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Here’s my pitch for an Oscar-bait film coming out in 2026. You ready?
An immigrant comes to the United States, mere pennies in her pocket,
determined to further her career in science.
She faces setbacks and resistance from authority figures,
and labors for decades in obscurity with barely any funding.
Finally, she’s given an ultimatum: Abandon her research, or lose her career.
She chooses her research, and because she does, she’s able to save untold millions of lives.
Sound like a good movie? ‘Cause it’s a true story: that of Katalin Karikó,
co-winner of the 2023 Nobel Prize in Physiology or Medicine and a person who is cooler than you.
Her work made mRNA-based vaccines, including the ones against COVID-19,
She might have saved your life, or that of someone you know.
And get ready, because her story is the best movie you will see all year.
[Intro music]
In the 1970s, scientists were just beginning to explore the possible uses of messenger RNA in medicine.
They knew that mRNA was the means by which the
instructions encoded in DNA actually got carried out.
The information in a gene gets copied onto a strand of mRNA,
which travels out into the cell to be translated into a protein and do stuff.
If scientists could write those instructions instead,
they could direct the cell to do practically anything. The mRNA vaccines we have today
provide a small snippet of a virus to teach the immune system what it looks like,
but these early pioneers were picturing everything up to and including treatments for cancer.
Katalin Karikó first learned about these ideas as an undergraduate,
and said to herself: Yeah, that’s how I’m gonna change the world.
She started her scientific career in her native Hungary, but when her funding dried up for the
first time, she moved to the U.S. You couldn’t bring money out of the then-communist country,
so she and her husband sold their car and hid the cash inside their daughter’s teddy bear.
Dr. Karikó eventually landed at the University of Pennsylvania
where she and a collaborator continued working with mRNA,
including how to get mRNA into cells and make them express genes they normally wouldn’t.
Then that collaborator bounced for a cushy private industry job and left Karikó with no funding.
There were a couple of reasons there wasn’t a lot of money for mRNA research in the 80s and 90s.
The idea that you could give a cell instructions to make a vaccine or
treat a disease still held true. But there were two serious problems.
One was just the difficulty of manufacturing RNA.
That stuff falls apart if you look at it the wrong way.
The other was the fact that for some reason, mRNA made in a lab triggers an immune response if you
try to put it in a living organism. It was way too unsafe to even consider putting in a person.
Dr. Karikó was working on this problem when the low point came
in 1995. Because she had no financial support, Penn gave her an ultimatum:
Either change the direction of her research, or take a pay cut and a demotion.
Karikó looked at all her work so far,
at the lifesaving potential she was convinced it held… and like a boss, she chose science.
[AIRHORNS]
But this is the part of the movie where the instruments swell, because not long after
this lowest of blows, she met the person she was going to share a Nobel Prize with.
She and immunologist Drew Weissman were literally fighting over a photocopier
when they struck up a conversation about science. And he was like “OK,
but can your RNA make a vaccine for HIV” and she was like “Yeah, just gimme a minute.”
[AIRHORN INTENSIFIES]
As it turns out, there are a couple of mRNA vaccines for HIV in human trials at the time we filmed this.
Anyway, Karikó and Weissman started up a collaboration in 1997. In 2005,
they and a couple others published what’s now a classic paper containing the key insights
that told the COVID-19 pandemic where to shove it.
Basically, they needed to figure out the difference between an organism’s native RNA,
which obviously does not make them sick, and synthetic RNA, which does.
The key seemed to be proteins called Toll-like receptors,
a part of your innate immune system that helps to recognize foreign substances within the body.
Among these foreign substances are RNA and DNA belonging to invading viruses and bacteria.
Somehow, Toll-like receptors can tell the difference between RNA that comes
from a virus, and RNA that comes from you.
The team realized that the RNA made by your cells undergoes specific modifications. The
bases that make up RNA, A, C, G, and U, can have small chemical
changes made to them without altering the information content of the RNA itself.
It still codes for the same product, it just has little “I live here, don’t eat me” bits on it.
In the paper, the team showed that the more modified an RNA strand was, the more Toll-like
receptors would pass it by. Meaning these tiny little chemical adjustments were the
key to getting a strand of RNA into a mouse – or a person – without triggering an immune response.
They also established that simply changing the base U, or uridine, to a slightly different
form called pseudouridine was good enough for Toll-like receptors to wave the mRNA through.
What’s more, mRNA with pseudouridine produced way more of its product in the cell than mRNA
with uridine did. That’s key when you’re trying to instruct a cell to make its own medicine.
The discovery should have been celebrated. It was finally possible
to realize the dream of using mRNA to write vaccines and other therapies.
But the scientific world mostly shrugged. The 2005
paper was rejected by top journals Nature and Science, and had to be published elsewhere.
A couple of small, obscure biotech startups did license the idea, though.
Their names were Moderna and BioNTech. You’ve probably never heard of them.
In 2013, Penn made their last mistake. Dr. Karikó petitioned to have her position reinstated,
given that she’d, like, solved the problem preventing a major
therapeutic strategy from being anything more than a gimmick.
They declined, and according to her, they said she was, “not of faculty quality.”
In one interview, she recalled telling them they should keep her lab how it was,
because it was going to be a museum one day.
[AIRHORN FURTHER INTENSIFIES] So she bounced to become a VP at BioNTech
– okay, cushy private industry job, but ya girl has earned it.
And we can kinda hit fast forward now because you know how this ends.
A few kinks still had to be figured out, like how to get the vaccine into people.
And even into the pandemic, scientists were still debating whether you actually needed
pseudouridine. A few tried to make vaccine candidates work without it.
Seems like the Nobel committee has let us know where they stand on that one.
But in 2020, when we needed it most, scientists were able to design vaccine
candidates almost instantly. And… they worked.
A lot of people worked on mRNA vaccines over the years. A lot of people other
than Karikó and Weissman deserve credit for bringing the pandemic under control.
But it is fair to say that if one determined scientist had not chosen
to stand by her research in 1995, a lot of people who are here today… would not be.
We’re pro-science around here, so whenever a Nobel prize comes out
we’re like “Hey! That’s awesome! Yay science!” But even we have to Google
when the prize goes to something like ‘asymmetric organocatalysis’ because
it’s just not immediately obvious how that’s going to affect most of our lives.
This one feels truly consequential. There’s not likely to be another Nobel in our
lifetimes that so /viscerally/ connects to our own experience.
Dr. Karikó, if you see this, thank you for everything.
Also did you really say that to your former boss because holy [bleep].
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Thanks for watching SciShow, and thank you Dr Karikó, for a truly girl boss-ing into the sun!
[Outro music]