Legacies: Moderna Chief Medical Officer Tal Zaks

This program’s original recording transcript is below. This transcription was created automatically during a live program so may contain inaccurate transcriptions of some words.

I'm Ari Goldstein and along with my colleague Sydney Yeager. It's a pleasure to welcome you to today's program at the Museum of Jewish heritage, living memorial to the Holocaust.

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And we're kicking off this evenings legacies program with Madonna's Chief Medical Officer tall Zacks, to whom we all owe a great debt of gratitude for being with us today, and of course for his life saving work to develop Madonna's Mr in a covert 19 vaccine.

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His legacies program is made possible with the gift from Mark Kirshner and honor, Nancy Fisher.

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Tall isn't conversation today with Maddie Khan, the culture director at Glamour magazine, and the granddaughter of Holocaust survivors. Maddie is currently writing a book about teen girls and activism titled young and restless for biking books, and you

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can find more of her work on Twitter and sub stack.

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During tall and Maddie discussion this evening, please feel free to share questions in the zoom q amp a box and we'll get to as many as we can during the hour.

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This program is being recorded and the video will be available tomorrow and the museum's YouTube channel.

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Without further ado, welcome Tom Maddie, feel free to get started.

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I'm so excited to be here. Yes.

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And wow there is an astounding number of people who are watching this, so we'll try to keep it interesting. And I know that probably many of the people who are here want to hear about what you've been up to over the past year and a bit, but let's start

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a little bit farther back. I'm curious to hear how you got interested in medicine in the first place, and whether you ever consider doing something else besides, saving all of our lives with record breaking worldwide amazing vaccines.

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Well first year. You're too kind. Thank you for agreeing to share the podium with me this evening.

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Yeah, in a funny way I think medicine was my rebellion, I grew up to a father who was a mathematician, in fact, his two brothers are also mathematician and logic was the all prevailing, you know, course of action if you will.

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And when I was growing up I was curious.

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You know, always surrounded by scientific thinking and deep logic but curious to see the impact that had on humanity on the actual people and so for me, it sort of became this escape if you will do something that had a more concrete impact.

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Yeah, so you were I'm sure many people have made the joke to you that you were at the loan Jewish boy whose parents weren't as excited that you went to become a doctor, but they probably dealt with it in the end I'm guessing, I'm guessing they came around,

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so it's it's funny you should ask I think my mom's always been proud of the fact you know typical Jewish mom.

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I think my dad came around to it, I think initially he thought I'd be, you know, another mathematician.

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He was, I think, quite well regarded in his field. I'm sad to say that I probably don't understand most of what he did.

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But I know that he rose to prominence and was well respected.

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But I think, you know, as I became an adult and he saw what it was I was doing. I think he was very proud. Yes deservedly so, um, well you grew up in Israel and we'll talk about that a little bit, and the difference that you felt in medicine in terms

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of coming here but let's actually, let's talk about that right now. And when you came to the US you came to study tumor immunology, what was the decision to come here to do research, like, and how did it feel different from the way you'd experienced medicine

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and particularly the human side of medicine and Israel.

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So, for me it was, it was a big choice at the time so I studied medicine in Israel but I was always curious about science so I actually took a bit of a detour and spent a few years doing some research ended up with an MD and a PhD in something that was

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then a backwaters of immunology called cancer immunology, and I had a wonderful opportunity to come in sort of explore it in much greater depth here at the National Institutes of Health, with Steve Rosenberg, and at the time I kind of felt like, you know,

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the sky's the limit in this country and Israel while it has phenomenal training and phenomenal sciences.

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I felt that I would probably have the ability to do more here and since as a kid I had grown up, sort of, flip flopping between the US and Israel, because my father was one of these wondering academics.

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It was relatively easy for me I have to say I think my family paid a bigger price. My wife joined me she's an Israeli and came here together I promised her if you know if this doesn't work out in a couple of months then we can always go back and you know,

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that was some 25 years ago. Yeah. Famous last words. It sounds like you had mentors here and people who welcomed you in this scientific community, what was sort of, if you could articulate for your career, the kind of prevailing wisdom that has driven

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you to pursue the different opportunities that you've pursued.

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Well I think I've been really fortunate you've asked me about the practice of medicine here and in Israel.

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And there are some big cultural differences for how we train at least back in the day Israel being a much more paternalistic society where you know you go to the doctor you expect him to give you the right answer and what do you mean there can be three

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right answers depending on what the patient wants right that's in the US, it's very different.

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It's also.

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I remember when I started my internal medicine. So here I was trained in Israel and because I had trained for longer than most us graduates, and I did some extra curricular things like spending four years as a nurse in the intensive care unit.

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While I was a medicine student, I came much more clinically prepared than most of my us colleagues and so I remember the first week we had grand rounds and I thought it went fine and then the second week I started the ICU and you know I asked a few questions,

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and at the end of rounds, my resident, the senior person kind of pulls me and closes the door and Wags on her finger at me and says, You know, I put my eye on you.

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You're that intern who actually asked questions. The first day on Grand Rounds you know you don't do that you first listen to your elders here right so okay i i gives the Rotenberg a lot of credit.

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I mean, translating science to medicine is probably something that I supposed to do based on on on him being a role model and he you know in that real, he is one of the most legendary people that I've ever seen and it's just been astounding to watch him

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and be able to train with him. Yeah, I mean we talked, we just talked a little bit about the differences in terms of the practice of medicine, asking questions always of course being the Jewish way so good on you for that.

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But on a personal level, moving here. How did it feel to sort of change your identity from being Israeli to having that be kind of hyphenated with being in America and I'm curious to since this is where in this venue, how it felt also to have to redefine

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if you did your relationship to Judaism, being in America, and raising your kids here instead of in Israel.

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So it's a very good question.

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I had thought about it long and hard, because as a kid, I had experienced sort of Judaism in the US, which is very different from the experience in Israel and it made me kind of realize that I think for many of us secular Jews growing up in Israel, the

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Holocaust was a point of rupture and our identity and our collective identity and if you look at it back, my grandparents who immigrated to Israel in the 30s.

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They actually you know did something that their parents thought was crazy and they left the religious way of life and they emigrated to this foreign country, my grandfather when he was 16 my grandma was he was, you know, 20, and basically history proved

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them right in a very sad way and I think that deep scar has meant that those of us who grew up second and third generation secular Jews in Israel, kind of felt like being Jewish is being Israel it's one in the same.

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We don't need to go to the synagogue, you know, figuratively once we land and we land in Bengal you and we sort of kiss the figurative muses and we're inside our own home.

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Where as for American Jews, Judaism is not like an Israel and nationalistic identity, it's actually a religious one and so Judaism has survived thanks to a religious identity and coming back as an adult here.

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You know, my wife, my wife was pregnant at the time our son was for.

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Once we decided to stay and became very clear to me that, for them to continue this identity meant that I had to relinquish my sort of view on what Judaism isn't actually embrace a more religious one.

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And so we sent our kids to the Jewish day school system they both graduated from Jewish high schools, and they. I think for them the definition of Judaism is much more religious than it is for me so I think on the family life.

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I've always been attuned to this subtle difference between Israelis and and and American Jews and look, I have my, My grandma's brother immigrated to the US and so I've got great cousins and a great antenna great uncle who live in DC and so and we've

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been in touch over the years and it's been phenomenal sort of to reconnect and understand what our identities are like, so that's that's at a personal level, I have to say that, you know, professionally it's been a somewhat more suddenly experience being

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in Israeli and being called tall Zacks, you know, within a nanosecond people will figure out yeah okay we figured out who this guy is. And I've never made any bones about it.

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In fact, quite the contrary, I often embrace. Some of the, you know, to occur Yiddish things if you will.

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Just as a way to joke and share my heritage and I do it very openly, you know.

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And in the beginning of September, it's when companies typically make their long range plans and it's always a very very tough time and I used to joke to people and say look this, these are the 10 terrible days.

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Yeah, we tell you about that. We got some atonement to do here right and when.

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In other example that have used is when, when we go in front of investors as a corporate spokesperson, we're supposed to read this forward looking statement.

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And very quickly on, you know, I remember I was in New York in a room full of bankers and the slide flashes up and I look at these guys and I'd say Look, let me explain this simply what the slides means is really just a modern legalese interpretation

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of an automatic thing that basically says since the time of the temple was was lost all prophecy has been given to fools. So whatever I'm about to prophesied, I'm a fool, but if you listen to me well that's on you and sort of I've embraced those elements

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of cultural heritage and found a way to, to make them part of my, my life right when somebody some does something foolish the folks at Madonna have often heard me say, you know, 50 wise men won't find the stone in a light that some full through and you've

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just thrown the stone in the light buddy, so what what was funny to me is one day, one of my colleagues came up to me and said how proud she was that I was so proud of my Jewishness and that that really struck a chord for me because I guess maybe as an

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Israeli not growing up here, realizing that what I'm doing maybe a little bit on the edge for some people in terms of, you know, having my identity front and center was was not not typical.

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Yeah, it's funny because I always feel like, Well my name speaks for itself to having a last name icon but you would be surprised how many people think it's Khan and then they're expecting someone very different than who they get.

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But I think that makes sense and I think, I think one of the things that is interesting to me is like this idea of bringing your whole self to work and figuring out how you maintain, you know some level of distance from the thing that you do and also

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throw your whole heart into it, in terms of your relationship to work.

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Is there any piece of you that the people at Madonna would be surprised any hobby they would be surprised to hear about or do you feel like this. This work has really been your life.

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Oh no, you know, so as as Rob will tell you quickly, you know, one of the greatest difficulties I have is actually, I enjoy what I do so much I have no hobbies.

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I mean, it got so bad that when I was starting.

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Seriously, I was starting to prepare for leaving Madonna she decided she needed to make me a play date and go find somebody to play with.

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Well, we wish you great luck I'm finding maybe you can take up knitting or something in your in your free time, but in terms of before, before we get to leave you, my dear.

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Now let's get to coming to Madonna I know that you've said that, Mr and a research was one of the things that drew you to this job, obviously that proved to be a good investment and something we are all grateful for.

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Mr. Ma is a new term probably too many of us or a term we have not heard since high school. So tell me about how you became interested in it and what you recognize as its potential incoming to Madonna, so everyone knows that intermediary that every cell

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in our body uses to translate the genetic code into what that cell is supposed to be doing.

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All of the cells in our body have the same DNA right but but every cell was different, or slightly different or very different. I mean just look at our body.

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We're made up of very different organs and very different cells. So the thing that makes every cell unique is the fact that they only produce part of the proteins that are instructed for in our DNA and that part is dictated by the messenger RNA and so

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this has been known now for many years. It's called the central dogma of biology.

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You know, as somebody whose life's mission is to has been to translate emerging science into medicine. When you come across a platform that has not yet been in the clinic but purports to actually take that very essence of translation as it's called in

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the cell at the molecular level, and use it to teach every cell in the body or the relevant cells in the body to make a protein for therapeutic content or in this case of vaccine.

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That was just something I couldn't let go of and so this was a little over six years ago when I first saw what Madonna was trying to do. The company had not yet put anything in the clinic, but just the question of, you know, if this were to work, what

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were the things that we could make out of it was was something I couldn't let go.

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At the time I was, I had a pretty nice job I was running all of oncology from one of the major pharmaceutical companies. But you know, I was turning 50, and a strange thing happens to you at a certain point in life, you start, you start looking for what's

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the next step and you start counting your time in reverse and the time that God's given me on this earth, what do I want to get done. And you realize that you the questions you ask are important.

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And so for me it was an opportunity to really join something that I thought was big. And I remember telling her at the time you know I don't know if this is going to work, but I'd rather fail trying to do something really, really important than succeed

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on something that's relatively incremental.

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Yeah, I mean I think we're all, we're all glad that you made that bad, um, I just want to say that I'm going to take a look at the q amp a section of the chat and have the q amp a function.

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So, at a bit later on so if people want to leave questions, don't worry we will get to them. But in the meantime, you know, I think this way of almost as soon as these vaccines proved to be effective as we were all following with, you know, great curiosity.

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There was also the articles that we would see about what the potential for this kind of technology and this approach to therapeutics what that could yield for you.

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You know now that you you joined moderna and now you're seeing what the company is doing. And what's going to come next. What is your hope for this approach to making vaccines.

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So I think this is going to clearly it already has revolutionized vaccines in terms of the potential. I think the safety and efficacy of the two Mr. Na vaccines that that have been launched are astounding.

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You know, people ask me well what's different between your vaccine and Pfizer and I tell them you're missing the the the real question the important question is, how similar are they, you know, in science were taught that we don't believe any experiment

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until it's replicated and we've just seen the most astounding scientific replication, you know in my lifetime of these two vaccines both demonstrating safety and efficacy now in hundreds of millions of people.

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I think there are other vaccines that will be developed are already being developed for other infectious diseases. We're trying to leverage the power of this technology for cancer that's a much more complicated problem I don't know if we'll succeed but

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we're certainly given an our best shot. And then there are many other applications, really, the breadth of what you can do this is astounding our collaborators astronauts in a car actually injecting the message that codes for a growth factor to repair

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the heart directly into the heart of people after they've had a myocardial infarction as a way to improve regeneration. We've got collaborators at another company vertex who are trying to use messenger RNA by inhalation to replace a missing protein for

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children with cystic fibrosis, in order to improve their lung functions. We at Madonna have already dosed young kids with hereditary errors of metabolism as they're called when they've got a problem in the gene that is encoding a critical enzyme.

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We're trying to replace that missing information just with messenger RNA.

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And when you give it IV The hope is that it will go to their internal organs and teach them how to make that protein. So I think we're just at the cusp of a revolution of what you can do with Mr.

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Na, and it's a wonderful era because I think you're seeing these kinds of medicines, if you know step back and look at him RNA medicines nucleotide medicine gene therapy, etc.

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It's truly remarkable hero of the translation of science into medicine.

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Yeah, I mean I think that is I think being at the cusp of this is so exciting and and I'm sure that many people look around at things that have become, you know elements that we associate with modern life and wonder, You know what could, what could potentially

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solve that problem or address that problem down the road but I also think as we all know, living in this information ecosystem that the more new amazing scientific breakthroughs that happen the more the misinformation ecosystem sort of rises up to meet

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those innovations and that's something that the vaccines have been targeted you yourself have been the target of. I'm curious how you think that people in the policy space people on the, you know, on the medicine and development side of things can do

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as best as they can to communicate around stages of development of these different therapeutics and how we can make sure that people understand these are safe.

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These are rigorously tested you know nothing is being pulled out of a box and then hand it to someone the next day.

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So that's something I've spent a lot of time thinking.

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Over the past 18 months, you know, as somebody who spent most of his career translating science and medicine. It was astounding to me to realize somewhat naively last year, that if we don't translate that medicine into politics but politics i don't mean

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mean it pejoratively politics is that which unites human beings to find shared meaning and do things for the greater good that we couldn't do alone.

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But if we don't translate what it is that we can accomplish into a language that people will understand. Broadly, then we will fail in the mission, and that realization, especially in the modern era of such divisive communication has really been an interesting

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journey for me, you know, it started when my mentor from my PhD mentor the late trigger psycho taught me as I was doing what I thought was really complicated science at the time he said looked up.

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If you can't explain what you're doing to somebody in kindergarten, you don't really understand what you're doing. Right. And that kind of stuck with me.

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As a physician, the toughest trick or skill that any physician needs to master is actually the ability to convey similar message in different languages to different people at different levels of comprehension, and I had no better teacher than Steve Rosenberg

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anybody who's seen Steve, Dr. Rosenberg with a patient knows immediately what I'm talking about. And yet here here's somebody who is as steeped in the most complex science that we've ever done has translated into cures for people with cancer, and yet

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finds a way to explain it to patients, regardless where they come from and I was fortunate to spend time with them.

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Coming back to, sort of, you know, as a pharmaceutical sponsor. It's been a struggle because while you know i i trust the veracity of the data that we're bringing forward.

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Obviously, I understand that people don't intuitively trust me and, unfortunately, the pharmaceutical industry over the years has become quite maligned in this country despite the phenomenal progress we've done and that's a paradox in and of itself.

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But as I've thought of okay how do you how do you address that, You know, I think we have a few simple tools.

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The first is to use plain language. I had the opportunity to when I went back to Israel early this this year, my sister in law asked me to go explain this vaccine to my nephew who's in 12, who's a 12 year old.

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So I went and I spent an hour with these 12 year olds thinking I'd tell them a story, I'll forget it and 30 seconds, they started fidgeting raising their hands and asked me questions.

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And let me tell you they had great questions and one of the questions was, well, so what about the side effects do people grow a tail when they get an MRI a vaccine.

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And I looked at the kid and nice.

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Right so and so you know what i said i said Look, I have to tell you, I have to investigate every such claim anywhere in the world so whenever somebody thinks that happens I asked them to drop their pants and show me.

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And so far I haven't seen any tales, but if you see somebody could you please please let me know because I'd love to see it too right and so they all burst out laughing, obviously, you know, more seriously I think it's the personal example so I talked

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about my mom getting vaccinated my kids getting vaccinated, of course I was vaccinated and then you try to leverage trusted voices in the community ultimately because not everybody's going to trust me.

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But I do think that vaccine hesitancy is really just emblematic of the current political and public discourse we find ourselves where there is no Arena in our public life, that there seems to I mean we seem to have lost that Gaussian distribution of opinions

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into the extremes and it's very hard to find middle ground these days so I've really become interested in, and how conceptually, can you actually engage people to find that common footing again, I think it's a problem that is much much larger than vaccine

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hesitancy percent.

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Yeah, and in this country and and that's another thing that I think is interesting in terms of you're coming here, you know, the American healthcare system has its own legacies of inequalities that has, you know people on across all into the political

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spectrum who have reason or feel they have reason to doubt vaccines for one reason or another, getting steeped in that part of the culture was any of that surprising to you or was that something that is that something that you feel is a factor of healthcare,

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you know all over the world, or is that unique to this country.

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Oh, I think there are elements that are unique to this country look at the end of this day, at the end of the day. This country was founded by people who believe in individualism and individual choice right it's one of the hallmarks of this great country

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and it's certainly one of the reasons I'm here if you look at my personal history.

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When you have a culture that is so deep and individualistic right of determination, dealing with a pandemic where you do things for the greater good. Yeah, that that doesn't intuitively work right and so you see countries where a more homogenous understanding

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of public good led them to more easily deal with a vaccine that I think in this country and that's still ongoing.

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I respect people's right for self determination I respect people's right for making choices for their own.

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I think that becomes really a difficult conversation when that right abuts on the danger to others. So I think if you don't want to get vaccinated that's fine, but I think you can't not get vaccinated and expect to be able to go work in a nursing home,

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right, and and go work in a hospital so those are the kind of trade offs that I think require some public dialogue and it's been happening in this country so overall I'm, I'm actually optimistic.

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Yeah, I'm the vaccine, the MRT vaccines, there were first developed so so early in the pandemic. I'm curious if you can take us back to that moment where you first realized that this thing that you had drawn you to this company was actually going to work

00:27:12.000 --> 00:27:26.000
and then how it felt just on an emotional level to get through so many bad periods in the pandemic knowing that this was on the way and knowing that it wasn't ready to be rolled out right right then.

00:27:26.000 --> 00:27:35.000
Well, it was, it was an interesting journey you know they were. I remember within 48 hours of the vaccine sequence being known.

00:27:35.000 --> 00:27:39.000
We put, we put the vaccine into production.

00:27:39.000 --> 00:27:54.000
And I came home that night and told my wife, you know it's it's it started, and my wife who happens to be not just an artist but also by chemist looked at me and said, Yeah, one guy publishing the sequence in China are you sure you got it right.

00:27:54.000 --> 00:28:08.000
For a second there. I started sweating and I immediately called some people don't worry it's been, you know, it's been sequenced across the world we got the right sequence, and that being said I still didn't completely sleep well until we saw first the

00:28:08.000 --> 00:28:11.000
mouse data, proving that indeed.

00:28:11.000 --> 00:28:24.000
You know we didn't screw up anything that's the right sequence mice and a protected followed shortly thereafter by the first clinical data in the phase one and that was now in May, where we demonstrated high levels of antibodies and people who've been

00:28:24.000 --> 00:28:37.000
vaccinated I think once we saw that I and my team were very optimistic I remember people ask me well what do you think the efficacy is going to be and I responded that, you know, hundreds of good number for me.

00:28:37.000 --> 00:28:39.000
Listen, and I worked quite well.

00:28:39.000 --> 00:28:54.000
We didn't know how will of course this was the first clinical Mr a vaccine trial ever done. But having such high levels of anybody that even exceeded the levels you saw in people who were sick with a virus was really really reassuring and.

00:28:54.000 --> 00:29:01.000
And I think that is the cornerstone of why our vaccine has been so effective.

00:29:01.000 --> 00:29:12.000
Yeah, Israel, and America and Israel and the rest of the world have been in this interesting dance during the pandemic where Israel has been giving us kind of a window into a few months ahead you see into the future a little bit and in the spring and

00:29:12.000 --> 00:29:23.000
that was really exciting. Now it feels a little ominous, in terms of how you're thinking, many people in the chat have asked us about boosters and not surprised.

00:29:23.000 --> 00:29:34.000
In terms of how you see this next phase of the pandemic what people say call learning to live with the pandemic. How do you think the US can respond to what we have seen from Israel so far.

00:29:34.000 --> 00:29:38.000
And what do you think the next step is.

00:29:38.000 --> 00:29:42.000
So let me try and break that apart of it.

00:29:42.000 --> 00:29:43.000
Israel.

00:29:43.000 --> 00:30:02.000
I'm super proud of what the what the country has done, both with us and with Pfizer in terms of being amongst the first to recognize the potential of MRSA vaccines, and to commit to actually purchasing enough for the population, ahead of knowing that

00:30:02.000 --> 00:30:18.000
this is going to work. I think was truly foresight, the way that the vaccination programs rolled out was a truly remarkable you know I remember being interviewed in German and on a German TV station of all places.

00:30:18.000 --> 00:30:33.000
When they asked me you know what can Israel teach Germany about how to roll out vaccines, and I basically said, you know, it's hard to teach a lesson here when you're operating in a country that has been under existential threat for since its inception.

00:30:33.000 --> 00:30:48.000
We know how to deal with existential threats, we must grow up and I think what you saw was was a part of it but it did took, take a lot of understanding wisdom and foresight and planning to get it done right initially and for that I applaud them I think

00:30:48.000 --> 00:31:05.000
the, the team on the ground in Israel is truly truly superb boosters. So, there's been a couple of interesting learnings here. The first is that we probably declared victory, a tad too soon thinking that you know one two punch was enough.

00:31:05.000 --> 00:31:20.000
There are many vaccines out there. And this is kind of basic immunology, where a prime and just one boost isn't optimal and you come back at six months to give a third dose we see that from Titus, you know, many of the pediatric vaccines are given over

00:31:20.000 --> 00:31:35.000
three doses, etc. And this is kind of basic immunology right you show something to the immune system once okay it clears it you come back with the booster well it wakes up, it hasn't really clear the problem could come back six months later, that thing

00:31:35.000 --> 00:31:50.000
you thought you cleared isn't really gone, then you continue to improve the immune response and what it means is that your immune response comes up higher stronger, it comes up faster, and it's going to be more durable, and that's, that's how evolution

00:31:50.000 --> 00:31:52.000
has trained our immune system.

00:31:52.000 --> 00:32:02.000
Now the initial data were so good after just two doses that we thought we solved the problem and certainly we expected it to last for at least six months if not a year or longer.

00:32:02.000 --> 00:32:20.000
And I think had the virus stayed the original virus and its overall infectivity that may have been the case, but then along came Delta. Right. And what a Delta teach us well, delta is a mutation that the virus has evolved, not really to escape the immune

00:32:20.000 --> 00:32:28.000
system that's not why Delta has evolved Delta has evolved, remember it evolved in Indian in a place where people were not vaccinated.

00:32:28.000 --> 00:32:40.000
It evolved to be that much more effective. And so if you look at the way the immune system recognizes Delta, it recognizes it almost as well as it does the original strains.

00:32:40.000 --> 00:32:53.000
The difference though is that delta can infect us so much more effectively and so much more efficiently, that now if the antibody levels have dropped it can actually gain a foothold so if I've been twice vaccinated and I walk down the street and somebody

00:32:53.000 --> 00:33:10.000
with Delta sneezes on me. The virus is so fast to attach itself and replicate that by the time my immune system wakes up and really you know that recall comes in the virus has already started to replicate and I can transmit it to others, and I can even

00:33:10.000 --> 00:33:23.000
become sick. The good news is that I'm still pretty well protected against severe disease. Because what's happened is, there's an arms race going on in my body between the immune system ramping up and the virus trying to take over right.

00:33:23.000 --> 00:33:27.000
And as long as I've been vaccinated twice.

00:33:27.000 --> 00:33:41.000
Then, we're still pretty well protected from severe disease. Now, all that means is that you would expect the third dose to be very effective because if the difference is not really an immune recognition it's just and how fast the virus replicates, then

00:33:41.000 --> 00:33:57.000
if I can boost up the immune system if I can improve my standing in that arms race, then I shouldn't be able to beat it back. And indeed, that's the case, we now have data from Israel showing that in adults over 60, as soon as they get the third dose.

00:33:57.000 --> 00:34:07.000
They again, reach more than 90% of protection, and now I'm not just talking protection against severe disease, we're back to talking about protection against even mild disease.

00:34:07.000 --> 00:34:21.000
So I do think boosters are in the future, certainly for people who are immunocompromised that that was clear from the get go, but also I think for the rest of the population, you're going to see a recommendation for booster Israel's already they're vaccinating

00:34:21.000 --> 00:34:34.000
people above the age of 40. I think the UK is not far behind and I think in the US, there's a, an expectation that starting in the second half of September once FDA has a chance to look at the totality of data there likely will be an approval for a booster

00:34:34.000 --> 00:34:45.000
shot in the US as well. Yeah, that's very comprehensive answer Thank you, um, I, a few people have dropped in questions about this and I'm actually one of the things I want to ask you about as well.

00:34:45.000 --> 00:34:58.000
I think one thing that this pandemic has done, especially to those of us who have not lived our whole lives under in a country under existential threat is raised the specter of fear in a way that people who have been privileged to have lived in relative

00:34:58.000 --> 00:35:13.000
comfort haven't experienced and I think all of us are reconsidering our risk assessment polishing off tools of evolution and human nature that we did not expect to need to use for you, knowing everything that you know having been so immersed in this,

00:35:13.000 --> 00:35:20.000
how has your sense of risk assessment and fear changed during the pandemic.

00:35:20.000 --> 00:35:34.000
That's a fascinating question so one of the things that saw that that's always been interesting to me is how, how we make decisions as human beings, you know, it turns out that that we're not as rational as we'd like to think there's a there's a great

00:35:34.000 --> 00:35:39.000
author and researcher by the name of

00:35:39.000 --> 00:35:54.000
denna reality who wrote a book, a few years ago called predictably irrational so so in some ways we're predictably So, but how we make decisions is really fascinating and it's a, it's a complicated problem because risk is a continuous variable, you can

00:35:54.000 --> 00:36:07.000
have a little bit a lot less, but the actions you take her off and binary you either do something, or you don't. So for each of us, there comes a tipping point do I want to get vaccinated well how big is the risk How big is the benefit What do I believe,

00:36:07.000 --> 00:36:15.000
but the decision to go get vaccinated is a binary either do it or I do not.

00:36:15.000 --> 00:36:17.000
I think for me personally.

00:36:17.000 --> 00:36:22.000
The benefit risk of the vaccines was always you know crystal clear.

00:36:22.000 --> 00:36:32.000
I had anticipated it based on the phase one data, and certainly as soon as we could get ourselves vaccinated. That was an obvious thing to do.

00:36:32.000 --> 00:36:42.000
The other elements, I think, are more complicated so the things that we do for vaccination.

00:36:42.000 --> 00:37:03.000
Those are to protect ourselves and to protect friends and family and society, well what about mask wearing. And now we come into a really, you know, interesting paradox, if you will, because we now know that this delta, we're probably protected, but actually

00:37:03.000 --> 00:37:08.000
it's very infected, and it's going to find people who aren't vaccinated.

00:37:08.000 --> 00:37:20.000
So do I wear a mask, even though there's no risk to me to protect somebody who doesn't want to get vaccinated right Why should I give up my personal liberty of seeing the faces of my colleagues in the office for those people who, who think this is all

00:37:20.000 --> 00:37:25.000
a hoax and don't want to protect themselves when it's available.

00:37:25.000 --> 00:37:30.000
And it's become a much more complicated math, if you will.

00:37:30.000 --> 00:37:47.000
I think what it's taught me personally, is first, you got a role model, whatever behavior to protect the population you believe is the right one, and that's at a personal level that's at a company level, whatever your social group is, I think, at Madonna

00:37:47.000 --> 00:38:00.000
we've gotten back to wearing masks in the office, but now mandating vaccination for all employees, which which we think is the right thing to do. But we also recognize that they're going to be people who are relatively under vaccinated or people who can't

00:38:00.000 --> 00:38:10.000
get vaccinated Of course there's the pediatric population. And so we do need to do whatever we can to minimize the risk to the extent that we can.

00:38:10.000 --> 00:38:21.000
But I've sort of, I think, learn to respect a much wider spectrum of people's opinions and behaviors because how you deal with this is, is very personal.

00:38:21.000 --> 00:38:38.000
And right now we see a gamut of behaviors in the US, and we're going to have to figure out how to, how to live with all of them, right, and impressed you may be the one person who the pandemic has made the more accepting of a wider range of opinions from

00:38:38.000 --> 00:38:52.000
from their fellow citizen so that's kudos to you for that. I have found it hard to be so generous, but I'll try to model your behavior. Um, I think something that we have, we've seen in in this country and you know you were talking about Israel being

00:38:52.000 --> 00:39:07.000
so quick to understand the potential of Mr. Na vaccines was this incredible buy in from governments that sometimes in the case of the US take them more hands off approach or don't tell these kinds of investments, as readily as they had, in this case,

00:39:07.000 --> 00:39:22.000
and that's continued you know under two administrations been in the business of getting, you know these vaccines or other therapeutics out the door. What do you think a good working relationship between the industry and government looks like so that you

00:39:22.000 --> 00:39:31.000
know we can have more medical breakthroughs of this kind at the speed that we found at you that this one came to the market.

00:39:31.000 --> 00:39:36.000
Well I think there's, there's a couple of elements here first.

00:39:36.000 --> 00:39:52.000
We're very fortunate in this country to have the FDA that we do and you know all of us take it for granted but we really shouldn't for two reasons. First, you have to realize that the amount of resources and talent that we must are as a society that's

00:39:52.000 --> 00:40:02.000
embodied in the FDA is quite unusual I'll give you a simple example. When you go to the FDA and you say hey I think this thing works, the FDA says yeah I don't care what you think.

00:40:02.000 --> 00:40:11.000
Show me the data they run their own analysis, and then they say we agree or we don't you go to most other regulatory agencies and you say hey I think this thing works.

00:40:11.000 --> 00:40:18.000
They will either say yeah we don't agree, can you analyze it this way or that way or the other way right they don't have the resources to do it themselves.

00:40:18.000 --> 00:40:24.000
And most of the rest of the world basically said oh the FDA approval. that's good enough for us.

00:40:24.000 --> 00:40:40.000
And so, the real heroes of the story of the last year were actually, my colleagues at FDA because, remember, I was one company, and I could always go hire other people overnight to come join the effort to try and do this right, Well, they really couldn't

00:40:40.000 --> 00:40:54.000
hire and train people so fast and they had to look at my data and Pfizer's data and JJ data and you know and plenty others, all with the world watching them on very very tight timelines because basically I came to them and said, Okay, here's the data.

00:40:54.000 --> 00:41:11.000
Now the clocks on you and the words looking at you How quickly can you approve this and so I am deeply, deeply grateful and and and have the utmost respect for how they handled it to the point that I actually don't think, and I may be an outlier here,

00:41:11.000 --> 00:41:17.000
but I don't think the bottleneck of getting vaccines or drugs approved or regulatory agencies.

00:41:17.000 --> 00:41:29.000
But I think the bottlenecks are actually being able to demonstrate the data to a sufficient standard. And once we have it regulators move pretty quickly.

00:41:29.000 --> 00:41:45.000
Now, it's true that the resources aren't infinite and in scrambling to meet the coven needs you know they beg burden took resources from other areas. So, obviously, we have to think carefully about the right level of funding and support for the FDA.

00:41:45.000 --> 00:42:00.000
But beyond that, one of the main reasons that we were able to move so quickly last year, is because we had a lot of cases and so when you run a very large trial and the trial is geared to show a difference of your vaccine, and there is rampant infection

00:42:00.000 --> 00:42:16.000
in your population, you very quickly see the cases pile up and when you tell the up you see they're all piling up on the placebo side okay. That's pretty clear this vaccine works in most other areas of drug development and vaccine development.

00:42:16.000 --> 00:42:32.000
We actually have to wait for those cases to occur for us to be able to show a difference and that's just how biology works so it's very it's very challenging actually to come to a conviction on a drug right vaccines ability to work.

00:42:32.000 --> 00:42:46.000
If you can't show the clinical data for that, and I, it's not really a regulatory hurdle. That's just the natural history of most diseases and our ability to be able to show that data.

00:42:46.000 --> 00:42:51.000
Right. This was so widespread the sample size group quite quickly.

00:42:51.000 --> 00:43:02.000
So having looked through the questions that people have for you I would say there's sort of an overwhelming number of people who want to talk to you about breakthrough infections, maybe we'll get to that but there are also a few people who are interested

00:43:02.000 --> 00:43:19.000
in more about your family story. You talked a little bit about your family's coming to Israel. And can you tell me a little bit more about how that story of survival has affected the way you see your work and what you do.

00:43:19.000 --> 00:43:23.000
So, by way of history.

00:43:23.000 --> 00:43:31.000
My grandparents, all four of them immigrated from Poland in the 30s.

00:43:31.000 --> 00:43:35.000
And so both my parents are Israelis I'm actually a second generation.

00:43:35.000 --> 00:43:51.000
It sort of hit me when my grandfather died. So typical secular household with very few, you know, aunts and cousins, if you will, although I was already second generation but when my grandfather died on his tombstone in Haifa, he asked to inscribe all

00:43:51.000 --> 00:44:10.000
the names of his siblings and their direct descendants because it's the only memory of their existence and boys that a long list. And I remember at his unveiling of his tombstone that sort of really hit hit home for me on my wife side.

00:44:10.000 --> 00:44:23.000
And you can see in the background. It's a print she made she's an artist, those are her grandparents at their wedding day they were actual Holocaust survivors who then managed to come to Israel, find each other again.

00:44:23.000 --> 00:44:31.000
After the war and come to Israel. It's the only picture of them that they managed to keep through the war and it's of their wedding day.

00:44:31.000 --> 00:44:47.000
Well, But I'll tell you when when my family was growing up, my son always wanted to go back and serve in the army. And since you know he grew up in Jewish High School and he was always close to Israel.

00:44:47.000 --> 00:45:01.000
He. I remember at the age of, 18, he was trying to convince me whether he should go back to serve or go to college, and you know of course we wanted him to go to college first that he wanted to serve and at one point I sat him down and I said, Look, I'm

00:45:01.000 --> 00:45:15.000
not going to tell you not to go to Israel to serve in the army, and he kind of opened his eyes I said my grandfather when he was 16. He left what his parents thought was right, and history proved him right now if you believe that your destiny is to go

00:45:15.000 --> 00:45:17.000
back and serve in the army.

00:45:17.000 --> 00:45:25.000
All I can say is, God be with you. And I wish you all the best, but it's your life to, to figure out.

00:45:25.000 --> 00:45:32.000
And so that's kind of, I think, you know, a joke to people at Madonna, have been with the company now a little over six years.

00:45:32.000 --> 00:45:40.000
The wandering Jew Gino type now has to get expressed again and it's time for me to wander a bit.

00:45:40.000 --> 00:45:59.000
But that search for that search for having an impact and doing it in a place where you can you can put your mark on the world i think that's that's something that's ingrained in us, culturally and certainly as Israelis growing up in Israel, between the

00:45:59.000 --> 00:46:08.000
sense of needing to achieve and the sense of persecution, that's probably my heritage.

00:46:08.000 --> 00:46:18.000
In terms of leaving your mark on the world I think that's a question now that we in places where we've been able to get vaccinated, we think a lot about people who aren't so lucky.

00:46:18.000 --> 00:46:32.000
And I think there has been, you know, I'll speak for myself on a personal level of feeling like a third shot offers me more protection like Sign me up I'm ready to walk back to on sign I get my third dose, I couldn't want anything more than to resume

00:46:32.000 --> 00:46:46.000
that brief window of normalcy that we got over the summer, where we got to set aside that fear for a little bit. I'm also aware that there are people in countries clamoring for their first doses, thinking about that thinking about you know the amazing

00:46:46.000 --> 00:46:58.000
production that Madonna and Pfizer and these other vaccine companies have been able to ramp up how do you think about equity and about what our responsibility is to the world, especially when you know we have a self interest in the world getting vaccinated

00:46:58.000 --> 00:47:05.000
because that is what's going to help you know stamp out other versions of this virus that could affect all of us.

00:47:05.000 --> 00:47:08.000
Um,

00:47:08.000 --> 00:47:09.000
it's a tough one.

00:47:09.000 --> 00:47:16.000
So, you know, I go back to the Talmud, the poor of your people come first. right.

00:47:16.000 --> 00:47:34.000
And for me, there is a moral imperative to first take care of your own not shirking their responsibility for the world. I think the way, Madonna has tried to do it and I'm super proud of it has been to invest from day one at risk as much as we could to

00:47:34.000 --> 00:47:50.000
ramp up manufacturing as much as we could, and then work diligently with governments as representatives of their people, to ensure that our supply could get as broad as possible in the world.

00:47:50.000 --> 00:47:56.000
Ultimately, there are political constraints to our ability to do that.

00:47:56.000 --> 00:48:00.000
And I think you've seen that play out on the world stage.

00:48:00.000 --> 00:48:08.000
Now that being said, I have to say that this is where I'm actually impressed by your generation and I see it in my kids.

00:48:08.000 --> 00:48:30.000
I think your generation is growing up in a world that is much more interconnected and has much more a sense of shared responsibility probably certainly with the challenging challenges that humanity now faces, pretty much together, and the response to

00:48:30.000 --> 00:48:42.000
which continues to be without enough equity, probably, whether it's dealing with vaccine shortages or global warming, frankly, and

00:48:42.000 --> 00:48:46.000
that is going to be I think a legacy for your generation Maddie.

00:48:46.000 --> 00:48:51.000
Right, I'm super excited to solve that problem I'll let you know when we figure that out.

00:48:51.000 --> 00:49:05.000
How long could it possibly take a, there are a few questions a few people who want to know about Madonna seeking FDA approval since you are extolling the virtue of your colleagues at the FDA, whether that is on the horizon, and whether that has any bearing

00:49:05.000 --> 00:49:13.000
on, you know the kinds of third doses that people get whether they should be getting the same third dose that they got for doses one too.

00:49:13.000 --> 00:49:29.000
So, yes it is on the horizon we filed anticipate in due course, we will get the full approval as well. I don't think the filing per se has bearing on the answer The answer is a scientific one I think the data I expect the data to bear out the ability

00:49:29.000 --> 00:49:44.000
to cross boost with an MRI a vaccine, irrespective of what your first dose was that's predicated both on some post scientific principles and Mrs a vaccine only shows the immune system that antigen very cleanly.

00:49:44.000 --> 00:49:53.000
And as I said from the outset, I think the similarities between the two MRA vaccines far outweigh any differences.

00:49:53.000 --> 00:49:58.000
The, that's the first point. The second point is that there are actually emerging data.

00:49:58.000 --> 00:50:10.000
The UK has run some studies showing that you can prime with one in boost with another and you actually get a pretty robust immune response. I believe the same will hold true for a third dose there's no reason not to.

00:50:10.000 --> 00:50:23.000
But we're going to have to wait to see the data. So ultimately, I'm going to have to defer to the data and the regulator's giving us the okay but I anticipate that this is what will happen in the coming weeks and months.

00:50:23.000 --> 00:50:35.000
Well jumping around a little bit now since questions are all over the place and I want to get to a good selection, someone asked what your relationship to Israel is now and we talked a little bit about how you shifted sort of an identity in, in moving

00:50:35.000 --> 00:50:45.000
to the states but I'm curious when you go back, whether you feel a sense of homecoming or whether you have that eerie feeling of being like a tourist in your own homeland.

00:50:45.000 --> 00:50:50.000
So, it's a, it's not a simple one right.

00:50:50.000 --> 00:50:58.000
The US has become my home this is where my kids are yet of course Israel is where I grew up, and I feel an immense sense of debt, and gratitude.

00:50:58.000 --> 00:51:05.000
You know, typically Israeli when I go home. The first week is like oh my god this is great, the second week is.

00:51:05.000 --> 00:51:11.000
Yeah, maybe not so the third week is why are you guys driving like crazy people get me out of here right.

00:51:11.000 --> 00:51:25.000
So, look more seriously I have to tell you one of the greatest moments of my life was when we went back this March, or I'm sorry, April, to Tel Aviv and we were having lunch in a restaurant outside at the end of the meal.

00:51:25.000 --> 00:51:35.000
Somebody stood up from the table next came over and said, Hey, are you that doctor that was on TV telling us everything was going to be okay.

00:51:35.000 --> 00:51:46.000
Can I shake your hand and say thank you, because you were a voice for optimism at a time that we thought we really had a dark future here and I have to tell you on a personal level that was super heartwarming.

00:51:46.000 --> 00:51:57.000
More to the point, I think you're going to see me find try and find ways to give back to the State of Israel from my professional perch. You know, as a drug developer.

00:51:57.000 --> 00:52:09.000
I have that sense of I think both gratitude and responsibility to give back. You know, I will find ways to do some.

00:52:09.000 --> 00:52:18.000
I'm struck by actually the thing that you just said because I think in in the when I've talked to scientists before particularly visa V, the pandemic and vaccine development.

00:52:18.000 --> 00:52:31.000
There's this strange combination that you just spoke to which is, you are group of people who are always looking to be proven wrong and data and question your own hypotheses, but you also have this optimism and this hope for what medicine can achieve,

00:52:31.000 --> 00:52:34.000
kind of in the short term, relatively speaking.

00:52:34.000 --> 00:52:52.000
It all happened really quickly, that balance for you of being realistic of second guessing yourself but also of having hope. How do you stay in that place I think a lot of us find it hard to be realist and be optimist at the same time.

00:52:52.000 --> 00:52:55.000
It's a great question.

00:52:55.000 --> 00:53:09.000
I think I'm very fortunate because I probably live at the edge of one of the greatest imbalances that anybody can can can imagine. I mean, look at the outset.

00:53:09.000 --> 00:53:15.000
I come from a Talmudic heritage which is every question is why not right. So you argue.

00:53:15.000 --> 00:53:20.000
I'm a medical oncologist, which means that when patients come to see me often.

00:53:20.000 --> 00:53:27.000
It's a tough conversation, and it's hard to be optimistic many times unfortunately still.

00:53:27.000 --> 00:53:39.000
I grew up in a scientific tradition that challenges every assumption, as you said, right, nothing is proven right until you try to disprove it five times over and if it's still standing, then it's probably true.

00:53:39.000 --> 00:53:54.000
Okay, that's a lot of pessimism stacked up right there. On the flip side, we live in an era of such phenomenal profound and rapid scientific development and and technological innovations that are just beautiful.

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And, and being able to be at the forefront of where you can see them emerge from the lab, from from the technologies that people are developing and see them applied to make a difference in people's life.

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How can you not be optimistic when you see the impact that we're actually able to deliver.

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It's hopeful and definitely feels contrary to so much other news hopeful. I'm curious how you're going to feel when the time comes for you to be outside of the system that you've been so immersed in to watch some of these developments happen not from

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your current in your current job, people are curious to know what your next career move is, we will wait to hear if you pick up any hobbies, but I'm also interested to know how you just feel about seeing things a little bit more from the outside and how

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much you want to keep your hand and, and the development of these, These next therapeutics.

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So I'll tell you, Maddie one of the most profound realizations for me over the past year was the importance of perspective, you know there were there was a point when we were running so fast that I had to disconnect on Saturdays, and it was about seven

00:55:00.000 --> 00:55:16.000
or eight weeks and we work 24 724 seven you know when when there's life at stake, there's no Sabbath right well, I just had to give my mind to rest and I realized when I disconnect on Saturdays it's not for religious purposes, but by god there's a reason

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people do that, or God commanded it, whichever you believe, which is, by the time the end of the day rolled in. I could actually think clearly about the week ahead, and forget the immediate and figure out what what was important and it taught me that

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without perspective, you often sacrifice what's important for what's urgent or what's immediate. And so taken back at a macro level now for me personally.

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This is a wonderful opportunity that wife, that life has afforded me to step back and really reimagine my own personal perspective so you won't see me, you know, leave I'm not going to go in and, you know, disappear from this cutting edge of translating

00:56:03.000 --> 00:56:19.000
science and medicine that's still going to remain my passion, but I do need some time to reengage to figure out my perspective, for the last six seven years have been immersed in messenger RNA sign says, I'm really curious, where's the frontier of medicine

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gone to in other you know it's a very wide and broad frontier. And I'm just curious to step back and understand what are other areas there and how else can I be effective and involved so I'm going to go satisfy my curiosity and I'm going to take some

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time to figure out a different perspective on it before I re engaging in with the same level of intensity.

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Now we're almost out of time but I wanted to ask you on that note, you must now be at the point where after having asked people for advice for many years people now ask you for advice and I'm sure people who are interested in this field and people who

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are just working in the fields of science and medicine in general come to you and ask for your advice, what is the piece of advice that you find yourself doling out most frequently. Make sure that you are asking important questions that you're devoting

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your time to the stuff that really matters to you.

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That's it. And how do people figure that out if they're not sure what is that thing that is motivating them and driving them well as Yogi Berra said when you see a fork in the road ticket.

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What a perfect. What a perfect note to end on. I think that we've covered many questions, although there is no shortage of information that you could give out about the third dose, if you want to do, but we'll leave it will leave that to the epidemiologist

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to share, and I just want to thank you so much for doing this it's been such a pleasure. Maddie the pleasures been mine thank you so much for the conversation.

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Thank you talent Maddie for this really informative and really amazing conversation. It's been a pleasure to listen to pleasures. Thanks for hosting us.

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I echo Sydney's thanks, and great things to mark Kirshner and Nancy Fisher whose generosity makes our legacies program possible. It really is pretty exciting to have heard from Pfizer CEO Albert Birla in February and you today tall and to think about

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all the amazing ways that the stories that we tell and preserve at the museum are intertwined with the most important things happening in the world today so you've given us a lot to think about all the we do at the museum is made possible through donor

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support so to those of you watching we hope you'll consider making a donation to support the museum or becoming a member, and certainly joining us for our upcoming programs which you can check out at the links in the zoom chat.