Tuesday, May 26, 2020

Text of Sheehy's comments re Covid-19, CIRM, Its Mission and Other Matters

The discussion at the May 23, 2020, meeting of the governing board of the California stem cell agency ranged from Covid-19 and the agency's strapped financial condition to its mission and priorities. One of the directors, Jeff Sheehy, elaborated on the matters and more when he responded to an inquiry following the meeting from the California Stem Cell Report.


The California Stem Cell Report has a policy of running verbatim comments from stem cell agency board members and other interested parties. If other readers would like to submit their comments on this subject or other stem cell matters, please direct them to djensen@californiastemcellreport.com.


Below is the verbatim text of Sheehy's comments.

"First, I felt a great deal of uncertainty around CIRM proposing a COVID program.  Having worked towards stem cell therapies for HIV since I came onto the board in 2004, I felt some skepticism around stem cell approaches targeting infectious diseases (ID).  Infectious disease has not been a particularly major focus of regenerative medicine efforts and many of the approaches we have tried have struggled.  I think there could be a role, but we have a long way to go.  


"I thought, in general, a focus on ID is a bit overdue, but I was very concerned about taking funds from sickle cell, where I think there is a strong case for believing we are on track for a cure using stem cell technology, and there are well constructed clinical trials such as the one we just funded.  


"Given that CIRM is using its last of its funding, I was also concerned about the funding needed.  One of the most telling moments in Friday's meeting was the descriptions by (CIRM Director) Dr. (Keith) Yamamoto (vice chancellor for science policy at UCSF) of the ready and ample availability of Covid funding from the NIH and other federal sources, not just in new funds but also the ability to repurpose existing grants towards Covid.


"Btw, I am not alone in my skepticism around stem cells for Covid-19.  I offer first the tweet from Dr. Sean Morrison, former head of ISSCR on March 29:


"'There is no stem cell therapy for Covid19. We would not expect stem cells to have any therapeutic value for people with Covid19.

@ISSCR'"


"Then a couple of weeks ago, Dr. Paul Knoepfler on his blog, the NICHE, offered this:

"'The idea of testing stem cells for Covid-19 may be music to the ears of some folks as an opportunity, but to me from the beginning it sounded mostly like a spaghetti on the wall road to trouble.

"'There is buzz out there that some kind of stem cells or other cells will help with COVID-19. The reality is that that’s probably not going to happen.

"'Even so, a whole range of people and firms are somewhat exaggerating and in a few cases outright hyping the odds of success. That is harming patients and the cell medicine field.'"


"I offer these two comments in support of my doubts.  But, I also feel the urgency surrounding Covid.  This is my second pandemic, having lived through HIV/AIDS and lost and continue to lose countless people that I care deeply about and living with the disease myself, having endured enormous stigma and outright hatred along with indifference from a president, seeing marginalized communities suffering death and disease disproportionately and indifference because people don't recognize the humanity of the populations most impacted, feeling triggered and re-traumatized by this second pandemic and the enormous stupidity from all points in trying to make a disease fit their self described perceptions of reality in the face of what is real and undeniable.


"I voted to support the COVID program despite my doubts due to urgency, but we know what tools work against infectious diseases -- antivirals and vaccines, and I became an enthusiastic and vocal supporter of the vital research opportunity for convalescent plasma.  Convalescent plasma is about as far removed from CIRM as a project could be--a technology at least 100 years old with zero barriers to receiving funding from any source.  But, in the absence of a vaccine or antivirals, it represented to me the best and most rational chance to make a difference in patients now. Plus, Zaia et al at City of Hope have the cell handling and manufacturing ability to address some of the factors limiting use and evaluation of convalescent plasma, e.g. potency and consistency of product to name a couple.


"After having participated in reviews, our two clinical projects are the convalescent plasma one and an ongoing $14 million trial for mesenchymal stem cells for ARDS, the lung complication suffered by critical COVID patients necessitating ventilator support.  That UCSF/UC Davis trial is already treating COVID patients at SF General and in Houston to name a couple of sites, and it was supportable because we were availing more patients of access to that therapy like we are doing with convalescent plasma. But both approaches are well supported outside of CIRM and the $750K we gave each project.  


"The $150K Discovery projects we funded are interesting, but they are very early in development and given the time and money it takes to move from discovery into translation into clinical trials, these antiviral products could likely be superseded by the host of antiviral products in trials around the world.

In that context, we did see a couple of interesting vaccine proposals that were very far afield and did not score in the fundable range.  I had a feeling -- having looked at the vaccine trials underway (and I'm not an expert btw)  -- that they seemed very much based in the most part on proven tech that a far-out, left field approach might be useful to explore.  HIV has been stubbornly resistant to vaccine development, so I'm very cautious about that field.  I was heartened to hear (CIRM Director) Dr. (Kristiina) Vuori from Sanford Burnham opine that she thought that current vaccine approaches were, to paraphrase, following usual pathways, and I thought I heard a suggestion that opening up CIRM to vaccine work might elicit something novel.


"However, the board thought otherwise and I defer to their wisdom.


"I would note that I was intrigued by the discussion around CIRM's mission.  As Dr. (Gil) Sambrano (CIRM vice president for portfolio development) noted, stem cells are ubiquitous in the body, and I took that to mean that one could either be elastic or inelastic in accepting products.  A vaccine, for instance, would almost necessarily  impact T memory stem cells, which are a crucial part of the adaptive immune response to disease (and a vaccine).  We have begun to recognize the limits of stem cell centric therapies through our VRO for gene therapy.


"I then asked myself, does CIRM hews to its original mission per Prop. 71?  I looked up the original funding mission for the Grants Working Group :


"'(C) In order to ensure that institute funding does not duplicate or supplant existing funding, a high priority shall be placed on funding pluripotent stem cell and progenitor cell research that cannot, or is unlikely to, receive timely or sufficient federal funding, unencumbered by limitations that would impede the research. In this regard, other research categories funded by the National Institutes of Health shall not be funded by the institute....Notwithstanding subparagraph (C), other scientific and medical research and technologies may be funded by the institute if at least two-thirds of a quorum of the members of the Scientific and Medical Research Funding Working Group recommend to the ICOC that such a research proposal is a vital research opportunity.'


"With the federal ban ended, all of CIRM's research is really a vital research opportunity by default at this point.  Per COVID and ample federal funding, any funding in that arena is about as far afield as one could get.


"Even with fetal tissue research, which, btw, has fallen off the radar in the media and with some in Congress and the Administration, I can guarantee no one is talking about banning that.  You simple cannot develop vaccines or antivirals without mice with humanized immune systems created by using fetal tissue.


"To sum up, I'm not really sure what the board is trying to accomplish with its COVID program.  I'm not sure that the board has a clear, coherent view of the scope of CIRM's research.  And I am not sure the board has a clear idea of what the scientific mission of CIRM should be in the event that new funding comes from the voters.


"I would note as an aside that CIRM has never submitted its scientific program, including all grants made and their impact, to a rigorous, independent scientific review.  


"In short, I don't think we really know at CIRM where we've been and where we want to go.  We have anecdotes...."


(Sheehy’s own ellipses in the last paragraph)


2 comments:

  1. This verbatim comment from Irv Weissman is a relay from an email. "This statement (in Sheehy's comments) is incorrect: 'Even with fetal tissue research, which, btw, has fallen off the radar in the media and with some in Congress and the Administration, I can guarantee no one is talking about banning that. You simply cannot develop vaccines or antivirals without mice with humanized immune systems created by using fetal tissue.'

    "Check with NIH, NIAID,HHS. The first to suffer from the executive order banning the use of fetal tissue in NIH funded research is the HIV and other drug, infection, and therapy testing labs at UCSF led by Cheryl Stoddart and at NIAID labs in Bethesda and Montana. If the ban has been rescinded,that would be important, but if still enforced, it affects NIH supported labs and NIH supported trainees, including those replicating the pathology and immunology of the SARS viruses."

    ReplyDelete
  2. Anonymous8:52 PM

    Take a deep breath, Irv, your bias is showing (Stem Cells, Inc...)

    ReplyDelete