Potential cure for Type I diabetes and the evil of for-profit drugs and medicine.

[barts]

For profit medicine, be it drugs or procedures, is a murderous way of running a nation's health care system. Case in point, researchers at Harvard University have done human experiments that suggest a possible cure (yes, cure) for Type I diabetes, Diabetes May Be Reversed by Long-Used Vaccine for TB.

However, when the researchers,

...tried to interest every major drugmaker in developing the vaccine as a possible cure for diabetes. All told her there wasn’t enough money to be made in a cure that used an inexpensive, generically available vaccine, Faustman said.

Perhaps this is a long shot, but limited human trials so far show potential to help almost 3 million people in the US alone.

Insulin injections help control Type 1 diabetes for the 3 million Americans with the disease, though there is no cure for the condition usually diagnosed in childhood. Results of the trial showed that two of the three patients given BCG had signs of renewed insulin production. The researchers now plan a larger study that could yield results in three to five years.

It is a travesty that this potential for a cure is not being pursued with the maximum urgency. Is that happening? No. The researchers are,

...trying to raise money to pay for the expensive larger human trials. Her lab so far has received $11 million of the $25 million needed to pay for the next stage of testing. All of the money is coming from private donors, the largest of which is the Iacocca Family Foundation.

This is the social (I would argue criminal) abomination that is for profit medicine. For the medical industry there is big money in 3 million people needing drugs for life. As a consequence, letting them suffer and die is good business.

Let me suggest that if the researchers do, indeed, find a cure for Type I diabetes the medical industry, aided and abetted by their bought and paid for friends in Congress,and the drug companies' FDA will do all they can to suppress and deny those suffering with Type I diabetes a cure.

A medical system that fails to pursue cures for conditions like Type I diabetes needs to scrapped and replaced by policies, systems, procedures, and, indeed, people who are interested in promoting health not disease to increase profits.

[HoleyCarbonGrid]

For profit medicine, be it drugs or procedures, is a murderous way of running a nation's health care system. Case in point, researchers at Harvard University have done human experiments that suggest a possible cure (yes, cure) for Type I diabetes, Diabetes May Be Reversed by Long-Used Vaccine for TB

As someone who's learned about the drug industry for nearly a decade now, let me give you some figures. It takes, on average, 10-15 years and over a billion dollar investment for a company to come up with a usable drug. The initial research, done by chemists and chemical biologists, is only a fraction of the cost - in other words, the sort of work that leads to headlines like "Disease X may be cured by Y," - because such work is usually from preliminary in vitro work.

Preliminary in vitro work, and even the chemical synthesis and/or discovery that goes into it, is incredibly important. However, that's not all that makes a usable drug - or cure - for any particular disease. In fact, far more important are toxicity, and judging of drug-drug interactions or biotoxicity (in other words: toxicity after administration). Those stages - including clinical trials - take up the vast bulk of the cost of a particular therapeutic, often nearly 90% of the total cost.

With that said, there's absolutely no doubt that pharmaceutical companies do not pursue potentially therapeutic compounds simply because they will not be profitable. That's one of the major failings of the modern pharmaceutical industry.

To quote George Merck, someone whose ideology has been largely forgotten in modern pharmaceuticals:

We try never to forget that medicine is for the people. It is not for the profits. The profits follow, and if we have remembered that, they have never failed to appear. The better we have remembered it, the larger they have been.

The problem is largely that the pharmaceutical industry follows cost-benefit projections rather than develop a successful therapeutic, and then worry about cost later. There are several examples of therapeutics which initially seemed to be cost-ineffective, but ended up having much wider efficacy than originally imagined.

The point being that the modern pharmaceutical indstury, as a whole, has major flaws - one of them being overriding profit motive, despite the capacity to develop further therapeutic compounds. However, the interests of the pharmaceutical industry and academia are (almost) completely separate - the interest of the academic community is in developing compounds of potential efficacy, for diseases which have no therapeutic remedy, or at least minimal therapeutic remedy. The pharmaceutical industry, in contrast, is interested in creating compounds of incredibly high and specific therapeutic efficacy, for diseases which may or may not have a remedy available - and do it all for profit.

In other words, if you want to indict anything for the "failure," of modern pharmaceuticals, indict capitalism. Or realize that it's a humanly-flawed system, in which incredible work is done, but which falls short of it's incredible potential both due to profit motive and the complicated nature of both study and approval.

[Angry Citizen]

Interesting, but color me skeptical. Type one diabetes occurs because your immune system eats a certain kind of cell in your pancreas. I don't see how a TB vaccine could regrow the cells - that sounds more like something stem cell research would offer.

[barts]

Interesting, but color me skeptical. Type one diabetes occurs because your immune system eats a certain kind of cell in your pancreas. I don't see how a TB vaccine could regrow the cells - that sounds more like something stem cell research would offer.

Because you personally don't "see how a TB vaccine could regrow the cells" are you suggesting the research should not be funded and not go forward?

[Yarn]

Interesting, but color me skeptical. Type one diabetes occurs because your immune system eats a certain kind of cell in your pancreas. I don't see how a TB vaccine could regrow the cells - that sounds more like something stem cell research would offer.

It is mechanistically plausible

The vaccine, a weakened form of the tuberculosis bacteria, stimulates production of TNF, a cell-signaling protein that plays a role in cell death. With more TNF, the body can attack those harmful immune cells while leaving the rest of the body’s defenses intact. The vaccine is approved by the U.S. Food and Drug Administration for tuberculosis though it isn’t generally recommended for use in the U.S. The vaccine also is approved to fight bladder cancer...

Insulin injections help control Type 1 diabetes for the 3 million Americans with the disease, though there is no cure for the condition usually diagnosed in childhood. Results of the trial showed that two of the three patients given BCG had signs of renewed insulin production. The researchers now plan a larger study that could yield results in three to five years.

Diabetes May Be Reversed by Long-Used Vaccine for TB - Bloomberg

2-3 patients is a damned small sample size though.

There is some evidence to suggest that the body will naturally replace the B cells. In that case, insulin shot dependence would be eliminated so long as whatever killed the B cells in the first place is removed as an obstacle to the regeneration of an adequate number for the body's needs:

The researchers, led by Dr. Pedro L. Herrera, demonstrated that beta cells will spontaneously regenerate after near-total beta cell destruction in mice and the majority of the regenerated beta cells are derived from alpha cells that had been reprogrammed, or converted, into beta cells. Using a unique model of diabetes in mice, in which nearly all of the beta cells are rapidly destroyed, the researchers found that if the mice were maintained on insulin therapy, beta cells were slowly and spontaneously restored, eventually eliminating the need for insulin replacement. Alpha cells normally reside alongside beta cells in the pancreas and secrete a hormone called glucagon, which works opposite to insulin to regulate the levels of sugar in the blood. Alpha cells are not attacked by the autoimmune processes that destroy beta cells and causes type 1 diabetes.

Pancreas Cells Spontaneously Change Insulin cells

Ultimately, even stem cell treatments would be futile unless a way is found to prevent the immune system from wiping out replacements regardless of their origin.

I'd also be curious as to whether the "harmful immune cells" have some beneficial functions as well as the horrible one. If they do, and they presumably do because, why else would they exist?, this treatment, though probably net positive, wouldn't come without deliterious side effects.

If the beta cell killing cells are chemicaly distinctive from the immune system in general, and hence may be separately targeted, and if they aren't intrinsically that important in the broad scheme of things like dispensing with real pathogens (bacteria, viruses, and toxins) and killing cancerous cells, then i'd bet sooner or later this disease will be cured. Now, that could be years from now, or it could be decades. Hence the concern over funding.

[HoleyCarbonGrid]

Color me skeptical as well.

Consider the following:

The vaccine, a weakened form of the tuberculosis bacteria, stimulates production of TNF, a cell-signaling protein that plays a role in cell death. With more TNF, the body can attack those harmful immune cells while leaving the rest of the body’s defenses intact. The vaccine is approved by the U.S. Food and Drug Administration for tuberculosis though it isn’t generally recommended for use in the U.S. The vaccine also is approved to fight bladder cancer.
Study Results

In the study, researchers administered two doses of the BCG vaccine to three patients who had been diagnosed with Type 1 diabetes. The patients were followed for 20 weeks and two of the three were found to have an increase in the death of the insulin-harming cells and a rise in elevation in C-peptide levels, suggesting the production of insulin.
“These patients have been told their pancreases were dead,” Faustman said. “We can take those people, give them a very low dose twice and see their pancreases kick in and start to make small amounts of insulin.”

I find a few problems here. First, any time you promote cell death (apoptosis) you encounter unwanted side-effects - this is why all cancer drugs, to date, have terrible side effects. In other words, while this therapy may be effective, it's unlikely that it lacks harmful effects that outweigh its benefits.

Second, a 33% increase in death of insulin-harming cells cannot be specifically correlated to the effect of the drug. Nor can the rise in elevation of C-peptide levels - in short, a lot more research has to be done before a conclusive link can be drawn between administration of the drug and the desired effect. But it seems like it may warrant further study.

To put that into context, if the drug causes a 33% increase in death, but you have a million problematic cells in your body, that means at maximum efficacy, the drug still leaves roughly 300 thousand problematic cells.

So barts, as an honest question - if you're so convinced this is a cure - at what effective concentration must we administer this "cure," to have an effect?

Consider concentration in terms of, say... micrograms per liter, or micromolar per liter. Lower is better.

[HoleyCarbonGrid]

Ultimately, even stem cell treatments would be futile unless a way is found to prevent the immune system from wiping out replacements regardless of their origin.

I'd also be curious as to whether the "harmful immune cells" have some beneficial functions as well as the horrible one. If they do, and they presumably do because, why else would they exist?, this treatment, though probably net positive, wouldn't come without deliterious side effects.

If the beta cell killing cells are chemicaly distinctive from the immune system in general, and hence may be separately targeted, and if they aren't intrinsically that important in the broad scheme of things like dispensing with real pathogens (bacteria, viruses, and toxins) and killing cancerous cells, then i'd bet sooner or later this disease will be cured. Now, that could be years from now, or it could be decades. Hence the concern over funding.

Hence the problems with a "cure," - both from a biomedical standpoint, and a pharmaceutical standpoint.

Look, if we want to consider a "cure," to involve anything that eliminates the disease and leaves its host alive - then cancer was "cured," decades ago with chemotherapy. Sure, it's not always effective - but it kills cancer cells, and (at least generally) leaves its patients alive.

The problem is in how one defines a "cure," - if a cure is a permanent fix, no longer requiring medication, or of a cure is a permanent fix as in successful remission of the disease with continued medication.

Diabetes, in general, is already "cured," in the second definition - it is treatable, with long lifetimes and minimal impact to lifestyle, albeit with high costs of medicine and care.

A "cure," for diabetes on the other hand, in terms of the first definition - then requires greater efficacy than what's already around - and without side-effects (as current therapeutics are generally as free of side-effects as can be found) and without continuing medication costs.

Cancer, HIV, and several other diseases are also "cured," in terms of the second definition though. I am by no means saying that we should stop looking for final cures - only that it isn't an indictment of modern medicine that none has been found yet.

[barts]

So barts, as an honest question - if you're so convinced this is a cure - at what effective concentration must we administer this "cure," to have an effect?

It seems to me that I haven't made any assertions about whether this is a cure or not.

I have suggested that it is an abomination that the US for-profit "medical" system has created a system where something that some researchers have demonstrated might be a potential cure for a disease that affects over 3 million people in the US alone are going hat in had to private foundations and donors to raise the funds necessary to do trials. Perhaps that is acceptable to you.

Or is it your view that these researchers have not demonstrated anything worthwhile pursuing and ought to be denied funds to further their research?

Lastly, it is ridiculous to ask me "what effective concentration must we administer this 'cure,' to have an effect?" I can't fathom why you'd even pose such an absurd question to me or anyone at this stage of the research. The whole purpose of further research is to determine these matters.

[HoleyCarbonGrid]

It seems to me that I haven't made any assertions about whether this is a cure or not.

Which belies the title to this thread, but regardless...

I have suggested that it is an abomination that the US for-profit "medical" system has created a system where something that some researchers have demonstrated might be a potential cure for a disease that affects over 3 million people in the US alone are going hat in had to private foundations and donors to raise the funds necessary to do trials. Perhaps that is acceptable to you.

Or is it your view that these researchers have not demonstrated anything worthwhile pursuing and ought to be denied funds to further their research?

Lastly, it is ridiculous to ask me "what effective concentration must we administer this 'cure,' to have an effect?" I can't fathom why you'd even pose such an absurd question to me or anyone at this stage of the research. The whole purpose of further research is to determine these matters.

Acceptable to me? Well, quite frankly, yes.

That requires one have a reasonable view of what pharmaceutical companies do, and a further reasonable view of what academic research accomplishes.

Have they demonstrated enough efficacy to warrant additional research? Perhaps - but that's why I asked for an effective concentration. Same for pharmaceutical companies.

In general, an "EC50," (that is, effective concentration to kill 50% of the target cells and/or virus) has to be below a few hundred nanomolar (that is, 10^-9 moles per liter of plasma) to be an effective drug.

I ask for such figures because above that value, harmful side-effects are almost universally more problematic than the therapeutic value. Below that value, it's a problem of pharmacokinetics and metabolism - neither of which I know in this case. As an (I'd say) generally well-informed participator in this debate, I think such figures are incredibly important. In fact, I'm quite curious if you can provide primary scientific literature to support such therapeutic use - if for no other reason than my own curiosity.

Look, if you want drug companies to "cure," quite literally every disease known to man - they already have those compounds in hand. The problem isn't coming up with something that will treat or cure a disease. The problem is doing so in such a way that doesn't create more problems than it helps, in decreasing drug-drug interactions (say: "curing," diabetes while not affecting blood pressure medicines, and the two diseases [diabetes and hyptertension] are almost always related) or in decreasing side effects.

As I said, if your definition is "treat the problem with continued medication," then diabetes, cancer, hypterension, high blood cholesterol, schizophrenia, depression, etc. etc. etc. have already been cured.

The problem is finding permanent cures that do not have the existing drawbacks of current medications. The treatment that is the topic of this thread, from the sources you've provided and the limited amount of information I've have the time to find about it, does not surpass those problems. As such, it is no more a "cure," than insulin therapy and attendant drugs is.

So, does it warrant further research? Almost definitely. So are anti-cancer therapies, and any number of active research areas.

Are pharmaceutical companies somehow negligent for not researching, applying to the FDA, or selling it as " cure," now? Absolutely not. Trust me - as soon as more is known, and it seems like it will be an effective therapy, some pharmaceutical company will spend a few hundred million dollars to buy a patent from a university and run with it.

The system is working as intended in the U.S.A. (aside from an overall lack of funding for the NIH and other federal agencies that fund basic research into such problems). That doesn't mean that the system itself doesn't have problems - only that, as it's been designed and funded, it's terribly effective at its job.

**Edited for bad word choice.

[Yarn]

Hence the problems with a "cure," - both from a biomedical standpoint, and a pharmaceutical standpoint.

Look, if we want to consider a "cure," to involve anything that eliminates the disease and leaves its host alive - then cancer was "cured," decades ago with chemotherapy. Sure, it's not always effective - but it kills cancer cells, and (at least generally) leaves its patients alive.

The problem is in how one defines a "cure," - if a cure is a permanent fix, no longer requiring medication, or of a cure is a permanent fix as in successful remission of the disease with continued medication.

Diabetes, in general, is already "cured," in the second definition - it is treatable, with long lifetimes and minimal impact to lifestyle, albeit with high costs of medicine and care.

A "cure," for diabetes on the other hand, in terms of the first definition - then requires greater efficacy than what's already around - and without side-effects (as current therapeutics are generally as free of side-effects as can be found) and without continuing medication costs.

Cancer, HIV, and several other diseases are also "cured," in terms of the second definition though. I am by no means saying that we should stop looking for final cures - only that it isn't an indictment of modern medicine that none has been found yet.

I suppose so. We also ought to note that if the beta cell killers regenerate, you would still need regular shots to suppress them. So in that case it would not be a permanent "cure".

I know HIV is staved off for a finite time because of immune cell regeneration, but eventually the body looses the capacity to replace what is lost, so if you took shots long enough, you might not need them anymore.

[barts]

Which belies the title to this thread, but regardless...

The word "potential" was not clear?

Have they demonstrated enough efficacy to warrant additional research? Perhaps - but that's why I asked for an effective concentration.

Just a thought, but wouldn't funds for research be needed to determine "effective concentration"? And if funds aren't available until "effective concentration" is demonstrated isn't that the classic Catch 22. Is it reasonable to confound research with such arbitrary standards? I don't think so.

Look, if you want drug companies to "cure," quite literally every disease known to man

Looking at the OP, I am at loss to see where I suggested that drug companies should 'cure' quite literally ever disease known to man. Just sayin' but I'd prefer you debate the points I make, not points you imagine I made.

The system is working as intended in the U.S.A. (aside from an overall lack of funding for the NIH and other federal agencies that fund basic research into such problems). That doesn't mean that the system itself doesn't have problems - only that, as it's been designed and funded, it's terribly effective at its job.

I totally agree that the "system is working as intended in the U.S.A." and that "it's terribly effective at its job" which is enriching the medical industry with a general disregard for patients' health and well-being.

[barts]

Trust me - as soon as more is known, and it seems like it will be an effective therapy, some pharmaceutical company will spend a few hundred million dollars to buy a patent from a university and run with it.

And patent in hand, charge diabetes sufferers tens of thousands of dollars for the "cure" if that is, in fact, what this turns out to be. Better the government spends a few hundred million dollars and provide the cure at little or no cost, but of course that would be socialized medicine and, as we know, the fabric of American culture is so fragile that it would be rent asunder if diabetes sufferers got a break that didn't enrich drug companies.