In 1995, Katalin Karikó had hit a low point.
A biochemist at the University of Pennsylvania,
she'd devoted her entire career to turning mRNA,
one of the most important building blocks of life,
into a whole new field of medicine.
But it just wasn't happening.
Everybody argued that RNA
is so transient and degrades
and it will never be medicine.
I knew that it can be used for everything
and, you know, kind of a Cassandra feeling
that I can see the future
and nobody believes me.
Karikó's grant applications were rejected.
She was demoted, endured a cancer scare,
but she stuck with it.
She spent weekends and holidays
doing research and experiments.
And in 2005, Karikó and her colleague Drew Weissman
published a breakthrough study
confirming the therapeutic use of mRNA,
research which would underpin the success
of mRNA Covid vaccines today.
When the first Covid-19 vaccine was approved,
I was extremely excited.
I thought it was a changed moment for mRNA.
What we've been seeing in animals was real,
and it works in people.
And that's the most important thing.
mRNA has gone from a rejected idea
to a powerful weapon helping to end the pandemic.
And applications of this technology
could provide a cure for diseases beyond Covid.
Messenger RNA, or mRNA,
is a genetic material
that copies instructions from our DNA.
Our cells use these instructions to make proteins,
which carry out different functions
in the human body.
mRNAs are responsible for everything our body does,
from breathing air to eating food,
to walking, to sleeping, to thinking.
Covid vaccines from Pfizer-BioNTech
and Moderna are based on this mRNA mechanism.
Unlike traditional vaccines
using dead or weakened viruses,
mRNA vaccines use the genetic information
of the virus.
Scientists make an mRNA that codes for the spike protein
of SARS-CoV-2, the virus that caused Covid-19.
Then the mRNA is put inside a lipid coating
and injected into the human body.
The cell reads the mRNA
and starts to make harmless spike proteins of its own,
which triggers the immune system
to produce antibodies against the virus.
The way that mRNA vaccines work
is similar to really all vaccines.
What they're doing is they're presenting
a protein or proteins from a pathogen,
and they're causing our bodies
to make an immune response
against those proteins or protein.
When you make an inactivated virus vaccine,
you have to isolate the virus.
You have to grow it up in eggs.
You have to figure out how to grow it in eggs.
You have to purify it and activate it,
and formulate it.
With mRNA, you only need the sequence.
You don't need the virus.
So it's a very simple vaccine to make.
This means that making mRNA vaccines
is faster than making traditional ones.
But the journey for mRNA to break into mainstream medicine
has been long and challenging.
mRNA was first discovered in 1961.
But it wasn't until 1984 that scientists were able
to recreate it in the lab.
In the 1990s, as scientists knew more
about the make-up of human DNA,
gene therapy became popular,
inserting a gene into a patient's cells
to treat or prevent disease.
But most researchers gave little thought
to using mRNA as a vaccine or a drug,
despite its close relationship with DNA.
I argued that the messenger RNA
is more like a conventional drug.
You can apply,
and then if you see a beneficial effect,
you can reapply, and then the healing is done,
rather than a gene therapy
where you are delivering the gene
and you cannot control.
But many rejected Karikó's idea,
arguing mRNA therapies didn't look feasible.
The immune system is hypervigilant
against foreign RNA entering the body,
and so the injected lab-made RNA caused inflammation
which destroyed it before it could start
to trigger an immune response.
And even worse, that inflammation
could be life-threatening.
In 1997, Karikó met Drew Weissman,
a respected immunologist
and they started to collaborate.
The big discovery was we figured out
by modifying the nucleoside.
So RNA has four letters
that code for a protein.
Each letter is a nucleoside or a base.
We modified those bases
and that reduced and got rid of the inflammation.
When we altered uridine and we had a pseudouridine,
we found that not only we have an RNA which is non-immunogenic,
but we had a very high level of protein production.
The amount of protein made from the RNA
increases about a thousand fold.
You get rid of inflammation
and you increase potency in the same step.
So it was like a dream come true.
They published the key research
and filed a patent, which was later licensed
to Moderna and BioNTech,
the companies making mRNA Covid vaccines today.
Karikó also started to work for BioNTech in 2013.
But there was another hurdle-
how to deliver mRNA to targeted cells.
mRNA is notoriously fragile,
and enzymes in the human body can break it down.
So you really need to have it protected
from the enzymes and other kinds of things in the body.
You could call them the bad guy, so to speak.
And if you don't, then the therapy won't work at all,
it would be non-existent.
As early as the 1970s,
chemical engineer Robert Langer
and his colleague Judah Folkman
proved that it's possible
to deliver molecules like RNA
inside tiny particles without destroying them.
The nanoparticles Langer used were made of polymers,
not lipids as used in today's mRNA Covid vaccines.
So we were trying to put DNA and RNA
into tiny particles and deliver them.
I failed the first 200 times when I did it.
And by the way, that was also widely criticized.
So I got my first nine grants turned down.
I couldn't get a job, you know, a faculty job
at the chemical engineering department,
which was my area.
But today Langer is a renowned scientist
with over 900 issued patents.
In 2010, he co-founded Moderna
and still sits on its board.
After decades of development,
the main biological roadblocks were cleared,
but mRNA technology had never been used
outside of clinical trials until recently.
In the last few minutes we've heard
the first coronavirus vaccine
has been approved for use in the UK.
This is being manufactured
by the U.S. pharmaceutical company Pfizer
and its partner BioNTech.
And here is the first person
in line to get it.
In the following months, mRNA vaccines
from both Pfizer-BioNTech and Moderna
were cleared in multiple countries.
Taking less than a year from the lab into people's arms,
these are the fastest vaccines
that have ever been developed,
both with a 95% efficacy rate.
But some people are concerned
that these vaccines are hastily made.
The speed of making the vaccine,
the 10 months that it took.
There's very good reasons
that people need to understand why that happened.
It was an emergency.
It was a pandemic.
All of the clinical trials were done at the same time.
All of the testing was done together.
No corners were cut.
There were no safety issues that were ignored.
Everything was done exactly the same
as every other vaccine.
In December 2020,
Karikó and Weissman were given the Covid vaccines
they had contributed to.
People were waiting for the healthcare workers
in line there to get their vaccines.
And, you know, they clapped.
And then I cried.
About 3.2 billion doses of mRNA Covid vaccines
are expected to be given in 2021.
And now mRNA may also be used to help fight
future pandemics and diseases
that current medicines struggle to treat.
The mRNA is just an instruction
for the cell to make the protein.
We can target the messenger RNA to certain organs,
certain cell types, bone marrow,
and then can perform different kind of treatment.
There are many different applications
for messenger RNA.
I mean, you know, at Moderna,
they're working on heart disease,
they're working on personalized cancer vaccines.
They're working on rare diseases.
I think the next big act for RNA
are probably gonna be more vaccines.
Last summer, we started working
on a pan-coronavirus vaccine.
So there've been three coronavirus epidemics
and pandemics in the past 20 years.
You have to assume there's gonna be more.
Can we make a vaccine that prevents
against all of those bat coronaviruses
that have the potential to infect people
and start another epidemic or pandemic?
I think that the pan-influenza and pan-coronavirus
are gonna be the most exciting RNA vaccines
to come out in the future.
mRNA has been proven now as a really impressive
and powerful new technology,
and the application of mRNA goes, of course,
very straight approaches to develop mRNA vaccines
against other infectious diseases.
And we are already doing that.
We have started that early on
for developing influenza-based mRNA vaccines.
We are developing mRNA vaccines
against tuberculosis, against HIV.
BioNTech has also been studying
the technology in cancer for two decades
and has a cancer vaccine in Phase II clinical trials.
They are hoping the cancer field might see
its first messenger RNA drug approvals
in two or three years.
There's no guarantee that other mRNA vaccines and drugs
will succeed like they have with COVID-19,
but Karikó remains undaunted by the challenge.
That's the most important thing,
to accomplish something
and, meanwhile, to be happy.
As long as I was in the lab, I had fun.
It is just such a joy.
Even if things didn't work out
how I expected.