Uğur Şahin and Özlem Türeci: Meet the scientist couple driving an mRNA vaccine revolution | TED

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2021-08-03 ・ TED


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Uğur Şahin and Özlem Türeci: Meet the scientist couple driving an mRNA vaccine revolution | TED

185,573 views ・ 2021-08-03

TED


Please double-click on the English subtitles below to play the video.

00:13
Chris Anderson: Dr. Şahin and Dr. Türeci, welcome.
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Such a treat to speak with you.
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Özlem Türeci: Thank you very much, Chris.
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It's a pleasure to be here.
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CA: So tell me, as you think back over the last 18 months,
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what words pop to mind for you?
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ÖT: Well, one word which comes to mind is breathless.
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It was indeed a breathless 16, 17 months for us.
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When we started in January last year,
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it was already at that time clear to us that we were already in a pandemic.
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What was not known was how fast this pandemic would evolve
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and whether we would have the time in the first place
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to have a vaccine ready soon enough in due time.
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And understanding this,
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it meant for us that there was not even one day to lose.
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And this was the mindset of the entire team
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here in Mainz and at BioNTech
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and later on also of our partners which were involved,
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Pfizer and others,
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to keep going and be fast.
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CA: I mean, it's so extraordinary that the ideas and the work in your minds
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have now impacted hundreds of millions,
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perhaps billions of people.
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That must feel overwhelming.
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And yet, I know at the same time,
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you don't believe in this notion of a flash-in-the-pan ideas.
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Steven Johnson, the author, in his book "Where [Good] Ideas Come From,"
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speaks of the slow hunch,
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that the best ideas happen over many years.
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And I know that you believe that is true in your case.
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I'd like us to go back a couple of decades to -- tell us how this began.
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How did you meet?
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ÖT: We met on an oncohematology ward,
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Uğur being a young physician,
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and I was still in medical school training on ward.
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Which means we met in one of the worlds
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which became important to us,
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the world of patient care,
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of treating oncohematology patients.
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And we soon found out
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that there was a second world which we liked,
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namely the world of science.
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We were haunted by the same dilemma,
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namely that whereas there was not much we could offer our cancer patients,
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there were so many potential technologies we encountered in the lab
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which could address this.
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So one of our shared visions
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was to bridge this dilemma
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by working on bringing science and technology fast.
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And that's an important word here.
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Fast to the patient's bedside to address high medical need.
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CA: So I think the first company you founded nearly 20 years ago
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was to use the power of the human immune system to tackle cancer.
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Uğur Şahin: We were always interested in using the patient's immune system
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to fight cancer and other type of diseases.
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As immunologists, we knew how powerful the human immune system is.
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But it was also clear that the human immune system,
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in the case of cancer,
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did not fight cancer cells.
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It could fight it, but it didn't.
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04:01
And for that, we wanted to develop immunotherapies.
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That means treatments that use the power of the immune system
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and redirect the power of the immune system to cancer cells.
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It was clear that in the university setting,
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we could not continue to develop monoclonal antibodies
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because the cost for development of monoclonal antibodies
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before you can start a clinical trial,
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was in the range of 20, 30 million euros,
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and therefore we decided to start a company to get the funding.
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CA: Now, soon after you started this company,
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you decided to get married.
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Tell me about your wedding day.
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ÖT: Day was well planned, a quick wedding.
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And thereafter we went back to the laboratory
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and our guests at our wedding, that was basically our team,
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our research team.
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So no time to lose, Chris.
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CA: (Laughs)
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That was a pretty special honeymoon.
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I mean, it seems like your love for each other
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is very much bound up in your love for this work
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and your sense of the importance of this work.
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How would you characterize those intersecting relationships there?
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UŞ: We are really two scientists.
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At the end of the day, we love what we do,
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and for us,
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we don't differentiate between work and life balance.
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It's for us really a privilege to be scientists,
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to be able to do what we love.
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And therefore, we combine our normal life with our professional life.
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And therefore, this is pretty normal for us.
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CA: So talk to me about this extraordinary molecule RNA,
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and how you got interested in it and how it became, as I understand it,
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an increasing focus of your work.
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And indeed, it led to the founding of BioNTech.
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Talk about that.
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UŞ: Yeah, mRNA is a natural molecule,
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it's one of the first molecules of life.
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It is a carrier of genetic information.
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But in contrast to DNA, it's not stable.
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So it can be used to transfer information to human cells.
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And the human cells can use this information to build proteins,
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which can be used for therapeutic settings,
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for example, to make a protein which is a vaccine,
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or to make a protein which is an antibody,
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or to make a protein which is another type of drug.
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And we were fascinated by this molecule class,
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because it was very clear
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that mRNA can be produced pretty fast, within a few days.
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And we were, as MDs,
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we were particularly interested to develop personalized medicines.
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That means a treatment and immunotherapy
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specifically designed for a cancer patient,
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because one of the key challenges in cancer treatment,
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is that every patient has a different tumor.
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If you compare two tumors of two patients
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with the same type of tumor,
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the similarity of the tumors is less than three percent
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and 97 percent is really unique.
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And today, it's still not possible
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to address the uniqueness of the tumor of a patient.
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And therefore,
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we were seeking for a technology which could be used for immunotherapy
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and which could be used to develop a treatment
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within the shortest possible time.
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The idea to get the genetic sequence of the tumor
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and then make a vaccine which is personalized,
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within a few weeks.
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CA: Is it fair to say
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that almost all of the significant things that happen to us biologically
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are actions done by proteins,
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and that it's mRNA that actually makes those proteins?
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If you can understand the language of mRNA,
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you can get involved in pretty much everything of significance
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to the well-being of a human being.
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ÖT: Exactly.
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So in principle,
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the information instructions are in the DNA.
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These have to be translated into protein
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because proteins are the actors which keep our cells alive
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and our organism functional.
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And the way how to translate
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what is instructed by DNA
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in a fashion that it is well-timed
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and happens at the right places, into protein,
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there is messenger RNA.
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Messenger RNA sort of instructs when
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and how much of which protein has to be built
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in order to ensure the activity of our body.
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CA: So you can almost think of DNA
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as the sort of The Oxford English Dictionary of Language.
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It sort of sits there as the reference point.
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But for the actual living work,
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the living work of language out there in the world instructing things,
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that is done by mRNA.
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UŞ: Yeah, absolutely, it is possible.
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So the human cells,
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exactly, DNA is like a library.
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If you have the platform for the messenger RNA therapy,
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you can deliver any type of message
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and the body cells ensure that the message is translated
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into the right protein.
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ÖT: A high advantage of mRNA is that it is so versatile.
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You can deliver all sorts of messages, as Uğur has called them.
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On the one hand, you can deliver the blueprint for the protein
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which you want to be produced in this cell.
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But you can, with the same molecule,
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also design into the mRNA
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instructions how this protein should be built,
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instructions to the protein factories of the cell.
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So you can define
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whether you want this protein to be built in high amounts
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or for a long duration,
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how the pharmacokinetics of this protein should be in the cell.
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CA: So talk about January of last year
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when you first heard about this new virus that was spreading.
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UŞ: So in the end of January,
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we read a paper published about this outbreak in Wuhan,
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and realized that this new outbreak
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has all features to become a global pandemic,
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and we were concerned that our life will change,
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that this outbreak could change the fate of mankind.
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And we knew that we have this messenger RNA technology,
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which was actually developed for personalized cancer therapy.
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But the idea of personalized cancer therapy
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is to get the genetic information of the patient
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and then make a vaccine as fast as possible.
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And we had now the same situation.
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It was not a personalized vaccine,
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but it was a genetic information of the virus,
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which was released two weeks earlier.
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And so this genetic information of this virus was available,
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and our task was to make a vaccine as fast as possible.
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And the challenge at that time point was,
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there was almost nothing known about this virus.
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It was a completely new virus.
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We had some assumptions
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which target which molecule encoded by the virus
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could be the right target.
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That means the molecule which can be used
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to precisely engineer an immune attack.
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This is the spike protein.
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It is on the surface of the virus.
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And there's not only one copy of the spike protein on the virus,
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but multiple in the range of 20, 25, 30 spike proteins.
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And the spike protein has two functions.
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One function is really to enable that the virus sticks to human cells.
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For example, it sticks to cells in the human lung.
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And the second is that the spike protein acts as a key.
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It allows the virus to enter into the cells.
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Our goal was to engineer an immune response.
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CA: You've got a slide showing the T-cell response to your vaccine.
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How long were you into the process before you saw this
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and you saw, wow, there really is a spectacular response going on here?
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ÖT: We saw this already in the animal models
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because they are also meant to assess the immune response.
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And what is shown on this slide
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is on the left side, a lymph node
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from a setting where there was no RNA treatment or RNA vaccination.
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And on the right side, a lymph node of a treated organism,
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in this case, an animal.
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And the localization matters.
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And we have constructed our RNA nanoparticles,
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with encapsulation into lipids
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such that the mRNA is carried into lymph nodes,
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not just anywhere, it's carried into lymph nodes
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and in the lymph nodes
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it reaches a very special cell type, which is called dendritic cells,
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and these cells are coaches of the immune system.
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So they are the generals which call all the different special forces
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and train them on the wanted poster of attacker.
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And it's very important that you reach those cells.
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On the right side, you can see the effect of reaching those cells.
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You see many red dots.
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And these are T-cells which have been trained to recognize the antigen,
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the protein which mRNA has delivered,
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and they have expanded to a sort of army of clones, so to say.
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So all these red dots are an army
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which only knows one goal,
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namely attacking this specific protein encoded by the mRNA.
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CA: So it's really stunning
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that within just a few days of your looking at this sequence
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of the most dangerous pathogen to hit humanity in 100 years, I guess,
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that you were able to come up with these these candidate vaccines.
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And I guess over the course of the next weeks and months,
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you had growing confidence that, wow, this was going to work.
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It wasn't until the results of the human trials came out,
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I guess in November of last year,
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that you really knew.
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Tell us about that moment.
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ÖT: It was a Sunday when we were waiting for these results,
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which are assessed in such trials by an independent committee
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and Uğur said, "So let's see how the data will look like."
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It was not clear whether it would be a thumbs up or down.
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And we were very relieved.
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And I felt blessed to hear that the vaccine was efficacious
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and it was highly efficacious, over 90 percent.
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CA: And that more than 90 percent almost disguises the full extent,
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because that's just against any kind of level of infection of COVID.
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Severe infection and fatalities were almost completely protected against,
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I think.
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And it must have been an ecstatic moment for you.
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Certainly was for so many people around the world.
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UŞ: Yes, absolutely.
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So this was a Sunday evening,
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and there were a handful of people
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knowing that an effective vaccine is existing against this global pandemic.
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And we were so excited and so happy
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and we shared of course this information the next day.
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CA: So based on what's happened this time around
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and the amazing acceleration,
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compared with any other vaccine development,
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I mean, if we were hit by another virus,
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could you picture that next time
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we could accelerate the time line further still if need be?
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UŞ: Yes, Chris, this is an excellent question.
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Actually, the world was not prepared to deal with such a pandemic.
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The science and the vaccine developers reacted in an excellent fashion.
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And it is incredible and wonderful
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that it was possible to come up with an effective vaccine
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while a pandemic is ongoing, in less than 12 months.
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But the challenges that we have at the moment
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is that we don't have sufficient production capacity.
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Ideally, we would be prepared the next time,
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not only to develop a vaccine in light speed,
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but also to to make and distribute the vaccine in light speed.
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So what we need now is an additional element which was not existing,
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is manufacturing capacity.
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And idle manufacturing capacity.
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We must be bringing us into a position
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that we can produce 12 billion doses of vaccine,
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if you consider prime boost, within less than six months.
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And this is technically possible.
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So this can be done if governments
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and international organizations invest into manufacturing capacity,
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invest into keeping this idle capacity,
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and also come up with a standard time span and process
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to enable even faster response.
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So we in principle,
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we might be able to manage to come up with a vaccine
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and start distribution in even less than eight months.
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CA: What does what's happened in this last year tell you now
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about the prospects for using mRNA to treat cancer
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and indeed other diseases?
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Where is this heading?
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UŞ: What we have now is now an approved technology
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and a first approved product.
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The development of the coronavirus mRNA vaccine shows the power
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of the mRNA
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and it shows also the safety of this approach.
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And it shows
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that it opens up a door for new technology
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and for new type of treatments.
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And the mRNA molecules
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that we are currently using for cancer,
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we have more than 10 products now in clinical development,
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are diverse against different types of cancer.
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We are very confident that the success that we have generated now
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for our infectious disease vaccines
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can be continued with our cancer immunotherapies.
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CA: Some people may hear this
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and say this is just another type of drug that's coming along.
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But I think on the mental model you're talking about,
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we should think about it as much more revolutionary than that,
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that typically a drug, a traditional drug, kind of changes the chemical environment,
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the background of an entire area of the body.
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But your --
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If you understand the language of mRNA,
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you can do something much more specific and precise.
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Is that something like a fair way to think about it?
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ÖT: Yes, indeed.
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It could be the next revolution
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in the biopharm landscape.
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UŞ: At the end of the day, disease is a situation
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where the communication between cells is disturbed.
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So, for example, autoimmune disease is a disease condition
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where immune cells attack normal cells.
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And indeed, we could engineer messenger RNA therapies
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which could teach the immune system to stop to do that,
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without inhibiting the whole immune system,
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by just communicating with the immune cells which are attacking.
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We could be precise and more specific.
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21:27
CA: The success of BioNTech over the last couple of years,
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I think the value of the company has rocketed
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because of the amazingness of what's happened.
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I mean, it's made you both extremely wealthy,
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I think you're both billionaires now.
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How have you been able to respond to that?
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Sometimes so much money brings its own problems with it.
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Is that proving a distraction?
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21:51
ÖT: For a company
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which sees innovation as its core mission,
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too much money is never a problem.
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Because innovation really means that you have to invest.
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Otherwise, we will only have two type of products
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22:12
or incremental improvement
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for solutions of high medical need.
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UŞ: It really gives us the chance to transform our company.
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So we were when we started --
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When we compare ourselves with the situation we had
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at the beginning of 2020,
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we had a number of product candidates in clinical testing,
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22:38
but the company required funding every year or every second year.
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Now we have a situation to really address the full vision of the company.
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We started BioNTech
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with the idea really to provide novel treatments
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wherever there is a high unmet medical need.
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And we now can do that in a much larger and broader scale,
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and bring our innovations faster to patients.
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23:09
CA: You are both from families who immigrated from Turkey to Germany.
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Immigrants have faced hard times in many countries, including Germany.
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23:19
And yet you, I think,
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23:22
have helped transform the debate about immigration,
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23:24
in Germany and elsewhere,
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just by the extraordinary success that you've achieved
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creating this world-leading company in Germany.
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Do you take joy for the impact you may have had on this issue?
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UŞ: It is somehow surprising
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because the way how we do science,
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and how we recognize how people work effectively in teams together
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is not to us from where the person is coming,
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but what the person can contribute.
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So in our company, we have employees from more than 60 countries.
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So we are an international group of scientists,
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as any other research institution.
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So we have to recognize that globalization really helps
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to bring people, scientists or other engineers into one place,
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24:23
allowing to work together
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and to come with extraordinary results.
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For us, this is somehow surprising that this is seen as special.
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It is just the way how excellent research and science work.
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24:38
CA: Well, it's extraordinary and inspiring what you've achieved,
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24:41
and it'll be very exciting to track progress over the coming years.
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24:45
Thank you so much. Thank you.
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