Canada cures cancer, nobody cares

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His Divine Shadow
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Canada cures cancer, nobody cares

Post by His Divine Shadow »

Or so this article claims anyway. Posting here so people in the know-how can gauge its veracity:
http://hubpages.com/hub/Scientists_cure ... kes_notice

Canadian researchers find a simple cure for cancer, but major pharmaceutical companies are not interested.

Researchers at the University of Alberta, in Edmonton, Canada have cured cancer last week, yet there is a little ripple in the news or in TV. It is a simple technique using very basic drug. The method employs dichloroacetate, which is currently used to treat metabolic disorders. So, there is no concern of side effects or about their long term effects.

This drug doesn’t require a patent, so anyone can employ it widely and cheaply compared to the costly cancer drugs produced by major pharmaceutical companies.

Canadian scientists tested this dichloroacetate (DCA) on human’s cells; it killed lung, breast and brain cancer cells and left the healthy cells alone. It was tested on Rats inflicted with severe tumors; their cells shrank when they were fed with water supplemented with DCA. The drug is widely available and the technique is easy to use, why the major drug companies are not involved? Or the Media interested in this find?

In human bodies there is a natural cancer fighting human cell, the mitochondria, but they need to be triggered to be effective. Scientists used to think that these mitochondria cells were damaged and thus ineffective against cancer. So they used to focus on glycolysis, which is less effective in curing cancer and more wasteful. The drug manufacturers focused on this glycolysis method to fight cancer. This DCA on the other hand doesn’t rely on glycolysis instead on mitochondria; it triggers the mitochondria which in turn fights the cancer cells.

The side effect of this is it also reactivates a process called apoptosis. You see, mitochondria contain an all-too-important self-destruct button that can't be pressed in cancer cells. Without it, tumors grow larger as cells refuse to be extinguished. Fully functioning mitochondria, thanks to DCA, can once again die.

With glycolysis turned off, the body produces less lactic acid, so the bad tissue around cancer cells doesn't break down and seed new tumors.

Pharmaceutical companies are not investing in this research because DCA method cannot be patented, without a patent they can’t make money, like they are doing now with their AIDS Patent. Since the pharmaceutical companies won’t develop this, the article says other independent laboratories should start producing this drug and do more research to confirm all the above findings and produce drugs. All the groundwork can be done in collaboration with the Universities, who will be glad to assist in such research and can develop an effective drug for curing cancer.

You can access the original research for this cancer here.

This article wants to raise awareness for this study, hope some independent companies and small startup will pick up this idea and produce these drugs, because the big companies won’t touch it for a long time.
I remain sceptical, because I am not sure cancers are all that alike that a single drug or mechanism about them could be targeted. Isn't that the biggest problem anyway, how different the myriad of cancers are. Also mainstream media catchphrases etc.
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Re: Canada cures cancer, nobody cares

Post by Justforfun000 »

I saw a friend post this on Facebook...Trust me. It's pseudoscience. You simply CANNOT cure all cancers with a magic bullet. It's incredibly insulting to the cancer researchers and their endless quest to even find effective treatments for specific forms that doesn't kill the victim before the cancer does..

Cancer is probably the worst, common scourge of the century..and unfortunately the longer we all live..the more chance we will all have a brush with it..
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Re: Canada cures cancer, nobody cares

Post by wautd »

dichloroacetate
They know about this molecule a long time. It's not the first time I hear about it anyway.
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Re: Canada cures cancer, nobody cares

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PZ Myers addressed this nonsense on his blog: Dichloroacetate and Cancer
So many people have sent me this sensationalistic article, "Scientists cure cancer, but no one takes notice", that I guess I have to respond. I sure wish it were true, but you should be able to tell from how poorly it is written and the ridiculous inaccuracies (mitochondria are cells that fight cancers?) that you should be suspicious. The radical, exaggerated claims make the truth of the story highly unlikely.
Researchers at the University of Alberta, in Edmonton, Canada have cured cancer last week, yet there is a little ripple in the news or in TV. It is a simple technique using very basic drug. The method employs dichloroacetate, which is currently used to treat metabolic disorders. So, there is no concern of side effects or about their long term effects.
The simple summary is this: that claim is a lie. There have been no clinical trials of dichloroacetate (DCA) in cancer patients, so there is no basis for claiming they have a cure; some, but not all, cancers might respond in promising ways to the drug, while others are likely to be resistant (cancer is not one disease!); and there are potential neurotoxic side effects, especially when used in conjunction with other chemotherapies.

So we have one popular account that is badly written and makes exaggerated claims. There is also a university press release, the source for the sloppy popular account, that doesn't contain the egregious stupidities but does tend to inflate basic research studies into an unwarranted clinical significance. And then, of course, there are the actual peer reviewed papers that describe the research and rationale, and also the reservations, on DCA. It's like a game of telephone: you can actually trace the account from the sober science paper to the enthusiastic press release to the web account with its extravagant claims of a simple, cheap cure for cancer, and see how the story is gradually corrupted. It would be funny if the final result wasn't going to dupe a lot of desperate people.

But there is a germ of truth to the story, in that DCA does have potential. Here's how it works.

There are two major pathways that we use to extract energy from sugar. One is glycolysis, which extracts two ATP molecules from each molecule of sugar, and doesn't require oxygen. Then there is glucose oxidation, which as you might guess from the name, does require oxygen, but which takes the byproducts of glycolysis and burns them completely to produce 36 ATP. So there's the tradeoff: if your cells are oxygen-starved, or hypoxic, they can still get energy from sugar, but it's relatively inefficient, but if they do have access to oxygen, they can extract much more. This is why you breathe, and why your heart beats, and why you have an elaborate circulatory system to deliver oxygenated blood to your tissues: without oxygen, you suffer a catastrophic hit to the efficiency of energy production.

gly-go.jpeg

Another feature of these two energy-producing pathways is that they are in different cellular compartments. Glycolysis takes place in the cytoplasm, while glucose oxidation occurs in the mitochondria. There is a gate-keeping enzyme, pyruvate dehydrogenase kinase (PDK), that regulates the flow of pyruvate, a product of the glycolysis pathway, into the mitochondria for oxidation. If PDK is active, it suppresses the transport of pyruvate into the mitochondria, and the cell is forced to rely on glycolysis, even if oxygen is available. If PDK is inactivated, pyruvate is shuttled into the mitochondria, even if oxygen is low.

This is where DCA comes in. DCA inhibits PDK, forcing cells to use the more efficient form of energy production. That sounds like a strange way to make a cancer cell uncomfortable, but the other factor here is that mitochondria are primary regulators of apoptosis, or cell suicide. They are loaded with sensors and enzymes that react to abnormalities in the cell (like being cancerous!) by activating a self-destruct mechanism. Shut down the mitochondra, you shut down the self-destruct mechanism that polices the cell. So the idea is a little indirect: by goosing the mitochondria, we also wake up the safety switch that, if all goes well, will cause the cell to spontaneously kill itself.

There are good reasons to think this might work. Many cancer cells arise in hypoxic environments; a poorly vascularized tumor, for instance, is going to be oxygen starved in the absence of blood flow, and the inhibition of mitochondria may be a factor in their survival. There is a well-known phenomenon called the Warburg effect, in which cancer cells will rely on glycolysis even when oxygen is available, suggesting that they have suppressed their mitochondria.

DCA also seems like a relatively safe drug. It's been used for a long time in patients with metabolic disorders, or with metabolic side effects from other problems.
A large number of children and adults have been exposed to DCA over the past 40 years, including healthy volunteers and subjects with diverse disease states. Since its first description in 1969, DCA has been studied to alleviate the symptoms or the haemodynamic consequences of the lactic acidosis complicating severe malaria, sepsis, congestive heart failure, burns, cirrhosis, liver transplantation and congenital mitochondrial diseases. Single-arm and randomised trials of DCA used doses ranging from 12.5 to 100 mg kg-1 day-1 orally or intravenously). Although DCA was universally effective in lowering lactate levels, it did not alter the course of the primary disease (for example sepsis).
This is encouraging. It means there is a body of work already published on the effects of DCA, which should simplify the process of moving it into clinical trials. The authors, however, very clearly indicate that it won't be a magic bullet affecting all cancers, but that some are likely candidates.
Dichloroacetate could be tested in a variety of cancer types. The realisation that (i) a diverse group of signalling pathways and oncogenes result in resistance to apoptosis and a glycolytic phenotype, (ii) the majority of carcinomas have hyperpolarised/ remodeled mitochondria, and (iii) most solid tumours have increased glucose uptake on PET imaging, suggest that DCA might be effective in a large number of diverse tumours. However, direct preclinical evidence of anticancer effects of DCA has been published only with non-small cell lung cancer, glioblastoma and breast, endometrial and prostate cancer. In addition, the lack of mitochondrial hyperpolarisation in certain types of cancer, including oat cell lung cancer, lymphomas, neuroblastomas and sarcomas, suggest that DCA might not be effective in such cases. Cancers with limited or no meaningful therapeutic options like recurrent glioblastoma or advanced lung cancer should be on top of the list of cancers to be studied.
Notice that the only work done so far is preclinical: that means it has been tested in mouse models, tissue culture, but hasn't really been tried in cancer patients yet. The authors come right out and say that, express some possible reservations about its effectiveness, and suggest what needs to be done next.
No patient with cancer has received DCA within a clinical trial. It is unknown whether previously studied dose ranges will achieve cytotoxic intra-tumoral concentrations of DCA. In addition, the overall nutritional and metabolic profile of patients with advanced cancer differs from those in the published DCA studies. Furthermore, pre-exposure to neurotoxic chemotherapy may predispose to DCA neurotoxicity. Carefully performed phase I dose escalation and phase II trials with serial tissue biopsies are required to define the maximally tolerated, and biologically active dose. Clinical trials with DCA will need to carefully monitor neurotoxicity and establish clear dose-reduction strategies to manage toxicities. Furthermore, the pharmacokinetics in the cancer population will need to be defined.
Do not rush out and buy DCA and gurgle it down as a cancer preventative. We don't know that it works — the safe concentrations for you may not be sufficient to kill any cancer cells, and the concentrations needed to kill cancer cells may be so high that it will do horrible, unpredicted, and dangerous things to you (some work with patients with congenital mitochondrial disorders also revealed some degree of peripheral neuropathy, for instance). This is why we have clinical trials: to work out safe and effective doses, look for dangerous interactions with other drugs — and if you have cancer, you're already on a complicated cocktail of drugs — and detect unexpected side effects.

We should be urging further investigation of this promising drug with the beginning of clinical trials, but it's far too early to be babbling about "cancer cures". There have been lots of drugs that look great in the lab and have excellent rationales for why they should work, but the reality of cancer is that it is complicated and diverse and there are many more pitfalls between a drug that poisons cancer cells in a petri dish and a drug that actually works well in the more complex environment of a human being.

One other factor that inflames the conspiracy nuts over this drug is that DCA is simple, dirt-cheap, and completely unpatentable — there is no economic incentive for a pharmaceutical company to invest a gigantic bucket of money in clinical trials, because there is no hope for a return on the investment.

This is why an independent academic community with research funded for knowledge rather than profit is so important, and really emphasizes why we cannot afford to privatize all biomedical research. The authors propose a plan for progressing without the involvement of the pharmaceutical industry.
Funding for such trials would be a challenge for the academic community as DCA is a generic drug and early industry support might be limited. Fundraising from philanthropies might be possible to support early phase I - II or small phase III trials. However, if these trials suggest a favourable efficacy and toxicity, the public will be further motivated to directly fund these efforts and national cancer organisations like the NCI, might be inspired to directly contribute to the design and structure of larger trials. It is important to note that even if DCA does not prove to be the 'dawn of a new era', initiation and completion of clinical trials with a generic compound will be a task of tremendous symbolic and practical significance. At this point the 'dogma' that trials of systemic anticancer therapy cannot happen without industry support, suppresses the potential of many promising drugs that might not be financially attractive for pharmaceutical manufacturers. In that sense, the clinical evaluation of DCA, in addition to its scientific rationale, will be by itself another paradigm shift.
I can't blame the industry for not following up on this: a clinical trial costs millions of dollars, and even if DCA pans out, there is no profit at all to be gained from it. For this research, we have to turn to public support (they have an interest in better cancer treatments!) and to scientists and doctors themselves, who of course have a great personal interest in seeing their patients get better.
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Re: Canada cures cancer, nobody cares

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Yeaah pretty much what I figured then.
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Re: Canada cures cancer, nobody cares

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Researchers at the University of Alberta, in Edmonton, Canada have cured cancer last week, yet there is a little ripple in the news or in TV. It is a simple technique using very basic drug. The method employs dichloroacetate, which is currently used to treat metabolic disorders. So, there is no concern of side effects or about their long term effects.
Yes, let's just ignore the clinical study of DCA in children with MELAS, and syndrome involving problems with the mitochondria, that had to be discontinued due to nerve toxicity in all patients involved. Yes, I'd say there should be some concern with side effects and/or long term effects in at least some people...
Canadian scientists tested this dichloroacetate (DCA) on human’s cells; it killed lung, breast and brain cancer cells and left the healthy cells alone.
Tests on human cells in a test tube or petri dish does not mean the thing tested will work the same in a living human body.
It was tested on Rats inflicted with severe tumors; their cells shrank when they were fed with water supplemented with DCA. The drug is widely available and the technique is easy to use, why the major drug companies are not involved? Or the Media interested in this find?
Probably because they actually read of the real science involved and realized this is not a magic elixir.
In human bodies there is a natural cancer fighting human cell, the mitochondria, but they need to be triggered to be effective. Scientists used to think that these mitochondria cells were damaged and thus ineffective against cancer. So they used to focus on glycolysis, which is less effective in curing cancer and more wasteful. The drug manufacturers focused on this glycolysis method to fight cancer. This DCA on the other hand doesn’t rely on glycolysis instead on mitochondria; it triggers the mitochondria which in turn fights the cancer cells.

The side effect of this is it also reactivates a process called apoptosis. You see, mitochondria contain an all-too-important self-destruct button that can't be pressed in cancer cells. Without it, tumors grow larger as cells refuse to be extinguished. Fully functioning mitochondria, thanks to DCA, can once again die.
This is a gross mischaracterization of the role of mitochondria in cells and the process of apoptosis. It is poorly and sloppily written by someone who clearly does not understand what the hell is being discussed.
Pharmaceutical companies are not investing in this research because DCA method cannot be patented, without a patent they can’t make money,
Right, that's why no one manufactures asprin anymore... oh, wait...

Flat out wrong. Of course you can make money without a patent. Every generic drug in the pharmacopeia is off patent yet they're still made. Just another gross factual error in this article.
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Re: Canada cures cancer, nobody cares

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Furthermore, you can patent specific drug combinations. For example: paracetamol? Not really. Paracetamol with caffeine marketed under a trade brand? Certainly!

The rules are just different, in that you compete a lot more with these drugs. When you have a patent all the profits are yours, but hey it's not like there's a gigantic market for a magic cancer curing elixir or anything...
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Re: Canada cures cancer, nobody cares

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His Divine Shadow wrote:I remain sceptical, because I am not sure cancers are all that alike that a single drug or mechanism about them could be targeted. Isn't that the biggest problem anyway, how different the myriad of cancers are. Also mainstream media catchphrases etc.
You could target all cancer cells easily. Say, high doses of cyanide.

That drug works pretty well:D:D:D:D


Ok, let's talk about side effects. Everyone here knows about targeted therapies right? They're "smart" drugs which home in on specific cancer cells and avoid healthy cells, so, voila, less side effects. Sounds like a miracle isn't it?

Herceptin. Side effect? Cardiac dysfunction.

Velcade. Side effect? Neuropathy. Including some very painful cases.

Erbitux. Well, probably one of the better ones. Just some skin reaction and swelling, including sensitivity to light. You're given anti-histamines to prevent some of the side effects, so at least there's SOME way to avoid them.

Is it any wonder that miracle cures are so popular?
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Re: Canada cures cancer, nobody cares

Post by mr friendly guy »

In human bodies there is a natural cancer fighting human cell, the mitochondria, but they need to be triggered to be effective
Mitochondria isn't a cell. It can be thought of as the "power plant" for a cell. When Star Trek Voyager, yep you heard that right, Star Trek Voyager is more accurate than this article, you know something is wrong. *

* there was an episode where the EMH lectures Naomi Wildman on the the mitochondria and he knew its function, but also understood enough of the evolution of it and its incorporation into human cells from outside sources.
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Re: Canada cures cancer, nobody cares

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more or less already said above, but worth repeating outside of the wall-of-text of that professional rebuttal.

-Cancer is a catch-all name for cadres of different illnesses, people claiming you can cure them all (or even a significant quantity of them) with a single thing should trigger an alarm in your head.

-Anything has drawbacks, which is much more true in medical field due to the fact most biochemical workings are linked together. If you encounter a cure without any adverse effect, then it's safe to assume it is not real.
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Re: Canada cures cancer, nobody cares

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Yeah, this one was pretty rich. I have to admit that I didn't even go so far as to read the peer-reviewed article. I figured it was a crock when the popular press article made drug companies eeeeevil conspirators for not starting clinical trials...despite the fact that the study finished last week. Um, that's not how it works.

This is a good example of why we need publicly funded research, though. Generic drug companies rely on low costs, so they're not going to fund clinical trials by and large...but if the trial's done, they could definitely step in to make the drug.
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Re: Canada cures cancer, nobody cares

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I had a friend narrowly pull through lung cancer (she didn't smoke, just unlucky) by way of some last-ditch "Well you're a terminal case anyway, what is there to lose?" experimental treatments. It was absolutely brutal on her, not just her own problems, but seeing the other patients die around her. Especially the kids.

Having had this small glimpse of Fucking Serious Cancer Research makes claims of a miracle cure ridiculous. If such a thing existed these people would be ALL THE FUCK OVER IT and giving it to the children they would otherwise watch die. Guns to their heads wouldn't stop them.
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Re: Canada cures cancer, nobody cares

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Broomstick wrote: Right, that's why no one manufactures asprin anymore... oh, wait...

Flat out wrong. Of course you can make money without a patent. Every generic drug in the pharmacopeia is off patent yet they're still made. Just another gross factual error in this article.
A more precise way of putting it would be to say that without a patent you can't make enough money to recoup the cost of the clinical trials.
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Re: Canada cures cancer, nobody cares

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PeZook wrote:Furthermore, you can patent specific drug combinations. For example: paracetamol? Not really. Paracetamol with caffeine marketed under a trade brand? Certainly!
Only if you can show that there is some sort of unexpected result when you mix paracetamol with caffeine. Simply adding a known drug/ingredient/whatever to another known drug/ingredient/whatever won't get you a patent, unless you've discovered some unexpected benefit to the new formulation that would not have been obvious to other researchers.
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Re: Canada cures cancer, nobody cares

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But if that's the case, they should be able to get a patent for a radical new therapy using a common drug, shouldn't they?
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Re: Canada cures cancer, nobody cares

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PeZook wrote:But if that's the case, they should be able to get a patent for a radical new therapy using a common drug, shouldn't they?
They couldn't patent the substance of the drug itself, but they could patent the use of the drug for treating the disease (assuming the fact that the drug is useful for treating the disease is an "unexpected result").
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Re: Canada cures cancer, nobody cares

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sciguy wrote:
PeZook wrote:But if that's the case, they should be able to get a patent for a radical new therapy using a common drug, shouldn't they?
They couldn't patent the substance of the drug itself, but they could patent the use of the drug for treating the disease (assuming the fact that the drug is useful for treating the disease is an "unexpected result").
That seems pretty suspect to me, even if it's actually what the patent laws say. A situation where a hospital has large stocks of a generic drug on hand but aren't allowed to use them to treat somebody even though they know that it would work and be safe because they haven't paid thousands of dollars/Euros/pounds/whatever to somebody who didn't even make the drug is very undesirable.
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Re: Canada cures cancer, nobody cares

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Psychic_Sandwich wrote:That seems pretty suspect to me, even if it's actually what the patent laws say. A situation where a hospital has large stocks of a generic drug on hand but aren't allowed to use them to treat somebody even though they know that it would work and be safe because they haven't paid thousands of dollars/Euros/pounds/whatever to somebody who didn't even make the drug is very undesirable.
Is it substantially worse than a hospital having to pay thousands to a drug company for a patented drug that could be synthesized and sold for peanuts by any of that company's competitors?
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Re: Canada cures cancer, nobody cares

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sciguy wrote:
Psychic_Sandwich wrote:That seems pretty suspect to me, even if it's actually what the patent laws say. A situation where a hospital has large stocks of a generic drug on hand but aren't allowed to use them to treat somebody even though they know that it would work and be safe because they haven't paid thousands of dollars/Euros/pounds/whatever to somebody who didn't even make the drug is very undesirable.
Is it substantially worse than a hospital having to pay thousands to a drug company for a patented drug that could be synthesized and sold for peanuts by any of that company's competitors?
If they're the only people allowed to manufacture it, then they're the only people allowed to manufacture it. My objection is to the idea that they should have the ability to restrict how something potentially widely available is used, not to the idea of patents; being the sole legal manufacturer and telling everybody how to use a generic drug that you don't hold rights over are two different situations.
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Re: Canada cures cancer, nobody cares

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Psychic_Sandwich wrote:
sciguy wrote:
PeZook wrote:But if that's the case, they should be able to get a patent for a radical new therapy using a common drug, shouldn't they?
They couldn't patent the substance of the drug itself, but they could patent the use of the drug for treating the disease (assuming the fact that the drug is useful for treating the disease is an "unexpected result").
That seems pretty suspect to me, even if it's actually what the patent laws say. A situation where a hospital has large stocks of a generic drug on hand but aren't allowed to use them to treat somebody even though they know that it would work and be safe because they haven't paid thousands of dollars/Euros/pounds/whatever to somebody who didn't even make the drug is very undesirable.
There's the practice of "off-label use" where any drug can be prescribed for something where clinical trials have not been performed but the doctor feels the medication may be useful. Perfectly legal at least in the US. Big Pharma hates it, but it's done all the time. One of the situations they hate the most is the use of bevacizumab for wet macular degeneration, at around $40 a dose, versus the use of ranibizumab at around $1600 a dose.
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Re: Canada cures cancer, nobody cares

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sciguy wrote:
PeZook wrote:Furthermore, you can patent specific drug combinations. For example: paracetamol? Not really. Paracetamol with caffeine marketed under a trade brand? Certainly!
Only if you can show that there is some sort of unexpected result when you mix paracetamol with caffeine. Simply adding a known drug/ingredient/whatever to another known drug/ingredient/whatever won't get you a patent, unless you've discovered some unexpected benefit to the new formulation that would not have been obvious to other researchers.
Caffeine is known to increase the uptake of many drugs into the body, so mixing paracetamol/aceitminophen with caffeine increases the uptake from the gut and makes it work faster than if you just took paracetamol/aceitminophen by itself. So, it should be able to be patented by that logic, then.
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TOSDOC
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Re: Canada cures cancer, nobody cares

Post by TOSDOC »

mr friendly guy wrote:
In human bodies there is a natural cancer fighting human cell, the mitochondria, but they need to be triggered to be effective
Mitochondria isn't a cell. It can be thought of as the "power plant" for a cell. When Star Trek Voyager, yep you heard that right, Star Trek Voyager is more accurate than this article, you know something is wrong. *

* there was an episode where the EMH lectures Naomi Wildman on the the mitochondria and he knew its function, but also understood enough of the evolution of it and its incorporation into human cells from outside sources.
I think what the article's author meant to write was midichlorians.
"In the long run, however, there can be no excuse for any individual not knowing what it is possible for him to know. Why shouldn't he?" --Elliot Grosvenor, Voyage of the Space Beagle
sciguy
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Re: Canada cures cancer, nobody cares

Post by sciguy »

Psychic_Sandwich wrote:If they're the only people allowed to manufacture it, then they're the only people allowed to manufacture it. My objection is to the idea that they should have the ability to restrict how something potentially widely available is used, not to the idea of patents; being the sole legal manufacturer and telling everybody how to use a generic drug that you don't hold rights over are two different situations.
I understand what you're saying, I just don't see that big of a practical difference between the two scenarios; in both cases there's an artificial price barrier.
Broomstick wrote: There's the practice of "off-label use" where any drug can be prescribed for something where clinical trials have not been performed but the doctor feels the medication may be useful. Perfectly legal at least in the US. Big Pharma hates it, but it's done all the time. One of the situations they hate the most is the use of bevacizumab for wet macular degeneration, at around $40 a dose, versus the use of ranibizumab at around $1600 a dose.
There's nothing illegal per se about off-label drug use, but if the off-label use infringes on someone's method-of-use patent, then it certainly can be illegal.
Akhlut wrote:Caffeine is known to increase the uptake of many drugs into the body, so mixing paracetamol/aceitminophen with caffeine increases the uptake from the gut and makes it work faster than if you just took paracetamol/aceitminophen by itself. So, it should be able to be patented by that logic, then.
No, if it's known to pharmacologists/doctors/whoever that caffeine has that effect, than it would likely not be patentable, because the result is not unexpected.
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