Why Did the JDRF Try to Discredit Cure Research?

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Arguably the most influential voicein diabetes research is the JuvenileDiabetes Research Foundation(JDRF). They award more than 500 researchgrants in all.

In recent years, the JDRF has focused itsfunding on two areas: embryonic stem cellresearch and islet transplantation. Theorganization spent $1 million last year in thecampaign to pass Proposition 71, California’sembryonic stem cell research initiative,and sent representatives to Washington tolobby the federal government to loosen itsrestrictions on embryonic stem cell research.

But there are many who question thenotion that a cure lies in the direction oftransplantation.

Among the concerns with a “transplant cure” are the needfor an ongoing regimen of volatile anti-rejection drugs andthe availability and expense of donor beta cells.

Even if these challenges can be overcome, anotherissue lurks in the background. After a transplant, theautoimmune disease that caused diabetes in the first placemay attack and kill the newly transplanted islet cells.According to some observers, the uneven long-term successrates of early transplant recipients might be due to such alatent autoimmune response.

The Plight of Denise Faustman

Diabetes Health has been following the research of DeniseFaustman, MD, of Massachusetts General Hospital inBoston since her research into this autoimmune processwas published in the November 14, 2003 issue of Science.

Faustman’s research reversed type 1 in mice by identifyingthe immune system defect involved in the destruction ofinsulin-producing cells and developing a therapy to stopthe autoimmune system from attacking these cells. Usingspleen cells from nondiabetic mice, the researchers wereable to stop the destruction of islets in the immune systemsof diabetic mice.

When Faustman approached the JDRF with a requestto replicate the research in humans (which would costmillions of dollars), the reviewers took a pass. This shouldcome as no surprise, however, as the JDRF approves 500grants a year but has to say no to many more.

And Faustman’s approach was unconventional—somewould even say revolutionary. So the JDRF’s reluctance tofund her research might be understandable.

The New York Times Article and the Reaction

What may be more difficult to explain, however, is thefoundation’s response to an article in the November 9,2004, issue of The New York Times. In the article “I Begto Differ: A Diabetes Researcher Forges Her Own Pathto a Cure,” journalist Gina Kolata addressed Faustman’sinability to secure funding for her research through backersthat included pharmaceutical companies and the JDRF.Kolata said that the reason for the resistance was simple:“ . . . her findings, which raise the possibility that aninexpensive, readily available drug might effectivelytreat type 1 or juvenile diabetes, challenge widespreadassumptions. Many diabetes researchers insist that acure lies instead in research on stem cells and islet celltransplants.”

Two members of the diabetes community—DianeMathis, MD, and Christophe Benoist, MD, both scientificcolleagues of Faustman at Harvard Medical School—readKolata’s article and were upset enough to send a letter tothe editors.

Both Mathis and Benoist hold prestigious positions at theJDRF Center for Islet Transplantation at Harvard MedicalSchool. In their letter, they write:“This piece claims that Dr. Denise Faustman ofMassachusetts General Hospital has, revolutionarily, curedmice of type 1 diabetes and insinuates that, were it notfor the jealousy of scientific colleagues and the conflict ofinterest of funding agencies, would be testing her provenmethod in human diabetes patients. We would like to refutesome of the more glaring of the many incorrect statementsunderlying these claims . . .”

The letter also contained assertions and implications thatFaustman’s earlier research efforts—published in the June21, 1991, issue of Science and the December 1999 issue ofMolecular and Cellular Biology—had not been repeatable.

The editors at The New York Times declined to print theletter from Mathis and Benoist. In reply to a request byDiabetes Health, a New York Times editor explained, “Afterreceiving the letter from Dr. Mathis and Dr. Benoist, we didcontact Dr. Denise Faustman for her response, as we wouldcontact anyone who was the subject of such charges. Afterexamining the letter, the response and other material,we concluded that there was nothing in the article thatwarranted 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 itsown hands.

Richard Insel, MD, executive vice president for researchat 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 TheCenter for Science in the Public Interest, is disturbed by the JDRF goingto these lengths to discredit Faustman.

“It is shocking to see that scientists, rather than evaluating something onits merits, would spend so much time attacking the messenger. You haveto wonder, what is their real motivation? You would think that scientistsconnected with the JDRF would be pursuing every effective cure, notattacking approaches that rival their own.”

Not Funding Faustman’s Research, But Replicating It

Though the JDRF repeatedly chose not to fund Faustman’s research andsubsequently criticized its merit, they have swiftly moved to replicate it.New projects are underway by a number of JDRF-funded researchers todemonstrate the mechanisms for pancreatic cell regeneration.

Diane Mathis herself is heading up a new $5 million JDRF project: IsletRegeneration During Reversal of Autoimmune Diabetes in NOD Mice.Curiously, the name of this study is nearly identical to the title of thepaper Faustman published in the November 14, 2003 issue of Science:“Islet Regeneration During the Reversal of Autoimmune Diabetes inNOD Mice.”

Another interesting detail appears in the JDRF’s IRS 990 form forthe 2002 tax year. This is the annual tax return required of nonprofitorganizations. Unlike personal returns, the 990 is a matter of publicrecord.

To determine whether a particular organization is worthy of theirfinancial support, major donors closely scrutinize the full content ofsuch returns. In an attachment labeled “Grants and Allocations,” theJDRF could have chosen to feature any of its 500 grantees. Instead, thefirst 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 andtransplant therapy. But they chose to give headline space in a sectiondevoted to grants and allocations to a researcher they had repeatedlydeclined to fund. It may be worth noting that the JDRF return fortax year 2002 was filed on February 11, 2004—three months afterFaustman’s Science article appeared.

Questions Left Unanswered

It is said that imitation is the sincerest form of flattery. If that’s the case, theJDRF may have changed its tune regarding Faustman. Their March 2, 2005,announcement of an international “dream team” to study the regeneration ofislets may indicate a positive development in the search for a cure. But for themillions affected by this disease, the pattern of their recent actions may raisequestions that aren’t answered in their press releases or fundraising brochures.


Diabetes Health interviewed BillAhearn, vice president of strategiccommunications for the Juvenile DiabetesResearch Foundation, for additionalperspectives on the issue.

Q: The JDRF is the most significant private forcein the pursuit of a cure for type 1 diabetes.Individuals directly affected by diabetes want toknow that the substantial amount of time andmoney that they contribute to such research is beingspent wisely. The letter written by Drs. Mathis andBenoist and the JDRF’s widely distributed e-mail hascaused many in the diabetes community to questionthe JDRF’s motives. Does the JDRF continue to standbehind the critiques of Denise Faustman’s workexpressed in the Mathis-Benoist letter and in thesubsequent e-mail?

A:The [e-mail] message said that it’s importantthat you not come away with the idea thata cure has been found and that no one is willingto fund it . . . The problem with the [New YorkTimes] article was that there were a lot of sweepingallegations about the reasons why we and othersrejected that proposal [to fund Dr. Faustman’sresearch]. We provide to the scientist—in this caseDrs. Faustman and Nathan—that we will not talkabout the specific reasons for declining it . . . Thereare opposite opinions to what was printed in thatNew York Times article. We stand behind the factthat there are opposite opinions . . . The reason wesent that letter around was because we didn’t havethe ability to send our own critique around… Thatletter 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 doyou know if the system works well? We stilldon’t have a cure for diabetes yet.

A:I agree with you entirely, and it’s somethingthat vexes us as much as it bothers anyone.The idea of JDRF is to get out of business as soonas humanly possible. It doesn’t mean there hasn’tbeen progress over time. And if you look at medicalhistory, there’s been approximately one diseasecured to my knowledge—that’s polio. Everyone elseis actually spending a lot more money than we’vespent on type 1 diabetes, and they haven’t reachedthat endpoint yet.


Shortly before press time,Diabetes Health receivedthis letter from Peter VanEtten, President and CEO ofthe 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.

Regards,
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 articlethinking 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.

Thanks.

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

Dear Editor,

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 pr
gression 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.

Sincerely,

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


Below is the link to the New York Times article abstract. Purchase the entire article for $2.95.

http://query.nytimes.com/gst/abstract.html?res=FA0C1FF838580C7A8CDDA80994DC404482&incamp=archive:search

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