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

Commentary

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.

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.

Wily consumers will look to domestic sparkling wines as summer heats up

Commentary

The French city of Rheims is the centre of Champagne production. It lies right at the 49th Parallel North, east of Paris.

Conventional wisdom states that the vitis vinifera, or common wine grapes, can only be grown in temperate climates between 30 and 50 degrees of latitude. Global warming is stretching this zone northward, but of the major wine regions of the world Champagne is certainly considered to be a “cool climate” growing zone.

Some regular wine, especially Pinot Noir, is made in Champagne, but its cool climate really does make it best suited to sparkling wines, particularly those made in the traditional Champagne way. When yeast turns sugar into alcohol the byproduct of that fermentation is carbon dioxide.

I have been in wineries when grape juice was being turned into wine and got dizzy from all the extra CO2. The bubbles in most sparkling wines come from that process, but in this case a second fermentation is kickstarted by the winemaker, who adds a dose of sugar to the wine in the bottle.

It’s thought that Champagne became the centre of sparkling wine production in the 17th century when glass bottles became widely used. Wine that had stopped fermenting because of cold winter weather was put into bottles, and started fermenting again when warm spring weather restarted the process. In any event, to counter balance the sugar added for the second fermentation that makes the wine sparkling, it’s best to begin with a wine that is strongly acidic. High acidity is a hallmark of cool climate wines.

The effect of cool climate on Champagne was not lost on wine producers in this country. The bigger producers all make some kind of sparkling wine in the “traditional method.” And there are smaller, family-run wineries across Canada making sparkling wines, with centres of excellence in the Annapolis Valley, Niagara Peninsula and Okanagan Valley.

Champagne is famously a luxury item, and like most luxury products, its consumers are willing to pay high prices for a guarantee of quality.

According to the Comité Champagne website, the latest production numbers were for a bit more than 230,000,000 bottles annually. (Most Champagne is “non-vintage” and made by blending wines made in different years, so presumably this figure is fairly stable.) Consumption is about evenly split between France and export markets.

In France there are many smaller houses that compete for consumers, including “grower Champagnes” made by the families that tend the vines. The export markets, however, are dominated by handful of large producers who buy grapes from multiple sources. So, while Champagne may be a luxury brand, what’s sold in Canada is made on a scale much more in line with a mass consumer product.

This summer in Canada looks to be one of celebration. Families and friends will be reunited after months of little or no contact. Milestones and accomplishments will be toasted and people will get together safely under the cover of vaccination. Bottles of sparkling wine will be opened and enjoyed. Many consumers will pay more for the sparkling wines that come from Champagne. But many wily ones will instead look to domestic bubbles made in the traditional method, that cost less and come from one of the cool climate regions within our borders.

Three pioneering Canadian sparkling wine families and producers that are widely available across Canada are:

Benjamin Bridge in Nova Scotia: https://benjaminbridge.com/

Henry of Pelham in Ontario: https://henryofpelham.com/

Blue Mountain Vineyard and Cellars in British Columbia: https://www.bluemountainwinery.com/