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Fighting It Out Over Stem Cells

This is going to sound weird, but remember stem cells? I know that they’re still an active and important area of research and all, but I’m referring more to the period of political enthusiasm about fifteen years ago. Elected officials at the gubernatorial and national level all had positions on stem cell research, and there were some pretty extravagant promises thrown around. That legacy lives on in the form of countless dubious “stem-cell therapies” that are available to you if you’re willing to pay cash to be injected with something-or-other.

The San Francisco Chronicle has taken a look back at the state of California’s efforts in the area, which were (fittingly) some of the largest and most expensive. That was Proposition 71, in 2004, a ballot measure to create the California Institute for Regenerative Medicine and funding it with three billion dollars. What’s happened? What you’d have expected, if you knew the field at all (or were familiar with basic research in general). None of the bigger promises made during the campaign to fund the CIRM have come true. No approved therapies have come out of the work yet – and that’s one of the class of promises that were most egregious, in California and elsewhere. Just imagine the time it takes from discovery to approval for something like this, and then factor in that the needed discovery hadn’t even been made yet. But if you don’t know anything much about stem cells, or regulatory approvals, or medicine in general, the idea of get-out-of-that-wheelchair cures being just around the corner becomes more plausible.

It’s not like the CIRM money has all been wasted, of course. There’s been a lot of basic research done, and there certainly has been a lot that needed to be done. The amount of brush to be cleared in human developmental cell biology is just monumental. A quick thought the way that all of your body, all the bodies of every human being, comes each from their own single cell will make that clear. If you want stem cell therapies to regenerate organs – as who doesn’t – then you’re asking for a thorough understanding of that process. You may well be asking to do even more than it can tell us how to do.

California’s voters are now going to decide whether to renew the CIRM itself and its funding, and (as that article makes clear) a big argument is how to measure the progress so far. If you measure it against what was known and what had been accomplished then versus what’s been done since, you can make a case, for sure. If you measure it against the promises made at the time, though, things look bad. And that informs how you’re going to campaign for renewal: do you point at what’s been done and make the argument that it’s been a success, or do you promise them miracle cures again, because now they just have to be around the corner after all this work, eh?

The article goes into great detail about how the three billion has been spent (and pretty much all of it has, or has been committed). And I have to say, I don’t see how you could have done a more reasonable job of it. The splits between basic and applied/translational research, between industry and academia, between embryonic and adult stem cell work, etc., all look perfectly defensible to me. The money has not been thrown away – it’s just been thrown at a huge and difficult problem, the sort of problem that can soak up three billion dollars with no sign of difficulty. The problem, I believe, is that the proponents of the measure oversold it, and how those promises are coming back around in contact with biomedical reality.The initiative’s main advocate (Silicon Valley’s Robert Klein) was essential to getting the entire CIRM underway, but he’s also been involved in some unrealistic expectations (and doesn’t seem to have much time for critics). Adding to the problem is the legal status of the CIRM itself, which has some critics saying that it’s not accountable enough to the legislature or the public.

So if you want to see the conflict between politics, science, and funding played out right in front of you, here’s the place. There’s a lot to learn about public attitudes towards biomedical research, too, not all of them pleasant things to take on board. The question is whether there’s going to be another funding initiative on the ballot in 2020, and if it will pass if so. This argument will be getting larger and louder.

16 comments on “Fighting It Out Over Stem Cells”

  1. Miguel Sanchez says:

    Derek, this is a great and reasonable write up that I plan to share with non-bio friends/family who have questions about the CIRM.

    However to be that guy and throw my anecdata in here… Just at my small CA research institute, the amount of poor science that has been funded by CIRM is staggering. I would say that roughly half the CIRM money we have received has gone to research programs that are prima facie bad science but the PIs are well connected so hey shut up. I don’t think any outright fraud has been published, but the taxpayers of CA are for damn sure not getting their moneys worth on these investments here.

    1. loupgarous says:

      Oddly, the closest thing stem-cell research has had to a genuine academic misconduct scandal was the misadventures of Catherine Verfaillie’s group in Belgium and Minnesota – one of her trainees authored a paper with duplicated microphotographs and all the other signposts on the way to Retraction City (at least two others were also retracted).

      Interestingly, Verfaillie’s group got a bunch of funding from the Belgian government. This time it was right-wing politicians handing out the cash, because she claimed to have found a specific type of adult-derived stem cells (termed multipotent adult progenitor cells (MAPC) – no fetal tissue, so it was a return volley in the ideological wars over where researchers get their stem cell lines from (California fired first by funding CIRM in response to the Bush administration’s ban on funding work using fetal-derived lines of stem cells).

  2. cancer_man says:

    “… the idea of get-out-of-that-wheelchair cures being just around the corner becomes more plausible.”

    The 2016 results at Stanford looked pretty good and heart patches for heart failure patients being developed at the U of Wisconsin-Madison and at the U of Arizona look very promising.

    1. johnnyboy says:

      “Look very promising” can also be a euphemism for “not actually working”. I was looking at stem cells for post-MI regeneration in preclinical models 10 years ago, and it was also “very promising”, ie. not actually working. The idea that you’re going to put some stem cells into/onto/around a fibrous scar and they’re magically going to turn it into functioning myocardium is based on a lot of magical thinking.

  3. Chrispy says:

    “The problem, I believe, is that the proponents of the measure oversold it, and how those promises are coming back around in contact with biomedical reality.”

    Really? Scientists over-hyping proposed research, claiming that breakthroughs and cures will come much more quickly than is possible? Surely this reprehensible behavior is an outlier, and the offending parties will be held accountable!/s

    Honestly, with science getting more expensive and competitive all the time, and grant money simply not keeping pace, is has become not just acceptable but required for the potential of your research to be overblown if you have any prayer of getting funded. This is a bitter pill for scientists with integrity.

    As Feinman recounted in his Cargo Cult Science commencement speech:
    “I was a little surprised when I was talking to a friend who was going to go on the radio. He does work on cosmology and astronomy, and he wondered how he would explain what the applications of this work were. “Well,” I said, “there aren’t any.” He said, “Yes, but then we won’t get support for more research of this kind.” I think that’s kind of dishonest. If you’re representing yourself as a scientist, then you should explain to the layman what you’re doing—and if they don’t want to support you under those circumstances, then that’s their decision.”

    1. Ironically, I was a graduate student in astronomy not long after that speech, and I was startled to see some research proposals in other subfields that drew tenuous connections to cosmology on the belief that this improved their chances of being funded.

  4. DrDoom says:

    Remember that a significant political motivation for this was as an anti-Bush, pro-abortion protest. With Yamanaka having deflated that balloon, I predict far less interest. (That’s also why the scientific quality of what was funded never mattered much.)

    1. Wonky Chemist says:

      “Remember that a significant political motivation for this was as an anti-Bush, pro-abortion protest.”

      Alternatively a motivation for this was to ensure a collection of theocrats didn’t block the development of therapies for a variety of illnesses. Framing is fun.

  5. WWCody says:

    Also, this was paid for with bond money, which means that the state will be paying off the loan long after the research money has stopped. Far better to pay for research with present taxes than future debt.

    1. DanielT says:

      WWCody while I don’t want to get into the merits or not of this particular initiative (I just don’t know enough about it to comment), there is a good case to be made for funding scientific research via bonds. Just like long lived infrustucture (i.e. roads, bridges, etc) most of the benefit of scientific research is enjoyed by the people of the future. I think it would be an excellent idea if basic research was funded from specific bond issues rather than out of the present taxes.

      1. KevinH says:

        That’s an intriguing perspective. It does introduce a certain moral hazard, of course–it’s always easier to decide that a project is worth funding as long as *someone else* is going to pay for it. And one can start to have endless amusing arguments about the appropriate amortization period…do we charge basic biology to our children, and basic physics to our grandchildren? And research spending has immediate non-research benefits–as straight-up economic stimulus, there are worse options.

        That said, the whole “bond issue” thing is a bit of a shell game. The difference between “We’ll cut $1 billion from the Department of Transportation budget and use it for research, then issue $1 billion in Highway bonds” and “We’ll issue $1 billion in Science bonds” is in the marketing and politics, rather than anything practical.

  6. myma says:

    In today’s day and age, isn’t most funding coming from VC’s (a fair chunk of whom live in California), and if the topic is not being funded by VC’s then why not? At this point after a decade or so, if nothing has spun out that any VC of any pedigree is interested in, maybe it isn’t very good.
    $3b. That is a lot of bridges and viaducts. Especially in a state with earthquake and water supply problems.

    1. David Jensen says:

      VCs are generally too timid for stem cell research. They have shied away from it for a variety of reasons, including the controversy over religious objections as well as for financial reasons. One of the goals of the agency has been to “de-risk” private stem cell investments because of the VC fears about a lack of return.

    2. eub says:

      Well, for that it has to be “really right around the corner by this time for sure I won’t pull the football away.” If the best guess now is 10 years for any return — I have no idea, but 10 years to commercial use in humans strikes me as >checks watch< quite soon — few VCs would have any interest. They're used to exiting in more like 5 years after being assured it would be 3…

      Hm, actually VC exit times have gotten longer than I thought, I see median numbers 7+ years. Maybe the money that's thirsty for biotech is desperate enough that it would go for the 15 year play if you call it 10?

  7. HTSguy says:

    Actually, $3b is about 1/2 the cost of the replacement San Francisco Bay Bridge. “Simply” (maybe not so simple) repairing the spillway on the Oroville Dam cost over $1b. In an expensive state like California, money does not go as far as you might expect.

  8. David Jensen says:

    If you are looking for a little more detailed information about the California stem cell agency and its current status, below is a link to a list of recent articles dealing with the nearly 14-year-old effort. They all can be found on the California Stem Cell Report which has covered the agency since January 2005.
    http://californiastemcellreport.blogspot.com/2018/09/better-than-hope-to-no-more-cash.html

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