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Science
Conor O’Kane

Early mRNA research considered ‘too novel’ for funding

Hungarian biochemist Katalin Kariko's breakthrough research on mRNA was continually set back by a lack of funding. Photo: Getty Images

Globally, scientists’ access to public grant funding is ultra-competitive, but as associate professor Conor O’Kane argues, the competition to effectively address funding criteria means scientists are pressured to play it safe with research proposals – including early mRNA research

Comment: Scientists are stifling research novelty in order to secure highly competitive public grant funding because they over-conform to the perceived funding criteria.

When a scientist successfully acquires a publicly-funded grant, it sends a signal of research quality and value. However as our just-published research shows, hyper-competition for public grant funding can compromise the value created from successfully funded research.

We found scientists must balance their desire to do the research they want to do against the insistence of funding bodies to have the criteria they set addressed appropriately.

While this two-way interaction between scientists and funding bodies increases the quality and value of funded research, it also stifles research novelty and human capital development.

Case study: Demotions and job insecurity

Underpinning the development of the Pfizer-BioNTech and Moderna Covid-19 vaccines in 2020 was a body of work dating back to the early 1990s on messenger RNA (mRNA) led by Katalin Kariko, a Hungarian biochemist who immigrated to the US to pursue her science career.

An interesting subplot to Kariko’s breakthrough contribution is how often her research progress with mRNA was almost derailed by upheavals in her career and in particular a lack of funding.

Kariko’s applications for research grant support were rejected over and over again, failing to successfully acquire a single major grant from the National Institutes of Health throughout her career.

Consequently, Kariko had to contend with demotions, a lack of career progression and job insecurity as she periodically sought out new labs, supervisors and teams with access to research resources she could not attain herself.

According to Kariko, because her own work on mRNA work was too unorthodox for the grant funding system “we couldn’t get money then because it was too novel”.

In reflecting on Kariko’s achievements and journey, an editorial in the Harvard Crimson argued that science funding mechanisms were failing society, concluding “the fact stands, the system failed to support mRNA research, and most researchers would have pivoted”.

How does public grant funding work in NZ?

In New Zealand, public grant funding involves science teams, led by a scientist in the role of principal investigator (PI), submitting research proposals to government-resourced funding bodies (e.g., Health Research Council, Ministry of Business, Innovation and Employment's (MBIE) Endeavour/Smart Ideas funds, or the Royal Society’s Marsden fund).

Successful grants range from mid-range hundreds of thousands, to a million or two, with some MBIE grants significantly more. Public grant funding benefits scientists (not only getting to do their research, but also reputational benefits) and institutions such as universities (an important source of income, conveying prestige).

For society, such funding traditionally supported high-risk upstream research activities (i.e. basic research) that have complemented or in some cases propelled industry-driven innovations that have benefitted and transformed people's lives in various ways.

However, as conveyed in the story of Kariko, getting funded is not easy. In fact, as an industry, public grant funding is notoriously hypercompetitive (success rates can be below 10 percent).

This raises interesting questions about how PIs manage these hyper-competitive conditions and what we can learn from the experiences of those who are successfully funded.

Scientists are playing it safe to secure grants

In our research, we interviewed more than 40 PIs who led successfully funded research grants, some of whom had secured multiple grants and sat on review panels.

We identified a set of criteria that scientists address when preparing grant applications:

1) Research feasibility (can the research be done?)

2) Research alignment (the proposed research aligns with funding body priorities)

3) Team credentials (the team has suitable expertise and track record).

It is understandable that funding body review panels want to make good (not wasteful) decisions and support interesting research that is doable, aligned with their mandate and being undertaken by capable scientists.

However, beyond this, our findings identified some less favourable outcomes arising from the hyper-competition. To differentiate grant proposals effectively, scientists are pushed to over-address the criteria of feasibility, alignment, and team formation. Such over-conformance is counterproductive to value creation because science teams make suboptimal trade-offs with their grant.

For instance, with feasibility, science teams emphasise probability and predictability on outcomes over possibility, risk taking and the unknown.

Further, scientists are nudged towards crafting more prescribed and structured research processes with less scope to adapt and explore new and exciting avenues of inquiry that naturally emerge over the course of their research.

With alignment, scientists mould their research, both in terms of topic and timing, to the priorities of funding bodies. With increasing expectations around translation and impact in science, teams are encouraged to incorporate a short- as opposed long-term focus.

Finally, regarding team credentials, team perception is key but this results in the exploitation, and therefore reinforcement, of science hierarchies.

We find evidence of the ‘false investigator’ phenomenon, which involves the inclusion of high status collaborators on grant proposals without clear expectations on how they will actively contribute to the research. This gamesmanship disadvantages the development of, and lowers morale among, emerging scholars, and also results in the formation of ‘safer’ teams being prioritised over the quality of research ideas.

What are the implications?

While the experience of Katlin Kariko shows how novel longer-term research ideas term can get squeezed out by grant funding, our research points to a more nuanced form of value loss arising from the hyper-competition.

The value loss we highlight accompanies grant funding success - it is the cost of grant funding success. To understand this cost, envisage a scenario where Kariko and colleagues responded to grant submission feedback, pivoted their research objectives, and pursued a different (but funded) research trajectory.

The costs our research highlight are originality, risk-taking, flexibility and human capital development, all of which jeopardise the ability of publicly-funded science to create societal value. It is important, therefore, that policy makers ensure they provide enough resources dedicated to supporting novel, early-stage, and higher-risk research.

Alternatively, they may wish to explore new ways to organise the science system with respect to grant funding in ways that can continue to harness the best teams and ideas but with less value loss as a by-product. A further consideration for public funding agencies is how they account for equality and diversity and supporting scientists at all career stages.

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