Viewpoint

Sean Speer: The decades long resistance to mRNA vaccines shows the need for reform

We might never have gotten mRNA vaccines if we relied solely on peer review
Barbara Violo, pharmacist and owner of The Junction Chemist Pharmacy, draws up a dose of the Pfizer-BioNTech COVID-19 vaccine, in Toronto, Friday, June 18, 2021. Nathan Denette/The Canadian Press.

One of the most extraordinary stories of the pandemic is that of Katalin Karikó, a Hungarian-born, American-based scientist whose decades-long research on the therapeutic possibilities of mRNA led to the COVID-19 vaccine and ultimately saved the world.

What makes it so extraordinary is it only happened because of Karikó’s own single-minded determination and dogged persistence. Notwithstanding recent historical revisionism on the part of different academic institutions and funding agencies to assume some credit for the miraculous progress on mRNA vaccines, the truth is actually closer to the opposite.

Karikó’s enormous personal contribution deserves the recent mix of admiration and accolades – including a future Nobel Prize – precisely because she overcame various institutional obstacles to produce such a major breakthrough. Her greatest accomplishment is both simple yet profound: she resisted the academic blob that upholds the peer-review process as the so-called “gold standard” and instead chose to stay steadfast in her vision of something different and better.

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Her experience reflects a broader indictment of the conformity and clubbyness of modern academia and the failings of peer review as a barrier to progress. It therein provides a crucial lesson as we think about how to reform post-secondary institutions, design better research funding programs, and ultimately create the conditions for greater progress in science and other fields of discovery.

As others have documented, Karikó faced ongoing discouragement and outright resistance from the scientific establishment for more than two decades. Her funding proposals were consistently rejected, she was professionally demoted, and her ideas were, by and large, ostracized by the most powerful figures in the world of academic research and scholarship. She was the quintessential outsider in an world marked by insiderism.

Karikó’s main transgressions were two-fold: first, her worked deviated from the pre-existing body of knowledge; and second, she wasn’t, by all accounts, “adept at the competitive game of science.” In today’s world of highly-specialized academic gatekeepers, these are disqualifying traits. Our current system of peer review for research funding and scholarly publishing preferences a combination of insularity and incrementalism over broad-mindedness and breakthroughs.

It’s hard to overstate how devastating these setbacks must have been for Karikó as an aspiring scholar. They would have led to a forked road for most in the same position: disappear into academic obscurity or succumb to the peer pressure to conform to conventional research methods and priorities.

But she courageously chose a third option. She accepted the professional indignity and financial consequences of a demotion in order to continue pursuing her research in mRNA. As a former colleague recently wrote: “Karikó lived that nightmare, but stuck to her passions. She was too committed to the promise of mRNA to switch to other, perhaps more easily fundable projects.”

As we now know, this proved to be an inspired choice. Her ongoing work on mRNA – the genetic script that carries DNA instructions to each cell’s protein-making machinery – eventually produced a significant breakthrough. It has since formed the basis of the Moderna and Pfizer vaccines and now holds out the potential to revolutionize the treatment of cancer and various infectious diseases.

Karikó’s period in the scientific wilderness is a fundamental failure of the modern peer review system – it reflects what one writer describes as the “sociology of science.” Her experience is a sign that we’ve granted too much power and influence to peer reviewers.

Her ideas were ostracized by the most powerful figures in the world of academic research and scholarship.

Peer review is supposed to be a quality control mechanism. Its goal is to ensure that research and scholarship meet high standards in terms of evidence and rigour by subjecting it to scrutiny by experts in the same field. These reviewers carry significant sway: their recommendations ultimately determine whether a manuscript or grant proposal is accepted, rejected, or improved before publication or approval.

The process is generally well intended and broadly supported among scholars. A 2008 survey of academics, for instance, found that about two thirds were satisfied with the peer review system and 85 percent believed that “scientific communications is greatly helped by peer review.”

But Karikó’s case reveals a major flaw in the system: the process which is supposed to protect against flawed scholarship has come to narrow the horizons of scientific inquiry and reduce the scope of scholarly debate. These inadvertent consequences are arguably worse than the problems that peer review is trying to solve. While we may have less bad scholarship on the margins, it has come at the greater cost of the growing conformity of ideas and a slowdown of progress.

A major source of this problem is the growing hyper-specialization in most academic fields. The world of research and scholarship is increasingly marked by an intra-conversation among a small number of experts within narrow sub-fields. These highly-specialized scholars not only often know one another, but they frequently have direct relationships as co-authors, research collaborators, and PhD supervisors.

In such a narrowly specialized world, peer reviewers are necessarily selected from these small groups of experts. Even with “blind reviews” and the involvement of multiple reviewers, it’s hard to overcome the inherent challenge of insularity. Most research fields are so small that it’s often apparent to reviewers who the author or grant applicant is based on citations, subject, or writing style.

This can lead to an inherent bias in favour of the research priorities, methods, and ideas of the dominant experts in the field. It’s not necessarily the case that reviewers are doing this on purpose. The argument here isn’t that peer review is a backscratching exercise in which scholars in narrow sub-fields favour one another in order to deliberately control the flow of research funding or the articles published in prestigious journals. But that’s essentially the unintentional effect.

It produces a gatekeeper dynamic that tends to preference incrementalism over breakthroughs and which in turn sends a powerful signal to aspiring scholars: don’t diverge too far from the dominant methods and priorities or risk being marginalized by one’s peers.

Karikó’s experience should lead to reforms on how we judge and support academic research. We ought to reduce the scope of peer review (or at least make it less definitive in determining funding or publication decisions), target research funding to younger, less established scholars, and create new funding institutions dedicated to supporting genuine research breakthroughs. These types of institutional and policy changes can help us to pushback against intellectual conformity and renew our collective commitment to progress.

The ultimate measure of success should be that future Karikós don’t fall through the cracks. The opportunity costs in the form of forgone breakthroughs like the mRNA vaccines are far too great for our societies. If her extraordinary experience teaches us this lesson, it will be another thing for which we owe her our debt.

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