Imagine for a second the absolute, the pinnacle
of professional recognition, the kind of moment
that just defines a whole lifetime of work. For
a scientist, I mean, there's really only one
peak that fits that description, right? It's
a Nobel Prize. It has to be. That phone call
from Stockholm, I mean, it changes everything.
It's the signal to the entire world that you
haven't just done a good job. You fundamentally
altered the course of human history. Exactly.
Fundamentally altered it. So hold that image
in your mind. The confetti, the press conferences,
the King of Sweden handing you a medal, just
the ultimate final validation. The victory lap.
Yes. Now, I want you to hard cut away from that.
Yeah. Just wipe the slate completely clean. Okay.
Where are we going with this? It's 1985. We're
at a border crossing. Hungary. And it's a gray,
tense scene. You can picture it. Soviet block
guards, machine guns, dogs sniffing the wheel
wells of the cars. Yeah. Not a friendly place.
And inside this one old Lada, there's a family.
They're trying to leave the country for good.
A father, a mother, and a two -year -old girl.
And the most valuable thing in that car isn't
the luggage. It's not the passports. It's not
even the car itself. No. It's a teddy bear. A
teddy bear. A simple teddy bear sitting right
there in the lap of that two -year -old girl.
Because stuff deep inside the batting of that
bear, right where a kid would squeeze it for
comfort, is roughly 900 British pounds. Which,
you know, to us today, that might not sound like
a fortune. But in 1985 Hungary, behind the Iron
Curtain. That was an astronomical sum of money.
Right. It was their entire life savings. They'd
sold their car, sold off their furniture. They
scraped together every single forint they had.
And then exchanged it on the black market, which
was incredibly risky in itself. The stakes just
couldn't be higher. I mean, if one of those border
guards decides to just squeeze that bear a little
too hard. Yeah. They find that cash. Oh, it's
not a fine. It's jail time. The career is over.
The dream is dead. Everything is gone. And that
money smuggled inside a child's stuffed animal
was essentially the seed capital for a scientific
revolution. Today, we are doing a deep dive into
the story of Catalin Caricarico. And you're right.
Usually when this story gets told, we start at
the finish line. We talk about the 2023 Nobel
Prize in Physiology or Medicine. We talk about
the COVID -19 vaccines that saved, I mean, literally
millions of lives. We focus on the victory lap.
But our mission for this deep dive is it's different.
We need to look at the 40 years of, frankly,
darkness that came before all the confetti. This
isn't just a biography of a scientist. This is
a case study in resilience. It's a story about
the blindness of institutional academia and how
a biological hack. that was ignored, underfunded,
and even mocked for decades, ended up rewriting
the source code of modern medicine. It is the
ultimate survivor story. And to really, truly
understand the magnitude of what Carrico achieved,
you have to understand just how close this technology
came to to never existing at all. It was on a
knife's edge for decades. So let's rewind the
tape. We're not starting in some high -tech lab
at UPenn or BioNTech. We're going way, way back
to the source. We need to understand the environment
that forged this person. We are going to Kisushlas,
Hungary. Kariko was born on January 17, 1955.
And, you know, when we use that phrase, humble
beginnings, I think we often gloss over what
it really means. Yeah, it becomes a cliche. It
does. But in post -war Hungary, in the countryside,
this was a life stripped down to the absolute
essentials. We're talking about a small adobe
home. Made of mud brick. Exactly. Only one room
heated in the winter, no television, no refrigerator.
And the detail that always gets me, no running
water. Wow. So you're not just turning on a tap.
You are physically pumping water from a well
every single day. It's a very physical, very
direct existence. Her father, Janos, was a butcher.
Her mother was a bookkeeper. So you have this
really interesting mix right from the start.
How so? Well, you've got the practical, visceral
reality of biology right there in the butcher
shop, and then you've got the precision of numbers
and ledgers from her mother. It's the hands -on
and the analytical all in one household. But
there's a shadow hanging over this family, isn't
there? It wasn't just about being poor. There
was a political weight. A very heavy one. You
have to remember the context. 1956, the Hungarian
Revolution. Right, against the Soviets. It was
a nationwide uprising against the government
and its Soviet policies, and it was crushed.
just brutally put down and carco's father janos
he participated in that revolution and in a soviet
satellite state in the 50s and 60s you don't
just move on from participating in a revolution
no the state remembers the state always remembers
he was punished for it he lost his job for a
time so kari grows up in this environment where
well where authority is dangerous, she sees her
own father, a strong, hardworking man, having
to navigate a system that is fundamentally suspicious
of him. That has to implant a very specific kind
of worldview in a child. I think so. You learn
early on that the system isn't always right.
You learn that institutions can be wrong, and
that sometimes you have to survive in spite of
them, not because of them. And yet, despite the
lack of resources, or maybe, you know, because
she had to find entertainment in the world right
around her, she becomes an academic prodigy.
She was just. Relentless. By primary school,
she's already placing third in the entire country
in biology competitions. She had this raw, unfiltered
curiosity about nature. She wasn't learning biology
from an iPad or a screen. No, she was learning
it from the plants in the garden and the animals
in the yard. Exactly. It was real and tangible
to her. So she excels. She eventually moves on
to the University of Saged. She gets her bachelor
of science in 78, her Ph .D. in 82. She lands
a good job at the Biological Research Center,
the BRC. On paper, she's on the perfect path.
She is. But this brings us to a part of her history
that is, well, it's really complex and, frankly,
pretty terrifying. The intel asset. That's the
one. So decades after the fact, it comes out
that from 1978 to 1985, her name was listed in
the files of the communist secret police as an
intelligence asset. And when that news broke,
it could have been a career ending scandal. It
could have been. But we really need to parse
this with extreme care because the nuance here
is everything. It is. And Karikora has been incredibly
transparent about this chapter of her life. She
wasn't a volunteer spy. She wasn't an informant.
She was a victim of that very system we just
described. How did it happen? The authorities
approached her. They knew her father's history
as a so -called counter -revolutionary. And they
essentially, they blackmailed her. The choice
was laid out in no uncertain terms. So it was
an ultimatum. A brutal one. Sign this recruitment
paper or your father will face severe reprisals
and your own scientific career, which you've
worked so hard for, will be terminated immediately.
My God. It's a literal dead end. You sign the
paper or you lose your entire life's work and
you endanger your family. There was no choice.
So she signed. But, and this is the absolute
crucial part that's been corroborated by the
historical records, she maintained she never
acted as an active agent. So she never informed
on anyone. Never. In intelligence terms, she
was what you'd call a paper agent. She existed
in a file to satisfy some bureaucrat's quota,
but she never reported on her colleagues. She
never provided operational information. She walked
this incredible razor's edge of appearing to
comply while doing absolutely nothing to harm
anyone. Imagine the psychological weight of that,
though. You're in your 20s. You're trying to
decode the fundamental secrets of life in the
lab. And you have the secret police technically
breathing down your neck. It's a pressure cooker.
It has to force you to be self -reliant. You
learn you cannot trust the institution to protect
you. Your survival is up to you. And eventually
that pressure cooker does explode. But what's
so interesting is that it wasn't the police that
finally drove her out of Hungary. It was something
much more mundane, something scientists everywhere
can relate to. Funding. It almost always comes
down to funding. In 1985, her lab at the BRC,
it just, it lost its funding. The money dried
up. So she had no resources to continue her research.
Zero. And for a scientist like Carco, I mean,
not doing research is like not breathing. So
she starts looking abroad desperately. She gets
an offer. She gets a job offer from Temple University
in Philadelphia. It's a lifeline. And that brings
us right back to that. gray morning at the border
crossing, the decision to just leave everything
they know behind. Let's go back to that teddy
bear for a minute. It's 1985. She's with her
husband, Bella Francia, and their daughter, Susan,
who's just a toddler. They sell the car. They
have to go to the black market to get British
pounds. Because you couldn't legally just take
currency out of the country. Right. There were
strict limits. You were allowed to leave with
a tiny amount of cash, maybe enough for a taxi
ride, but certainly not enough to start a new
life in America. So smuggling was the only option.
And if that guard had just been having a bad
day, if he had picked up the bear and felt something
crinkle? We would not be having this conversation.
It's terrifying to think about. There would likely
be no Pfizer or Moderna COVID vaccine in 2020.
The course of the pandemic would have been completely
different. So much history hinged on a piece
of batting and a stuffed toy. But they make it
through. They land in America, the land of opportunity.
Or so the brochure says. But the reality for
an immigrant, even a brilliant PhD scientist,
is often a lot grittier than that. She starts
her postdoctoral work at Temple University. And
to be fair, scientifically, this was actually
a pretty exciting time for her. She wasn't just,
you know, washing test tubes in a corner. No,
she was right in the thick of it. This is the
mid -80s. She's participating in clinical trials
using something called double -stranded RNA or
DSRNA. And they were investigating treatments
for HIV AIDS and chronic fatigue syndrome. This
was cutting -edge stuff at the time. So what
was the mechanism? What were they actually trying
to do with this RNA? They were studying something
called interferon induction. Okay, let's break
that down for the listener. Interferon. What
is it? Think of interferon as the bodies. It's
citywide air raid siren. When a cell detects
a viral invader, it starts pumping out these
proteins, interferons to tell all the neighboring
cells shields up. There is an intruder. Stop
replicating now. OK, so it's an alarm system.
A very powerful one. And Corico was working on
using RNA to artificially trigger that siren
to sort of preemptively boost the immune system's
defense against viruses. That sounds incredibly
promising. Groundbreaking even for the 80s. It
was. The science was fast. Fascinating. But the
workplace dynamic, that was an absolute disaster.
She was working for a man named Robert J. Suhodolnik.
And this relationship turns into a complete nightmare.
It really does. Look, the mentor -mentee relationship
in academia is incredibly powerful. Your mentor,
your PI, they hold the keys to your visa, your
funding, your reputation, everything. It's a
huge power imbalance. Huge one. And in 1988,
Kuriko received a job offer from Johns Hopkins
University. Which is the big leagues. I mean,
that's the Ivy League of Medicine. Yeah. Massive
step up. A huge step up. But she made a tactical
error. And maybe it was out of excitement or
maybe just naivety about the cutthroat nature
of academic politics. She accepted the offer
from Hopkins before she told Sue Hedelnik she
was leaving. Oof. And he didn't take it well.
He took it as a personal betrayal. And his reaction
was... It was vindictive on a level that is just
hard to comprehend. What did he do? Because Carrico
was a foreign national, her visa status was tied
directly to her employment at Temple. Suedolnik
knew this. And he threatened her with deportation.
He actually played the deportation card. on a
scientist in his own lab. He went even further.
He contacted the U .S. immigration authorities
himself and reported her claiming she was in
the U .S. illegally or that she was violating
her visa status. That is just astonishing. You
have a brilliant scientist trying to advance
her career and her boss calls immigration on
her because his ego is bruised. And it worked,
at least in the short term. Johns Hopkins got
spooked and withdrew the offer. They just...
They didn't want to deal with the legal mess.
So she's stuck. She's in legal limbo. She had
to fight an extradition order. She's facing the
very real possibility of being sent back to Hungary,
where she now has no job and has burned bridges
by leaving in the first place. She did fight
it, though. She did. She won the legal battle
eventually. But Suedolnyk didn't stop there.
He started bad -mouthing her to other institutions.
In the small, insular world of academic research,
a bad reference from your principal investigator
is the kiss of death. She was effectively blacklisted.
I think most people would have quit. I honestly
think I would have quit at that point. Okay,
America doesn't want me. My boss is actively
sabotaging me. I'm going home. And it really
speaks to that iron -willed resilience we talked
about forged back in Hungary. She didn't quit.
She found a temporary refuge at the Uniformed
Services University of the Health Sciences in
Bethesda. A bridge job. Exactly. It kept her
in the country, kept her working with signal
protein interferons again. But the real story,
the one that leads to the Nodal Prize, that begins
when she finally lands a position at the University
of Pennsylvania in 1989. UPenn. This is the chapter
I always think of as the wilderness. That's a
good way to put it. She gets hired to work with
a cardiologist named Elliot Barnathan. And this
is where she decides to bet her entire career,
everything she has, on messenger RNA. Which to
us, sitting here today, having had an mRNA vaccine
shot into our arms, sounds like a great bet,
a brilliant move. Of course. But we have to contextualize
this. In 1989, betting your career on mRNA was
considered scientific suicide. Why? What was
the reputation of the molecule back then? It
was a scientific backwater. a dead end. To understand
why, you have to look at the central dogma of
biology. DNA makes RNA and RNA makes protein.
DNA is the hard drive. It's stable. It's permanent.
It holds the master blueprints. Protein is the
product. It's the muscle, the enzyme, the thing
that does the work. And mRNA is just the messenger.
It's just the memo. It's the sticky note that
carries the instruction from the hard drive in
the nucleus to the protein factory in the cytoplasm.
And sticky notes are fragile. They're temporary.
Extremely. mRNA is designed to be transient.
The cell is supposed to read it and then destroy
it immediately. In the lab, if you even look
at it wrong, it degrades. It just turns into
mush. On top of all that, making synthetic mRNA
was prohibitively expensive. So the scientific
consensus at the time was, you can't make a drug
out of this stuff. It's too unstable, too expensive,
and the body will just chew it up. It's a dead
end. 100%. All the money, all the excitement
was around DNA gene therapy, the idea of going
in and fixing the hard drive permanently. But
Caruso saw the danger in that. What danger? If
you edit the DNA, you change the code forever.
If you make a mistake, it's a permanent mistake.
It's passed down to every new cell. But with
mRNA? It's a software patch. It's temporary.
Her vision was... What if we don't need to permanently
change a patient's genetics? What if we just
send in a temporary instruction? Hey, body, make
this specific protein for a few days to heal
this wound or fight this virus or replace this
missing enzyme. You're turning the patient's
own body into the drug factory. Precisely. It's
a brilliant, elegant concept. But in the 90s,
nobody wanted to fund a skyscraper built out
of wet tissue paper. So she wrote grants. Constantly.
She submitted grant after grant after grant.
I want to use mRNA to treat cystic fibrosis.
Rejected. I want to use mRNA to treat stroke.
Rejected. And in academia, grants are oxygen.
They are. If you don't bring in money, you are
seen as a liability to the university. You're
taking up space. And this leads us to 1995. The
year of the demotion. This is a pivotal and I
think incredibly painful moment in her story.
Kiriko was on the tenure track. She was working
toward becoming a full professor. That means
job security, respect, your own lab. The whole
thing. To dream. The academic dream. But because
she could not get funding for her crazy mRNA
ideas, UPenn gave her an ultimatum. They didn't
just deny her tenure, they demoted her. They
knocked her down from the tenure track, they
cut her salary. They essentially told her, you
are no longer a professor -in -waiting, you are
now just a senior research associate. This mRNA
thing is a hobby, not a career path. That is
just, it's so humiliating. You're a PhD, you've
been working for decades, and your employer...
Basically tells you that you've failed. Professionally
devastating. And her working conditions reflected
that status change. She wasn't working in some
gleaming, well -funded institute. She was often
relegated to the edges, relying on the kindness
of other researchers like Barnathan and later
David Langer to just give her some bench space.
Can I work in this corner of your lab? So why
did she stay? I keep coming back to this. Why
stay at an institution that so clearly didn't
value her? or her work. Because she believed
the science was true. It's as simple and as complicated
as that. She knew that if she could just solve
the stability and the inflammation problem, the
potential was limitless. She couldn't walk away
from the puzzle. And then after all this struggle,
serendipity strikes. And it strikes in the most
mundane place imaginable. The photocopier. I
love this part of the story. It's 1997. She's
standing at the copy machine at UPenn, probably
copying yet another rejection letter or some
journal articles. And she just starts chatting
with the new guy. Drew Weissman. He had just
arrived at UPenn from the National Institutes
of Health, the NIH. He was an immunologist, a
vaccine guy. And he was frustrated because he
was looking for a new way to develop an HIV vaccine.
But all the old methods were too slow and ineffective.
So you have this collision. Carrico, the obsessive
biochemist who can make any RNA you want, but
has zero money. And zero institutional respect.
And Weissman, the respected immunologist who
has startup funding from his new position but
needs a new technology platform. It was the missing
piece for both of them. A perfect marriage of
skills. They started talking. Carrico basically
told them, I can make any RNA you want. Weissman
was intrigued. He decided to use some of his
startup money to fund her work. And they formed
a partnership. Peanut butter and jelly. Exactly.
But let's be really clear here. Just because
they teamed up didn't mean it started working
right away. They immediately ran into... to a
massive biological brick wall. The inflammation
problem. This was the hurdle that had stopped
everyone else in the field dead in their tracks.
When Caraco made the synthetic mRNA in the test
tube and they injected it into mice. The mice
didn't just make the protein. They got really,
really sick. Sick how? What did it look like?
They looked like they had a massive viral infection.
Their fur ruffled up. They became lethargic.
They stopped eating and moving. Their immune
systems were launching an all -out attack on
the mRNA. So the body looked at this synthetic
message and said, intruder, red alert, kill it.
Right. Our bodies have these ancient sensors.
They're called toll -like receptors. They're
the sentries at the gate. Their entire job is
to patrol for foreign -looking genetic material
like the RNA from a virus. When they saw Carrico's
synthetic mRNA, they pulled the fire alarm. This
triggered a huge cascade that not only destroyed
the mRNA, but also caused massive systemic inflammation.
So it's game over. You can't have a medicine
that makes the patient sick and on top of that
gets destroyed before it can even do its job.
Most scientists would have stopped there. They
would have said, OK, the critics were right all
along. It's toxic. It doesn't work. But this
is where Kuriko's detective brain kicks in. She
did something brilliant. She looked closely at
her control group. What was the control? She
was using transfer RNA or tRNA as a comparison.
tRNA is a natural form of RNA that's abundant
in all of our cells. And she noticed something
crucial. When she injected the natural tRNA,
the mice didn't get sick. The toll -like receptors
didn't fire. The alarm stayed silent. So the
body was totally cool with the natural tRNA,
but it hated her synthetic mRNA. So why? What
was the difference? That was a billion -dollar
question. She looked at the chemistry. RNA is
built from four letters, four nucleosides. A,
C, G, and U stands for uridine. Okay, A, C, G,
U. Got it. Through a series of painstaking experiments,
she and Weissman figured out that the toll -like
receptors were specifically reacting to the uridine.
The U was the red flag that was giving away the
intruder. Wait, tRNA has uridine in it too, doesn't
it? It does. But here's the aha moment. In natural
tRNA... The uridine is often chemically modified.
It wears a disguise. One of the most common of
those modifications is called pseudoridine. It's
basically uridine that's been sort of rotated
slightly at the molecular level. It's the same
number of atoms, but it's arranged in a different
shape. And Carrico's hypothesis was, what if
the immune system is blind to this specific shape?
What if I replaced the normal uridine in my synthetic
mRNA with this modified pseudoridine? It's like
putting a fake mustache in glasses on the intruder
so the bouncer lits them right into the club.
A molecular mustache. That's a perfect analogy.
Yes. So they went back to the lab. It was tedious,
painstaking work. They had to synthesize new
strands of mRNA where every single U was swapped
out for pseudoridine. What happened? They injected
it into the mice. They waited. And the mice were
fine. No sickness? No fur ruffling, no lethargy,
no sickness at all. And crucially, when they
checked, the cells were pumping out the desired
protein in massive quantities. Way more than
before. They work. It worked. The immune system
completely ignored the message, but the cell's
protein -making factories read it perfectly.
This was the breakthrough. This was it. They
had turned a toxic, inflammatory molecule into
a stealthy, potent medicine. That is the eureka
moment. That is the moment the world changed,
even if the world didn't have a clue yet. They
were ecstatic. They wrote up the paper. This
was going to be huge. They sent it to Nature.
And Nature immediately cleared the front page
for them. Nature rejected it within 24 hours.
Didn't even send it out for... full review. So
they sent it to science. Science rejected it,
too. But why? How could they not see the importance
of this? Because in the grand scheme of science
at the time, it seemed niche. It was a paper
on RNA modification. It seemed like a minor biochemical
curiosity, not a medical revolution. The reviewers,
the editors, they just didn't grasp the enormous
implication that this single change solved the
fundamental barrier to mRNA therapeutics. So
it did get published eventually, though. Yes.
It found a home in the journal Immunity in 2005.
a very respectable journal, but not one of the
absolute top -tier blockbusters. And even after
it was published, crickets. Nothing. Curry Co.
has said she expected her phone to start ringing
off the hook. It didn't ring once. That is just...
It's heartbreaking. You solve the puzzle that
stumped everyone for decades and nobody cares.
But they kept going. They knew what they had.
They now had the core technology, the nucleoside
modified mRNA. They filed for patents. And this
brings us to the commercialization phase, which
involves what I honestly think is one of the
biggest business blunders in the history of university
tech transfer. The UPenn blunder. Absolutely.
So Carrico and Weissman had founded a small company,
RNRX. But under university rules, UPenn owned.
the intellectual property, the patents. Okay,
that's standard. It is. And UPenn's tech transfer
office looked at these patents for this weird
modified RNA and they said... We don't see much
value here. Exactly. They shot the license around.
Nobody from Big Pharma was interested. So UPenn
decided to just... cut their losses. They sold
the exclusive license to the patent to a small
lab supply company in Wisconsin called CellScript.
A lab supply company, not a biotech firm. No,
a company that sells reagents to other scientists.
It was run by a guy named Gary Dahl, who, to
his credit, saw the value for research tools.
But UPenn sold the rights for a relatively tiny
amount. Reports say it was around $300 ,000.
They sold the Golden Goose for the price of a
mid -range suburban house. And here's the gut
-punching twist. A few years later, a venture
capital firm called Flagship Pioneering, which
was backing this hot new startup called Moderna,
they came calling. They contacted Carrico directly.
They said, we've read your 2005 paper. We think
this is the future. We want to license this technology.
And she had to tell them. She had to say, I'm
sorry, I can't help you. It's not available.
The university that demoted me also sold the
rights to my life's work to a guy in Wisconsin.
Oh, their phone call must have been excruciating.
Just imagine that. It forced Moderna and later
a German company called BioNTech to go to sell
script and pay millions upon millions in sub
licensing fees. UPenn missed out on what would
have become a multibillion dollar royalty stream.
And this had to be the final straw for Carrico
at UPenn. The writing was on the wall. She realized
she was never going to get the respect or support
she deserved there. So in 2013. BioNTech, which
was a small German startup at the time, but one
founded on the promise of mRNA, offered her a
job. And not just any job. No. They offered her
a vice presidency. They understood the technology.
They valued her. They saw her as a pioneer. Not
a problem. So she leaves. She finally moves to
Germany. She commuted, actually, for a long time,
living out of a suitcase again. She was finally
in an environment that got it. They promoted
her to senior VP by 2019. She was home. Now,
before we get to the pandemic, there's one last
crucial piece of the puzzle we need to put on
the board. We have the mRNA, the message, we
have the pseudodyne, the molecular disguise,
but we still need a delivery truck. Correct.
You can't just inject naked mRNA into the bloodstream.
There are enzymes in our body called RNAs that
are designed to do one thing, find and destroy
free -floating RNA. Your message would be eaten
up in seconds. It needs armor. And that armor
is the lipid mannoparticle. The LNP. Basically,
tiny little balls of fat. Caraco had actually
collaborated on this problem with a scientist
named Ian McLaughlin at a company called Techmira
way back in 2006. So this wasn't a new idea either.
No. The work on delivery systems was happening
in parallel. The idea is to encapsulate the fragile
mRNA inside this lipid shell. The LNP protects
its precious cargo as it travels through the
body. Then, when it reaches a cell, its fatty
outer layer fuses with the fatty cell membrane,
and it releases the mRNA inside. It's like a
microscopic Trojan horse made of soap bubbles.
That's a great way to think about it. So by the
end of 2019, all the pieces are finally on the
board. You have the modified non -inflammatory
RNA. You have the LNP delivery system. of two
companies, BioNTech and Moderna, that have spent
years figuring out how to manufacture the stuff
at scale. It was a loaded gun just waiting for
a target. And in January of 2020, the target
appeared, a novel coronavirus emerging out of
Wuhan, China. The world panicked. I mean, I remember
it vividly. Governments shut down, economies
ground to a halt. But inside BioNTech and Moderna,
there wasn't panic. There was a sprint. Right.
Because they had this platform technology, they
didn't have to invent a vaccine from scratch.
This is the part I think so many people misunderstood
during the pandemic. I remember hearing it constantly.
Oh, it was rushed. Vaccines take 10 years to
develop. How did they do this in 10 months? It's
the biggest misconception of the whole crisis.
It didn't take 10 months. It took 10 months,
plus the 25 years of Carrico and Weissman struggling
in the dark, being rejected and demoted. They
just had to plug the new code in. That's it.
As soon as the genetic sequence of the SARS -CoV
-2 virus was published online, they just took
the genetic code for the spike. protein, pasted
it into their existing mRNA template, and hit
print. Udur Shaheen at BioNTech designed their
vaccine in a single weekend. The rest of the
time was spent on manufacturing scale -up and
the necessary clinical trials to prove safety
and efficacy. But the core science, the invention.
That was ready because of those decades of rejection
and persistence. And the result was just. Yeah.
It was spectacular. Over 90 % efficacy against
the original strain. It saved millions of lives.
It allowed society to reopen. It is arguably
the greatest medical and manufacturing feat of
the 21st century. And finally, finally, the world
caught up to Kadi Kariko. The avalanche of awards.
It was surreal to watch it happen in real time.
She went from being a completely unknown scientist
to being on the cover of magazines, Time magazine's
hero of the year. The Lasker Award, which they
call the American Nobel, the Tang Prize, and
then the big one. October 2nd, 2023, the Nobel
Prize in Physiology or Medicine, the summit.
I love her reaction to it. She didn't give some
big ego -driven speech. Her quote was something
like, I dreamt about doing research, not getting
an award. It's so consistent with her entire
story. She is a solver of puzzles. She was never
in it for the fame or the money. She was in it
because she was obsessed with the question and
wanted to find the answer. So let's bring the
story up to the present moment. We're recording
this in January of 2026, a little over two years
have passed since the Nobel. What has she been
up to? Well, she certainly hasn't retired to
a beach somewhere. In October 2023, just after
the prize was announced, she published her autobiography,
Breaking Through My Life in Science. Which is
a fantastic and very fitting title. It is. It
became an instant bestseller in Hungary. By 2025,
it had been translated into nine different languages.
It won the Libri Literary Prize in 2024 and the
Asimov Prize in May of 2025. It's really becoming
a canonical text for young scientists, a story
of persistence. And she did something really
special with the prize money, didn't she? She
did. You know, the Nobel comes with a significant
cash award, over a million dollars. In April
of 2024, she donated more than half a million
dollars of that money right back to her alma
mater, the University of Sigid. The place where
it all started. Full circle. Giving back to the
institution that educated her, making sure the
next generation has resources and opportunities
that she didn't have. And speaking of full circles,
in November of 2024, she returned to Temple University.
The scene of the crime. Exactly. The scene of
the deportation threat. She went back to that
campus, not as a vulnerable immigrant postdoc,
but as a Nobel laureate to give a lecture. Wow.
That must have been an incredibly powerful moment.
A definitive, quiet vindication. And the accolades
kept coming. In May 2025, she was elected to
the U .S. National Academy of Sciences, which
is one of the highest honors for an American
scientist. So what's her status now? Is she still
at BioNTech? She left her executive role at BioNTech
in 2022, even before the Nobel, to devote more
time to pure research. She's currently a professor
at Saged. And in the ultimate irony, she's also
affiliated with UPenn, who now celebrate her
as one of their greatest luminaries. Funny how
that works. Once you win the Nobel, the university
that demoted you and sold your patent for pennies
suddenly puts your face on the front of the brochure.
Success has many fathers. Failure is an orphan.
We have to mention one other person in this story
before we look to the future. Her daughter, Susan
Francia. The little girl with the teddy bear
full of cash. She didn't do too badly for herself
either. No, not at all. Susan grew up watching
her mother's relentless seven days a week work
ethic. She clearly absorbed that intensity. Susan
Francia went on to become a two -time Olympic
gold medalist in rowing for Team USA. That is
just an insane family stat sheet. Mom has a Nobel
Prize in medicine. Daughter has two Olympic gold
medals. It really speaks to a certain genetic
or maybe environmental drive, a capacity for
enduring pain and discomfort for a distant goal.
Whether it's rowing a boat until your lungs burn
or pipetting clear liquids until your eyes blur,
they simply do not know how to quit. So what
does all of this mean for us now? We have the
COVID vaccine. It's part of our lives. But I've
heard you say before that calling this vaccine
technology is like calling the Internet email
technology. It's just it's way too small description.
It is so much bigger than just vaccines. We need
to stop thinking of mRNA as just for infectious
diseases. We need to think of it as a drug platform,
a new way of making medicine. Explain that shift
in thinking. Okay, think about most drugs today.
If you're a diabetic, you inject insulin. Insulin
is a protein. To get that insulin, we have to
build these massive billion -dollar factories
to grow the protein in giant vats of bacteria,
then purify it, bottle it, and keep it cold all
the way to the patient. It's a complex, expensive
industrial process. It is. Carico's technology
completely flips that model on its head. Instead
of making the protein in a factory, we just write
the instruction code in the mRNA for that protein.
package it in an LNP, we inject the code, and
the patient's own cells become the factory. So
you can make the body manufacture its own medicine
on demand. Exactly. This opens the door to something
called protein replacement therapy. Think of
genetic diseases like hemophilia or cystic fibrosis,
where the body is missing one specific crucial
protein. We can just send the email with the
blueprints, and for a short time, the body can
make what it's missing and fix itself. What about
cancer? That's the one everyone always asks about.
That's the holy grail, immuno -oncology. The
idea is that we can take a biopsy of a patient
-specific tumor. sequence its DNA, find the unique
mutations that make it different from healthy
cells, and then create a custom mRNA vaccine
that teaches that patient's immune system to
recognize and hunt down only those cancer cells
wherever they are in the body. It's truly personalized
medicine made to order. Heart disease. They're
already working on it. Injecting mRNA directly
into the heart muscle after a heart attack, a
condition called ischemia, to tell the cells
to grow new blood vessels and heal the damaged
tissue. It honestly sounds like science. It's
rapidly becoming science fact. We're also looking
at using mRNA to temporarily express proteins
that can reprogram cells to generate pluripotent
stem cells, basically rebooting older cells to
a younger, more flexible state. The horizon is
just. It's limitless. This is a new branch of
medicine, comparable to the discovery of antibiotics
or the invention of recombinant DNA. And it all
goes back to that basement lab, to that demotion.
To that one scientist who wouldn't give up. It
does. As we wrap up this deep dive, I want to
leave our listeners with one final, maybe provocative
thought. We celebrate Kati Kariko today. We should.
She's a hero. She has a household name in science.
But we have to talk about survivor bias. Exactly.
We know her story because she made it. She survived.
She survived the secret police in Hungary. She
survived the deportation threats at Temple. She
survived the constant grant rejections, the demotion,
the lack of funding at UPenn. But you have to
ask yourself, how many other Carcos were there?
That is a haunting question. How many brilliant
scientists were there in the 90s or the 2000s
who had an idea that was just as big, just as
revolutionary as mRNA, but they got demoted and
they couldn't take the financial hit and had
to leave science, or their boss threatened them
and they just went home? Or they got rejected
by nature and science three times in a row and
just decided, well, I guess I'm wrong. And those
ideas, those potential cures, they just died
in a trash can. Exactly. We will never know what
we missed, what cures we don't have today, because
our academic system is fundamentally designed
to fund the consensus, not the outliers. The
system loves the safe bet. It is terrible at
recognizing the kind of genius that, at first
glance, looks like a mistake. And for decades,
Kadi Kariko looked like a mistake to them. For
40 years, she looked like a failure to the scientific
establishment. I want to leave you with that
final image. Not the Nobel ceremony in Stockholm.
Not all the applause. I want you to picture a
woman in her 40s. She has just been demoted by
her university. She is working in a cramped,
borrowed corner of a lab. She is transferring
clear, invisible liquid from one plastic tube
to another. She has no funding. Her bosses think
she is wasting her time. But she keeps working.
She holds the key to saving the world in her
hands. She just doesn't know that the applause
is still 20 years away. He just keeps working.
She just keeps working. That's the lesson. That
is the legacy of Kathleen Carrico. So to all
our listeners, look for the outliers in your
own field, the people who are stubbornly, obsessively
working on something that everyone else thinks
is weird or a waste of time. They might just
be on to something big. Thanks for listening
to The Deep Dive. Thank you.