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  • 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.

In 1995, Katalin Karikó had hit a low point.

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