Medical Researchers: What are the stumbling blocks to this diabetes research?

[toadspittle]

A Diabetes Researcher Forges Her Own Path to a Cure (Published 2004)

…

Diabetes occurs when a white blood cell, part of the body’s immune system, migrates to the pancreas and mistakenly sees islet cells as foreign tissue. It then multiplies and destroys the islets. But, Dr. Faustman learned, she could block the white cells by supplying them with a piece of protein that signaled that the islet cells were normal cells, rather than foreign invaders.

She also had to stop the attack that was under way in the pancreas. That required killing the white cells that were doing the attacking. Her solution was to give an off-patent drug, BCG, that is inexpensive, $11 a vial, and approved for use as an immune system stimulant. It elicits the release of an immune system hormone, tumor necrosis factor, that kills activated white cells.

After Dr. Faustman gave the mice the two types of treatment, the attack on the islets stopped.

Then, to her astonishment, something else happened: the islet cells grew back, a development that went against everything known by scientists.

The implications, Dr. Nathan said, were enormous. The diabetic mice, he said, had had extremely high blood sugar levels for weeks and would die without insulin. Researchers had successfully intervened earlier in the disease with these animals but not once diabetes was so firmly established.

“No one had cured them,” he said. “Here was this treatment that we thought would get them ready for a transplant but - eureka! - the diabetes was cured.”

If Dr. Faustman’s findings could be applied to humans, there would be no need for islet cell transplants. Embryonic stem cells, which many researchers believed might be turned into islet cells, eliminating the need to get islets for transplants from cadavers, would also be unnecessary.

…

Mr. Iacocca’s check, and the money he wants to raise, will pay for the initial phase of a clinical trial, the first step for finding out. Dr. Nathan, who will direct the trial, will ask whether BCG kills the islet-destroying white blood cells of patients in the same way it does in mice and, if so, at what dose. Dr. Faustman is working on a blood test that will immediately assess the effects of BCG by determining whether the dangerous white cells are being destroyed.

…

“I can’t wait for the pharmaceutical companies or even government tax money to fund what looks promising,” Mr. Iacocca said. **“They are not known for high risk ** and they are also slow to react. We are trying to get a cure.”

I don’t get it. The drug is approved for human use. It’s cheap. Where’s the high risk? What’s standing in her way?

[Nametag]

I don’t get it. The drug is approved for human use. It’s cheap. Where’s the high risk? What’s standing in her way?

Ethics. Human experimentation is not undertaken lightly. This effect has only worked in mice. Tumor Necrosis Factor is an important and powerful actor in the immune system, and not to be screwed around with – “not known for high risk” is a little disingenuous. BCG is NOT just a drug, it’s a VACCINE – a live-bacterium tuberculosis vaccine derived from mycobacterium bovis. It’s also used to stimulate the immune system in fighting certain cancers. Even though doctors can legally use drugs for off-label uses, that’s not a license for recklessly endangering patients.

[Loopydude]

My WAGs:

-Mice aren’t men. Lots (and lots and lots) of purported cures have been shown to work wonderfully in murine models of disease and yet have failed spectacularly in human subjects. There’s scant other reliable evidence to suggest that pancreatic islets can be regenerated in humans, so are her findings relevant to human biology? Much more work is required.

-That work is going to be expensive and difficult to control. In animal models of diabetes, you’re typically working within a well-established model with a well-described and defined genetic background (e.g. the NOD mouse). Typically, you grow a bunch of inbred mice and can predict with a high level of reliability when and how the disease will progress. You go in a just the right time (these experiments tend to be highly optimized) to mitigate some key pathophysiological process, witness a promising phenomena, and then…make claims you have a cure for diabetes? Maybe, but, most emphatically, maybe not. It’s easy for claims like this to be overhyped by people who don’t understand the models. Any endocrinologist could tell you the situation in the clinic with real human beings is much, much more ill-defined, uncontrolled, just messy in general and not amenable to simple mechanisms of disease progression that your average experimentalist relies upon.

-This is a generic compound she’s working with. So, you do the hugely expensive clinical trials that are needed to demonstrate the drug is a winner, at least in some cases, and then…make no money off of it. You’re now in the hole something like $200 million, and you’ll never recoup this investment. Any competitor can synthesize the drug themselves, using all of your research, and realise only gains, while you get hammered by investors for being an idiot capitalist. Pharma only wants to develop and market drugs it has some hope of making money off of. With no financial upside, there’s zero incentive to pursue it, and less-than-zero incentive when the findings are controversial.

-Being controversial and wrong in such a public way is a rather spectacular means of professional self-destruction for the non-tenured. Dr. Faustman will live to fight another battle if she loses this one. Her post-docs and grad students may not be so lucky. High-risk, controversial projects that appear to refute all other data are not exactly the stuff graduate and post-graduate dreams are made of. Sometimes people want to be a bit more established before they go hunting down scientific kryptonite to play with. It’s a sad truth that the highly competative nature of the field can lead people to be risk-averse during some of their most productive and creative years. Dr. Faustman’s lab is probably working on this project in relative isolation, and hence people will be slow to come around, even if she’s 100% right about everything.

I have no idea if Dr. Faustman’s approach can be validated in people or not. I really hope they can be, and have no financial stake in the outcome either way. It’s often very hard to make claims that fly in the face of conventional wisdom, and this sad fact lays bare some of the imperfections of a system of inquiry that is run, quite simly, by fallible human beings (as we all are). She’s got a powerful (read: rich) ally in Iacocca, though, so she’s got access to the needed resources to further substantiate her claims. It would help a lot to get independent verification, of course. This is such a pressing public health issue that, if it is proven that Faustman’s approach is efficacious, I imagine the funding for trials will be found one way or another.