Stem cell monopoly: do not pass go, do not collect $200,000

UPDATE: NIH data backs up our conclusions: overfunding wastes precious resources–give the money to smaller labs.

Arguably the key driver of the exciting progress in stem cell research is funding.

Great ideas are the foundation of science, but funding makes great ideas become realities.

With the stakes so high in terms of helping patients through advancing stem cell research and the billions of dollars involved,  a very important question is whether the current model of funding stem cell research is ideal. Perhaps there are ways to “get more bang for the buck” in funding stem cell research.

The current paradigm of stem cell funding is a system of competition where scientists send in applications for funding, often in units of approximately $200,000/year over a 3-5 year period. This is an oversimplification, but it gives you the general idea.

The submitted applications are reviewed by groups of other scientists who give each application a score. In a general sense, the reviewers know that certain very good or bad scores mean an application will almost certainly be funded or not be funded. Then there is usually a range of scores that are in the grey zone.

Enormous stakes are riding on these scores and on which grants get funded. One could argue the entire field of stem cell research and regenerative medicine depends on this funding system. If the funding scores shift even in subtle ways, then the entire field will move in one direction or another.

So how do the reviewers decide on these critically important scores they give to in essence fund or not fund certain grants?

There are a number of criteria:

1) The investigator (who is the scientist? what is their track record in terms of getting funding in the past and publishing papers?)

2) Environment (what institution is the scientist at? what is the reputation and track record of that institution? what scientists are around the applicant that could be of help?)

3) Approach (is the science that they propose sound? will it work?)

4) Innovativeness (how novel is this?)

5) Impact (overall, how might this research change the field?)

Different funding agencies have different criteria, but generally these five are the important ones and the reviewers give scores in these kind of areas to each grant, ending up with an overall score that will determine funding.

In the current relatively difficult funding climate, the top 10% of applications are almost always funded. The next 10% below that have a reasonable chance.

One problem is that the current system is inherently biased to reward scientists who already have funding with more funding. It also rewards institutions that already have a lot of funding with even more funding.

Any given grant application as a whole is viewed through the filter of who the applicant scientist is and where they are doing the research. This bias tends to concentrate research funding, giving certain people and places a disproportionate share of funding.

So one might ask “if these scientists and institutions are the best, doesn’t it make sense that they should get more funding?” The simple answer might be “yes”, but if you dig deeper you realize that for the stem cell research field as a whole, the answer is “no”.

The first $200,000 per year in funding that an investigator gets in any give year has the highest impact. All funding after that has less and less impact. This “first funding” in a given area of research in any given year allows this researcher to continue to employ or to hire staff and buy the supplies needed to move this research forward. The second $200,000 is not as quite as high impact as the first, but still can make a huge difference by catalyzing the research of the particular lab to move forward more rapidly and impact the field.

Now imagine this same scientist gets a third unit of $200,000/year. The impact of this yet additional funding is even lower. The lab is already running well and this additional funding does not fundamentally change the research the way the 1st and maybe 2nd units of funding did.  If this investigator gets fourth, fifth, and maybe even 10th units, each of $200,000 per year, the impact of each unit goes down.  Imagine if instead those funds were given to multiple investigators who have relatively little funding, but who are just as good scientists, what will happen? The funding agency awarding the funds will see a higher overall impact of their investment.

The same principle applies to institutions, but on a larger scale. Institutions compete with each other for research funding as well and the review process is biased to reward institutions that have already had success in getting funding with more funding.  Once again, the “earlier” amounts of funding have far more impact. Institutions need to develop a critical mass of researchers and funding to advance their research. There is in essence a tipping point beyond which institutions can far more efficiently impact the field.  Some institutions have already achieved funding levels far beyond the tipping point. When funding agencies give these places more and more funding, the impact of each unit of funding is progressively lower and lower. The same funding awarded to an institution that has not crossed the tipping point could have exponentially higher impact on the field.

Someone once said “there is no monopoly on good ideas“. This is certainly true in the stem cell field and there is no monopoly on good science either. Well-funded people and places may have the best grantsmanship, but do not necessarily have the best ideas and are not necessarily the best equipped to do the science. Even so, funding agencies create an environment where certain institutions are rewarded with so much funding that virtual monopolies are created.

In so doing the funding agencies end up with less diverse portfolios and lower their impact on the field.

One potential solution to this problem is to “blind” reviewers to the identity of the applicants and the institutions that they come from. While in a blinded system, reviewers may still be able to guess who the applicant is, most often they cannot be sure. In theory this strictly merit-based system could work as it would reward the best science without bias, but to my knowledge no one uses such a system.

However, another approach that might work better in the “real world” is for funding agencies to fundamentally alter the process by which they decide what to fund. The single most important criteria in a new, better system would be impact of the funding where impact is defined not only by the potential impact of the proposed research but also the impact of funding that research. This may seem like a subtle distinction between the types of impact, but there’s an enormous difference.

For example, imagine a hypothetical world where two scientists (A and B) submit the identical research application to a funding agency, and scientists A and B have identical abilities as scientists, but scientist A already has $1,500,000/year in funding and scientist B only has $200,000/year in funding.  From a purely research impact perspective, the funding could go to either scientist. From a funding impact perspective, the funding would have far more impact going to scientist B.

Paradoxically, though, in the world that us scientists work in, 90% of the time the funding would in reality go to scientist A because  the reviewers (perhaps not even consciously) would be impressed by the funding and reputation that scientist A already has and the super-funded institution where they do their work.

If you buy my argument, you might realize that such a new system would shift funding to younger, newer scientists and also up-and-coming institutions. Yes, that is a likely reality of such a new system, but is that a bad thing? One might also wonder if the heaps of funding given to certain already well-funded scientists might allow them to pursue new and different ideas that they might otherwise not be able to study? In theory that’s possible, but I would argue that most of the time that does not happen.

There are scientists out there in the stem cell field with 6 or 10 or even more grants totaling millions of dollars per year in funding. There are loads of scientists just as “good” as the uber-funded ones, but who have relatively much less funding.

I think that no matter how “good” the well-funded scientists are, that the funding agencies have nonetheless lowered the impact of their dollars by over-funding some scientists and some institutions at the expense of others, where the funding would have more impact.


  1. Gutsy post as usual. I have often wondered why funding agencies just keep making the “rich get richer” in terms of grants. It’s gotta be a waste of funding at some point.

  2. But if you are the scientist who is uber-funded, you might see it differently. I agree with you though, Paul and Nick. There is a point beyond which the extra funds have little impact. I wish I could have ever reached that point myself 🙂 , but alas I haven’t.

  3. @JJ
    Once I had 6 grants totaling more than $1 million/year in funding.
    We spent it and I grew my lab, probably too big, but I confess (only because I am anonymous here) that we did not publish more or better papers than we do with only about $350K/year these days.

  4. Picture a graph where the Y axis is the impact of any given grant and X axis is cumulative total funding at the point the grant is given. There’s a very negative slope there. Impact goes down rapidly.

  5. Simple. Stanford, UCLA, and UCSF together have more impact on the stem cell field than all the other institutions combined.
    CIRM reviewers are doing their job and funding the best, highest impact research.

  6. @adl
    Adl, thanks for the excellent link.

    I find it very interesting that productivity is not clearly increased by giving scientists more than $400,000 in funding. NIGMS has a well-funded investigators policy that kicks in around $750K. Perhaps the limit should be lower. Other funding agencies might want to consider this kind of idea for funding stem cell research. Wow, giving scientists more than $700K decreased their productivity.
    Be sure to read the comments after that NIGMS article as they are very interesting too.

  7. I imagine that Stanford, UCLA, and UCSF outcompete the other California schools for funding at NIH by the same margin that they outcompete them for CIRM funding. In other words, this is not CIRM-specific.
    In fact the same is it true that across the country some places like Harvard vacuum up massive amounts of NIH funding, while other similar sized places don’t, right?
    Anyhow, that bit of NIH data argues convincingly that funding researchers beyond a certain point reduces impact and is wasteful.
    But now I’m wondering if you can really make the jump with this conclusion from the individual investigator to a whole institution? Does giving a place like Harvard more and more money continue to drive up its impact or does it plateau and even go down like it seems to do for the individual PI?

  8. @LisaP
    Lisa’s right in a general sense about this not being specific to CIRM.
    The NIH REPORTER Tool shows that the top CIRM-funded institutions receive dramatically more NIH grants specifically on stem cell research than do the other California institutions. I don’t know the dollar amounts or anything, but there’s a trend there.
    The bottom line is whether the lower impact of giving yet more funding to already uber-funded researchers is compelling enough reason to change grant policies? I think so. Maybe if I had a $1.5 million a year in funding myself I would say “no”, but I hope not.

  9. I’m not convinced that places like Stanford get more CIRM and NIH grants simply because they already have a great track record of getting grants. But there can be a circle there.
    More grants = more papers (up to a point) = more grants and so on…..
    That kind of thing is real.
    Stanford and Harvard are like stretch Cadillac limousines towing their own trains of fuel tanker trucks when it comes to stem cell research funding. Give them even more fuel tankers or give one or two tankers to someone else who at best has half a tank of gas? What’s the obvious choice?
    That new stem cell building in Palo Alto is so big they have their own zip code and room service.

  10. @anon
    Funding right now is just horrible all over no matter what agency you apply to, but it would seem less horrible if you happen to be at some “elite” places. The other day we had a faculty candidate visiting and they were from one of these “top tier” places and I found myself thinking “wow, they are from _____”….I realize that even I am biased in their favor just because where they are from. The irony is it is so un-scientific to think that way.

  11. It’s just human nature to be impressed by places like Harvard and Stanford. By association we are automatically impressed by scientists who are working there and as grant reviewers we give them higher scores because of this. It is very unscientific to do this, but scientists are humans beings and make mistakes and have biases. Funding agencies as a whole should strive not to be biased and if needed make rules to avoid it. In so doing they will increase their impact on science.

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