Commentary

Nature Reports Stem Cells
Published online: 3 January 2008 | doi:10.1038/stemcells.2007.134

State demands strain US stem cell scientists

Margaret Goodell¹

The US stem-cell controversy has spawned additional funding systems. These distract scientists and weaken the NIH

Margaret Goodell, Baylor College of Medicine

Living in Houston, away from the marketing for California's Proposition 71, I never imagined that California voters would approve $3 billion dollars for the seemingly distant promises offered by stem cell research. I clearly underestimated the exceedingly well-run campaign, as well as the backlash against President Bush that seemed to be one of the motivating factors for the vote. Perhaps I was also secretly hoping the proposition would fail, knowing that despite the top-ten standing of my medical school, Baylor College of Medicine, the proposition could reduce our ability to recruit stem cell scientists to Texas and then retain them. Thus, it was only on that November morning in 2004 when the voting results were announced that I finally began to think seriously about the profound and broad-ranging impact Proposition 71 could have.

Table 1. State government support for biomedical research. Sources: Individual state sources listed below as well as Rockefeller Institute Policy Brief by James Fossett (August 9, 2007).

The first effects became apparent quickly, when several other states started similar, albeit smaller, initiatives. Connecticut was one of the first: in November 2006, the state awarded $19.8 million to be administered in 21 grants and promised distributions totalling at least $100 million over 10 years. These grants included funds for human embryonic stem (ES) cell research provided to small liberal arts colleges with good, if modest, stem cell groups and much larger amounts given to major medical schools that initially had minor programmes. The potential impact of this infusion of cash into the research programmes of a small state cannot be overestimated. At least ten states have pledged or allocated funds for stem cell research (Table 1). Clearly, the local impact of these initiatives is high, as investigators can purchase equipment and hire staff on funds that would otherwise have been much harder to raise. The initiatives have also enabled scientists with a peripheral interest in stem cells to enter the field in droves. Their entry would certainly have proved more difficult if done through the National Institutes of Health (NIH), whose reviewing system is notoriously intolerant of people moving into new fields without a publication track record.

Overburdening reviewers

Soon after the initiatives were announced, those of us already active in the stem cell field began receiving invitations to review grants submitted to these state funding programmes. California set the bar high, mandating an efficient organization in which most of the money would go to research and not administration, using the highest ethical standards for distributing funds and requiring multiple layers of approval that included a panel with patient advocates. The designers of the programme recognized the potential for cronyism in disbursing funds and thus required that all grants be reviewed by scientists from outside the state. A review panel was set up, chaired by one of the field's most respected scientists, Stuart Orkin, who had many years of NIH review leadership under his belt. The initial panel begat additional panels, with a rapid pace of application requests and multiple rounds of review. Many of us who were invited onto these review panels initially agreed to participate at least partly out of curiosity.

In the meantime, we were also being invited to review for other states. This was on top of our regular commitments of reviewing for organizations from which we are eligible to receive funding, such as the NIH, and for charities, such as the Muscular Dystrophy Association and the American Heart Association. These charities, too, were receiving a skyrocketing number of stem cell project applications, and their own review process was becoming stretched. Overseas agencies were also initiating more funding for stem cell research and often requested United States reviewers to help keep their standards high. In the last three years, I have been asked to review for several western European organizations, as well as for programmes in Singapore, the Republic of Georgia and the United Arab Emirates. I could easily spend 100% of my time reviewing and none on my own work. So how do I (and others) decide how to spend my reviewing time? And what impact will all this have on the quality of reviews and ultimately on the quality of science?

First, we must consider the motivations of a reviewer. Traditionally, we review for organizations that also support (or have supported) us. We are members of that community and have something to gain by participating in it. The NIH is the prime example. Most of us who receive money from the NIH spend time reviewing for them, either as a full member of a study section or as an ad hoc reviewer. We do this because we feel an obligation to contribute our time to the organization that supports us. We also want to help maintain high, but fair, standards. We are curious about what our colleagues are doing, and we want to hone our own skills in grant writing so that we are up to date on the latest techniques and issues. We know that the NIH is funded by taxes, so we are also doing our duty to help ensure that the 'right thing' is being done with precious taxpayer money (so that at least we can face our parents and neighbours). Finally, we enjoy interacting with our colleagues during the review and are willing to sit on a panel run by a leader in the field. Often the process is intelligent, efficient and fair, with many opinions duly considered.

Second, there is the little issue of compensation. The NIH recognizes that reviewing takes time from our own work, and so it provides a token $200 honorarium per meeting day to recognize our efforts. Considering the 20 to 40 hours it takes to prepare the reviews for a typical study section, not to mention travel time, reviewing for the NIH is essentially done pro bono, with scientists donating their time to a system from which they derive other direct benefits when their own grants are reviewed. Those heroes who are regular members of an NIH study section participate three times per year, and I know one prominent immunologist who serves on two study sections, feeling that when money is tight, the leaders in the field have an even greater obligation to contribute their expertise.

Yet we accept when we are invited to review for programmes in which we do not participate and from which we expect no direct benefit. What compels us to do so? We can realize some personal benefit by keeping tabs on our colleagues's activities and satisfying some curiosity. But beyond that, we have little to gain. California's token honorarium is marginally higher than that from the NIH ($500 per meeting day), but far less than the $2,000 to $10,000 per day that professional consultants earn. So the California taxpayers are getting a great value from using outside reviewers. Most other states with their own initiatives have followed California's lead by requiring reviews from outside their system, offering honoraria such as $300 for 3 to 6 days of work. Even graduate students are paid better than this on an hourly basis!

What are the consequences of these additional review burdens? The immediate result is the exhaustion of many of the most experienced reviewers. Curiosity fades quickly, and we realize we would be better served honing our skills by writing our own grants rather than reading those of others. Often the programmes end up bringing on junior investigators with no reviewing practice or investigators with little knowledge of stem cells. This is a great experience for participating reviewers, but it could ultimately reduce the quality of reviewing and thus risk the misuse of funds.

Recommendations for states

What could the states do? They could, and should, offer compensation for reviewing that is more in line with the value of reviewers. Just because we scientists consider ourselves truth seekers doesn't mean we lack material needs. Compensation, in the absence of other benefits, is a reasonable incentive for reviewers. After all, the taxpayers have a vested interest in ensuring that reviewing is of high quality—and state governments are undoubtedly paying regular consulting rates in other arenas. Using the NIH salary cap as one guideline of monetary value, senior scientists are worth about $90 per hour in a 40-hour week. At this minimal rate (ignoring benefits), a 6-day review effort should be worth at least $4,000. At the current rate, universities are substantially supplementing the costs when members of their staff review grants, and neither the reviewers nor the universities derive much benefit from this.

Although paying reviewers closer to the market rate would not be cheap, taxpayers should be glad for the high-quality reviews. But is this ultimately a good solution? Even at higher rates, I expect there would still be reviewer fatigue, which would lead to many scientists simply refusing to review as they also need to work on their own research. One might also imagine that at true market rates, some investigators would become professional reviewers, simply flitting around from state to state in order to supplement their own incomes. Because the entire system is predicated on the belief that the investigators conducting the best science are best qualified to review, a system of professional reviewers is not a thought I relish. Perhaps states should pool their efforts to form a panel of self-interested reviewers who won't be allowed to evaluate their own state's applications. Ironically, the logical extension of this is to create a mini-NIH system outside the NIH.

State funding vs. the NIH

These thorny issues do inspire one to take a broader look at the overall impact of state-funded initiatives. There is no doubt that more states will initiate biomedical-research funding programmes to ensure that research talent is recruited to and retained in their states. California universities have already successfully drained some of the talent from within and outside the United States to help shore up their stem cell programmes and to better compete against other in-state universities for funds from the California Institute for Regenerative Medicine.

State legislatures fully recognize that the problem isn't simply a matter of a few scientists leaving for California, but the potential long-term economic and biomedical impact of losing researchers and the supporting industry in a specific popular research area. Voters in my own state of Texas just approved a $3 billion bond proposal to fund cancer research and prevention. Although stem cell research is not universally supported in such a conservative state, who could refuse money for cancer, particularly with superheroes like Lance Armstrong leading the charge? This could have a tremendous impact in Texas, which has a smaller number of internationally recognized research institutions than California does. I imagine that other conservative states will follow suit, finding other similarly palatable strategies for boosting research support while not directly funding stem cells.

Where will this lead? Will New Jersey focus on cancer now that its stem cell initiative failed? Will other states focus on spinal cord injury or autism? We could ultimately have 50 midsized funding organizations that would likely have widely varied agendas, styles and qualities. The research priorities of less-populated states could be driven by a few wealthy or powerful people with their own medical agendas.

For now, the power of the NIH as an arbiter of biomedical research priorities and quality has been seriously weakened. These state funding initiatives come at a time when NIH funding is extremely tight, and thus they are particularly welcome because so many investigators worry about obtaining or maintaining their own research grants; the rise of state funding further contributes to the probable weakening of the NIH. Researchers in some states could conceivably opt out of the NIH system entirely if their state funding programmes were sufficiently lucrative. This has many secondary implications, such as how institutional promotions committees weigh NIH funding as a measure of success.

Of course, these state initiatives could eventually be reamalgamated into the NIH—creating, dare I say it, a new NIH.

If the NIH wants to maintain its current influence on funding, it will have to adapt, which wouldn't be a bad thing. But for all its flaws, the NIH has helped make the United States the leader in biomedical research that it is today. It is extraordinary that an apparently minor decision to limit federal funding of human ES-cell research may ultimately lead to an enormous and unanticipated result: reducing the contribution of the federal government to the entire biomedical research enterprise. In 2008, the NIH will spend an estimated $639 million on stem cell research; a single state, California, is slated to spend $300 million. And as the NIH budget is capped, the influence of other funding sources is bound to increase.

Now we have the first reports of human induced pluripotent stem (iPS) cells. Although we still need human ES cells, the undoubted availability of diverse iPS cells in the near future will change the equation altogether. I expect it may make states even more eager to establish funding programmes to ensure they stay in the running. As we are still early in this state funding game, it seems to me a good time to broadly consider where this is all taking us, in case we want to make adjustments now. Perhaps the National Academies need to perform one of its thought-provoking studies on the future of biomedical research funding in the coming era.

State government support for biomedical research

California: California Institute of Regenerative Medicine
Connecticut: Connecticut Stem Cell Research Grant Project
Illinois: Illinois Regenerative Medicine Institute
Maryland: Maryland Stem Cell Commission
Massachusetts: Governor's Life Science Initiative
Minnesota: Stem Cell Institute
New Jersey: Stem Cell Institute of New Jersey, Rutgers, UMDNJ,State Commission on Science and Technology
New York: Empire State Stem Cell Trust Fund
Ohio: Center for Stem Cell and Regenerative Medicine

Author affiliation

1. Margaret Goodell is director of the Stem Cells and Regenerative Medicine Center at Baylor College of Medicine in Houston.