The Innovation System Behind Moderna’s Covid-19 Vaccine

Noubar Afeyan is cofounder and chair at Moderna Therapeutics, and CEO of Flagship Pioneering. He believes that the breakthrough in vaccine development behind Covid-19 was not a result of a chance event, but a repeatable process. Emergent discovery is a method that encourages unreasonable ideas and pushes back against future ideals. He says that this method can be applied to other industries than the life sciences. Afeyan, along with HBS professor Gary Pisano is coauthor of the HBR article "What Evolution Can Teach Us about Innovation"
CURT NICKISCH - Welcome to HBR IdeaCast, Harvard Business Review Im Curt Nickisch.

Moderna Therapeutics, a biotech company based in Cambridge, Massachusetts, was unknown to anyone at the start of 2020. It was 10 years old, and it didn't have any commercial products.

Moderna had sold millions upon millions of doses, one of the most powerful Covid-19 vaccines anywhere in the world, by the end of 2011. This commercial product was not the result of a lucky chance or a eureka moment. The vaccine, which was based on the most advanced messenger-RNA technology, was developed in a repeatable manner. Flagship Pioneering, a venture-creation firm, has used it numerous times.

Noubar Afeyan is here to discuss how to make breakthrough innovations in new domains. He is the cofounder, chair and CEO of Moderna. Afeyan co-authored the HBR article "What Evolution Can Teach Us about Innovation" with Gary Pisano from Harvard Business School.

NOUBAR AFEYAN - It's great to be here.

CURT NICKISCH - You are a biotech entrepreneur before you started Flagship Pioneering. This innovation and venture capital firm aims to systematize breakthrough innovations. What is wrong with the way people think about breakthrough innovation?

NOUBAR AFEYAN (English): Innovation drives the entire technology startup industry. Everyone is after innovation. In the twenty years that I have been involved with this type of work, I've noticed that people end up focusing on adjacencies.

Adjacency can be described as a logical extension to what has been done in many different directions. However, people can assess its likelihood of success. What value could it have? It dawned on me over time that they are able to do this because it is very proximal. It was easy to see.

While this makes sense, I'll also point out that funding comes from a variety of sources. It could be from the NIH to fund research or the incumbents to support their innovation efforts. Venture capital funds startups. All three types of funding are based on the validity of the idea by key opinion leaders or experts.

This is by definition its adjacent. It will be difficult to imagine how experts could predict what might be valuable 10 years hence. They will be authoritative on things that are happening now.

It's difficult to see how breakthroughs could be so close in. This presents a challenge: how can you make breakthroughs when your process favours things that are very close in? We began to wonder if there was another way to make breakthroughs and move closer from the present and now.

CURT NICKISCH It's like changing your mind.

NOUBAR AFEYAN - I think our cognitive skills are quite good at extrapolating. If you can only think of one or two steps beyond, you will have a pretty good idea of what it might be. When we start to think about things that are totally disconnected from the current reality, or what we call a discontinuity, we need our imagination. Even though engineers and scientists have the same creativity potential as architects and artists, we must remember that we are supposed to be grounded in truth. It can seem speculative when it appears to be a step away from current reality. It appears to be a fantasy, and therefore not scientific.

It's almost as if there is a gravitational field surrounding idea spaces. This force us back to the present and now because it's grounded, reasonable, and validated by others. The question is: Can you escape this field?

CURT NICKISCH (Yes). Messenger RNA, which is the technology that Modernas vaccine, COVID-19, is based on, might be an example. It was difficult for the scientists who worked on it to get their articles published. Now, it is possible that some of these scientists may win Nobel Prizes. It was difficult to get acceptance at first.

NOUBAR AFEYAN : This is the story that we hear in almost any field that has a disruptive application. Because once that happens, we look backwards and see the beginnings but with a new perspective on what ultimately happened.

The mRNA case is interesting because it involves people who have studied mRNA and described mRNA which is a natural molecular. Although the natural form of mRNA has been well studied and many Nobel Prizes have been awarded for it, the idea of using mRNA to deliver information in a synthetic structure was already considered problematic. This was because introducing an mRNA molecule to a cell would cause an antiviral reaction, similar to how cells react to viruses. The cell thinks it is being invaded.

This is how the field was at that time. Several years later, in the nineties, researchers at UPenn, along with a few other institutions, began to modify RNA, especially mRNA to understand the immune response.

It was not an immediate adjacency, but the ultimate therapeutic use of it as such was to come later. It is only when you use it to treat something that things change.

To achieve that goal, which is completely imagined, you look back at the science and everything suddenly becomes more relevant. So, when we looked at some of the work, we thought, "Okay, so if there are three, four modifications that were suggested, could 100 be tried?" There are many ways to deliver it to cells, but some of them have proven problematic or toxic. Could we then try 100?

CURT NICKISCH - It's almost like a Blue Ocean Strategy in biotech innovation. It's about finding a place that has a lot of value. You are a pioneer in this space, essentially figuring where to go.

NOUBAR AFEYAN (You know what I mean? You can work today on the next thing and then the future will be determined by what it succeeds in. Or you can aim for something that is not possible today but which you then pull towards the present and make it better.

They are just opposite forces. The one is a push to the next. The other is a pull from what we know, so you can add the pieces that will get you to where you want. It is to be open to taking the first step, to take a mental leap, and then to combine that with others to create a community leap. This allows you to get many people looking at the same area and asking, "Is there reason to believe?" Then you go out and create that future. This is how we see breakthroughs. You might ask, "Why should this lead to breakthroughs?"

It doesn't always result in breakthroughs. But it does lead to completely unexpected things. Because from the present, almost everything you do that is far enough away is not possible to compute, it is unreasonable. It's almost surprising how people find it so real. That's the beauty of a breakthrough.

CURT NICKISCH - Does it require different types of people? Are you required to hire different types of scientists in order to think differently? Is it about managing scientists in different ways at universities?

NOUBAR AFEYAN (English): The flippant answer is yes and then some. These are just two of the many reasons why I believe it is so. First, it's not something that is innate. You don't get it if you are born with it. This is something that I believe a lot scientists can achieve, provided that they are willing to let go of the strict constraints that their scientific fields may place on them.

It turns out that what we do and what we have done for the past 11 years is to create our own fellowship program. We bring in graduate students within one year of graduation, or MDs within one year of graduation, and then we allow them to participate in a summer fellowship to learn how this works.

As shock therapy, one of the first things we do is ask people to speak out in a comfortable environment. It's really fascinating to talk with people and ask them, "What was the most unreasonable thing you have ever said in your field?" And they will tell you. It is more common for people who are more successful than it is for others.

However, this uninhibited state of mind is what you should be open to exploring in order to uncover new possibilities. While some of this can be learned experientially, it is not for everyone. It is not for everyone, but we have seen a lot more people over the years who are able to leap and do rigorous science in the same space they've entered than they thought.

CURT NICKISCH - How can you, as a manager or leader of these organizations, create a culture where people feel free to say outrageous things?

NOUBAR AFEYAN - Leaders can't expect people to repeat unreasonable statements if they aren't willing to laugh at unreasonable statements, say ridiculous things, and admit to being wrong.

It's not only what you do, but also how you respond to crazy people. A sign that I keep at my desk says Trust your Crazy Ideas. It is an interesting play on words. If you don't trust it, you won't be able to stick with the idea and will move on to something safer. That's why it is okay to be in that type of environment.

The other question is, why should people believe that they can create value in this environment? Here I will simply mention the history of major breakthrough innovation, mRNA being one example. But if you go back to the roots of what became valuable, you'll quickly discover that many of the great and beautiful ideas came from ugly people.

They are rejected repeatedly in the first instance. This is not the exception. Each and every one. It is not an iPhone if you look back at the original iPhone. It is the same size as one of these iPad Pro large tablets. You wouldn't think that an iPhone would descend from that design.

What is the lesson here? It is not possible to conceive these beautiful things from the gates. They are never the ancestors for eventually disruptive things.

So I believe that there is a process called emergent discovery. However, there is also a process that describes the evolution and development of ideas. This process of emergence involves the emergence of variation, selection, and iterative cycles that produce an end result that you are surprised to have been derived from the initial starting point.

This is the same idea we used to create an emergent culture that doesn't look for beauty from the outside. They don't look for fairness. They are quite comfortable with creating other things. They don't stop there. But they do use it as a starting point. Only those descendants are what we end up working on. Although I don't know if it makes sense, this is how I describe it.

CURT NICKISCH: What are your biggest hurdles, and what can you do to make this process a success?

NOUBAR AFEYAN (English): First and foremost, seeking out affirmation from other people. Ironically, if something we are working on is thought to be a good idea and reasonable by others, then we shouldn't continue working on it. It's only a matter time before it becomes a commodity.

One time in a while, I Googled the term "commodity innovation", because many people wonder how you could have a commodity invention. To me, a commodity innovation is an innovation that can be made available to many people when it's made. The shared economy is a common innovation. You are right? Everyone can rent their house now. There are many factors that can help people win in this space.

We don't want to be involved in commodity innovation. We want to innovate in a way that is as safe and different as the commodity space.

CURT NICKISCH (Yes, that's right. The great thing about working in a non-adjacent area like this is that everything can be patentable and you can own it.

NOUBAR AFEYAN (Yes, it is). You can also create the entire space's scaffolding by creating the rules of engagement. You can also describe the field. You will be the first to discover where the landmines are. With mRNA, you will be the first to discover what causes it to travel to specific tissues. It will be your first to discover that mRNA behaves differently in non-human primate models, such as monkeys, than it does in mice.

There are many advantages to being first, even if patents are an important and enduring version. There are many other reasons you might ask, "Why doesn't everyone do that?" And the list of disadvantages is longer.

Pioneers often fail because it is easier to connect and reason than do things the right way. You also have others to learn from. People are available to give you feedback. There are many services available that will help you accomplish what you can today. They will not exist in the future. Right? Unimagined products have no supply chain. Imagine that in mRNA, last year the entire world was able to see how we went from producing enough mRNA for 2,000 patients to produce enough mRNA now to supply 200 million patients. At the start of 2020, there was no supply industry to produce mRNA. Zero.

Moderna and our colleagues at Pfizer had to make a tremendous effort to organize 7,000 companies in an unprecedented industry. The mRNA supply chain, not the mRNA sector. This would have never happened in normal times. This is another reason to focus on the present instead of unimaginable things.

There are many reasons to not do it. The exciting thing about it is, and this I want to stress, that you are basically discovering new value streams. This idea of a value reservoir, which is what we have, is actually innovation. Innovation is opening up new value pools. Either you're opening up new areas of existing value pools or you're creating entirely new pools of value. Think of a new resource you have discovered, a valuable mineral you discovered, or something else. You can be the driving force behind the success of your business if you are willing to jump and reach far beyond the boundaries.

There are many ways that you can make this happen, which brings me back to my question. Interestingly, there are examples of success in doing this, which we have accumulated over time, that encourages the next generation to say, Hey! This can be done. We can do it! This was already done.

CURT NICKISCH (Yes, that's right, I was surprised that Flagship Pioneering invests in so many companies a year. These are all new potential value pools you're trying to pursue. Are there other opportunities for non-biotech-tech innovation? It is just a question of how much of this works in life science and how it can be applied elsewhere.

NOUBAR AFEYAN (My impression is that there are some scientific advances that lead value generation and this approach has some interesting extra advantages over the traditional approach to innovation. As we are speaking today, I believe machine learning and artificial Intelligence is one of the most exciting areas of scientific disruptive potential. Why? Why? Because it is the generative aspect of that. Not the interpretive side, which looks at data patterns, large data, but rather the generative side, which can create new things we have never created before. This generative side is basically a new source for things that could be valuable. This is how you use it. This is an area where we have put in a lot more effort than just life science. We believe this emergent discovery method as a means to find these valuables can be very powerful. If you were to ask, "Can you do this everywhere?" This might also be useful in other areas of innovation and transformation.

One of the most interesting things has happened recently is that there are a lot of large-company leaders that I've known over the years who have taken an interest in what we were doing and asked, "Can we do it?" As a consumer-packaged goods company, can we, as an airline developer, say "Okay, how would it look?" These are real examples of what we could do if we tried to predict five, ten years in advance and then work backwards in the areas we were in.

I'm curious to see how these methods might be applied now that people have seen examples and realized that there are parts that can be repeated. This is not pure improvisation, nor a miracle kind of discovery. It's hard work.

CURT NICKISCH : Noubar, it was great to have your on-air presence to hear some of your most reasonable and unorthodox opinions. We are grateful for your expertise and knowledge.

NOUBAR AFEYAN : Thank you for having me.

CURT NICKISCH - This is Noubar Afeyan. He is co-founder, chair and CEO of Moderna Therapeutics. He is also the coauthor of HBR's article, What Evolution Can Teach us About Innovation.

Mary Dooe produced this episode. Rob Eckhardt provides technical support. Adam Buchholz manages our audio product. Thank you for listening to HBR IdeaCast. Im Curt Nickisch. That was fantastic. Yes. We are grateful.