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Columns

The Science Funding Crisis That Nearly Killed mRNA Vaccine Development

By Julie Heng, Crimson Opinion Writer
Julie Heng ’24 is a Crimson Editorial editor. Her column runs on alternate Tuesdays.

Last year, scientists developed mRNA Covid-19 vaccines at historic speed. That wouldn’t have happened if it weren’t for scientists like Katalin Kariko, who has laid the groundwork for mRNA vaccine development since the 1990s.

Kariko’s own career, however, nearly ended in 1995, and her story shows how science funding mechanisms in the U.S. have failed us.

After arriving in the U.S. from Hungary, Kariko sought to develop therapies using mRNA, pieces of genetic code that tell cells what proteins to make. Theoretically, you could artificially create mRNA that encoded instructions for enzymes or antibodies. Practically, however, it was a challenge to send synthetic mRNA into the body’s cells in the first place, and most scientists abandoned the field.

Not Kariko. Kariko sent out countless grant applications and received countless rejections in her pursuit of developing mRNA technology, and with no money coming in, the University of Pennsylvania demoted her.

At this point, with their reputation skewered, most scientists would let go of their research. But Kariko, despite being newly diagnosed with cancer, pressed on. From when Kariko was demoted from the University of Pennsylvania in 1995 to when she was kicked out of the lab in 2013, her salary barely changed, even as health insurance and parking costs went up — she was making less than the lab technicians she worked with.

“I could see that people around me, you know, they get the grants and they get the money,” Kariko said in an interview. She was never awarded a single major grant from the National Institutes of Health over the course of her career.

As I was talking to Kariko over Zoom, it was obvious how passionate she is about science. She told me about her excitement heading into the lab at 6 a.m. on Sundays.

“There's people from outside seeing me struggling or sweating. The whole thing is struggle, struggle,” Kariko told me. But “as long as you could see how [your research was] advancing, you didn't feel tiredness.”

I am in awe of Kariko’s service to science and her relentless determination despite countless grant rejections, not to mention demotion. But the fact stands: The system failed to support mRNA research, and most researchers would have pivoted.

“It's a complicated ecosystem,” Harvard Dean of Science Christopher Stubbs said in an interview with the Crimson. “People move their research in the direction where the resources exist for sure.”

Current grant funding can come from either private companies and foundations or the government. Funding in the public arena began after World War II, and the selection process has since greatly intensified. Individual researchers submit proposals to a government agency like the National Science Foundation or NIH, where a group of scientists evaluate the proposals and allocate funding to only about 10 percent of proposals. The National Cancer Institute’s funding line is even lower.

What this means is that current scientific research follows a “regression to the mean instead of aspiration to excellence,” according to Astronomy professor Avi Loeb. Since a vast majority of applications are rejected, funding mechanisms end up driving many researchers into non-academic positions or leaving many researchers in the field spending time writing grants and chasing more conservative trends, performing minor variations on trending or already-successful research experiments.

“Extraordinary conservatism leads to extraordinary ignorance,” said Loeb, who faced skepticism and ridicule from colleagues for hypothesizing that ʻOumuamua was an interstellar extraterrestrial object. “Because if you are not open-minded to discover new things, you will never find them.”

Most grant proposals ask for a breakdown of what you hope to accomplish in year one, two, and three. What’s backwards about this procedure is that the grant mechanism itself projects and ensures an expectation of what you’re hoping to accomplish. In fact, many researchers apply for grants having already finished half or most of the project.

Loeb recalled once submitting what he considered a “safe” grant proposal — a project he had already completed and slated for publication, only to receive a grant rejection that claimed the project could not be done.

“I feel like I'm serving the role of the kid saying the emperor has no clothes,” Loeb said. “I hate it when some of my colleagues are basically speaking responsibly: keeping an image and never making mistakes, and having their students and postdocs repeat what they did already and just making it even louder.”

So, how do we solve the funding issue? For one, we must increase funding overall to combat the scarcity and constraint of funding lines. More importantly, we must foster innovative research by specifically portioning funds for high-risk projects.

Kariko told me that despite every obstacle, she was driven from within by a love of science: “I don’t use a stick or carrot.” But many scientists in Kariko’s position, frustrated that available funding mechanisms did not recognize the importance of their work, would have given up. Furthermore, mRNA was intellectually interesting to Kariko, but nobody knew just how important it would be to humanity in 2020. If we fund projects that only advertise immediate and obvious benefits, then we’re shooting ourselves in the foot.

It is also paramount to make sure that these high-risk funds aren’t only given to established labs that have already made it and been winnowed out — perhaps, every lab should be given a chance to try one potentially major project.

At the end of the day, funding is supposed to fuel science, not hinder it. If the funding system is actively preventing groundbreaking research, we have to change that system.

Julie Heng ’24 is a Crimson Editorial editor. Her column runs on alternate Tuesdays.

Santiago R. Giner ’24 contributed reporting.

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