Homeroom with Sal & Vas Narasimhan - Wednesday, July 8

Hi everyone! Welcome to our homeroom live stream. I'm very excited about the conversation we're going to have in a few minutes. But before that, I will give my standard announcement: a reminder that Khan Academy is a not-for-profit organization with a mission of providing free world-class education for anyone, anywhere. And we only exist because of philanthropic donations from folks like yourself. So if you're in a position to do so, please think about donating.

I want to give a special shoutout to several corporations that have stepped up when they appreciated that Khan Academy was running at a deficit even before the COVID crisis, and our costs only went up—our server costs. We wanted to accelerate a whole series of programs, and so they've helped us close our deficit. We still have one, so we still need your help, but it's been huge support. Novartis, who we're going to talk to Vas Narasimhan in a few seconds, is one of those supporters; Bank of America, Google.org, AT&T, and Fastly. So thanks to all of them and our many other philanthropic and corporate supporters, and any of you who have donated or even I guess thought about donating.

So with that, I'm very excited to introduce Vas Narasimhan.

Vas: Good to be here!

Sal: Oh God, thanks for having me!

Vas: Hey, great, great, great to be here, Sal. It's really an honor. I think, as you know, my family has used Khan Academy for years—a huge part of our family in many ways—and we're honored as Novartis to be able to support your efforts.

Sal: No, no! Well, and we're honored that y'all are working with us. It's funny, when I was doing the, oh, you know, what light research I do before this, I realized that we are the exact same age, and that kind of created a bit of an existential moment in me because you run a large multinational, like hundred thousand plus person organization, and you know, I hang out in a walk-in closet making videos. It kind of made me ponder my life—

Vas: But no, not at all! You touch hundreds of millions of children all around the world; it's extraordinary work! So, but I'd love to hear, you know one of the things that we like to do, and you know I encourage anyone who's watching on YouTube or Facebook to start asking questions about really anything. But I think what we do, what I like to do here, especially because there's a lot of young people watching, is just understand how do you become—well first, what does Novartis do? I think many people know it's one of the largest pharmaceutical companies in the world, but also, and what's its focus? But I also, I'd like to understand how you ended up here. So maybe just start with, with you know, just make sure everyone understands what Novartis does and what its focus is, and then I'd love to go into your background.

Vas: Yeah, absolutely! So, Novartis is about a 250-year-old company beginning in the world of dye making in the 1700s, chemicals in the 1800s, pharmaceuticals in the 1900s. Today we're one of the largest companies in the world, one of the two or three largest makers of medicines in the world. We make about, on the order of 800, we reach about 800 million patients a year with our medicines. We've produced about 70 billion doses a year of medicine in about 150 countries, everything ranging from medicines to tackle heart disease and lung disease and cancer, all the way to malaria and leprosy medicine. But also very high-end technologies like gene therapies and cell therapies. We're also the second largest manufacturer of generic medicines in the world. So, a big, big remit, a big goal to impact public health and as a public health physician, it's really a dream job to have this opportunity.

As for myself, my parents were Indian immigrants. They came to the U.S. in the late 60s and early 1970s. I grew up in Pittsburgh, Pennsylvania, where I went to wonderful public schools there and then later in southern New Jersey. I'm very grateful for the incredible education and very dedicated, amazing parents that I had. I went to the University of Chicago, studied biology, went to Harvard Medical School, studied medicine, did a lot of work in developing countries. My passion in public health was in Africa, working in Africa, but also in Peru, India, and a few other locations.

But through kind of twists and turns, I ended up wanting to pursue the private sector approach to impacting health at a global scale. I was very interested in the science of developing drugs and medicines and how that could have a big impact. And so I came to Novartis in 2005, spent most of my career developing vaccines and drugs. I'm a member of the National Academy of Medicine in the United States because of the work I've done developing drugs and vaccines, and that led from one thing to another to me somehow being the CEO of this company as a physician scientist who always just had a big dream to impact the public health of the world.

Sal: No, thanks for that. And there's a lot there! I'm assuming most people have heard of Novartis, but you know, just the numbers that you just said, they were kind of mind-boggling. I mean, it's probably safe to say maybe everyone watching or at least a close relative of everyone watching is probably in some way, shape, or form taking, you know, some type of medication, hopefully being helped by some type of medication that's a Novartis drug. So that's incredible, incredible reach.

One question, and actually there's a question from YouTube, Anam Khan, no relation as far as I'm aware: how did you know what path and what career was best for you? How did you know it was your passion? Because you started as a—you went to medical school, you are a physician. Did at some point it switch? First you thought you were going to be a practicing physician, but then you thought, "Hey, what if I could help develop drugs or help scale therapies?"

Vas: Whatever my mother is still wondering when I'll become a cardiologist! But I think she's generally moved on from that discussion. I don’t exactly know; people often ask me, and actually just recently completing reading a great book by David Epstein called "Range", and it talks about how in the end building broad ranges of experience allows you to discover where your best fit is. So I think for probably ten years I did my medical studies; I had every intention of becoming a physician. I worked at the World Health Organization, worked quite a bit in public health in Africa. Some great leaders took a plunge into the private sector without knowing where it would go. I would say there were many twists and turns and many moments I would have thought this was not a good decision.

But then I ended up actually in the world of vaccines and I loved vaccines. I loved developing new vaccines for children and had the opportunity to work on a number of extraordinary vaccines. And one thing led to another.

I think the book talks about it; I think it's worth remembering in the world of education we want to build broad minds because the world is complex. And I think building more range in yourself from the disciplines you learn, how you can solve problems, how you can think, is what will ultimately make you successful. I think Khan Academy builds that in people.

And a question, there's a kind of a, I guess a very blunt or funny version of the question I was going to ask that someone YouTube A Z asks: How did you take over the company? Which I don't think you perceived your job as, but I guess I'll take a different version of it. What do you think? You know, when I was a kid and I saw someone become a CEO of a multinational organization like that, I'd be like, how did they do that? You know, there's a lot of smart people in the world. You know, there's hundreds of thousands of—you have a hundred thousand something employees. What do you think it was about you?

And, you know, either it was opportunities you got, you know, serendipity and things that you actively did, that kind of got you on that path.

Vas: Yeah, I'd say a couple of things. Again, I give tremendous credit to my parents and my wife; the three of them, with childhood, would certainly not be here at this moment. But, you know, I think it was a mixture of being able to understand the science of medicines and having a deep understanding of human biology and science combined with having learned how to translate that into business and numbers and financials, and how does that translate into the business world, and really being able to speak multiple languages—speak the language of science and speak the language of business.

But I think the third element— and it came back to my education at the University of Chicago, where I was educated in the great books—was a kind of deep understanding of purpose and values and mission and trying to instill that in an organization. And I think that combination, I think, when I was named CEO, I was not the traditional choice. I think our board took a huge chance in making me a CEO; there were a lot more traditional choices one could take than taking a physician scientist who mostly worked on developing drugs and vaccines. I think, if I'm not mistaken, I'm only one of maybe a handful in the whole biopharmaceutical industry who comes from more of an R&D background. But I think it was that mix and having that ability to cross those different disciplines and having a kind of very humanitarian approach or view—and we have a long journey to get there to actually realize that—but that was, I think, the kind of key elements.

Sal: Yeah, and given obviously Novartis, a major pharmaceutical company, but your background as a physician, you've helped develop vaccines. The obvious question— you could imagine a lot of questions coming in on social media about that. Judy Lenahan: when will a vaccine for COVID-19 become available, and what unanticipated roadblocks might delay it? And then Miran Ararat from Facebook is asking, if and when it gets developed, how long does it take for mass production and availability? What's your view on that?

I don't know if Novartis is explicitly doing activity there, but I'm sure you also have a general view of what's going on in the ecosystem.

Vas: Yeah, you know, I spent nine years, eight, nine years developing vaccines and working hard in that space. We ultimately sold our vaccines business, so we're not in the world of vaccines right now, but I can offer the perspective more of somebody who knows the space extremely well.

I think it's very important to understand what it takes to develop a vaccine and how different a vaccine is from a drug. In the case of a drug, we know a patient has a disease, and we're treating the disease, so the so-called risk-benefit equation is highly favored towards the drug because we know the patient is ill. In the case of a vaccine, we're immunizing somebody who's otherwise healthy, so the bar for safety is extremely high, and the bar for what the benefit of the vaccine is is also extremely high.

The FDA recently put out guidance, which actually was very much in line with what I expected. The FDA said they expect studies to be very large and well-controlled and said that studies should likely have thousands, if not tens of thousands, of patients. They expected the vaccine to have 50 percent efficacy at least, and they expected at minimum six months of follow-up for the patients who are in the trial, and longer if there was potentially a new technology that's being used.

All of that comes together, and I've been one of the people who consistently said, I mean, being realistic given that, you know, any drug you put into the clinic, any vaccine you put in the clinic has somewhere between a one and, at best, ten percent chance of making it. So if we put in a hundred, we probably will get one. If we really understand what we're doing, if we put in ten, we'll get one—really effective vaccine or drug. That's just the historical odds in our sector, and then you combine that with what the FDA just talked about.

I mean, I think it's realistic to expect a broadly available vaccine not before towards the latter part of next year. Now, could there be an upside case? Could everything work perfectly? Of course, and I understand that's a lot of where the discussion is, but it's important also to understand why we want a very safe vaccine and why it's so important in my mind to maintain the public trust. Probably over the last hundred years, vaccines, sanitation, and a handful of medicines have led to the remarkable gains in life expectancy where people, on average, in 1900 lived to about 30 years of age, and today, depending on where you are in the world, 80 to 90 years of age.

And what we don't want to do is undermine that belief in vaccines; that's so fundamentally important for a public health system.

Sal: I mean, there's several really powerful things you said. I mean, one, I thought that was a really interesting way to compare normal pharmaceutical drugs with a vaccine. As you mentioned, in the drug for regular drug development, someone has a disease, maybe a very serious disease, so you know they have it, and so you just have to see, hey, is the benefit of the drug even probabilistically better than, you know, the side effects or the risks? But a vaccine is a healthy person, and the side effects and the negatives are—you know, these things you have to look over thousands of people because even a small negative is not so good because you're giving it to healthy people.

And you also said that, so the expectation is probably the end of the calendar, next calendar year, so end of 2021 is your best guess?

Vas: It's my guess; it's just one person's guess. As you know, there are a lot of opinions out there, but I mean I think that would be remarkable to have a brand new virus show up and to have a vaccine out the door within two years is frankly unprecedented. It would not have happened, as far as I know, before in most cases in pandemics. We've generally had influenza; we've known how to manufacture influenza vaccines since about the 1950s at scale—very established technology. The only thing we're changing is the type of virus; we're not changing the manufacturing platform; we're not changing the nature of the immune response.

Now with COVID, we don't know what kind of immune response we need. We're trying to use very new technology platforms that have never been used in a large scale to navigate all that complexity. Within two years would be pretty remarkable.

Sal: Yeah, so you're seeing kind of a fairly bullish prediction to get to the end of the—because at least when you watch the news, and even if you hear governments around the world, it seems like their people are hopeful for three months or four months or, you know, by January. But it sounds like we should probably set our expectations. It would be a good outcome if we have a vaccine by, you know, November, December of 2021.

Vas: I would say yes. I mean, that's not necessarily what people are, understandably, what people are here. I understand why there's hope. Perhaps you could find a vaccine that you could use with certain populations, first responders, faster. But it's important to understand what's required from the data and the science, and the science and the data have to demonstrate you're not going to cause harm to patients who receive, or people who receive the vaccine.

And then you have a reasonable belief of strong efficacy. You'll see, you know, I spend a lot of time developing pediatric vaccines. As a simple thing like a high fever, as an example, if you have a high fever in some significant rate, 20, 30 percent of children who receive your vaccine, you could—and if you give that vaccine to tens of millions or hundreds of millions of people, you suddenly have lots of people showing up in the emergency room with fever related to the vaccine, which then leads to all other adverse consequences for the system.

So it's important to ensure that we have a vaccine we really believe in from an efficacy and safety standpoint, and I think experts in vaccines probably generally have that kind of perspective.

Sal: Yeah, and just to make sure everyone's on the same page, you know, the whole principle of immunization is to kind of inject something into your system that you can build your own immune response so that if the real thing shows up, so to speak, it's ready. And, you know, there's these notions of antibodies, which students can learn about on Khan Academy, which are kind of like tags for certain foreign substances that your body doesn’t want, and once things are tagged, then your immune system can go and clean up that stuff, kill that stuff, and so you want those tags, those antibodies.

Is the vaccine developed— is it essentially you get antibodies, you observe antibodies in people who already have the virus, COVID-19, and you take some of those, do you just inject them in someone else? You kind of denature them a little bit, but you know, but the proteins are still there; how does that work?

Vas: So there's a few things you can do. The, uh, what you just referred to, Sal, is so-called treatment with convalescent serum. So these are patients who have had the disease develop antibodies; you take the antibodies from those patients, you give it to patients affected by COVID, and you hope that transferring the antibodies can help. There have been mixed results so far with that; there's a lot of complexity in really ensuring you have an adequate so-called dose of the antibody, so we'll have to see if that bears out. But that's, of course, not a scalable solution.

So then the question is, how do you give components of the coronavirus COVID-19 to a human to generate a very robust immune response? An immune response has a few characteristics. One, that it has a high enough level of antibodies, as you mentioned, that can prevent, hopefully, the disease from taking hold in the person and hopefully also elicit what's called immune memory. Immune memory is the immune system's ability to restore cells, memory T cells, which can then come back if the infection were to happen at a later point in time. This allows for the vaccine to protect over a long period of time.

Now, right now, there's a number of different vaccine technologies that are being used to try to solve this problem. One is giving RNA, and so for the students listening, you know DNA goes to RNA goes to protein. So the idea here is if you give patients RNA, the cells in the body will turn that RNA into the COVID surface protein—so one of the proteins on the surface of the virus—and then the immune response will develop. Other approaches use DNA, and it's a similar sort of idea: can you get the cells to produce the COVID particle? The reason DNA and RNA are the first vaccines in the clinic is because they were very easy; they're much easier to do than isolating the actual parts of the virus.

So you have DNA and RNA vaccines. Another approach used by Oxford University is to actually have what's called an attenuated virus. In this case, a monkey adenovirus. You weaken that virus so that it doesn't cause infection in humans—no illness—but instead that virus is going to express portions of the COVID-19 virus, and again, you hope to create the immune response. So that's an attenuated virus-based approach, and then I'm just trying to simplify probably a very complex field. The other is so-called subunit virus, where you actually take the proteins from COVID-19.

So you take the surface proteins and combine them with another thing called an adjuvant, which really boosts the response, and you hope that that will elicit a strong immune response. This subunit-based approach is largely what we have for many of the vaccines people are used to getting or the attenuated virus-based approach. Other approaches— you could try to weaken the COVID-19 virus itself and provide. So all of these different things are being approached, but the idea of can we elicit a high antibody titer, can we create memory, and importantly, can we do this in a very, very safe way?

Sal: Right. Make sure I understand. So there's at the end of the day, you want to have essentially a low-risk either version or cousin version of the virus or a piece of the virus, essentially of a protein that your immune system can then learn to recognize with antibodies and the memory T cells and all the rest. And there's—you could do that by—I mean you wouldn't insert like an entire RNA of COVID, would you? Or it would be part of the RNA that would produce some of the proteins?

Vas: Yeah, so we only—we only typically insert part of the RNA, usually a coding RNA for one of the proteins. It turns out once RNA gets beyond a certain size, it's very hard to give it in the body and have it be stable long enough to get to the very cells.

Sal: Oh, this is—that’s a good point! So, and so what’s kind of the worst case, I mean, not to scare folks, and I know this isn't like you're—you know, this isn't the focus of Novartis, but you can imagine there's a ton of questions that are coming in for how long do you think this will last? Alina on YouTube is asking. I mean, I'm just curious your views.

Vas: Well, I think from a broader perspective, what's been remarkable to me is the scale of the medical response. When you look at it right now, we have close to 500 vaccines and drugs in assessment—I think close to 5,000 clinical trials in one stage or another—over 10,000 publications. So just like we saw an exponential increase in the virus, we've seen an exponential increase in the response.

We already know, and I think it's underestimated how remarkable it is; we've already discovered one drug called remdesivir, which is an antiviral drug, one steroid that the UK has now identified that already can improve patients' course with coronavirus. I think when many more of these trials read out of drugs that are being studied—we have, I think, 12 drugs being studied right now—you’re going to get a kind of collection of drugs that can enable you to reduce the severity of this disease, and also medical practice is learning so fast.

So that will hopefully give us some time. Then I expect the next, uh, hopefully effective therapies will be so-called antibody therapy. So rather than having the immune system generate a response, you can provide patients who get COVID-19 with antibodies that can hopefully target. There's a number of companies working on that, and all of that I hope will—and I believe, and maybe I'm an optimist as a physician scientist drug developer—that all of that will help us really attenuate or mitigate the overall burden of this pandemic, and that will buy us time to hopefully get the right vaccine.

It is worth noting, we never have still yet to develop a successful vaccine for HIV, which is an ongoing pandemic that started in the early 1980s. There are many viruses which I worked for years on trying to develop vaccines for—something called RSV, which causes a respiratory illness around the world; regular release, another virus called cytomegalovirus. There's a range of viruses that we've been working on for decades, and we were never able to figure out how to generate that strong immune response that we've been talking about, and that's just a dose of realism we have to live with.

Sal: Yeah, so the hope is, you know, the vaccine might take a year, it might take 18 months, it might take two years, but hopefully we get more remdesivir or that steroid-type treatment or other things that make it less scary; could open things up.

I mean, when you look at the, um, the general impact on the ecosystem, you have this question from YouTube: Ariana Christophdolis says, how do you think the pandemic will affect the long-term future of the pharmaceutical industry? Do you think sharing knowledge and science data will be more open within the industry? And I'll add, you know, are there just manufacturing things that we're building capacity to do in the future that will just have a more rapid response? How are you thinking about that? What are you seeing?

Vas: Yeah, I think so—two parts to that question. I think, you know, right now, the level of collaboration has been unprecedented. I co-chair an effort with Bill Gates and the Gates Foundation called the Gates COVID Accelerator. There we have 15 CEOs really sharing compound drug potential, drug libraries, sharing manufacturing capacity. There's two other big collaborations also running—one run by the National Institutes of Health, another informal collaboration. So there's been a pretty remarkable amount of collaboration in the industry, and I think what we're learning from this is there are areas in what we call the so-called pre-competitive space that I think can be a really powerful way to accelerate maybe in the future discoveries for cancer or heart disease; where if there's something, like, for instance, one of the things we collaborate on is how do you get a good animal assay for COVID, so that you know a drug might work in COVID. This sounds obvious, but it's really complicated.

And the more we can share our knowledge, the more—explain what that is. What is this? What is an animal assay?

Vas: So an assay, so what we want to do is, before we go into humans, we want to figure out is a drug active against COVID-19? So we have to take cells from an animal or human thing and what works best. And when we infect them with COVID, and we try to treat the cells with the drug to see if the drug is active. It turns out you can get lots of false positives with this, and how translatable is this into humans? And it seems like such a simple thing, but we've seen an amazing amount of complexity, which then could lead you to spend a lot of time on drugs that probably don't make sense to spend time on or chase drugs that should have been killed in the development process.

So that's one example, a simple example of where we're learning we can collaborate much more. Manufacturing capacity is another, so there's a lot of ways I think we're learning we can collaborate. Now I think for future pandemics, which I think was part of the question, I had the opportunity to lead Novartis's response to the 2009 swine flu pandemic. There, Novartis developed vaccines back then; we developed four vaccines within six months. But that was influenza, and as I mentioned, we could leverage existing technologies. We were able to produce, I think, over 500 million doses of vaccines and adjuvants for the world very quickly.

And it’s interesting; we know what's required, I think, to really manage pandemics. First, there are a series of locations around the world which are well understood, where we know animals and humans interact, and there's the possibility for viruses to move to animals and humans. They're called zoonotic hotspots—they're well mapped—and we can really surveil, do surveillance on these sites if we make the relevant investment.

Then we need to have a lot of transparency to rapidly know when something has jumped into humans, so that we don't lose time. Then we need two other things: we need warm capacity—we call it warm; it's a ready capacity for vaccine and drug production that could be rapidly scaled up. That's one of the challenges right now is we're trying to find enough manufacturing capacity, and we need public health systems that are prepared for these kinds of very rare high-risk events, and that's hard. You have to store personal protective equipment and other things for something that may never come, but when it does come, you’re ready. You have stockpiles ready and you can rapidly deploy them. These were the findings I think after SARS; these are the findings after swine flu; I suspect these will be the findings after this next pandemic.

Sal: No, that's super valuable, and you know, when we're having these interesting conversations, I completely lose track of time; I realize we're already out of time. Well, I mean, any finishing thoughts for—you know, there's a bunch of questions about young people who are interested in career tracks, you know, entering into the pharmaceutical industry. Obviously, y'all’s support for Khan Academy is in that spirit of how do we, you know, have more people be able to enter this clearly very important industry in the world? Any finishing, I guess, advice for young people thinking about careers in pharmaceuticals or biotech?

Vas: Yeah, I think the future in our industry like many industries is going to be continuing to marry different sectors together. So I think drug discovery today is not going to be what drug discovery is tomorrow. I would encourage all of the students listening to learn how to marry data science and technology with biology and chemistry, because so much now our work is shifting in that direction. How can you leverage technology to really speed up a lot of these efforts?

I would say build up also, as I said before, your range of understanding across different disciplines because you don't know where the world will take you. I never wanted to be the CEO, but yet here I am, so I think building range in yourself can help. And that includes—I mean, I'm a big believer in books and philosophy, and I think all of those things can really matter.

And then maybe my last comment I just wanted to add is, I, you know, I believe in this moment in time where we want to build a more equal society, where we tackle topics like structural inequalities and the problem of race in the United States, I think Khan Academy has a remarkable role to play. We know fundamentally educational systems can be empowered by great technology like Khan Academy. So, I learned that—I read a book called “Savage Inequalities” in 1994 talking about the inequities in educational systems in the United States. I firmly believe Khan Academy helps tackle that. So we're proud to be supporters and look forward to the collaboration.

Sal: Oh, appreciate that, and obviously, we agree! Well, thanks so much for taking time out; I'm sure, you know, I can only imagine how busy you are. So this really means a lot. Thank you for your support, and really, I mean that. Why aren’t you on like the news channels explaining about vaccines? Because I feel like we’re not getting that level of depth, so someone needs to give you a call if you have the time!

Vas: Yeah, maybe! Maybe I think maybe I'm too realistic! Maybe you're saying things they don't want to hear.

Sal: Well, thanks so much, Vas, and I hope we get a chance to do this again; this was a real treat!

Vas: Absolutely, take care! Thank everyone for listening!

Sal: Thank you! Well everyone, you know, yesterday someone asked, "What do I learn from these live streams?" or "What have I learned?" I think that was just another good example where, you know, on a book level—and obviously, I've taught on Khan Academy things about immunology and antibodies and T cells—but, you know, just talking to someone who's a real practitioner in the field, who's worked on vaccines, who runs one of the largest pharmaceutical companies in the world, you know, you just learn a whole new level of what's going on in the world.

So hopefully, you enjoyed that as much as I did. I mean, you know, there's some things to ponder—if this whole pandemic was a little bit longer than we might have expected—but hopefully you enjoyed that! I look forward to I'm not sure tomorrow, the day after; I need to look at my schedule. I live my life hour to hour, but I will see you all later this week at the homeroom. See you soon! Stay safe and healthy!