Uğur Şahin and Özlem Türeci
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Chris Anderson: Dr. Şahin and Dr. Türeci, welcome. Such a treat to speak with you.

Özlem Türeci: Thank you very much, Chris. It's a pleasure to be here.

CA: So tell me, as you think back over the last 18 months, what words pop to mind for you?

ÖT: Well, one word which comes to mind is breathless. It was indeed a breathless 16, 17 months for us. When we started in January last year, it was already at that time clear to us that we were already in a pandemic. What was not known was how fast this pandemic would evolve and whether we would have the time in the first place to have a vaccine ready soon enough in due time. And understanding this, it meant for us that there was not even one day to lose. And this was the mindset of the entire team here in Mainz and at BioNTech and later on also of our partners which were involved, Pfizer and others, to keep going and be fast.

CA: I mean, it's so extraordinary that the ideas and the work in your minds have now impacted hundreds of millions, perhaps billions of people. That must feel overwhelming. And yet, I know at the same time, you don't believe in this notion of a flash-in-the-pan ideas. Steven Johnson, the author, in his book "Where [Good] Ideas Come From," speaks of the slow hunch, that the best ideas happen over many years. And I know that you believe that is true in your case. I'd like us to go back a couple of decades to — tell us how this began. How did you meet?

ÖT: We met on an oncohematology ward, Uğur being a young physician, and I was still in medical school training on ward. Which means we met in one of the worlds which became important to us, the world of patient care, of treating oncohematology patients. And we soon found out that there was a second world which we liked, namely the world of science. We were haunted by the same dilemma, namely that whereas there was not much we could offer our cancer patients, there were so many potential technologies we encountered in the lab which could address this. So one of our shared visions was to bridge this dilemma by working on bringing science and technology fast. And that's an important word here. Fast to the patient's bedside to address high medical need.

CA: So I think the first company you founded nearly 20 years ago was to use the power of the human immune system to tackle cancer.

Uğur Şahin: We were always interested in using the patient's immune system to fight cancer and other type of diseases. As immunologists, we knew how powerful the human immune system is. But it was also clear that the human immune system, in the case of cancer, did not fight cancer cells. It could fight it, but it didn't. And for that, we wanted to develop immunotherapies. That means treatments that use the power of the immune system and redirect the power of the immune system to cancer cells. It was clear that in the university setting, we could not continue to develop monoclonal antibodies because the cost for development of monoclonal antibodies before you can start a clinical trial, was in the range of 20, 30 million euros, and therefore we decided to start a company to get the funding.

CA: Now, soon after you started this company, you decided to get married. Tell me about your wedding day.

ÖT: Day was well planned, a quick wedding. And thereafter we went back to the laboratory and our guests at our wedding, that was basically our team, our research team. So no time to lose, Chris.

CA: (Laughs) That was a pretty special honeymoon. I mean, it seems like your love for each other is very much bound up in your love for this work and your sense of the importance of this work. How would you characterize those intersecting relationships there?

UŞ: We are really two scientists. At the end of the day, we love what we do, and for us, we don't differentiate between work and life balance. It's for us really a privilege to be scientists, to be able to do what we love. And therefore, we combine our normal life with our professional life. And therefore, this is pretty normal for us.

CA: So talk to me about this extraordinary molecule RNA, and how you got interested in it and how it became, as I understand it, an increasing focus of your work. And indeed, it led to the founding of BioNTech. Talk about that.

UŞ: Yeah, mRNA is a natural molecule, it's one of the first molecules of life. It is a carrier of genetic information. But in contrast to DNA, it's not stable. So it can be used to transfer information to human cells. And the human cells can use this information to build proteins, which can be used for therapeutic settings, for example, to make a protein which is a vaccine, or to make a protein which is an antibody, or to make a protein which is another type of drug. And we were fascinated by this molecule class, because it was very clear that mRNA can be produced pretty fast, within a few days. And we were, as MDs, we were particularly interested to develop personalized medicines. That means a treatment and immunotherapy specifically designed for a cancer patient, because one of the key challenges in cancer treatment, is that every patient has a different tumor. If you compare two tumors of two patients with the same type of tumor, the similarity of the tumors is less than three percent and 97 percent is really unique. And today, it's still not possible to address the uniqueness of the tumor of a patient. And therefore, we were seeking for a technology which could be used for immunotherapy and which could be used to develop a treatment within the shortest possible time. The idea to get the genetic sequence of the tumor and then make a vaccine which is personalized, within a few weeks.

CA: Is it fair to say that almost all of the significant things that happen to us biologically are actions done by proteins, and that it's mRNA that actually makes those proteins? If you can understand the language of mRNA, you can get involved in pretty much everything of significance to the well-being of a human being.

ÖT: Exactly. So in principle, the information instructions are in the DNA. These have to be translated into protein because proteins are the actors which keep our cells alive and our organism functional. And the way how to translate what is instructed by DNA in a fashion that it is well-timed and happens at the right places, into protein, there is messenger RNA. Messenger RNA sort of instructs when and how much of which protein has to be built in order to ensure the activity of our body.

CA: So you can almost think of DNA as the sort of The Oxford English Dictionary of Language. It sort of sits there as the reference point. But for the actual living work, the living work of language out there in the world instructing things, that is done by mRNA.

UŞ: Yeah, absolutely, it is possible. So the human cells, exactly, DNA is like a library. If you have the platform for the messenger RNA therapy, you can deliver any type of message and the body cells ensure that the message is translated into the right protein.

ÖT: A high advantage of mRNA is that it is so versatile. You can deliver all sorts of messages, as Uğur has called them. On the one hand, you can deliver the blueprint for the protein which you want to be produced in this cell. But you can, with the same molecule, also design into the mRNA instructions how this protein should be built, instructions to the protein factories of the cell. So you can define whether you want this protein to be built in high amounts or for a long duration, how the pharmacokinetics of this protein should be in the cell.

CA: So talk about January of last year when you first heard about this new virus that was spreading.

UŞ: So in the end of January, we read a paper published about this outbreak in Wuhan, and realized that this new outbreak has all features to become a global pandemic, and we were concerned that our life will change, that this outbreak could change the fate of mankind. And we knew that we have this messenger RNA technology, which was actually developed for personalized cancer therapy. But the idea of personalized cancer therapy is to get the genetic information of the patient and then make a vaccine as fast as possible. And we had now the same situation. It was not a personalized vaccine, but it was a genetic information of the virus, which was released two weeks earlier. And so this genetic information of this virus was available, and our task was to make a vaccine as fast as possible. And the challenge at that time point was, there was almost nothing known about this virus. It was a completely new virus. We had some assumptions which target which molecule encoded by the virus could be the right target. That means the molecule which can be used to precisely engineer an immune attack. This is the spike protein. It is on the surface of the virus. And there's not only one copy of the spike protein on the virus, but multiple in the range of 20, 25, 30 spike proteins. And the spike protein has two functions. One function is really to enable that the virus sticks to human cells. For example, it sticks to cells in the human lung. And the second is that the spike protein acts as a key. It allows the virus to enter into the cells. Our goal was to engineer an immune response.

CA: You've got a slide showing the T-cell response to your vaccine. How long were you into the process before you saw this and you saw, wow, there really is a spectacular response going on here?

ÖT: We saw this already in the animal models because they are also meant to assess the immune response. And what is shown on this slide is on the left side, a lymph node from a setting where there was no RNA treatment or RNA vaccination. And on the right side, a lymph node of a treated organism, in this case, an animal. And the localization matters. And we have constructed our RNA nanoparticles, with encapsulation into lipids such that the mRNA is carried into lymph nodes, not just anywhere, it's carried into lymph nodes and in the lymph nodes it reaches a very special cell type, which is called dendritic cells, and these cells are coaches of the immune system. So they are the generals which call all the different special forces and train them on the wanted poster of attacker. And it's very important that you reach those cells. On the right side, you can see the effect of reaching those cells. You see many red dots. And these are T-cells which have been trained to recognize the antigen, the protein which mRNA has delivered, and they have expanded to a sort of army of clones, so to say. So all these red dots are an army which only knows one goal, namely attacking this specific protein encoded by the mRNA.

CA: So it's really stunning that within just a few days of your looking at this sequence of the most dangerous pathogen to hit humanity in 100 years, I guess, that you were able to come up with these these candidate vaccines. And I guess over the course of the next weeks and months, you had growing confidence that, wow, this was going to work. It wasn't until the results of the human trials came out, I guess in November of last year, that you really knew. Tell us about that moment.

ÖT: It was a Sunday when we were waiting for these results, which are assessed in such trials by an independent committee and Uğur said, "So let's see how the data will look like." It was not clear whether it would be a thumbs up or down. And we were very relieved. And I felt blessed to hear that the vaccine was efficacious and it was highly efficacious, over 90 percent.

CA: And that more than 90 percent almost disguises the full extent, because that's just against any kind of level of infection of COVID. Severe infection and fatalities were almost completely protected against, I think. And it must have been an ecstatic moment for you. Certainly was for so many people around the world.

UŞ: Yes, absolutely. So this was a Sunday evening, and there were a handful of people knowing that an effective vaccine is existing against this global pandemic. And we were so excited and so happy and we shared of course this information the next day.

CA: So based on what's happened this time around and the amazing acceleration, compared with any other vaccine development, I mean, if we were hit by another virus, could you picture that next time we could accelerate the time line further still if need be?

UŞ: Yes, Chris, this is an excellent question. Actually, the world was not prepared to deal with such a pandemic. The science and the vaccine developers reacted in an excellent fashion. And it is incredible and wonderful that it was possible to come up with an effective vaccine while a pandemic is ongoing, in less than 12 months. But the challenges that we have at the moment is that we don't have sufficient production capacity. Ideally, we would be prepared the next time, not only to develop a vaccine in light speed, but also to to make and distribute the vaccine in light speed. So what we need now is an additional element which was not existing, is manufacturing capacity. And idle manufacturing capacity. We must be bringing us into a position that we can produce 12 billion doses of vaccine, if you consider prime boost, within less than six months. And this is technically possible. So this can be done if governments and international organizations invest into manufacturing capacity, invest into keeping this idle capacity, and also come up with a standard time span and process to enable even faster response. So we in principle, we might be able to manage to come up with a vaccine and start distribution in even less than eight months.

CA: What does what's happened in this last year tell you now about the prospects for using mRNA to treat cancer and indeed other diseases? Where is this heading?

UŞ: What we have now is now an approved technology and a first approved product. The development of the coronavirus mRNA vaccine shows the power of the mRNA and it shows also the safety of this approach. And it shows that it opens up a door for new technology and for new type of treatments. And the mRNA molecules that we are currently using for cancer, we have more than 10 products now in clinical development, are diverse against different types of cancer. We are very confident that the success that we have generated now for our infectious disease vaccines can be continued with our cancer immunotherapies.

CA: Some people may hear this and say this is just another type of drug that's coming along. But I think on the mental model you're talking about, we should think about it as much more revolutionary than that, that typically a drug, a traditional drug, kind of changes the chemical environment, the background of an entire area of the body. But your — If you understand the language of mRNA, you can do something much more specific and precise. Is that something like a fair way to think about it?

ÖT: Yes, indeed. It could be the next revolution in the biopharm landscape.

UŞ: At the end of the day, disease is a situation where the communication between cells is disturbed. So, for example, autoimmune disease is a disease condition where immune cells attack normal cells. And indeed, we could engineer messenger RNA therapies which could teach the immune system to stop to do that, without inhibiting the whole immune system, by just communicating with the immune cells which are attacking. We could be precise and more specific.

CA: The success of BioNTech over the last couple of years, I think the value of the company has rocketed because of the amazingness of what's happened. I mean, it's made you both extremely wealthy, I think you're both billionaires now. How have you been able to respond to that? Sometimes so much money brings its own problems with it. Is that proving a distraction?

ÖT: For a company which sees innovation as its core mission, too much money is never a problem. Because innovation really means that you have to invest. Otherwise, we will only have two type of products or incremental improvement for solutions of high medical need.

UŞ: It really gives us the chance to transform our company. So we were when we started — When we compare ourselves with the situation we had at the beginning of 2020, we had a number of product candidates in clinical testing, but the company required funding every year or every second year. Now we have a situation to really address the full vision of the company. We started BioNTech with the idea really to provide novel treatments wherever there is a high unmet medical need. And we now can do that in a much larger and broader scale, and bring our innovations faster to patients.

CA: You are both from families who immigrated from Turkey to Germany. Immigrants have faced hard times in many countries, including Germany. And yet you, I think, have helped transform the debate about immigration, in Germany and elsewhere, just by the extraordinary success that you've achieved creating this world-leading company in Germany. Do you take joy for the impact you may have had on this issue?

UŞ: It is somehow surprising because the way how we do science, and how we recognize how people work effectively in teams together is not to us from where the person is coming, but what the person can contribute. So in our company, we have employees from more than 60 countries. So we are an international group of scientists, as any other research institution. So we have to recognize that globalization really helps to bring people, scientists or other engineers into one place, allowing to work together and to come with extraordinary results. For us, this is somehow surprising that this is seen as special. It is just the way how excellent research and science work.

CA: Well, it's extraordinary and inspiring what you've achieved, and it'll be very exciting to track progress over the coming years. Thank you so much. Thank you.