Speaker 1: On a warm September day in Berlin, Hungarian biochemist Catalan
Speaker 1: Cattico walks into the nearly century old auditorium at Berlin's
Speaker 1: chetty Tay Hospital. She takes her seat in the front
Speaker 1: row of a World Health Organization event. She surrounded by
Speaker 1: politicians and public health leaders. Just a year earlier, there
Speaker 1: would have been little reason for Catalan to be there
Speaker 1: at all. A few of the other guests would have
Speaker 1: even known her name, But now she's a guest of honor.
Speaker 1: Catalan spent her life researching messenger RNA, the tiny postal
Speaker 1: workers that carry genetic instructions inside cells. For decades, few
Speaker 1: paid attention to what she found that has now changed. Yes.
Speaker 1: Even at the event in September, German Chancellor Angelo Meeric
Speaker 1: called praises Catalan for not giving up. The German Chancellor
Speaker 1: tells the audience that Catalan's thirty years of effort laid
Speaker 1: the groundwork for our current fight against COVID nineteen. In
Speaker 1: her own remarks, Catalan says her collaborators deserve credit too.
Speaker 1: First of all, I would like to correct you because
Speaker 1: there are many, many people contributed to it, and I
Speaker 1: was just one of them. And I am glad that
Speaker 1: I go also goold have I am just representing all
Speaker 1: of those fellow scientists. Then she makes a plea, but
Speaker 1: the dignitaries in the audience to give people with ideas
Speaker 1: that seem crazy a chance. Those who who might have
Speaker 1: an idea which is too weird to support, maybe they
Speaker 1: get more support and sort of problems we were facing
Speaker 1: the future. Catalan doesn't stick around long for drinks. Afterward,
Speaker 1: She's at the co check In less than an hour,
Speaker 1: She's going to Budapest. They're painting her picture onto the
Speaker 1: side of a building there. She's only awards circuit, but
Speaker 1: she says she'd rather be back in her lab as
Speaker 1: soon as possible. Catalan helped lay the groundwork for a
Speaker 1: most important weapon against the deadly virus that has so
Speaker 1: far killed more than five million people around the globe.
Speaker 1: She never expected that, but she also showed the world
Speaker 1: the potential for a new technology, messenger RNA, And this
Speaker 1: is what Catalan had hoped for all along. This is
Speaker 1: a story about what most people would agree is the
Speaker 1: biggest success of the pandemic. Messenger RNA vaccines could never
Speaker 1: have proven themselves so quickly outside the crucible of that
Speaker 1: first pandemic year. The technology may well win some researchers
Speaker 1: and Nobel Prize. It will almost certainly have big implications
Speaker 1: for the future of medicine. Odds are you've taken one
Speaker 1: of these mr Anda vaccines yourself, and you might think
Speaker 1: you know the story of how they swooped onto the
Speaker 1: world stage so quickly, But odds are you don't know
Speaker 1: the half of it. This is also the story of
Speaker 1: as unlikely a bunch of world saving heroes as you'll
Speaker 1: ever encounter. My name is Naomi Kraski, and I'm a
Speaker 1: health journalist for Bloomberg News. In the first half of
Speaker 1: the season, you've heard about the lingering consequences of COVID
Speaker 1: for many patients and hospitals. Now we'll tell you about
Speaker 1: the consequences for science. They're a lot more hopeful. From
Speaker 1: the Prognosis podcast, this is Breakthrough. I first heard of
Speaker 1: messenger are A vaccines more than a year before the
Speaker 1: mysterious new virus emerged in Wuhan. The biggest buzz in
Speaker 1: the drug industry at that time was the idea of
Speaker 1: using the immune system to attack tumors and help cancer
Speaker 1: patients live longer. Scientists were trying a bunch of different
Speaker 1: ways to do this, and a source told me I
Speaker 1: should talk to the people at a German startup called BioNTech.
Speaker 1: Inside European biotech, everybody knew them, but outside that insular
Speaker 1: world a few people had ever heard of them. They
Speaker 1: were trying to make something that had failed many times before,
Speaker 1: a cancer vaccine, but they were trying to do it
Speaker 1: using messenger RNA. Here's BioNTech CEO Uger Shahin speaking at
Speaker 1: a tech conference called codex in. I think you have
Speaker 1: to dare to start without having all solutions in the hand,
Speaker 1: hoping that something would come up. It was fascinating stuff,
Speaker 1: full of hope and cutting edge science, but as is
Speaker 1: often the case in the risky business of biotech, it
Speaker 1: wasn't at all clear that the MR and A vaccines
Speaker 1: would actually work. I wrote a feature story for the
Speaker 1: news wire, then moved on to other topics and went
Speaker 1: on maternity leave. Then in January my boss called. He
Speaker 1: said a new story was keeping him busy, strange new
Speaker 1: coronavirus that had emerged in China and was spreading around
Speaker 1: the world. It's too bad you're not here now, he said.
Speaker 1: It'll probably be all over by the time you're back.
Speaker 1: Of course, when I came back to the office the
Speaker 1: next month, it wasn't over. It was spreading. I live
Speaker 1: in Germany. A few weeks later we went into our
Speaker 1: first lockdown, and it's still not over. The world has changed.
Speaker 1: We're still finding out just how much our story starts.
Speaker 1: In nine the modern study of human genetics was just
Speaker 1: getting going. Only eight years prior, scientists had discovered the
Speaker 1: double helix structure of DNA. Now they were trying to
Speaker 1: figure out how cells act on the instructions encoded in
Speaker 1: the genes. A team from the Pastor Institute in Paris
Speaker 1: identified an elusive molecule that copies pieces of genetic code
Speaker 1: and delivers its instructions into the machinery of the cell.
Speaker 1: They named it messenger RNA. RNA stands for ribonucleic acid,
Speaker 1: where DNA is a double strand RNA is a single strand.
Speaker 1: There are a few types of RNA that play important
Speaker 1: roles in sending DNA's instructions to cells, and messenger RNA
Speaker 1: is essentially leave the errand boy. One of the best
Speaker 1: explanations I've heard of how the biology works comes from
Speaker 1: Derek Rossy Harvard University stem cell biologists. M RNA is
Speaker 1: actually a necessary and obligate intermediate between genes, which are
Speaker 1: encoded in DNA and live in the nucleus, and proteins,
Speaker 1: which do all the busy work of the cell. But
Speaker 1: they're made in another part of the cell called the cytoplasm,
Speaker 1: so the two don't meet the nason the nucleus, protein
Speaker 1: synthesis is and the cytoplasm. So there had to be
Speaker 1: an intermediate molecule, which was discovered to be messenger RNA
Speaker 1: an appropriate an appropriate name. It carries the message encoded
Speaker 1: by the gene out to allow that sort of code
Speaker 1: to be turned into something that has utility, something that
Speaker 1: has function proteins, So DNA makes mRNA makes protein, makes
Speaker 1: all of life. Three French scientists shared a Nobel Prize
Speaker 1: in nineteen sixty five for the discovery of m r
Speaker 1: and A, but for decades after that, m RNA wasn't
Speaker 1: a very high profile area for research. Part of the
Speaker 1: reason was that the molecules fragile and hard to work with.
Speaker 1: Scientists didn't figure out how to synthesize it in the
Speaker 1: lab until in the nineteen nineties. The field Superstars focused
Speaker 1: on DNA instead. DNA was easier than RNA to work
Speaker 1: with and more stable. It was also in the limelight
Speaker 1: thanks to the mapping of the genome and the Human
Speaker 1: Genome Project that lasted from two thousand three. Scientists focused
Speaker 1: on the idea of curing illnesses by fixing errors in
Speaker 1: the genome, but there were a few exceptions researchers who
Speaker 1: stuck with m RNA despite the challenges both scientific and personal.
Speaker 1: One of them came from Hungary. By the time the
Speaker 1: pandemic was a year old, her name would be known
Speaker 1: around the world as the woman who pioneered mr and
Speaker 1: A vaccines. She would be covered endlessly in newspaper articles
Speaker 1: and TV shows. But each time I think I've learned
Speaker 1: everything about her story, something new turns up to surprise me.
Speaker 1: Catalan Cadko was born in Hungary. In she's in grade
Speaker 1: school when the first MR and A discoveries are being lauded.
Speaker 1: The Poster Institute and Nobel Prizes would have seemed very
Speaker 1: far away to her. She grows up under communism in
Speaker 1: gishuis Sarash, a small town in the countryside of eastern Hungary.
Speaker 1: Her father is a butcher, but she knows even as
Speaker 1: a teenager that she wants to be assigned best. Catalan
Speaker 1: declined to be interviewed for this podcast. I and others
Speaker 1: that Bloomberg had already spoken to her many times, and
Speaker 1: she said she wants to focus again on her work
Speaker 1: after being on the interview circuit. I get where she's
Speaker 1: coming from, so we decided to draw from what I
Speaker 1: think is her most unusual interview. She's spoken May with
Speaker 1: Clube Radio, an independent broadcaster based in Budapest. We've dubbed
Speaker 1: her voice from her native Hungarian Madam, I'm not a
Speaker 1: special person at all. I saw that my parents were called,
Speaker 1: and I also tried to help them. Along with my siblings.
Speaker 1: We studied odd that was our job as Catalan earned
Speaker 1: her PhD in Hungary at the University of second just
Speaker 1: a two hour drive from where she grew up. She
Speaker 1: started her postdoctoral research in the same city at the
Speaker 1: Biological Research Center of the Hungarian Academy of Sciences. In
Speaker 1: eight As a PhD student in Hungary, she worked with
Speaker 1: RNA for the first time. It was the start of
Speaker 1: a lifelong obsession. In she got the opportunity to move
Speaker 1: to the US for a job at Temple University in Philadelphia.
Speaker 1: She took it, moving with her husband and toddler daughter.
Speaker 1: The Hungarian government only allowed them to bring a hundred
Speaker 1: dollars with them. Legally, they sold another nine hundred pounds
Speaker 1: about one thousand, two hundred dollars into her daughter's teddy
Speaker 1: bear alment. We flew off. We didn't have any foreign renatives.
Speaker 1: We couldn't count on anyone to send us money. What
Speaker 1: she found wasn't what she had expected either. She says
Speaker 1: the lab wasn't as well equipped as the one back home,
Speaker 1: and one of the co workers doors and yelled. After
Speaker 1: a week she wanted to leave. She stayed out of
Speaker 1: necessity and out of hope. Were in survival mode, and
Speaker 1: I thought I would learn something interesting and we would survive.
Speaker 1: And this is what changes people, that they become so
Speaker 1: defenseless and they must rely on their talent and make
Speaker 1: do with the best they can. By nine, things were
Speaker 1: looking slightly better. Catalan got a research assistant professor position
Speaker 1: at the University of Pennsylvania. This was a chance to
Speaker 1: make a name for herself maybe eventually get tenure. Because
Speaker 1: of the way these jobs work, she was expected to
Speaker 1: win her own grant funding to support her research, but
Speaker 1: she ran into a big roadblock. She was still obsessed
Speaker 1: with m R and A. Well she had seen so
Speaker 1: far in her experiments convinced her that it would make
Speaker 1: a better medicine than d n A. But no, but
Speaker 1: the else agreed. She wrote a lot of grand proposals,
Speaker 1: at one point one every month, she told us, but
Speaker 1: nobody wanted to fund the experiments she wanted to do.
Speaker 1: Nobody wanted to fund work on m R and A.
Speaker 1: She didn't exactly make it easier on herself. One thing
Speaker 1: I learned from her Hungarian interview was that she wasn't
Speaker 1: a networker. Instead, she wanted to spend her time at
Speaker 1: the lab bench doing science. Should I always keep those
Speaker 1: meetings filled with small talk, which could have held my career?
Speaker 1: Those really drove me crazy. Even in stores if they
Speaker 1: were long lines, I thought, you're stealing my time, would you?
Speaker 1: Elliott barn Nathan was her boss at the time. He's
Speaker 1: a cardiologist who was then an associate professor of medicine
Speaker 1: at Penn. Elliott was later to leave academia for a
Speaker 1: drug industry career. He's an executive at Johnson and Johnson now,
Speaker 1: but he remembers Catalan. Well, so the first thing is
Speaker 1: she's incredibly hard working and and brilliant, I mean, really
Speaker 1: truly brilliant. And the thing that's interesting is that she's
Speaker 1: a voracious reader, and and so she would always read
Speaker 1: science and Nature and come into the lab this morning
Speaker 1: with the latest, you know, issue of science that you
Speaker 1: hadn't even come across my desk yet, and she had
Speaker 1: already read it and figured out somebody researching something completely
Speaker 1: different in a different content and a different disease entity.
Speaker 1: But there was a kernel here that was going to
Speaker 1: help us do the next step of what we needed
Speaker 1: to do. And she was always connecting the dots. Messenger
Speaker 1: r n a degree quickly in the body. There are
Speaker 1: enzymes that break loose mrn a down outside of cells,
Speaker 1: but it also goes away quite quickly once it's delivered
Speaker 1: its message inside the cell. Catalan thought that would actually
Speaker 1: be a good thing. She reasoned that you could use
Speaker 1: m RNA to flip a switch in the self for
Speaker 1: a limited period of time. Elliott told me the idea
Speaker 1: would be for it to have the desired effect then
Speaker 1: go away. But convincing the scientific establishment to give her
Speaker 1: experiments a chance proved very, very difficult. They could only
Speaker 1: see the challenge, not the potential benefit for them. mRNA
Speaker 1: was too fragile, too fleeting a dead end, so it
Speaker 1: was very It was very heretical back in those days.
Speaker 1: People said, oh, you're crazy, you know, m RNA will
Speaker 1: never work, it's too unstable. But she really firmly belowd
Speaker 1: She had a vision that it was doable. It was
Speaker 1: just we needed to figure out how to do it.
Speaker 1: Elliott used his own research funding to subsidize Catalan's experiments.
Speaker 1: They had some successes, but time and time again she
Speaker 1: failed to get grant funding. In she was stripped of
Speaker 1: her assistant professor title and demoted to essentially a glorified
Speaker 1: lab researcher. It seemed unlikely that she would ever get
Speaker 1: her own lab. People just couldn't see the see the
Speaker 1: truth of it. Unfortunately, it was a bitter blow. After
Speaker 1: making it all the way from Ural Hungary depend one
Speaker 1: of the top research institutions in the world, Catalan faced
Speaker 1: the very real possibility that she might have to stop
Speaker 1: doing the work that she loved. At the same time,
Speaker 1: she was dealing with a cancer scare and her husband
Speaker 1: was stuck back in Hungary for more than four months
Speaker 1: due to a processing to life for his green card.
Speaker 1: In the Hungarian radio show, she's interviewed alongside a singer
Speaker 1: named Zoran Stephan of It. The show has a unique format.
Speaker 1: It tries to put two people from totally different walks
Speaker 1: of life on the air together. In this case, Oron
Speaker 1: wrote Catalan's favorite song, a ballot called Diamond and Gold.
Speaker 1: She chokes up when she talks about listening to him
Speaker 1: sing when things got tough, that did That's offen. Oran
Speaker 1: released the song in the same year. Catalan moved to
Speaker 1: the US and was the frontman for two Hungarian rock
Speaker 1: bands in the nineteen sixties and nineteen seventies. Under a
Speaker 1: communist regime that opposed rock music, he knew a singer
Speaker 1: or two about persevering during tough times. Zorn's song is
Speaker 1: about how you need to work hard and stay the
Speaker 1: course to achieve your goals. Diamond and Gold of a
Speaker 1: nice shine, he says, but you need to dig deep
Speaker 1: to get it. This resonates with Catalan. She digs a
Speaker 1: long time before she hits pe dirt, and even when
Speaker 1: she does, she's one of only a few who recognizes
Speaker 1: what she's found. The first time I interviewed Catalan was
Speaker 1: in summer. Each time she speaks, I'm struck by how
Speaker 1: little bitterness she expresses about getting shut out by the
Speaker 1: academic establishment for so long. She sounds disappointed, yes, and
Speaker 1: sometimes frustrated. She also talks about how she really got
Speaker 1: a raise. She was hired at forty dollars, and two
Speaker 1: decades later she was making sixty dollars, which she says
Speaker 1: is less than what a laptech would make. But I
Speaker 1: got the impression that because she managed to keep on
Speaker 1: doing science, the lack of our cognition and low pay,
Speaker 1: these were secondary concerns. Here. She is earlier this year,
Speaker 1: speaking for a Bloomberg project about the one year anniversary
Speaker 1: of the pandemic. This is previously unaired audio. As long
Speaker 1: as I was in the lab and focus what I
Speaker 1: can do, I was very happy. I mean, at the weekends,
Speaker 1: long days. And my husband once said that, you know,
Speaker 1: probably my earning is first than in a McDonald's, because
Speaker 1: he collplated probably won all right, So as a biochemist
Speaker 1: in the nineteen nineties, she was probably making less per
Speaker 1: hour than I did at the time. Babysitting the kids
Speaker 1: on my street in Elliott barn Nathan, who was subsidizing
Speaker 1: Catalan's work at Penn, left the university to take a
Speaker 1: job at a biotech. She managed to find a spot
Speaker 1: in another lab, but she needed a close collaborator, someone
Speaker 1: enthusiastic about the science with the cloud, to ensure she
Speaker 1: could fund her projects. How she found this person is
Speaker 1: one of those great water cooler moments that will probably
Speaker 1: go down in science textbooks. In early Catalan started seeing
Speaker 1: a new face at the Xerox machine where she'd copy
Speaker 1: the academic journal articles that she read so eagerly. He
Speaker 1: was an immunologist named Drew Wiseman, fresh off a fellowship
Speaker 1: at Tony Fauci's lab at the National Institute's of Health.
Speaker 1: Drew was also a voracious suiteader of journal articles. Back
Speaker 1: in those days, you'd have to hunt them up in
Speaker 1: the library or somebody else's lab, then copy them and
Speaker 1: take them home. They weren't online. Drew says. They copied
Speaker 1: hundreds of articles before I ran into Katie Carrico over
Speaker 1: a Xerox machine and we would both sort of fight
Speaker 1: over it, but really just wait for each other to finish,
Speaker 1: and we started talking. Drew was interested in dendridic cells,
Speaker 1: which helped the immune system adapt to fight new intruders.
Speaker 1: They migrate throughout the body and collect foreign things, so
Speaker 1: that includes viruses, bacteria, parasites, tumor cells, and they bring
Speaker 1: those two lymph nodes where they start immune reaction. And
Speaker 1: why that's important for a vaccine is that they're the
Speaker 1: critical cell that picks up a vaccine and turns on
Speaker 1: the immune reactions. Drew wanted to work on an HIV vaccine.
Speaker 1: Catalan thought m RNA could help. We started talking and
Speaker 1: I told her about my interest in dendrodic cells and HIV,
Speaker 1: and she told me about her interest in m RNA.
Speaker 1: So we started working together and we started doing experiments
Speaker 1: together other and and that's where our collaboration started. It's
Speaker 1: important to note that up until then, Catalan wasn't really
Speaker 1: thinking about RNA as something you'd used to make a vaccine.
Speaker 1: She wanted to make treatments to use mRNA to spur
Speaker 1: the cells machinery to make a protein that the body
Speaker 1: needs to heal itself. In that sense, Wiseman's involvement broadened
Speaker 1: her perspective. I should also note that some experiments at
Speaker 1: that point had already shown the promise of using genetic
Speaker 1: material to spur the body's cells to produce vaccine. Researchers
Speaker 1: at Merk and Co. Were able to spurn immune response
Speaker 1: in mice by injecting them with DNA that contained instructions
Speaker 1: for influenza proteins. But seeing something working animals and having
Speaker 1: it work in humans, those are two very different things.
Speaker 1: The old line in this mice lie and and macacs exaggerate,
Speaker 1: So if it happens in a mouse, that's never a
Speaker 1: guarantee it'll happen in the human. The body has multiple
Speaker 1: lines of defense against any m RNA that looks like
Speaker 1: it might not belong. These guards are enzymes that will
Speaker 1: break down loose m RNA found outside a cell. If
Speaker 1: m RNA conduct those attacks and try to get inside
Speaker 1: a cell, its troubles aren't over. Derrick Rossi, Harvard stem
Speaker 1: cell scientists we heard from earlier, says the cell's first
Speaker 1: response is to do the exact opposite of what you'd
Speaker 1: want if you're going to use m RNA for a therapy.
Speaker 1: It's to stop making any proteins at all that doesn't
Speaker 1: want viral proteins being made in the cell. And then
Speaker 1: if the response is robust enough, it triggers these ultruastic
Speaker 1: self kill pathways uh and they die because it's better
Speaker 1: for the cell to die than it is to serve
Speaker 1: as a manufacturing facility for a hundred thousand viral particles. Essentially,
Speaker 1: the sell flips a self destruct swich. This makes a
Speaker 1: lot of sense from a biological standpoint. It ensures cells
Speaker 1: stay on track, make the right amount of the right protein,
Speaker 1: and don't get duped into producing a pathogen. But to
Speaker 1: use mr and A as a drug, Catalan and Drew
Speaker 1: had to figure out how to get it into the
Speaker 1: cell without flipping that self destruct switch. That was a
Speaker 1: lot of years of research. It's about seven years of
Speaker 1: work together. And what we did is we first had
Speaker 1: to figure out why it was inflammatory, So what receptors
Speaker 1: was it activating, How was it being recognized. So we
Speaker 1: found some receptors, other people found receptors. In total, there
Speaker 1: are seventeen of them, and we started to look at
Speaker 1: how RNA interacted with those receptors. They did years of
Speaker 1: painstaking experiments trying to disable the self destruct switch. Finally
Speaker 1: the breakthrough came in an unexpected place. You could say
Speaker 1: Look played a role. Look made possible by years of
Speaker 1: hard work. Catalan's old boss, Elliott Barnathan, explained it to me.
Speaker 1: She's a brilliant scientist, and you know, sometimes it's the
Speaker 1: controls that you use that really help you to make
Speaker 1: the advance. Is not necessarily what the experiment is, but
Speaker 1: how well controlled it was. The control group is the
Speaker 1: part of the experiment where you usually don't change anything,
Speaker 1: the part that's supposed to serve as a comparison to
Speaker 1: show whether the hypothesis you're testing is true. Catalan was
Speaker 1: using a special type of RNA called transfer rna as
Speaker 1: a control in one of her experiments. This t RNA
Speaker 1: has an important difference compared to mRNA. There's a different
Speaker 1: arrangement of a structural piece called uridine. So Catalan uses
Speaker 1: this t RNA in the control group and she notices
Speaker 1: something unusual. The immune response inflammation didn't happen in those cells.
Speaker 1: That was sort of the light bulb that went off
Speaker 1: in her head. She decides to make a slight modification
Speaker 1: to the RNA molecule to mimic what naturally occurs in
Speaker 1: transfer rna bingo. The cells don't try to fight off
Speaker 1: the foreign RNA, and even better, they make ten times
Speaker 1: as much protein, and so it was a double whammy.
Speaker 1: And that was really the fundamental patent that both Maderna
Speaker 1: and the fisor bio in tech vaccines use in terms
Speaker 1: of m RNA therapy. In two thousand five, Catalan Currico
Speaker 1: and Drew Wiseman published a paper laying out their method
Speaker 1: for modifying r n A. I asked Drew what he
Speaker 1: thought would happen next. So that was one of my
Speaker 1: more embarrassing moments, because what I said to Katie after
Speaker 1: the paper was published was that our phones are going
Speaker 1: to start ringing off the hook, and people are going
Speaker 1: to call us up and want to work with RNA,
Speaker 1: and drug companies are gonna want to use RNA, and
Speaker 1: our phones never ran. We would sit there looking at
Speaker 1: the phone, and nothing happened. In days and weeks and
Speaker 1: months and years went by and nothing happened. Nobody was interested.
Speaker 1: Even though we published how to make it work well
Speaker 1: and how to use it as a drug, nobody was interested.
Speaker 1: I find that astonishing. I asked him what he thought
Speaker 1: that was. You know, I think that even though we
Speaker 1: published that paper, they still said RNA is too difficult
Speaker 1: to work with and they just didn't want to work
Speaker 1: with RNA. Catalan said she felt like Cassandra, the mythological
Speaker 1: trojan priestess who finds that her gift of prophecy is
Speaker 1: really a curse. I mean, I knew that it can
Speaker 1: be used for everything, and you know, kind of a
Speaker 1: Cassandra feeling that I can see the future and nobody
Speaker 1: believes me. Catalan and Drew filed for a patent to
Speaker 1: keep on doing experiments, but it would take someone with
Speaker 1: more salesman skills to bring the technology to the limelight.
Speaker 1: Derek Rossi, who we heard from earlier, had been a
Speaker 1: postdoctorate fellow at Stanford University when Drew and Catalan published
Speaker 1: their study. He didn't read it at the time, but
Speaker 1: a few years later at Harvard he ran into it
Speaker 1: while trying to solve a problem in stem cell biology.
Speaker 1: He wanted to convert cells back into a state similar
Speaker 1: to that of an embryonic stem cell, a state from
Speaker 1: which a cell can turn into any type of cell
Speaker 1: in the body. A Japanese researcher named Shinya Yamanaka had
Speaker 1: shown this was possible, but he had used a virus
Speaker 1: to deliver the genetic cargo to reprogram the cells, which
Speaker 1: scarred the cell. Derek wanted to use m RNA instead.
Speaker 1: He decided to try a test protein first, something that
Speaker 1: would be easy to recognize if it worked. We encoded
Speaker 1: for the gene for the green fluorescent protein, which is
Speaker 1: a jellyfish gene that fluoresces green under a certain wavelength
Speaker 1: of light uh, and we synthesized that m RNA and
Speaker 1: then we put it onto cells human cells in a
Speaker 1: dish and we got a few green cells, but we
Speaker 1: got a lot of dead cells and bed cells. Of course,
Speaker 1: was not a our goal. We were not trying to
Speaker 1: make a plateful of dead cells. Nope, they wanted green cells,
Speaker 1: or rather, they wanted to get the cells to express
Speaker 1: this green fluorescent protein. So we realized we had another challenge.
Speaker 1: Why what was killing all these cells? When we introduced
Speaker 1: the mRNA they almost gave up. But then Derek turned
Speaker 1: to academic journals to see if anybody else had run
Speaker 1: into this issue, and that is where we came across
Speaker 1: the work of Captaalin Trico and Drew Weissman, whom in
Speaker 1: two thousand and five published a seminal paper which, by
Speaker 1: the way, got largely ignored by the academic press. Derek's
Speaker 1: team followed the instructions in the paper swapping the modified
Speaker 1: building blocks for the RNA. And now when we put
Speaker 1: that jellyfish mRNA onto cells, essentially all the cells in
Speaker 1: the dish where happy and blasting expression of this GFP protein.
Speaker 1: So we were no longer killing cells on mass in
Speaker 1: the dish. And that that discovery that they made, I
Speaker 1: believe is well, it's fundamental to this entire field. Uh
Speaker 1: And I believe it's going to earn them a Nobel
Speaker 1: prize because it really is what allows these mr and
Speaker 1: A vaccines and any mRNA therapeutic down the road. It's
Speaker 1: the enabling sort of peace to the puzzle. Derek's team
Speaker 1: published a paper in showing that they could use mr
Speaker 1: and A to reprogram human skin cells. Now this was
Speaker 1: sexy enough to get people's attention. It made a huge splash.
Speaker 1: You may have seen the headlines. Scientists can now take
Speaker 1: an ordinary cell from the body and transform it into
Speaker 1: a cell that's very similar to an embryonic stem cell.
Speaker 1: Most of the media reports were about the stem cells,
Speaker 1: not the mr and a technolo oology, and that was exciting. Indeed,
Speaker 1: from a basic science perspective, but Derek was already thinking
Speaker 1: about the broader potential, and I was thinking to myself, Okay,
Speaker 1: there's a lot of attention being given to the cell
Speaker 1: based aspect of this, but nobody's really sort of recognizing
Speaker 1: the modified m R and A based aspect. So I
Speaker 1: should go out and try to start a company around this,
Speaker 1: and that's that's the origin of Maderna. And I went
Speaker 1: out and convinced some early investors and people that has
Speaker 1: had potential, and it sort of launched launches the industry.
Speaker 1: I guess Harvard colleague introduced Derek to venture capital company
Speaker 1: Flagship Pioneering, which founded Moderna in operations began the next year.
Speaker 1: Industry veterans signed on, including Stefan pan Cell and experienced
Speaker 1: French executive who took the CEOs job at Moderna. The
Speaker 1: company stayed private for eight years, raising two point five
Speaker 1: billion dollars in venture capital and drug company investment. Along
Speaker 1: the way, then had one of the biggest I p
Speaker 1: O s in biotech history in December. Along the Way,
Speaker 1: Moderna earned a reputation for secrecy until it published a
Speaker 1: few scientific papers, preferring to keep its discoveries under wraps.
Speaker 1: Derek left the company he founded in to focus on
Speaker 1: his research. Catalan still reflects with wonder on how Bancel
Speaker 1: and Moderna were able to collect so much money when
Speaker 1: she wasn't even able to get a research grant. I concluded,
Speaker 1: probably I did not explain well because look, come, come
Speaker 1: a salesman the like Stefanson, poor, and when he goes
Speaker 1: to have a breakfast reader Sioan, then in ten minutes
Speaker 1: already two million dollar. He could convince him that that
Speaker 1: mRNA is good for everything. And I said the same
Speaker 1: to people, and they didn't even give me for the research.
Speaker 1: But in Germany, a very different competitor was also working
Speaker 1: on the m R and A technology. Husband wife team
Speaker 1: Uger Shahina notes them to Achi founded BioNTech in two
Speaker 1: thousand eight. Before Derrick Cross's work brought the idea of
Speaker 1: modified m R and A into the limelight, the pair
Speaker 1: had spent years pursuing immune based treatments for cancer. Starting
Speaker 1: in the nineteen nineties at the University Medical Center of
Speaker 1: the Johanna Schuttenberg University in minz Uger had started exploring
Speaker 1: m R and as delivery method in two thousand something.
Speaker 1: His wife once told me was considered a crazy idea
Speaker 1: at the time, where moderna was polished and corporate from
Speaker 1: the start. BioNTech an academic vibe who uses his university
Speaker 1: email address. They've published hundreds of scientific papers. Who were
Speaker 1: hired Catalan Cardicho away from PENN. They put out a
Speaker 1: press release saying that her work had opened a new
Speaker 1: field of therapy. She finally got her own lab just
Speaker 1: down the hall from the CEO S office. Catalan says
Speaker 1: she joined because she wanted to see her work in action.
Speaker 1: I wanted to see the first patient to be treated,
Speaker 1: some one person at least. I wanted to see that, okay,
Speaker 1: this modified Emma and he helped one one person at least.
Speaker 1: How the story would go from there, well, she never
Speaker 1: expected that. That's next time on Breakthrough. Next week on Breakthrough,
Speaker 1: we'll tell you about the frantic ten months of COVID
Speaker 1: nineteen vaccine development that silenced the doubters in the scientific community.
Speaker 1: At least it was highly likely that this is going
Speaker 1: to be a pandemic, and we started to discuss what
Speaker 1: we can do. This episode of Prognosis Breakthrough was written
Speaker 1: and reported by me Naomi Kresky. So for Foreheads is
Speaker 1: our senior producer. Carl Kevin Robinson Jr. Is our associate producer.
Speaker 1: Our theme music was composed and performed by Hannis Brown.
Speaker 1: Veronica Guyash did voice over, and Emma Cord, Bob Langrath,
Speaker 1: and Sultan Shimon contributed reporting. Rick Shine is our editor.
Speaker 1: Francesca Levy is the head of Bloomberg Podcasts. Be sure
Speaker 1: to subscribe if you haven't already. If you liked this episode,
Speaker 1: please leave us a review. It helps others find out
Speaker 1: about the show. Thanks for listening.