Thursday, April 17, 2014

NIH Action on Stem Cells: More Than 'Bureaucratic Bungling'

A national stem cell advocacy group this week ripped the National Institutes of Health (NIH) for “dismantling” its Center for Regenerative Medicine, describing the move as a "setback" for the entire field.

Bernard Siegel
GPI photo
The Genetics Policy Institute (GPI) said the action was a “huge disappointment” in an email sent out internationally by Bernard Siegel, executive director of the group, which stages the heavily attended World Stem Cell Summit.

The NIH move also has implications for the California Institute for Regenerative Medicine(CIRM), whose $3 billion program is down to its last $600 million.

The GPI was reacting to news in the journal Nature that the NIH said its center “will not continue in its present form.” The head of the NIH program, Mahendra Rao, took a job this month with the New York Stem Cell Foundation. James Anderson, director of the NIH’s Division of Program Coordination, Planning, and Strategic Initiatives, told Nature that the $52 million NIH effort was going to be rethought following a workshop in May.

Siegel said,
“The dismantling of the program appears to be a retreat by the United States from the translational imperative and a setback for the field at large. The patient community will be looking to Dr. Collins(head of the NIH) and others in NIH leadership to fulfill their commitment to stem cell development as a singular priority. Other countries are pouring in resources and moving full steam ahead. The NIH’s failure to continue the program represents more than just a case bureaucratic bungling. What we see here is a lack of vision and a public relations blunder. Years of valuable work and planning just tossed away. The scientific community and the public rightfully believes regenerative medicine will one day provide innovative treatments and cures to chronic diseases. The decision to tear down the Center for Regenerative Medicine, without first providing an alternative plan, undermines the credibility of NIH. A huge disappointment."

Asked for a response this week by the California Stem Cell Report, Amanda Fine, a public affairs specialist at the NIH, said in an email,
“The NIH Intramural Center for Regenerative Medicine has not closed.  This is a fast evolving area of science and NIH decided to step back and reassess what the field needs in 2014 and beyond and where NIH can have the greatest impact. NIH is holding a workshop tentatively scheduled for May 5 that will convene a group of experts in the field to address current obstacles to translation of cell therapies and will help prioritize a number of requirements that the larger community has articulated through white papers over the past two years.  NIH will consider the feedback from the workshop and establish a set of goals for the CRM.

Initially, Fine asked that the NIH statement not be attributed to a specific individual but later
said it could be attributed to James Anderson, who also made the statements to Nature.

Public details of the NIH program and its problems are murky. But the NIH action has implications for the California stem cell agency, which is scheduled to run out of cash for new awards in 2017. The agency is attempting to raise funds to continue beyond that point.

The agency could use the news to argue that now, more than ever, it is necessary to support stem cell research efforts in California because of weak federal support, which ebbs and flows depending on political vagaries. On the other hand, some might interpret the NIH rollback as a sign that those well-informed in the field have judged it to be less-than-ready for prime time, an argument that could be extended to California's efforts.

What the NIH action clearly does is create more uncertainty concerning progress in stem cell research. Uncertainty is an anathema to businesses that may be considering where to invest hundreds of millions of dollars.
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  1. Anonymous11:08 AM

    NIH CRM should be on the same page with Congress and the public to support and fund human embryonic stem cell (hESC) research, not waste millions and millions of taxpayer money on frauds. iPS cells, more recent acid-dipping adult cells or any claims of making ESC from skin or adult, have no use for patients, all propaganda, not real science. The Congress and public are pushing to make more clinical-grade hESC lines for patients. In contrast, Mahendra Rao spearheaded millions and millions of NIH funding, as well as a big piece of CIRM funding, to companies with industry connection to himself like Lonza, cellular dynamics, Coriell to make thousands of useless iPS cell lines, dried up both NIH and CIRM funding, surprised it was not closed any sooner.

  2. Anonymous10:02 AM

    The NIH and CIRM needs to stay away from trying to find some product they can mass produce and focus on adipose derived adult mesenchymal stem cells to care for patients on a case by case method. There definitely would be more advancements for the NIH and CIRM to be happy about than their fancy laboratories and administration buildings which is all they have to show from the $3 Billion tax payer funds they received.

  3. Anonymous4:58 AM

    The NIH and the CIRM should invest monies in autologous stem cells instead of embryonic, iPS cells or other "designer cells," all of which have failed to produce few, if any, real world results for patients. patients are tired of being told to wait yet another decade or two; many of us are running out of time.

  4. Anonymous2:31 PM

    NIH CRM spent $24 million on iPS cell lines at Lonza and CDI?

    Advance 5 therapeutics through clinical trials with only $28 million?

    Is CIRM wasting money by spending $20 million per stem cell therapeutic?

    Where is the critical thinking on the part of GPI or other bloggers that bemoan the “loss” of NIH CRM without clearly articulating what NIH CRM was, what it was doing, and what it hoped to achieve. Was the budget of NIH CRM insufficient or were its goals too grandiose or diffuse?

    What was the real mission of the NIH CRM beyond the platitudes? What was the valuable work and planning it produced? It seems to have been some combination of autologous iPSCs and allogeneic iPSCs without any clear direction. Just because it has “regenerative medicine” or “stem cell” in the title does not mean it automatically deserves funding.

    What does the stem cell community need from a NIH CRM? Why will it be missed?

    1. Jeanne Loring9:12 AM

      The NIH CRM under Manhendra Rao's leadership accomplished a great deal- but it just didn't make headlines. There was- and is- a tremendous amount of groundwork to be done- unlike CIRM, which doesn't fund establishment of necessary quality control assays, safety standards, informed consent procedures, and federal regulatory agency pathways, the NIH center put its funding into giving us a set of procedures and mechanisms to get iPSC therapies to the clinic, from start to finish.

      This is a tremendous help to those of us who want to avoid all of the common pitfalls in developing autologous iPSC therapies. I just wish that Mahendra could have initiated a cell therapy for Parkinson's disease, which was his fervent hope.

      That is my hope, too, and it would have been so much easier for me- and a great deal less expensive- to have a clear path established that I- and everyone else who is funded by CIRM, the New York Stem Cell Foundation, and other non-federal agencies- could follow.

      It is tragic that the NIH and the other funding agencies couldn't work together so that those of us who are developing therapies don't have to reinvent everything every time.

      Mahendra didn't make headlines, but he did much more important work, which will benefit us all. I am sorry that he was thwarted in his main goal, but CIRM should embrace the ideas he promoted- pick up where Mahendra left off in developing quality control standards and safety standards that may seem boring but will give stem cell therapies credibility and hasten their path to being accepted therapeutics.

  5. Anonymous3:10 PM

    If the goal of NIH CRM was autologous iPSC therapy, why give Lonza and CDI $24 million to create iPS CELL LINES?

    The iPSC LINES are just a starting material in the making of an allogeneic therapeutic cell type. If allogeneic iPSC therapies were the goal, with $24 million spent on starting material there wasn’t much money left for therapeutic development, let alone clinical trials. Remember that CIRM is spending $10-20 million per therapeutic disease team (to either get to the clinic OR get through a Phase 1 trial – both cases with a therapeutic candidate, not just starting material, already in hand).

    Somebody didn’t do the cell therapeutic development budget math up front; 5 autologous or allogeneic iPSC therapies in clinical trials for just $52 million is wildly optimistic, especially when half the money was spent on allogeneic iPSC starting material.

    In this rapidly moving field, the starting material of today may or may not be the optimal starting material of tomorrow. The “if you build it [an iPSC line], they will come” mentality is not appropriate here. Therapeutic cell types have functional attributes which are beneficial in a disease model, which is a long distance, and millions of dollars, from an iPSC line.And then you get to do, and need to fund, the safety studies.

    1. Jeanne Loring6:19 PM

      Anonymous, were you responding to my message? If so, then you misunderstand. The goal of the NIH CRM was to establish the mechanisms to get iPSCs to clinical trials. iPSCs have never been approved by the FDA, so everything, from the proper informed consent to quality control assays, like standardized genomic analyses, pluripotency testing, and release criteria for transplantable cells need to be in place. CIRM is leaving all those details to individual grantees, and that is not only wasteful, but it also encourages CIRM grantees to do the minimum possible to get FDA approval. For example, the FDA doesn't require any genomic information about the cells, so there's no incentive to raise the standards.

      I'm not talking about animal safety testing, which almost certainly has to be done for each cell line, but instead I'm talking about what should be done in the preclinical phase to ensure the safety of pluripotent cells. Wouldn't it be great if we could sequence or SNP genotype the final preparation and have nearly 100% confidence that it wouldn't be tumorigenic? That could be done by a parallel animal and genomic study, but neither extramural NIH nor CIRM will fund such a study…it doesnt test a hypothesis and it won't generate headlines.

      I don't know the price tags for the CDI and Lonza subcontracts, but I understand that Mahendra, like many of us, did not have the resources on site to generate and differentiate iPSCs under GMP conditions. Lonza does that. And CDI makes more iPSC lines than anyone else and has the grant to make the iPSC bank for CIRM. So whether he was asking them to make cells or to develop or validate quality control assays, they were the clear choice.

      Why are you so angry about the NIH?

  6. A well-informed scientist, who asked not to be identified, has emailed comments directly to the California Stem Cell Report on the NIH action on its Center for Regenerative Medicine and the departure of its chief, Mahendra Rao. In summary, the scientist said the center had “very little money” ($52 million) and needed support from other institutes within the NIH. The commentator said Rao had become “fed up” with the bureaucracy and internal politics at the NIH that were necessary to build support for the center's effort. Rao, in the view of this scientist, was talented but did not have the right set of skills to negotiate the NIH's byways. The most significant component in the NIH action, however, was inadequate funding, the scientist said. He/she “guessed” that “the (May) strategy meeting at NIH will focus on redefining, i.e..downsizing the project to a scale that the NIH can afford and still say that they  has a program in regenerative medicine.  Under these terms, the next director will almost certainly come from within the NIH.” The scientist said, “By the way, this should not interfere with the extramural grants that many institutes make to support stem cell research within federal guidelines. Although limited in scope, these continue to be an important source of funding within the field, especially since the advent of iPS cells.”

  7. Jeanne Loring9:50 AM

    The well-informed scientist is right. I was one of the final candidates for the NIH CRM directorship job that Mahendra took, and when I interviewed at the NIH, I arranged to talk to an old friend who is high up in the NIH hierarchy. I asked this person how he/she negotiated the bureaucracy and competing interests of the NIH, and she/he confirmed my impression that the real skills required for the job were not at all within my repertoire, and required knowledge of the system that would take too long to acquire. I contacted the search committee when I returned home and recommended that they hire Mahendra, who had been at the NIH before and had a far better understanding of how to get things done there.

    I would have lasted for a much shorter time in that job than Mahendra did, and I greatly appreciate what he was able to accomplish before frustration overcame him.

    Unfortunately, I can see the signs of CIRM becoming less focused on its mission and more like the NIH. Infighting, favoritism, and conflict are becoming more and more evident in the glimpses inside CIRM that I can see at the public meetings of the ICOC. I hope that the new president can restore CIRM's focus and use his/her power to reinvigorate the shared vision that made CIRM such a remarkable organization.

    1. Anonymous10:29 PM

      Thank you Jeanne, David, and the "well-informed scientist",

      I have no anger, only dismay at the cursory attention paid to this potentially important development relevant to the field of "Regen Med".

      Nothing of substance was being investigated or reported on the "demise" of the NIH CRM in the bloggosphere, even though several sites claim to track the "important" developments in the field. To quote one: "To be a good reviewer, data should always trump big names in importance."

      All US citizens, CA resident disproportionately so, should ask questions about the expenditure of NIH funds. If CA is leading the way (with $3 Billion) in regenerative medicine funding, and that funding is going to expire, they should be questioning how NIH may take over leadership, or should they take over leadership, or what is the direction that that leadership should take.

      I am not a troll, and am happy to have begun a thoughtful conversation about the roll of NIH funding in cellular therapeutic development.

      From a previous comment:

      NIH Center for Regenerative Medicine (CRM) Closure: acknowledgement, but no real commentary from the blogosphere on this potentially important development.

      Are bloggers fearful of questioning NIH?

      Was NIH CRM a non-entity to the stem cell community?

      Was NIH CRM an obvious money pit ($23.4MM in contracts for iPS cell lines)?

      DID CIRM initiatives make NIH CRM redundant/obsolete?


      It would seem that the budget realities were consistent with the reviewer opinions that only a single project could be moved forward toward the clinic. This problem is even more acute if, as quoted (“he had hoped that five trials would be funded”) the funds were designed to get clinical trials funded as well as completing preclinical work.