced with arsenic. Such controls were already in place for DCA. However when people started taking DCA like aspirin tablets the FDA successfully took it off the market. It's that action by the FDA I've got a problem with - nothing more and nothing less.

seb30

Just a simple question: without a proper clinical trial, how do you know this? How do you know that DCA does not have any annoying side-effect on the population you propose to give it?

The "population" self-medicating were terminal cancer patients with nothing left to lose. They'd already greatly suffered through, unsucessfully at that, approved chemotherapy. DCA had been previously subscribed for many years to children suffering acute lactic acidosis. Those kids took much higher doses for periods as long as a few years. The lactic acidosis still killed them eventually but the side effect of long term treatment with DCA was well known to be reversible peripheral neuropathy. The self-medicants taking the highest doses they dared reported exactly the same thing - tingling in the hands that ceased shortly after discontinuing DCA and/or lowering the dosage.

I followed this all very closely until Tassano was shut down. I also know that Tassano's manufacturing line for DCA was designed by a well-known PhD chemist who had a long history of setting up the manufacture of FDA-approved synthetic chemo-therapy. This is all public information. The chemist wasn't hiding and described the technique being used in great detail. The DCA was tested for purity by two reputable agencies and found to be as pure as advertised. In fact it was purer than the previously available pharmaceutical grade DCA.

Maybe Tassano should have been licensed and supervised. I would have no qualms about that. But the fact of the matter is that Tassano didn't have a market until the FDA ordered the extant licensed purveyor of pharmaceutical grade DCA to stop selling to anyone without prior written FDA authorization.

When you get into a situation like that where there is high demand for an illicit substance a black market develops and you get things like the guy in Canada who got busted recently for selling lactose and saying it was DCA. This was just all very wrong on many levels. The FDA should have never got involved and rather let people who wanted to buy pharmaceutical grade DCA from a reputable chemical supply house continue buying it. In the meantime nobody was stopping anyone from conducting formal clinical trials with DCA. That was and continues to be hobbled by the simple fact that the compound can't be patented so there's no profit potential to pay for hideously expensive clinical trials. The proof of that pudding is that in 3 years a grand total of 5 people with a prognosis of 14 months until death from an extremely aggressive, difficult to treat brain cancer have received treatment. And what do the researchers who conducted the trial have to say about that? - "due to the small number of patients in the trial we can make no firm conclusions". Just friggin' lovely.

Bronze Dog

It's funny that Dave is singing praises for caveat emptor, when life spans are getting longer because its opposite: vende emptor has been practiced thanks to organizations like the FDA.

I didn't mean it quite the way you took it. What I meant by caveat emptor is that the buyer should beware of the consequences of his decision in how, when, and where to use whatever it is he is buying. I have no problem at all with FDA requiring food and drug manufacturers to comply with laws regarding truth in advertising, accurate labels, quality controls, warnings of known or suspected health risks, and things of that nature. I would go so far as to say the FDA doesn't do enough in that regard as opposed to saying it does too much.

However, once these measures assure a buyer that what he's buying is what's on the label then how, when, and where he uses that product is his responsibility. I object to many laws aimed to protect the stupid from their own stupidity. It puts an undue, unfair burden on those able to make well informed decisions.

Take Rob for example (commented previously in this thread). He's clearly a bright guy who was well informed on the risk/reward aspects of his decision to self-medicate with DCA and he credits it, probably rightly, with saving his life. I cannot in good conscience support putting up roadblocks in the way of others who find themselves in situations similar to Rob's just because they might not be as bright or diligent in fact finding before making a decision.

@DaveScot

What was the name of this supply company? Were they selling it as a cancer treatment or cure? If that was the case, then the FDA was fully and correctly justified in stopping them. If they were selling it as a treatment/cure for cancer, but did not have an NDA for that indication, then they were in violation of the law.

Even if that is not the case, all distributors of a pharmaceutical product must be authorized to distribute the product. So, if they were selling to distributors that were not registered and authorized by FDA, then, again, they were in violation of the law. There are a variety of regulatory requirements that apply to distributors of drugs.

Do you have evidence that they were in compliance with all of the relevant regulations to support your assertion that they were inappropriately shut down?

@Todd

I didn't write down the name of the supply house. Looking again the only US source I can find of pharmaceutical grade is

http://www.intlab.org/DetailPage.asp?ProductCode=1528424

The website doesn't look familiar but it could have changed. All I really remember is it was a chemical supply house on the west coast with thousands of products. One day >99% sodium dichloroacetate was listed for sale with no restrictions and the next time I looked a restriction had been added about needing some sort of FDA authorization number before they'd ship it to you. I found it through this link:

http://www.chemexper.com/search/cas/2156561.html

I don't know what regulations exist to assure product purity from chemical supply houses. DCA wasn't and still isn't a "pharmaceutical product". It's a simple, common chemical. Saying "pharmaceutical DCA" is like saying "pharmaceutical table salt". All I know is it was listed as "pharmaceutical grade >99%". Lesser grades are 97% and 98%.

More of the backstory is that I'd exchanged a number emails with Jim Tassano as he'd discovered DCA reading my blog. He found out too late to acquire any DCA from the US supplier. He imported some from a Chinese supplier but when he had it tested the impurities in the >99% pure product weren't to his liking due to the standard production process employed by pretty much everyone at the time. He wanted a purer product. There were no toxic levels of anything in the Chinese product but it wasn't as good as you could possibly get with state of the art synthesis. So he collaborated with a PhD chemist at UC Berkeley who had much experience with synthesizing FDA-approved chemo-therapeutic compounds. They employed a more expensive process that used a tuned-laser to drive the reaction which didn't produce (IIRC) trichloroacetate as a reaction byproduct. It was all written up, including the name of the chemist that set up the production line, on Tassano's website "buyDCA.com" as well as the two independent laboratories that assayed the product. The FDA forced him to shut down the website altogether but you might be able to find the process description etcetera on archive.org. At the time I googled the chemist's name and he was legit with a CV online at UC Berkeley listing all the related work he'd done.

I seem to recall reading somewhere of the source of DCA Michelakis was using. It doesn't appear in his patent on using DCA in cancer but Michelakis was originally reseaching its use in accelerating recovery from a certain kind of heart surgery. IIRC his source was the same US chemical supply house I'd found which makes sense as that was, as far as I could determine at the time, the only US supplier of pharmaceutical grade product. Keep in mind DCA was a simple inexpensive chemical that isn't really used by anyone for anything except for treating a few rather rare health disorders. The total annual US sales of it before 2007 was probably less than $10,000. It's more of an undesirable side-product of other reactions than anything else before then and is present at a few ppm, along with trichloroacetate, in any chlorinated drinking water. It was really very much under the radar. The FDA didn't care about it beyond setting some limit in how many parts per million were acceptable in drinking water.

@Todd

To explicitely answer your question about whether the chemical supply house was marketing DCA as a medical product the answer is no. It's just one more of thousands of chemicals they sell categorized by industry designators like CAS and formula. For sodium dichloroacetate those are:

RN: 2156-56-1
MF: C2HCl2NaO2
MW: 150.92451

That, and the purity, is the only thing advertised.

My 6 year old son has one of the rare forms of brain cancer. He has had radiation and for the most part high dose chemo. We thought he was doing well but the docs now thing he has a coating of cancer cells covering his brain and spinal cord. There is no eveidence yet in scans and such, but they feel that he is showing symptoms of this. So I'm looking around at comments and reading articles like any crazed parent who loves her child would do and am left wondering... There are side effects to this drug but no where near those of high dose chemo... So if you are only given a few months weeks or days to live... Whats the harm in the doctors giving some thing that may help and in all honesty wont make the situation any worse. At least it gives you a small measure of hope. My son has pineoblastoma that has spread to his spine. It is a rare thing so theres not a whole lot of research out there... Why not try this on those of us who have nothing left, not even a lot of time...

Sarah you have captured the two key aspects here:
Why deny hope by not permitting an experimental treatment when no alternatives are forthcoming?
Clinical support is essential however so you should seek it elsewhere if your current clinical team won't co-operate.
DCA is a toxic chemical even when it is pure. Search DCA MSDS (material safety data sheet) for further information.

Sarah,

I am using DCA. If my son had a cancer like yours I would give him DCA if all else failed. Even sooner since I have personal experience. Hopefully your doctor will agree. That said I have NO knowledge that DCA would work for your son.

Call the Medicor clinic in Toronto. They use DCA on many patients. DCA causes peripheral neuropathy (PN) and constipation for me. What I have heard is that the PN is far less common in children. I am 66 and the older you are the more it seems to affect you. The constipation is something only I have experienced AFAIK.

And I can live with both.

I originally got DCA for my Dad's prostate cancer and never gave it to him (once small dose soon before he died last fall). Wish I had now.

One thing good about DCA is it crosses the blood brain barrier.

>99% sodium dichloroacetate was listed for saleï¼
http://www.lookchem.com/cas-215/2156-56-1.html

My mom got stage IV NSCL Cancer, Can I ask her doctor @ BC Cancer Agency to give her DCA treatment? If not where else she can get the DCA treatment in Canada?

No. You actually need to read the article instead.

Some basic rules before commenting on a blog or forum:

1) If you find an article through Google, before commenting go to the first page and see what is under discussion.

2) Get to know the place, lurk for a while.

3) Become familiar with the writing style, especially in how issues are discussed.

4) Actually read the article and comments before commenting.

5) Try to proof read your comments (okay, we don't all do that).

6) If you think you want to bring a subject up to the participants' attention, please use the search box on the upper left side of this page to see if it has been discussed before.

7) If you get an error when posting a comment, before posting again... open another window to see if it was actually posted.

I understand the need for reproducible studies to verify claimed results; indde I often argue with people promoting "alternative" therapies about this. However, as someone with Stage 4 colon cancer mets to liver with lots of small tumors making it unresectable, and basically holding steady with a small reduction in tumors after Oxaliplatin has been discontinued for two months, and now Avastin as well, and with severe liver damage, I do increasingly wonder about the advisability of denying treatments which hold some promise, while probably causing less damage than mainline treatments. Does anyone know how to obtain DCA, and whether there are oncologists in Boston who will agree to work with this as part of a regimen? I don't believe it is a miracle cure, but I would like as long and comfortable a survival as possible, and I don't see chemo as the best way to obtain that.

Now, I understand that there would need to be less confounding variable for a study like this, but you can't ethically give patients no treatment. Thus, I'd assume that any trials would have to use other measures.
The only thing I don't understand is why stage four cancer patients wouldn't be given more options when it comes to innovated or untested treatments. The mortality rate for stage four patients is high enough that we should be more forgiving with treatment options.
I'm sure that hope, even when false, does lead to higher survival rates.

Jackie:

I'm sure that hope, even when false, does lead to higher survival rates.

Not really. Sometimes they are given hope at the expense of the wallets, and often made to suffer more. Some of the alternative therapies involve painful procedures, drugs with not so nice side effects and other ways erode their quality of life. Plus, some alternative practitioners have refused to allow their patients pain relief (100+ page pdf).

Terminal patients are not told to go home and die. There are palliative treatments that ensure a decent quality to the end of their life, including pain relief.

For a good book about the subject is The Emperor of All Maladies.

Jackie, you should read more of this site, especially the more recent ones on cancer and the suffering caused by those who only offer hope, but not help.

And go to your local library and check out the book The Emperor of All Maladies. It is a wonderful read, and you will learn that there is more than providing hope.

You might also check out this blog article from today about the same subject.

http://theness.com/neurologicablog/index.php/another-cure-for-cancer/

The prescribed, off-label, therapeutic use of a cheap drug whose toxicity is known in no way hampers conducting controlled trials among groups of informed and willing patients. What is the logic of denying cancer patients at large the option of trying a drug that will not do them much harm, and may improve their health significantly?

"Worse, simply using a drug like DCA outside the auspices of well-designed clinical trials will virtually guarantee that we will never know for sure whether the drug actually works."
Orac, could you please explain how you come to this conclusion? I fail to see any evidence in your article that supports such a strong statement. I can't see any causal link between those individuals self-medicating and "well-designed clinical trials". Are you perhaps referring to someone killing themselves or causing serious harm through an overdose? Although I still fail to see how even that would virtually guarantee the failure of clinical trials.
P.S. I first read of DCA today on NS and reached your blog via their links, so no, I'm not a die-hard DS supporter!

They've put this on the university web site: http://www.dca.med.ualberta.ca/Home/Updates/2007-03-15_Update.cfm So whether you think this is a cure or not, it doesn't matter. You are not a doctor or researcher to negate this information. These people believe that this has merit, so it is not a myth. You must change this to 'true.'

Dear Necromancers, please continue discussion on more recent article:
http://scienceblogs.com/insolence/2011/05/the_dca_zombie_arises_again.p…

Fab review thank you very much:)

From reading your article it becomes clear that BigPharma and the government should be required to donate a % of their vast profits to independent research NGO's that will test ALL alternative 'cures' offered and conduct extensive clinical trials to establish efficacy.

Where a 'cure' is found to be efficient, those companies who apply to produce and market that new drug or medicien, should be required to pay a % of the manufacturing cost back to the NGO.

The more success stories that occurred, the more revenue received, and the less required from BigPharma and the government.

The issue of health is NOT a political situation, folk with cancer care not one jot whether something has been clinically tested, they care about surviving and being cured.

Current medical science seems ineffective using treatments that seemingly kill more people than they 'cure'.

The time has come when medical research needs to be outside of business control, and firmly in the hands of scientists and chemists who have NO BigPharma masters to pander to, then, and only then, can real research be conducted with no financial spur.

Once a treatment/drug/medicine had been proven efficient and safe, then BigPharma or whoever could bid to gain the right to manufacture and distribute the drug.

In this way research costs could be recovered, and scientists, doctors and the medical community could be unbiased and objective about their research

You say that DCA needs a full trial before you will accept it's efficacy. Do you accept that the chemical is not patentable and therefore not likely to ever pass the nearly billion dollar phase III study you require?

The polio vaccine never went through a phase III clinical trial. Do you reject that the polio vaccine effected the eradication of polio?

If I told you that rice cakes were effective against cancer, would you be against my advice to patients that there is no harm in them trying in advance of a clinical trial?

If so, why are you opposed to using DCA, under medical supervision, considering that DCA has been used safely in humans since the 1940's?

Please check my website www.martincwiner.com/dca for further information.

Interesting, but GBM never has that kind of response when using RT & TMZ, check out all the data if you don't believe me, DCA seems to have increased lifespan in some of those patients by 100%.
Please post a link where RT & TMZ or any other chemo agent has regressed a GBM tumor.

Hello, I like this article, is technical and gives the amount of accessible knowledge to the reader so it understands a sane take on such a medical subject.
But I am still intrigued by something. Knowing that Cancer is such a violent and spread disease, If the the Michelakis' studies and trials have had even a tiny bit of success, why they haven't been followed by a larger and more detailed study, thus proofing if the DCA is really useful or not? Can the scientist and the pharmaceutical companies say that they have at heart the people's health and interest, and not the monetary gain, if they don't do this?

Regards.

Thanks for all the research, but you don't need to slam special creation just because you don't believe in it. Unless you want to call evolution a "pseudoscience" too, both theories (and that's all they are) attempt to understand the evidence of our world. No need to try to discredit one or the other when they're doing the same thing.

@ magex

You're right, except for one little problem. Evolution actually provides testable predictions. Predictions that have been tested and shown true. Special creation doesn't.

So, they're not doing the same thing.

Er, magex, you might want to check the scientific definition of the word 'theory'. (Hint: =/= 'just an idea')

This story is doing the rounds again on Facebook, and I'm posting as a patent expert to try to defuse one of the many misleading aspects of this story no science-bloggers seem to be willing to talk about: DCA being "unpatentable" so the drug companies won't finance research.

At least in Europe, it is confirmed practice that a new dosage regime of a known medicament can still be patented.

http://archive.epo.org/epo/pubs/oj010/10_10/10_4560.pdf

So, saying that DCA isn't patentable is literally true: DCA by itself cannot be patented.

But that does NOT prevent someone who develops DCA into a usable cancer treatment from obtaining a patent for their time, effort and investment.

The "DCA is unpatentable so big-pharma won't touch it" angle is a huge part of the conspiracy theory that is keeping this story alive. Please, bloggers and science-writers, if you want to cut this story down, go for the jugular.

The comments here reflect, for me, a higher level of thoughtfulness than I've seen elsewhere...thank you all for that.

Regarding the general sentiment that pharmaceutical companies ultimately have the 'greater good' as their goal is, like so many things, true of some within that industry, to be fair. At the same time, I have personally seen some serious manipulation, purely for profit in my opinion, of 'old' tried and true medications.

I've been on some form or other of maintenance meds for asthma a good part of my life. For now, I will just talk about what is maybe the worst of my personal observations.

Albuterol is a commonly used fast acting med for when you need immediate relief. I have seen albuterol formulations change maybe twelve to fifteen times throughout my life. Each time, when I have inquired about why the old, working-just-fine, version was being replaced, I have been given some vague explanation that the FDA had determined that one or other of the ingredients (usually to do with whatever component made it an aerosol) was a bit toxic and not good for the general environment, so that version had to be removed....even though I had perhaps been routinely, daily inhaling it directly into MY lungs for months or years....as I have each and every other apparently 'bad' formulation that had been previously approved.

And so, with each change, generic was no longer available until the new patents for the new safer concoctions again expired. And each time I had to pay a much higher price, because I had to use a Brand name until the generic was allowed....which is currently the case, again, as I purchase Proventil....which has had a serious edge over others in the albuterol market for decades it would seem.

And that is just one tiny example coming from one relatively insignificant long time, heavily-invested customer of the pharmaceutical industry and its sister exploiter, the insurance industry.

As one of the millions currently unemployed, I have also had the horror of being without health insurance for a while, but my bottom line is that I paid in a substantial amount of money to insurance companies, doctors and drug companies and am only now sort of getting a break from the financial strain....I fortunately live in an area with a decent public healthcare system. If I was having to pay the monthly cost to be on albuterol or the couple other meds I've needed for years, I'm pretty sure I would be dead, because I could not afford them!

Now, maybe I'm too cynical, but when I look at the fact that asthma medications are something now commonly needed and being purchased by Americans almost as often as anti-depressants and pain killers...and if you had personally observed this questionable trend of re-patenting the same drugs over and over through little tweaks in the formula supposedly at the behest of the FDA (whose only aim, we're told, is to keep consumers safe), wouldn't you be just a little skeptical of the bottom-line intentions of the pharmaceutical industry...and even the FDA.

So sorry to have left the question mark off of the last sentence (which should have had one) in my earlier comment...I somehow missed that. If editing was possible, after the fact, it would have been fixed..:-)

læs & Gem!!!

Mary,

I agree with you about the patenting arms race. It really nicely highlights Geoff's point about DCA, too. Absolutely old stuff can be patented. You just need a sufficiently novel method. But this isn't something you can blame the FDA for. They are not in charge of patents; that's the patent office, and if you've been following the computer industry, you'd see just how screwed up that system is. Basically, the patent office is massively overloaded; they simply cannot do a thorough job with their patent reviews and keep up with the load.

The FDA, meanwhile, handles new drug applications and approvals for new generics. For a new formulation of an old drug, the process is much simplified; after all, the basic ingredient is already approved. All you need to prove now is that the new formulation is safe and does what it claims to do. (For generics, it's easier still; they just have to prove that it meets the specs of the original drug application and is manufactured according to the appropriate standards.) They do not have authority to refuse applications on the basis of being offended by a profit motive. Their writ is only to rule on safety, efficacy, purity, etc. Financial or convenience burden to patients is generally not a concern at this stage. The idea is that the free market will sort it out; an unpleasant drug will not compete well, and most people like to pay less money if they can.

Albuterol is an interesting example. That's a fascinating case study in how everybody has their own interests, and can unintentionally collude to produce a lousy situation for the consumer. Generic manufacturers actually could make generic inhalers now, yet they don't. Basically, industry dragged its collective heels. It wasn't intentional, I'm sure; it's just a result of everybody acting logically in their own interests. Sometimes that doesn't work out, and I don't know what the answer is.