A Talk with Denise Faustman: The Hope is “in the Mechanism”

I was fortunate to have the opportunity to meet with the legendary Dr. Denise Faustman for a latte and a long talk last week in Boston. While I expected her to be smart as a whip, what I didn’t expect was the bubbly personality. She has an infectious giggle and a glimmer in her eyes when she talks about her work (which she is excellent at promoting, btw — her PR manager sought me out). I was as charmed by her personage as I was fascinated by her story.

Indeed, little in the field of diabetes has ever excited as much fervor — and at the same time as much furor — as Dr. Faustman’s cure research for type 1 diabetes. In 2001, she reported a scientific breakthrough in her lab: diabetic mice were actually cured using a “cheap, generic drug” called BCG. Yet other scientists have had difficulty replicating her results, or believing, as she does, that transitioning the treatment to humans was at all feasible.

Her work has been so controversial, in fact, that she’s had to reach outside the traditional sphere of research funding (NIH, JDRF) to finance her work. To date, she’s raised $11M in “philanthropy money” from individual donors and private organizations, including the Lee Iocacca Foundation.

To countless patients and their families, Dr. Faustman is a great angel of hope. Yet there are many in the medical world who continue to doubt the integrity of her work.

I’ll admit that I went into this interview feeling quite ambiguous, but as a type 1 diabetic myself, I find it simply impossible not to cheer her on (or at least cross your fingers that she’s onto something real).

[Editor’s Note: For a little more on the 'deep science' that Faustman is pursuing, see this excellent two-part series from Diabetes Self-Management.]

Now, without further ado, a record of our conversation:

DBMine) Dr. Faustman, I’m sure you’re aware that we have to be careful about getting people’s hopes up. Do you use the C-word (cure) when you talk about your work?

DF) The C-word is an interesting word. If you ask different people, the answers are staggeringly diverse. How do you define ‘cure,’ anyway? For example, is sticking a donor pancreas or transplanted cells into someone really a cure?

I view the word “cure” as normal blood sugars in a person not on immuno-supression drugs and who has no complications.

No one’s been able to establish this in long-term diabetics for any period of time.  It would be historic if we could do so.

DBMine) OK, so I have to start by asking you: others have tried the BCG vaccine for treating diabetes in various studies, but were not able to replicate the pancreas cell regeneration that you saw in your mice. Why pursue an approach that may very well be ineffective?

DF) BCG induces a substance called TNF, that is known to kill off the ‘bad’ T-cells — the ones that attack the insulin-producing cells. We had screened generic drugs to find out which ones product TNF or mimic its action, and we identified BCG.

The problem was the mechanism. (Other researchers) didn’t know the right dosing, and that’s what we’re trying to figure out. That’s like saying “we conducted three trials and gave subjects one unit of insulin, and that wasn’t effective — so insulin must not be effective.” You have to get the delivery mechanism, or the dosing, right.

DBMine) But other scientists did initially have some success with BCG in mice as well. Why did they drop it?

DF) Many researchers are strictly “mouse doctors” — they don’t work on humans. And the stupidity of the mouse doctors with BCG was they gave a vaccine dose that was something like 750 times the animal’s body weight — so maybe they gave 20 units to a diabetic mouse and it was OK for a while. Then you try giving, say, one unit to humans and nothing happens…

We believe that the correct way to move trials forward is to experiment with the dosage and to monitor the T-cell burden for efficacy.

DBMine) This sounds reasonable. But again, why have other scientists rejected your approach, including the decision-makers at JDRF?

DF) I don’t know why other researchers rejected it. Maybe there’s jealousy over who’s going to get credit for pancreas regeneration.

As far as funding goes, this is disease reversal we’re talking about, with a cheap generic drug. What’s the economic model for that? The drug companies were very straightforward with us that “it’s an interesting problem, but there’s no profit in pursuing it.”

Also, we’re looking at treating long-term Type 1 diabetics. No one else is studying them. A funding pool like the TrialNet program only supports pre-diabetics and new-onset patients. We couldn’t even apply for funding.

DBMine) So how exactly is your first human trial set up?

DF) It’s based on the mechanism. We have six pairs of people and we’re giving them two injections, four weeks apart — very tiny doses — for a period of six months. We’re doing intense monitoring of biomarkers every week. We draw four vials of blood and conduct exhaustive testing to see if anything has changed. The purpose is to create longer and longer intervals of a disease-free state in these patients.

What we’re doing in the lab is developing new blood tests, something like “the next glucose monitor for T-cells.” Half our lab is engineers. We’re actually developing 12 different immunological assays, or new measures, to monitor T-cell count, monitor cell death, separate the blood, etc. Then we can see if one factor should correlate with BCG and the removal of the bad T-cells.

DBMine) Wait, so you only have 12 people in your study? How can you draw conclusions from such a tiny sample size?

DF) That’s why this is so different than your typical pharma-based treatment research. We don’t need thousands of patients to evaluate a drug that already has an impeccable safety record and a know path of action. This is a cheap, generic drug that has been on the market for 10 years already — used to treat tuberculosis. We just require intense blood testing. For this, we sought out 12 people with zero pancreas function and negative C-peptide levels, so by clinical standards their pancreas is dead.

We can do faster, tighter clinical trials to hone in on whether things are working or not working. We can also save a ton of money because we don’t even need to file for FDA approval — each FDA submission costs $250,000.

DBMine) I heard that some patients were driving up to your lab at Mass General to give blood for the study. What is that about?

DF) Yes, we didn’t solicit it, but the response has been overwhelming. People call us and email us from all over the world.  They want to come and give blood that we can use for additional testing. We now have 4 people a day, 5 days a week booked about three years in advance!

We don’t keep a blood bank. The blood has to be tested immediately and then discarded. But we’ll have an amazing amount of data.

DBMine) Wow, can anyone participate?

DF) We don’t take patients below the age of 8. They have to be old enough to articulate themselves that they want to do this and why. It can’t just be the parent pushing them. I didn’t go into pediatrics because I didn’t want to be mean to kids — and I’m not poking them unless they really want to do it.

DBMine) So what would you consider a success for your Phase I trials?

If we can isolate and validate these T-cell markers for use in Phase II: which one will give us the best notion of sensitivity and specificity for defining T-cell removal in the next phase?

The big questions to answer are: Are these assays we’re working on reproducible? Can we follow someone for six months and get the same data every time? Can we get the kinetics right to use this cheap vaccine in humans to make it effective? The data should be out around January or February of 2010.

DBMine) What if none of them stands out as showing real promise? Would you halt the project?

No. Then we’d select some markers based on budget, simplicity, ease of execution, etc. and keep experimenting.

DBMine) Isn’t this very risky? It sounds like the whole thing could fall apart.

DF) Of course, it is risky because who wants to take the risk in an area where nothing’s ever been tested before?

The easier path would be to go the established route — but why not do something ground-breaking? Why stick to a safe career for decades when you have the chance to take the risk of trying something significant, that could create a giant leap forward in medicine?

We may fail, but we still think we should be at least trying this approach.

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They say there’s a fine line between genius and madness; only time will tell. But either way, I admire Dr. Faustman’s spirit and her spunk. And of course, any Harvard researcher hot on the trail of a possible cure for diabetes is commendable in my book — whether or not she’s the one to eventually crack the code.