How Our Brutal Science System Almost Cost Us A Pioneer Of mRNA Vaccines

Pfizer and BioNTech's COVID-19 vaccine. (Matthew Horwood/Getty Images)
Pfizer and BioNTech's COVID-19 vaccine. (Matthew Horwood/Getty Images)

Lately, my social media feeds have been filled with "vaxxies" — selfies of health care friends getting COVID-19 vaccines and gushing about how the shots brought them hope or relief. Many express gratitude for the science that yielded the vaccines.

When I got my own shot — after working the chaotic first surge at an understaffed hospital in March and April — I felt an added emotion: awe.

You see, I witnessed some of the early scientific heartbreaks that came before the historic vaccine victories. And I found myself simply awestruck by the scientists I knew who persevered in spite of our system of scientific research.

The system helped lead to progress, but it also demoralized a junior researcher to the point that anyone of less grit and determination would have just given up long before the groundwork for today’s vaccines was laid.

An Existential Career Threat

Here’s my story: 20 years ago, I worked part-time in a tumble-down laboratory in a dusty corner of an old medical school building at the University of Pennsylvania, where I was an undergrad. For three years, I studied HIV replication in T-cells under researchers Drew Weissman and Katalin Karikó.

These days, they are coronavirus vaccine heroes, but back then, their very early work on mRNA vaccines aimed to fight HIV. After spending my first four months in the lab on an experiment that never worked, I learned that good science is really, really hard.

I didn’t know it at the time, but I also absorbed what I later could describe as the sociology of science — how the sausage is made — and it wasn’t always pretty.

From the photo album of author David Scales (second from right), the lab team that included Katalin Kariko (third from left.)
From the photo album of author David Scales (second from right), the 2001 lab team that included Katalin Karikó (third from left.)

While Weissman was an expert at designing experiments, I remember him most for his generosity. He made sure all contributors in the lab shared the credit, from the lab tech and lowly undergrad all the way to fellow researcher Karikó.

Still, Karikó was struggling. Her science was fantastic, but she was less adept at the competitive game of science. She tried again and again to win grants, and each time, her applications were rejected.

Eventually, in the mid-1990s, she suffered the academic indignity of demotion, meaning she was taken off the academic ladder that leads to becoming a professor. We never discussed it personally because by the time I joined the lab, Karikó’s history was still only discussed in hushed tones as a cautionary tale for young scientists.

I learned that while universities pay the salaries of many of their professors in English or anthropology, they expect faculty in the medical schools to pay their own way with either clinical work or external research funding. This puts tremendous financial pressure on eager young medical researchers, sometimes leading them not to the projects that are most needed or that they are most passionate about, but to the projects that will get them funding.

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. Eventually, the university stopped supporting her.

It’s hard to describe what this moment means to people who have never worked in science at a university, but it is more than the frustration of an experiment not working or laudable work going unrecognized. It is an existential career threat. Everything you have worked for your entire life is suddenly in jeopardy. It is a forced career change on the assumption that if you can’t get the grants, you’re not a good enough scientist.

Clearly, this was a false assumption in Karikó’s case. She was a dynamo, with a passion for science that rubbed off on those around her. I remember one lab meeting where she arrived with a copy of Science or Nature magazine, absorbed in a new study that showed some cool biological feature of how cells reacted under stress. It wasn't her area of research, yet she was still in awe of the beauty and intricacy our cells are imbued with, and her enthusiasm was infectious.

A Scientist To Her Core

She also shared jaw-dropping anecdotes about working as a scientist in the Eastern Bloc, from the cutthroat competition in school to the practice of smoking cigarettes in the lab (except when someone opened a container of very flammable ether).

For Karikó, who had persevered under those extraordinarily difficult circumstances in communist Hungary, demotion was particularly bitter. Most people in such circumstances end up leaving the university, but she pressed on.

I think she had to. Mark Doty, a poet, visited and gave a talk my senior year at Penn. Afterwards, a student and aspiring poet asked when and how Doty knew he was willing to endure the sacrifices it took to be a poet, with all the rejections, the financial struggle and the economic instability.

Doty said that he couldn’t not be a poet. He tried other things and just wasn’t happy. For him, it wasn’t a choice. Seeing Karikó get so excited about scientific findings that weren’t even related to her research, I got a similar sense about her too: she couldn’t not be a scientist. It was baked into her bones. Luckily for us, now.

It’s the secret you don’t learn in school. We know doing good science is hard. But it isn’t only difficult because divining nature’s secrets is a unique challenge. It is unbelievably, brutally difficult for all of the other non-science skills that are needed but not explicitly taught: writing grants (“grantsmanship”), getting invited to speak at conferences, building collaborative research relationships, having the political awareness to attract allies and mentors within a department or university who can help find support for you.

It’s the sociology of doing science at a university that makes science even harder than it already is. Usually, stories like Karikó’s end in obscurity and disappointment. Add in being a woman and an immigrant, and it makes her perseverance even more inspiring.

You Were Right, Kati

For me, seeing such an impressive mentor struggle so hard acted as a powerful push away from doing science. I spent a year abroad studying history and philosophy of science, learning the social processes by which scientific facts become solidified, then studied medicine and sociology.

But lately, I have found myself drawn back to science, as empirical facts are dismissed with a tweet. If anything, the problems Karikó faced have gotten worse over the past 20 years. It is high time for scientists to save science. But, at its best, science can produce beauty, wonder and, occasionally, through the hard work of very dedicated individuals, it can produce technologies that save millions of lives.

The coronavirus vaccine has demonstrated that we need good science - and good scientists - now more than ever. And we need to make sure that they stay in science, one way or another.

Academic science failed Karikó. But when she contacted me in 2015, I saw she had moved to the private sector, a common path for researchers when a university stops offering support. I was glad to see she had landed on her feet. And now, I watch in awe, like the rest of the world, as the technology she helped developed leads to one of the most spectacular victories in the history of science - a vaccine for a deadly pandemic developed in less than one year.

So, my vaccination day was an emotional one. As the lipid-encapsulated mRNA molecules went into my arm, I reminisced about Kati and Drew, and the lab circa 2000. And I thought: You were right, Kati. You were right.

The recent
The recent "vaxxie" of author David Scales (courtesy David Scales).

Dr. David Scales is a physician and assistant professor of medicine at Weill Cornell Medical College. He can be found on Twitter @davidascales. The views and opinions expressed in this piece are those of the author and do not necessarily reflect the official policy or position of Weill Cornell Medical College.



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