Thursday, June 23, 2016

Stem Cells, Long Odds and the 'Invisible Hand of Hype'

The headline on the California story pretty much told it all: "Stem Cells: Where Science, Hope and Hype Meet."

It could have added that it is also a meeting place for Big Pharma, Big Academia and Big Politics.

All of those yeasty ingredients are embodied in the $3 billion California stem cell agency, which is plugging away at developing a therapy promised to voters 11 years ago during a $36 million ballot campaign..

The headline appeared on the KQED Web site, a public television and radio outlet in San Francisco. The city, coincidentally, is where the world's largest aggregation of stem cell researchers, the International Society for Stem Cell Research (ISSCR), is meeting today. The conference is also just across the San Francisco Bay from Oakland, where the stem cell agency is headquartered.

Danielle Venton wrote the article for KQED. She covered a bit of the history of the California Institute for Regenerative Medicine or CIRM, as the agency is formally known. She noted that the agency is now participating in 16 clinical trials, although it has yet to chalk up production of a commercial therapy.

Venton wrote,
"(T)he frustration many voters feel about CIRM may have more to do with the problematic way researchers, institutional communicators and the media talk about scientific progress in general, and stem cells in particular, than it does with the agency’s performance.
Timothy Caulfield
"'There has always been this high-stakes, extreme rhetoric around stem cells,' says Timothy Caulfield, who teaches science and health policy at the University of Alberta. Caulfield says because stem cell research was so embattled, many spoke of its promise in hyperbolic terms.

"'People had to make bold statements about the future of stem cells in order to counteract those that wanted to have strict laws to stop it. So you have to say, ‘This is going to save lives. This is going to cure a variety of diseases.’ Right from the beginning, the late ’90s, you have that language appearing in the popular press.”  
Venton reported that the international scientists' group, the ISSCR, is "trying to tone things down" with new guidelines about how to talk about stem cell research and its impact. She said the effort "may be facing long odds." She quoted Caulfield as saying,
“It’s really the invisible hand of hype. In most cases these pressures are largely unconscious — whether you’re talking about the media, the researchers, the institutions or the funding agencies.”
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6 comments:

  1. Anonymous11:23 AM

    Japan recent clinical trial found serious spontaneous mutations with transplanted iPSC-derived RPE cells, now requires iPSCs to be used as allogeneic rather than autologous transplants. iPSC is actually a camouflage for cloning. Genomic instability and mutations have been a big problem for somatic nuclear transfer. None of the iPSC techniques made any improvement, but even worse than somatic nuclear transfer. CIRM gave a lot of money to make and bank iPSC, which have little use for therapies. But iPSC have been backed by a group of very prestigious scientists, in 2009, they made a clueless Obama relax ban on cloning, during his terms, a huge amount of NIH funding or almost all the stem cell funding of NIH has gone to iPSC. Those Nobel laureates did not know iPSC were made with the same mechanisms of oncogenesis, have to spend so much federal and state money to go to clinical trials to find out? probably not.

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  2. Anonymous, I have to correct your statement that "serious spontaneous mutations" caused the change from autologous to allogeneic iPSCs in Japan. Dr. Masayo Takahashi talked about this study at the ISSCR meeting on Tuesday, June 21. The genomic variant in the iPSCs was not a serious mutation- it has no link to cancer and may have been already present in the patient. This kind of variant, called a "copy number variant" is quite common in normal people- I have some cnvs myself. The safety of iPSCs in general is not a serious concern- please see our publication: http://www.nature.com/ncomms/2016/160219/ncomms10536/full/ncomms10536.html
    Contact me directly if you can't access it.
    Use of allogeneic iPSC banks for cell therapy is feasible in Japan because of the genetic homogeneity of the population- Dr. Takahashi is now using an iPSC line that matches 17% of the Japanese population. Unfortunately, this isn't possible in the highly diverse population in the US.

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  3. Dear Anonymous: I heard a talk from Dr. Masayo Takahashi on Tuesday June 21 at the ISSCR meeting, and I want to correct some of your assumptions with some facts.

    "Serious spontaneous mutations with transplanted iPSC...": Dr. Takahashi started a trial for macular degeneration with the intention of using patient-specific iPSCs for cell therapy. Whole genome sequencing of an iPSC clone from the second patient revealed a copy number variation in a gene called STS. Copy number variations are quite common in normal people- I have some myself. The variant is not lined to cancer, and it may have been present in the patient before reprogramming.

    The switch to allogeneic iPSCs was not because of mutations but was a result of the development of a bank of iPSCs that are HLA-matched to much of the Japanese patients. It will be less expensive because fewer cell lines will need to be used.

    Genomic instability in iPSCs: True: long term culture of iPSCs selects for fast-growing, apoptosis-resistant subpopulations. Improved culture methods and frequent checks of the cultures avoids this.
    False: reprogramming of cells to iPSCs causes mutations. Reprogramming is the not the same as oncogenesis and does NOT induce cancer-associated mutations (http://www.ncbi.nlm.nih.gov/pubmed/26892726).

    I'm happy to answer any other questions you have...but not as "Anonymous".

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    Replies
    1. Anonymous3:00 PM

      Dr. Loring has some multi-million iPSC grants from CIRM, maybe COI to tone down the seriousness, doing some touch ups with your Japan partner in ISSCR. How many times all the tobacco company testified, even in front of Congress, that cigarettes do no harm while millions got lung cancer from smoking. Oncogenesis in fact is reprogramming, Dr. Loring do not have to rewrite the text book & swear identical in public just because of your obvious COI.

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    2. @Anonymous - Dr. Loring's explanation is factual and can be confirmed in multiple independent scientific articles and news articles.

      Japan has a strong incentive to switch to allogeneic iPSCs (as explained above) and Masayo Takahashi's trial was halted in order to incorporate this switch. Jun Takahashi, is also planning to use allogeneic iPSCs for Parkinson's disease (PD) - they will both use the same banked cells, as will many others, so the potential economic and standardization benefits are obvious.

      Interestingly, Dr. Loring and Jun Takahashi are both working on therapies for PD but using autologous and allogeneic cells respectively. By your logic this would make them competitors, but there's so much still to learn about this field that support for good clinical science is in everybody's interest.

      If that's a conflict of interests, then you'd better include the other 10,000+ stem cell scientists and patient advocates, who are all supporting progress in any way they can.

      Delete
  4. The information I provided is either from work published from my own lab or from Dr. Takahashi's talk at ISSCR. You should read the paper I cited.

    ReplyDelete