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    The Karikó problem: Lessons for funding basic research



    New scientific institutes are arising all over the place nowadays: Arcadia Science, New Science, Arc Institute, Activate, Actuate, Astera, Convergent Research, and extra. They’re often funded by Silicon Valley and have daring ambitions to advance scientific progress extra rapidly.

    Why this flurry of exercise? In any case, the Nationwide Institutes of Well being spent nearly $43 billion on biomedical analysis in 2021, and the Nationwide Science Basis spent nearly $8.5 billion on different areas of science. Why would anybody wish to trouble with funding a small fraction of a % of that?

    As a result of they’re satisfied that the present system of science funding is uncreative and rigid and that it’s time to strive new approaches. For instance, one frequent argument is that we have to “fund people not projects,” which means we have to discover the sensible and visionary scientists and provides them funding that isn’t tied to slim tasks.


    As a lot as I like this concept, I fear a couple of completely different downside, one which not one of the new initiatives to this point would essentially repair. I name it the Karikó downside.

    Katalin Karikó is the now-celebrated scientist who, together with a colleague, revealed a key paper in 2005 on messenger RNA. Her discovery in the end shaped the idea for 2 Covid-19 vaccines: one made by Pfizer and BioNTech, the place Karikó now works, and one made by Moderna.


    However Karikó wasn’t at all times celebrated. Removed from it.

    She earned her PhD in biochemistry on the College of Szeged in Hungary, at the moment ranked by US Information because the 712th best university globally.

    She emigrated to the U.S. in 1985 together with her husband and then-young daughter to take a postdoc place at Temple College in Philadelphia, and ultimately bought a job as a non-tenure-track analysis assistant professor on the College of Pennsylvania. However she was demoted in 1995 as a result of, irrespective of what number of occasions she utilized for NIH funding for her mRNA analysis, she by no means bought a grant for it.

    As one in every of her former colleagues wrote, “by the point I joined the lab, Karikó’s historical past was nonetheless solely mentioned in hushed tones as a cautionary story for younger scientists.” Karikó herself has said that after such a demotion, it’s frequent to “simply say goodbye and go away as a result of it’s so horrible.”

    But she persevered. A few years after her embarrassing demotion, she bumped into immunologist Drew Weissman at the office copy machine and struck up a dialog about mRNA. Weissman was intrigued, and requested Karikó to return work in his lab. Finally, the pair discovered methods to modify mRNA simply sufficient that it will nonetheless work, however with out triggering the physique’s immune system to kill off the molecule first. That led to their groundbreaking 2005 paper (which, by the way in which, was acknowledged as groundbreaking solely looking back: on the time it was “summarily rejected” by the distinguished journals Nature and Science, with Nature commenting that it was simply an “incremental contribution“).

    It’s a miracle that Karikó caught in academia for thus lengthy after being handled this fashion.

    That’s why we must always fear concerning the invisible Karikós: the individuals with good concepts that weren’t common on the time who dropped out of academia. It’s unlikely that she was the one particular person on this planet who had an fascinating thought in 1985 that might have changed into a groundbreaking discovery over the subsequent few a long time.

    We’ll by no means know what we missed.

    That makes me take into consideration the “fund the particular person, not the undertaking” method. To be clear, this could possibly be an ideal thought, and it’s properly value experimenting with. However would Karikó herself have completed any higher with that method?

    It’s onerous to think about. At Karikó’s demotion in 1995, nobody would have stated, “Right here’s a 40-year-old Hungarian scientist who went to a reasonably obscure college, who has zero well-known mentors vouching for her, who has spent some 10 years engaged on an issue that nobody thinks is solvable, and who began in a non-tenure track position solely to get demoted from there. Let’s give her a number of million {dollars} in unrestricted funding over the subsequent 10 years.”

    So right here’s the Karikó downside in a nutshell: Anybody can establish Karikó looking back, given her persistence and her eventual discoveries. However what can we do proper now to search out the 2022 variations of Karikó who merely don’t (but) seem like the “visionaries” or “geniuses” who can be eligible for “particular person not undertaking” funding?

    My reply? Bend over backward to fund a extra various vary of individuals and concepts, even intentionally together with concepts which can be at the moment perceived as unpopular, unworkable, obscure, and the like. In any case, many scientific discoveries will be traced again to origins that didn’t appear promising — like CRISPR, which started with a Spanish examine on salt-loving archaebacteria in 1993 — and even to concepts which can be actively opposed by the institution.

    To make certain, the success price of this method is perhaps low. But when we funded 10,000 individuals who regarded like a youthful Karikó, and solely one in every of them did one thing that may have the influence of her mRNA analysis, that may be properly value it.

    Stuart Buck is the chief director of the Good Science Venture and a senior advisor to the Social Science Analysis Council.


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