Why Did the JDRF Try to Discredit Cure Research?
Arguably the most influential voice in diabetes research is the Juvenile Diabetes Research Foundation (JDRF). They award more than 500 research grants in all.
In recent years, the JDRF has focused its funding on two areas: embryonic stem cell research and islet transplantation. The organization spent $1 million last year in the campaign to pass Proposition 71, California’s embryonic stem cell research initiative, and sent representatives to Washington to lobby the federal government to loosen its restrictions on embryonic stem cell research.
But there are many who question the notion that a cure lies in the direction of transplantation.
Among the concerns with a “transplant cure” are the need for an ongoing regimen of volatile anti-rejection drugs and the availability and expense of donor beta cells.
Even if these challenges can be overcome, another issue lurks in the background. After a transplant, the autoimmune disease that caused diabetes in the first place may attack and kill the newly transplanted islet cells. According to some observers, the uneven long-term success rates of early transplant recipients might be due to such a latent autoimmune response.
The Plight of Denise Faustman
Diabetes Health has been following the research of Denise Faustman, MD, of Massachusetts General Hospital in Boston since her research into this autoimmune process was published in the November 14, 2003 issue of Science.
Faustman’s research reversed type 1 in mice by identifying the immune system defect involved in the destruction of insulin-producing cells and developing a therapy to stop the autoimmune system from attacking these cells. Using spleen cells from nondiabetic mice, the researchers were able to stop the destruction of islets in the immune systems of diabetic mice.
When Faustman approached the JDRF with a request to replicate the research in humans (which would cost millions of dollars), the reviewers took a pass. This should come as no surprise, however, as the JDRF approves 500 grants a year but has to say no to many more.
And Faustman’s approach was unconventional—some would even say revolutionary. So the JDRF’s reluctance to fund her research might be understandable.
The New York Times Article and the Reaction
What may be more difficult to explain, however, is the foundation’s response to an article in the November 9, 2004, issue of The New York Times. In the article “I Beg to Differ: A Diabetes Researcher Forges Her Own Path to a Cure,” journalist Gina Kolata addressed Faustman’s inability to secure funding for her research through backers that included pharmaceutical companies and the JDRF. Kolata said that the reason for the resistance was simple: “ . . . her findings, which raise the possibility that an inexpensive, readily available drug might effectively treat type 1 or juvenile diabetes, challenge widespread assumptions. Many diabetes researchers insist that a cure lies instead in research on stem cells and islet cell transplants.”
Two members of the diabetes community—Diane Mathis, MD, and Christophe Benoist, MD, both scientific colleagues of Faustman at Harvard Medical School—read Kolata’s article and were upset enough to send a letter to the editors.
Both Mathis and Benoist hold prestigious positions at the JDRF Center for Islet Transplantation at Harvard Medical School. In their letter, they write: “This piece claims that Dr. Denise Faustman of Massachusetts General Hospital has, revolutionarily, cured mice of type 1 diabetes and insinuates that, were it not for the jealousy of scientific colleagues and the conflict of interest of funding agencies, would be testing her proven method in human diabetes patients. We would like to refute some of the more glaring of the many incorrect statements underlying these claims . . .”
The letter also contained assertions and implications that Faustman’s earlier research efforts—published in the June 21, 1991, issue of Science and the December 1999 issue of Molecular and Cellular Biology—had not been repeatable.
The editors at The New York Times declined to print the letter from Mathis and Benoist. In reply to a request by Diabetes Health, a New York Times editor explained, “After receiving the letter from Dr. Mathis and Dr. Benoist, we did contact Dr. Denise Faustman for her response, as we would contact anyone who was the subject of such charges. After examining the letter, the response and other material, we concluded that there was nothing in the article that warranted a correction.”
The JDRF Sends an E-Mail
When The New York Times did not publish the Mathis- Benoist critique, the JDRF decided to take matters into its own hands.
Richard Insel, MD, executive vice president for research at the JDRF, circulated an e-mail to JDRF chapters around the country containing the unpublished Mathis and Benoist letter.
Merrill Goozner, director of the Integrity in Science Project for The Center for Science in the Public Interest, is disturbed by the JDRF going to these lengths to discredit Faustman.
“It is shocking to see that scientists, rather than evaluating something on its merits, would spend so much time attacking the messenger. You have to wonder, what is their real motivation? You would think that scientists connected with the JDRF would be pursuing every effective cure, not attacking approaches that rival their own.”
Not Funding Faustman’s Research, But Replicating It
Though the JDRF repeatedly chose not to fund Faustman’s research and subsequently criticized its merit, they have swiftly moved to replicate it. New projects are underway by a number of JDRF-funded researchers to demonstrate the mechanisms for pancreatic cell regeneration.
Diane Mathis herself is heading up a new $5 million JDRF project: Islet Regeneration During Reversal of Autoimmune Diabetes in NOD Mice. Curiously, the name of this study is nearly identical to the title of the paper Faustman published in the November 14, 2003 issue of Science: “Islet Regeneration During the Reversal of Autoimmune Diabetes in NOD Mice.”
Another interesting detail appears in the JDRF’s IRS 990 form for the 2002 tax year. This is the annual tax return required of nonprofit organizations. Unlike personal returns, the 990 is a matter of public record.
To determine whether a particular organization is worthy of their financial support, major donors closely scrutinize the full content of such returns. In an attachment labeled “Grants and Allocations,” the JDRF could have chosen to feature any of its 500 grantees. Instead, the first item in the first column of the first page reproduced from JDRF e- Newsletter #36 states, “A research team . . . headed by Denise Faustman, MD, PhD, reports it has reversed type 1 diabetes in mice . . . ”
The JDRF had plenty of success stories in stem cell research and transplant therapy. But they chose to give headline space in a section devoted to grants and allocations to a researcher they had repeatedly declined to fund. It may be worth noting that the JDRF return for tax year 2002 was filed on February 11, 2004—three months after Faustman’s Science article appeared.
Questions Left Unanswered
It is said that imitation is the sincerest form of flattery. If that’s the case, the JDRF may have changed its tune regarding Faustman. Their March 2, 2005, announcement of an international “dream team” to study the regeneration of islets may indicate a positive development in the search for a cure. But for the millions affected by this disease, the pattern of their recent actions may raise questions that aren’t answered in their press releases or fundraising brochures.
Diabetes Health interviewed Bill Ahearn, vice president of strategic communications for the Juvenile Diabetes Research Foundation, for additional perspectives on the issue.
Q: The JDRF is the most significant private force in the pursuit of a cure for type 1 diabetes. Individuals directly affected by diabetes want to know that the substantial amount of time and money that they contribute to such research is being spent wisely. The letter written by Drs. Mathis and Benoist and the JDRF’s widely distributed e-mail has caused many in the diabetes community to question the JDRF’s motives. Does the JDRF continue to stand behind the critiques of Denise Faustman’s work expressed in the Mathis-Benoist letter and in the subsequent e-mail?
A:The [e-mail] message said that it’s important that you not come away with the idea that a cure has been found and that no one is willing to fund it . . . The problem with the [New York Times] article was that there were a lot of sweeping allegations about the reasons why we and others rejected that proposal [to fund Dr. Faustman’s research]. We provide to the scientist—in this case Drs. Faustman and Nathan—that we will not talk about the specific reasons for declining it . . . There are opposite opinions to what was printed in that New York Times article. We stand behind the fact that there are opposite opinions . . . The reason we sent that letter around was because we didn’t have the ability to send our own critique around... That letter was a proxy for our ability to say, well, look, there might be two sides to this story.
Q: In determining who gets JDRF grants, how do you know if the system works well? We still don’t have a cure for diabetes yet.
A:I agree with you entirely, and it’s something that vexes us as much as it bothers anyone. The idea of JDRF is to get out of business as soon as humanly possible. It doesn’t mean there hasn’t been progress over time. And if you look at medical history, there’s been approximately one disease cured to my knowledge—that’s polio. Everyone else is actually spending a lot more money than we’ve spent on type 1 diabetes, and they haven’t reached that endpoint yet.
Shortly before press time, Diabetes Health received this letter from Peter Van Etten, President and CEO of the JDRF.
April 8, 2005
Over the last year, we have been asked why the JDRF does not currently support Dr. Denise Faustman. We would like to take this opportunity to clear up some of the misconceptions surrounding the JDRF and Dr. Faustman.
The JDRF and Dr. Faustman have a long history of working together. The research application by Dr. Faustman and Dr. David Nathan was one of many regeneration proposals the JDRF reviewed last year. It was also one of the many that we chose not to fund. That decision reflects a change in JDRF’s significant focus on, or ongoing support for, regeneration science. Dr. Nathan and Dr. Faustman’s request to JDRF was for only a fraction of the funds necessary to initiate her clinical trials. The funding for her clinical trials primarily has and will come from the generous commitment of the Iacocca Foundation.
JDRF has actively supported regeneration research for the past 10 years. By the end of this year, we will have funded some $10 million in science related to the endogenous regeneration of beta cells as a possible cure for type 1 diabetes, including studies to replicate Dr. Faustman’s findings in mice. We remain very excited about the potential for regeneration in general. It was been one of our six therapeutic goal areas since early 2003. JDRF has a very close relationship with the Iacocca Foundation, and a long history of partnering with them on research projects. The Iacocca Foundation and Massachusetts General Hospital continue their efforts to raise money for Dr. Nathan and Dr. Faustman’s clinical trials through www.joinleenow.org. We wish them the best of luck.
Peter Van Etten
President and CEO
Juvenile Diabetes Research Foundation
The original email from Dr. Richard Insel, JDRF VP for Research.
Date: Sun, 14 Nov 2004 17:01:33
To JDRF Executive Directors:
In the event that you didn't see it, Tuesday's New York Times included an article on a Massachusetts researcher's work with type 1 diabetes Diabetes Researcher Forges Her Own Path to a Cure").
To provide you with some information on that research, in general, and on the New York Times article, in particular -- in the event you are asked about them by staff, volunteers, donors, or prospects -- attached is a letter sent to the New York Times by a Harvard diabetes researcher reacting to Tuesday's article.
Hopefully, people you talk with won't come away from this article thinking that a cure has been found, but no one is willing to fund it. As you know, we would go to the ends of the earth to fund science that would cure type 1 diabetes.
Dr. Richard Insel
Executive Vice President for Research
Below is the unpublished New York Times letter that was circulated by the JDRF to its chapters.
November 10, 2004
We are disappointed that the New York Times chose to publish an article that did not present both sides of a scientific debate. We refer to the article "I Beg to Differ: A Diabetes Researcher Forges Her Own Path to a Cure" published on Nov. 9, 2004. This piece claims that Dr. Denise Faustman of Massachusetts General Hospital has, revolutionarily, cured mice of type-1 diabetes and insinuates that, were it not for the jealousy of scientific colleagues and the conflict-of-interest of funding agencies, would be testing her proven method in human diabetes patients. We would like to refute some of the more glaring of the many incorrect statements underlying these claims:
The Nov. 9 article opens with the eye-catching remark that Dr. Faustman is the only scientist to have cured diabetes in mice. This statement is patently false. Multiple scientific groups have cured diabetes in mice by multiple means. In fact, two of the most promising clinical trials currently being conducted on type-1 diabetes patients are based on a report published in the Proceedings of the National Academy of Sciences in 1994 that injection of a particular antibody into mice cures them of their diabetes.
It is disappointing that the article quotes one of Dr. Faustman's close colleagues that "most of the things" she has found "turned out to be true". A better source may have been the public record, which shows that two of Dr. Faustman's most visible scientific contributions, a report in Science in 1991 and another in Molecular and Cellular Biology in 1999, were soon followed by letters-to-the-editor from highly respected research groups at multiple universities around the country attesting that these findings were not repeatable and/or were being misinterpreted.
But it is perhaps most important to correct the misconception that the curative procedure Dr Faustman has used in mice is ready for translation to humans. This procedure entails injecting two major ingredients into recently diabetic mice. The first is a drug similar to one called BCG that is a common component of vaccines, such as the vaccine against TB. The second is an enormous quantity of spleen cells - the equivalent in humans would be the injection of cells from 5 human spleens over a period of 4 years. This procedure simply can't be done in humans. In recognition of this fact, Dr. Faustman and colleagues have approval only to test the effect of BCG alone on diabetes, but it is not known to what extent this drug alone reproduces the previously described effects in mice. We suggest that the article should have reported that the clinical effects of BCG on type-1 diabetes have already been evaluated in humans in several other contexts. In one published study, injection of this drug into diabetic adults had no effect on their progression to disease. In two other studies, it has been found that children at risk of developing type-1 diabetes actually developed overt disease more rapidly when they had been vaccinated with BCG. Clearly, doctors must be prudent in administering this drug to patients.
Lastly, a comment on the insinuations in the article that translation of Dr. Faustman's mouse work to the cure of human diabetes is being held up by the petty jealousies or inconsequential bickering of scientific colleagues, and by the conflict-of-interest of pharmaceutical companies and funding agencies. Although such a "black-sheep" strategy can be an effective one, a quick glance at the facts should serve to show how inappropriate it is. The National Institutes of Health and, through the generosity of many individual donors, private organizations such as the Juvenile Diabetes Research Foundation are currently devoting hundreds of millions of dollars to research on type-1 diabetes. Large fractions of their funds have been set aside for human clinical trials, and there is active promotion to move promising preventative and curative strategies from mice to humans, from the bench to the bedside, as quickly as possible. As a direct result, there are currently some quite promising leads under active investigation. However, to protect patients from useless or even harmful interventions, any proposed clinical trial must pass scientific (and sometimes lay) review before being funded. It would have balanced the article to report that Dr. Faustman's work has not so far been able to pass the objective reviews of the agencies she has applied to. And to report that she has never even applied to the largest government agency that funds clinical trials on individuals with, or at risk of, type-1 diabetes (TrialNet).
We offer our most heartfelt apologies, on behalf of Dr. Faustman, to the individuals with type-1 diabetes, and their families, for having their expectations cruelly raised by the Nov 9th article. We sincerely hope that your readers will not lose their confidence in scientists and in the scientific process. Rest assured that we are aware of the critical need for a cure and are painfully cognizant of our inability to produce one so far. But also be assured that we are doing our utmost to find one as soon as we possibly can, and that there are other avenues that truly do offer hope.
Diane Mathis, Ph. D. and Christophe Benoist, M. D., Ph. D.
Heads, Section on Immunology and Immunogenetics, Joslin Diabetes Center;
Professors of Medicine, Harvard Medical School
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