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Desperately Seeking Cures: Medical research isn’t making progress rapidly enough.
Newsweek Magazine states on its cover: “Desperately Seeking Cures: Medical research isn’t making progress rapidly enough.” (Full article) Their key observation is that the academic medical research world is structured with incentives that perversely favor glamourous discoveries, not cures. The article does not cover diabetes research. I decided that today I would apply it to my area of interest, juvenile diabetes. So this is today’s question:
Why is there no cure for type 1 diabetes?
I want to approach the question logically. Is a cure possible in five years? Is there enough funding available? Then what is to be done?
Is a cure possible?
Yes. We know exactly how to recognize a cure for diabetes: a therapeutic intervention that results in normal blood sugar. That’s it; normal blood sugar is necessary and sufficient, so normal blood sugar is the cure. With a continuous glucose monitor, you can show a diabetic is cured, continuously. The only effective means known to reduce blood sugar is minute-by-minute replacement of the natural hormone insulin (which is missing in diabetics). There is no reason in principle that another compound or hormone could control blood sugar, but there is no plausible candidate. So, in the short term of the next few years, insulin delivery is the only game. We can conclude that curing diabetes is a drug delivery problem.
Insulin is abundant; the challenge is to deliver it in the precise amount needed. The gold standard is natural islet function. We know that islet insulin secretion is affected by many things; mostly blood sugar, but also other blood components, hormones, and nerves (the brain stimulates insulin secretion even before eating begins). All the known mechanical means for injection of insulin (including the ‘artificial pancreas’) fall far short of the islet gold standard. The failure is easy to understand. The response time of an islet is 1-5 minutes. The response time of the artificial pancreas is an hour. So the challenge is like driving a ton of tractor-trailer over a gocart track. It cannot be done no matter what the level of driving skill because the sharp turns needed are out of the question.
Since only islets meet the gold standard for insulin delivery and blood glucose control, this leaves only one hope. Restoring islet function is the cure for type 1 diabetes.
Restoration of islet function means islet regeneration (your own islets regrow) or islet replacement (islets are implanted). Islet regeneration is essentially unknown in actual human diabetics. But islet replacement using the standard human cadaver islet transplantation protocol can normalize blood sugar (cure the diabetes) for months or years. Human islet transplantation is little used because of the side effects of immune suppression drugs.
Islet regeneration will not be a clinical reality in the next five years. It does not happen spontaneously and therapeutic interventions to make it happen are unknown. It is the subject of much academic research, and the primary focus of the Sanford Project in South Dakota. When it succeeds, it will be a cure. It will not succeed in a big way for decades in my estimation.
My conclusion is simple. A cure is possible in five years, namely islet transplantation without immune suppression drugs.
Is there enough funding?
Between NIH, JDRF, ADA, and Venture investors billions of dollars has been spent. That seems like it ought to be enough.
Insulin was discovered on a shoestring budget. The Edmonton protocol was invented on a shoestring budget. Is there a reason that the actual advances are found by people who don’t get funding because they are outside the mainstream? As I can tell you from personal experience, being outside conventional funding systems is liberating. You can take risks. And your passion for accomplishing something real is liberated.
There is more than enough funding for diabetes research to reach a cure. The problem is that most of the research is toward expanding knowledge of diabetes. This is what academic scientists are paid to do as Newsweek observed. When they say they are working to find a cure, they probably mean it, but they are wrong. The incentives academic scientists experience prevent them from finding a cure. Their work is graded in two ways: do they get grants? and do they publish papers in peer-review journals? Grants are awarded by a process that essentially values the opinions of other scientists on the academic treadmill producing a closed shop of ideas. New ideas are not welcome because they are innovative (believe it or not, a reviewer that calls a new idea ‘innovative’ has killed the possibility of funding by peer reviewed grants). The ideal academic project is to study the effect of a single gene on some aspect of diabetes. Because molecular genetics is so new the study probably has not been done, and it will yield publishable information. And all medical researchers agree genetic studies are worth doing. The only problem is that such studies do nothing to advance the cure.
The NIH position is that if they fund expansion of knowledge of diabetes we get closer to a cure. That assertion is repeated so often, and accepted without question by the politicians and press, that it can be regarded as settled truth. The problem for me is I don’t see any evidence that it is in fact true. For example the vast majority of studies in islet transplantation are done in mice. As I have explained on other essays on the site, mouse metabolism is completely different than human glucose metabolism so metabolic results in mice do not predict success in humans. Similar arguments apply to mouse versus human immune systems. Yet every month (it seems) some academic announces that diabetes has been cured in NOD diabetic mice. And the press echoes the announcement without question! Such studies actually slow down progress toward the cure by diverting resources to worthless mouse studies.
Then what is to be done?
I can only speak for myself and the people working with my group. We are doing it. We believe that islet transplantation without immune suppression drugs is the closest we will get a to a cure in the next five years. We have mapped out our plan to do it, and are moving on it as fast as possible with the funding we have. But our funding is free of academic incentives so we are free to pursue our passion for a cure. We are developing the Islet Sheet encapsulation system, the perfection of which will not expand knowledge very much by academic standards.
My group invents medical technologies that solve medical problems. The resulting products are bought by medical providers. We do not exist to expand knowledge of disease; we work to improve medical care. And we work for profits. The profits from the inventions we have already put on the market through partners are funding our diabetes research. In addition animal studies with our collaborators at UC Irvine are funded by the Hanuman Medical Foundation. So I answer to my investors (who want to profit from Islet Sheet sales) and the Solving Diabetes Project Advisors at the Foundation. The chief advisor is Dr. Andrew Drexler, Chair of Endocrinology at UCLA, and he is a clinician, and is looking for a clinical cure. Andy certainly does not mind expanding knowledge but he wants to cure his patients more. So the incentives for Cerco Medical and the Hanuman Medical Foundation’s “Solving Diabetes Project” are aligned with the cure.
So how do you cure diabetes? Couple a group with proven success in cell therapy and a plan to apply cell therapy to diabetes with the incentives to cure type 1 diabetes. Simple but rarely tried. If you agree it should be tried, you know where to send your money.
I agree with you, although I would re-emphasize a point discussed with you earlier, that there remains an as yet imperfectly quantified contribution of autoimmune processes and genetics to the picture of diabetic complications which euglycemia may not correct. The fact that some pre-diabetics with impaired glucose tolerance but without hyperglycemia still have diabetic neuropathy suggests that neuropathy either develops from extremely subtle glucose excesses or from processes which precede hyperglycemia entirely. (See M. Polydefkis, et al, “New Insights into Diabetic Polyneuropathy,” Journal of the American Medican Assocation, vol. 290, p. 1371 (2003); cf. M. Dobretsov, et al, “Early Diabetic Neuropathy: Triggers and Mechanisms,” World Journal of Gastroenterology, vol. 13, no. 2, p. 175 (2003); R. Young, et al, “Chronic and Remitting Painful Diabetic Polyneuropathy,” Diabetes Care, vol. 11, p. 34 (1988)).
Clearly, the balance between the energy invested in basic research as opposed to therapeutics has shifted too far towards the former in the last half century, largely under the academic pressures you identify. President Truman declared war on cancer in 1950, and then once again in 1972 President Nixon declared another war on cancer, and both projects were backed by large funding efforts which generated encyclopedias full of basic research data and very little clinical progress, as anyone familiar with the dismal cure rates for lung and pancreatic cancer can testify. There is in contrast a lot to be said for the kind of intelligent superficiality which made salicylates available to medicine from Antiquity until today, even though their mechanism of action was not identified until the 1970s. Diabetology now needs an Edison more than it needs a Newton.
One factor you didn’t mention which I would have included is the financial interests of the pharmaceutical industry. Every time I see another ad for the myriad of often expensive gadgets offered to bridge the gap between normoglycemia and the blood sugar levels that can now be achieved with the present, inadequate tools, I realize how much money is invested in the basic treatment for diabetes continuing to stagnate. I half expect to read in the newspaper five years from now that Big Pharma has acquired Cerco Medical, Scott King is now vice-president for new product development for a salary of $8,000,000 a year, and the islet sheet encapsulation technology is being re-designed as an environmentally sensitive replacement for Teflon on frying pans.
Has anyone ever done the research on how much it actually costs for the manufacturer to make a bottle of insulin vs. how much it costs a diabetic to buy one? Your title is correct….The cure is 5 years away AND ALWAYS WILL BE. I, as well as many other Americans, believe there are several people getting rich off from this devastating disease, so why cure it? Can anyone out there prove this theory wrong? If so…email me – I’d love to hear from you!
On my comment left above….Scott – I am not demoralizing your efforts to finding a cure. I applaud you for taking the steps to go above and beyond, and as mentioned in some of your articles you have run into funding constraints on this project. Maybe we could ask the companies that are producing all these new insulins and diabetic medications/devices while making a 5,000% profit to step-up to the plate. If Obama put a hoarding law into effect tomorrow – there’s no doubt in my mind that diabetes as well as several other diseases would be cured. Hey – by any chance did you ask the FDA for any contributions? I am not trying to cast a negative shadow where there is positive light and I am past venting at this stage. I just think it’s time for our government and medical society to stand up and answer the questions that are asked so often…. Why can a company make an $80.00 profit off from a bottle of insulin or other diabetic prescription/device? Is any of that money being filtered back into research for diabetes? If so, where is the documentation? It’s wonderful that we have Scott working on a “cure”, however – I think we need more advocates to go after the real truth behind the reasons why a cure has not yet been found. If we can send a man to the moon – we can certainly figure out how to get a pancreas to generate islets again!
Danielle, I plan to devote a future column to the costs of making a medical product like insulin compared with the price charged. Not only do I run a medical research company, I used to be a medical investment analyst on Wall Street so I know something about it.
On opposition of entrenched interests to curing diseases, the situation is very complicated. I think the main problem is that incentives in the medical business are perverse, rewarding good (but not curative) therapies for major chronic diseases. That is another really big topic.
The government already spends enough m oney to cure diseases through the NIH. But most of the money is going to expand knowledge, not cures. So members of the public should push congress to cure diseases, not study them.