The Man Who Led the Creation of Moderna’s Covid Vaccine Shares His Powerful Insight and Vision: Tal Zaks (#140)

Welcome to the Three Takeaways podcast, which features short, memorable conversations with the world's best thinkers, business leaders, writers, politicians, scientists, and other newsmakers. Each episode ends with the three key takeaways that person has learned over their lives and their careers.
And now your host and board member of schools at Harvard, Princeton, and Columbia, Lynn Toman. Hi, everyone.
It's Lynn Toman. Welcome to another Three Takeaways episode.
Today, I'm excited to be with Tal Zaks, who is chief medical officer of Moderna from 2015 to 2021. Before that, he worked at Sanofi GSK and the National Cancer Institute, and he's also been a professor at both the University of Pennsylvania and at Tufts.
At Moderna, Tal oversaw the development of the Moderna COVID vaccine, so he's responsible for developing the vaccine that has protected hundreds of millions of people around the world from COVID. I'm excited to find out what we really know about the safety of mRNA vaccines, why the

U.S. is the leader in drug discovery, how he sees the future of drug discovery, and what it would

take to accelerate the discovery of new drugs and treatments for cancer and other diseases.

Welcome, Tal, and thanks so much for your work on the Moderna vaccine and also for our conversation today.

Thank you, Lynn. It's a real pleasure to be here today.
The pleasure is mine. Tal, what makes mRNA vaccines new and different? Well, the unique feature of mRNA vaccines really is part of what makes mRNA medicines at large unique, which is we figured out with messenger RNA how to turn something that is an inherent biological property of all of our cells in the body into a way to make new medicines.
In essence, what messenger RNA is, it's the instruction set that tells every cell in our body which unique proteins to make. When you think about it, what makes a cell unique is the protein that it makes.
For example, insulin is a protein. It is made by a very certain type of cells in our body, in our pancreas.
If you can actually take that kind of molecule, a messenger RNA, and think of it as an information molecule. It's essentially the same molecule, but because it has different sequences, it ends up encoding for different proteins in different cells.
And so the ability to take this molecule and change the information it encodes and then introduce it to cells allows us to essentially teach a cell to make a protein that has a medicinal effect. In the case of the vaccines, what we do is actually a relatively simple application of this technology.
We know what a virus is. We know what the proteins on a virus are.
Everybody now is familiar with the spike protein of COVID as being the thing that our immune system recognizes. And what the mRNA vaccine allows us to do is basically code for the sequence of that spike protein, but introduce it in a way that teaches the immune system to recognize the virus without actually seeing the entire virus.

We don't need the virus for our vaccine. In fact, we've never had the virus at Moderna in any place in time.
All we have is the information. And if we just take that critical piece of information of what codes for the right thing the immune system will recognize, which is the spike protein, and we introduce it in an mRNA molecule as part of a vaccine, then it teaches our body to recognize the virus before it has ever seen the virus.
And that's exactly what a good vaccine does. So the mRNA vaccine is different also because it essentially tells the body to produce the vaccine itself.
It's just the directions. It's not introducing an attenuated virus into our bodies.
That's exactly right. There is no risk of anybody getting infected from COVID from a vaccine with mRNA because there's no virus there.
And in fact, it's just information of just that one spike protein. And once the immune system sees that, it generates antibodies, it generates the other elements of the immune response that are required then to protect us.
And what do we really know about the safety of mRNA vaccines and how do we know it? These mRNA vaccines are probably the best studied medicine in the history of mankind. If you think about it, we've treated billions of people with this, and we've done this in a modern era of data collection.
We've done this under regulatory oversight that requires every company that is manufacturing and distributing the vaccine to actually very carefully record

any adverse events, any side effects that people from the field tell us. And so when we launched this vaccine, there was a lot of effort.
This is kind of the iceberg that goes under the water. But we had to set up massive systems of data collection so that anytime somebody from the field gets any side effect that they're not expecting, they actually call us and we're obligated to look at that data, follow up and evaluate it.
And the end result of that is a very good understanding of even the rare side effects here. And the proof of the pudding is if you look at some of the vaccine platforms, you've seen side effects that occur at one in several hundred thousand cases have still been reported, validated, and at the end of the day deemed to be true.
What makes the U.S. the leader in drug discovery? I think the U.S.
has two very critical components. The first is the depth and breadth of the science that we have.
And the second is the unique ability for private-public partnerships at the deepest level, such that we can deploy public capital through things like our National Institutes of Health to advance the science. And then we're able to deploy private capital, or in some cases when the companies are public, public capital, but in the context of a commercial entity to seek a return on that investment and therefore enable risk-taking, which otherwise is very hard to justify.
And I think those two components are what make this country unique. And if you look at the number of medicines and the quality and the effect of the medicines that have been developed in the United States in the last 50 years, it's astounding.
And there's nowhere on earth that comes even close. And for me and what I've actually lived through in the last several decades has been that marriage of depth in science, public commitment to science, but also the ability of a capitalistic for-profit return on invested mindset that allows us to take risks even when many of those ultimate endeavors will fail.
And look, if you talk about a cancer vaccine, which is close to my heart, we've tried many, many times and have failed many, many times. I think more recently, we've had what looks like finally the beginning of a success with an mRNA vaccine, a personalized vaccine for cancer.
But it's that kind of investment and persistence that is required. And you can have that if there's an expected return on that investment.
I don't see that same level of commitments in other countries. The COVID vaccines were not developed by the largest pharma companies, but by smaller companies and ones that were not vaccine makers.
Why do you think that was the case? I've often scratched my head on that one. I think it's a combination of two factors.
I think the first is, and I'll speak for Moderna and BioNTech, for us at Moderna, it was clear from the get-go that there were many potential applications for messenger RNA, but vaccines was

probably the low-hanging fruit just from a technology standpoint. And without going into too much details, if you think about vaccine as a medicine, it's a little bit of medicine and you give it relatively infrequently.
So that's easier to envision than taking an IV infusion once a week. So we knew that for this technology, vaccines made sense.

And in fact, back in 2015, when I had just joined Moderna, in my first all-employee town hall, I sort of tongue-in-cheek gave a presentation that explained to everybody why it was we cared so deeply about vaccines. And I used the story of influenza, the flu pandemic of 1918.
We always feared that the next one is around the corner. And we believed that this technology was uniquely well-suited to that.
And so if you fast forward then just five years to 2020, by the time COVID hit, we at Moderna had already been able to immunize people, to use messenger RNA as a vaccine for eight different viruses. And in small clinical trials in people, we were able to demonstrate that in all cases, in eight out of eight, we were able to mount an immune response that we thought was going to be relevant.
And so COVID for us was actually the ninth one that came along. It was the big one, but we were well-prepared with this technology.
And frankly, BioNTech, who was doing similar technology development alongside us in 2017, had already partnered with Pfizer to look at influenza, flu, and whether mRNA would work because we'd published our data in flu as the first publication of a messenger RNA vaccine that actually works in people. And I'm very proud to have been part of that.
Back in 2016, we showed that this could indeed work. And so I think BioNTech and Moderna were very uniquely suited from a technology development standpoint to start chasing this.
Our technology also enabled us to move

quickly. I think the other pharma companies, and I give Albert Burl and Pfizer a lot of credit for having seen the potential and jumped on it, and they were there neck and neck with us, and that's why the world today, the Western world, has two very successful mRNA vaccines for COVID.
I think the other large pharma players had technologies that were a bit older and they were slower to get there. By the time they reacted, we were off to the races and their technologies were slower to begin with.
But it was the small companies who were more nimble, who had technology that could move quicker, that ended up being the ones who actually proved this. And I think it's a combination of being at the forefront of scientific innovation and having the agility to move.
And frankly, look, in a small company, and this goes back to the capitalistic environment, your success is not guaranteed. Your back is to the wall.
And so that creates a sense of urgency that is quite unique to small companies who are still not bringing in any revenue. You just talked about scientific innovation.
How do you see the future of health care and developing new drugs and treatments with mRNA, artificial intelligence and other new technologies? I've never been more excited. In fact, one of the reasons I left Moderna was because I had to take some time to satisfy my curiosity in terms of everything else that was happening that was not just mRNA.
I think we've proven the concept for mRNA, certainly in infectious disease vaccines. It's probably the most successful vaccine platform to ever have launched.
So I'm very excited about the potential

opportunities for that technology. You mentioned artificial intelligence and machine learning.

I think that that is where we're going to see a huge change. It's going to take time because one

of the interesting aspects is that science and technology actually operate to a different

time cycle than drug development does. Science moves very fast.
Machine learning moves fastest

that's the takes time. You have to go enroll patients.
You have to figure out what it is you need to do. You have to wait.
You have to show an effect. There's regulatory considerations.
But I do think machine learning has many interesting applications that I'm just curious to see evolve and be part of. And as a result, the ability to actually diagnose and ultimately treat people is going to significantly improve.
It will change our relationship to knowledge in all domains, including medicine. And that will, I think, change how we look at medicine writ large.
And I think that revolution is going to be fascinating to watch and hopefully be part of. I can't wait for that to happen.
And how can government accelerate other discoveries and treatments for other diseases? Well, I think there's really two critical components. The first is to continue in terms of the investments in basic science.
And I think the other one is really to think carefully about the regulatory framework by which we approve drugs and we reimburse drugs. I worry about a regulatory framework that is easy to point to the risk, but you have to remember always that approving a drug is a question of benefit versus risks.
And I give the current FDA leadership a lot of high marks. In fact, the FDA in my book are the unsung heroes of the COVID vaccines, because while the private sector could always go hire another thousand people, build another factory, the FDA, as our civil service, actually with the same headcount, more or less, went to phenomenal length to cut timelines, give guidance, look at data and come to the conclusions.
So I do think we need to strengthen the civil service institutions, first and foremost,