Stuff You Should Know - Short Stuff: The Return of Bill Gates!

Episode Date: August 12, 2020

Our old pal Bill Gates is back for a very special short stuff where we talk all about Covid vaccines and therapeutics. Learn more about your ad-choices at https://www.iheartpodcastnetwork.comSee omnystudio.com/listener for privacy information.

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Find out how much at Airbnb.ca slash host. Hey, and welcome to the short stuff. I'm Josh. There's Chuck. There's Bill Gates. No time to explain. This is short stuff. Let's get to it. Go. Thanks for coming back and joining us, Bill, to talk about COVID and vaccines and therapeutics. And, you know, we've got a short window here, so let's dive right in. And I guess my first question is, let's kind of level set and find out where we are with vaccines and how it all works with multiple vaccines being worked on and how that kind of goes in the end.

Well, there's fortunately a lot of different vaccine constructs using most of the approaches that we know. And as we get these out in larger human studies and eventually have a human emergency youth authorization, we'll start to understand for the various candidates how much they prevent disease transmission, how much they prevent how often you get sick, whether they work in the elderly, and what type of duration they have. And so there'll be quite a range on those parameters for these vaccines. You know, eventually we want one that's both very good at transmission blocking and preventing sickness and has duration and is cheap so that we get out to a large part of the entire global

population and bring the pandemic to an end. One of the things that you brought up, though, is that we want like all of these different factors that make basically like a perfect vaccine. But I read one of your posts on your Gates notes blogs and you said that that's probably not going to happen right out of the gate. Is there a benefit from having multiple vaccines kind of working in conjunction or is it the best route to just kind of keep going after that magic perfect vaccine that works as close to perfect as we can get? Well, particularly for the developing countries, we won't be able to afford to go out a whole lot of times. And so, you know, the U.S. has funded a lot of the R&D. Our foundation and a group we're part of called CEPI has also funded

R&D, but well less than what the U.S. itself has done. And that's got a really good pipeline, you know, the AstraZeneca probably will come out first, then Johnson & Johnson, then Novavax, then Sanofi. Those are the four that are most promising because they're clearly low cost. Moderna and Pfizer are in that same timeframe, but probably pretty expensive and may only end up being used in rich countries. So that's the, it's a question of affordability, not necessarily efficacy. Yeah, well, of the six, the likelihood that they all work without side effects is pretty low. Now, the phase one studies, that's pretty small numbers and you're not going out to find sick people. But there you can see what the antibody response looks like. And if you use some very

advanced tools, you can look at the other side of the immune system, the T-cell side, and try to engage what type of responses you're getting there. And I have to say that all these vaccines look pretty good. You know, the Novavax, which just came out this week has the best numbers. But, you know, this kind of respiratory disease protecting your lungs is easier than many other vaccination tasks like malaria or HIV or TB. So, I mean, I hate to keep harping on the multiple vaccine thing, but are we looking at a situation in six, eight months to a year where families are going to have to research which one works best or is it sort of a regional availability or monetary availability? How will that work? Well, certainly in the United States, the government

will have a clear opinion about the first one that's rolling out. And, you know, if that first vaccine adds enough transmission blocking, then what you have is you have whatever previous protection we get from other coronavirus family viruses and the immunity we get from the natural infection for this coronavirus plus whoever we vaccinate. And so, between those three, you can get up to herd immunity where the total number of cases is very small pretty quickly, probably adding 20, 25% to the US population to the vaccinated would do that. And so, that's, you know, 70 million people to be vaccinated and almost all these vaccines unfortunately are going to require two doses. So, that's 140 million doses. The various efforts are

building their factories in parallel, at least with the scale for the United States. We're trying to make sure factories get built for the entire world, which is, you know, the US is only 5% to the world's population. So, that's a 20 times harder problem. And the rest of the world is not as rich of getting enough money is very difficult. The US is one of the countries where you could decide to go with the first generation vaccine and then decide that its efficacy was limited enough that you would four months later say, no, now you also need to go and get this vaccine. After all, you know, the economic damage we're trying to put an end to is trillions and trillions. And, you know, making these vaccines and deploying them, assuming there's no side

effects, that's just billions. So, you know, it's highly leveraged investment. You kind of mentioned that, you know, we also need to be focusing on other parts of the world, too, low and middle income countries who can't necessarily afford to throw billions of dollars at this problem. How do we help other countries and other human beings that just don't happen to live in the United States or Canada or the UK or Australia? How do we help them? Is it just a matter of direct aid? Is it a matter of sharing research? Is it a matter of just pumping out a bunch of doses and shipping them over there? Or is it a thing where if we in the United States pay a bunch of money for a vaccine that's going to make it that much more likely for the pharma companies to sell

it for low or no cost to other countries? What's the economics of that? Yeah, typically, the vaccine companies for the poorest countries, developing countries that a group called GOBI that we support and US government, other government support, it does the buying for these poor countries. The vaccine manufacturers agree that they're not getting any profit, nor are they recovering for their fixed costs, their R&D and trial type costs. They're just getting close to that marginal cost. And that makes sense because they're not giving up something they would get otherwise. And so all these manufacturers will have tiered pricing. The price to the rich countries, middle income countries and the poorest countries will be different. Some of the companies have

agreed to make no profit. So when they price to the rich and the middle income, they'll just recover their fixed costs. And the poor countries, it's just that marginal cost. A number of these constructs look like they'll be around $2 per dose, perhaps even less. Yeah, many of these constructs are very productive, including the adenovirus, which is AstraZeneca and JNJ, and the subunit protein, which includes Novavax and the Sanofi approaches. The RNA platform, which you can think I'm kind of leaving that out, in the long run, we're very enthusiastic about that because the speed of development and having generic factories, even when you don't know which pathogen you're going after, will work very well for that. So we've been funding that for about a decade. Unfortunately,

it's in terms of scaling up the manufacturing and a portion of it called the lipid, the costs are still higher than these other approaches. So for the big world, I doubt those vaccines, which includes Moderna and Pfizer, BioNTech, I doubt they'll play much of a role. And what you're talking about just now, you're talking about different types of vaccines that are being tested. So there's an RNA vaccine that Moderna is working on that has never, a vaccine's never been produced using RNA, right? That's right. This would be the first one. Can you just talk a little bit about how an RNA vaccine differs from, you know, say an adenovirus vaccine or even a flu vaccine? Well, RNA is the name of these molecules that are like the software code that tell your cells what proteins

to manufacture. And, you know, so the software idea here is that instead of actually sending the particles for the immune system to recognize and get ready to attack, you actually send some lines of instructions, the RNA, that tell your own cells to make that protein. And then once they make it, then the immune system sees that. And so the amount of RNA you need to send could be way smaller because the instructions are smaller than the actual proteins themselves. Now, we still have to package up the RNA to get it inside the cells, and that creates some cost. That's the so-called lipid. But the basic idea is really brilliant. And in the future of vaccines, this will be a critical way to make vaccines because the speed and the cost will get figured out.

And you'll just have these general factories, whether it's for malaria or cancer vaccines. And so it's great, Moderna and BioNTech, Keirbeck. These are companies that were founded based on using that particular approach. Well, let's take a quick break, everybody, and we will be right back with Bill Gates. Hey, friends, when you're staying at an Airbnb, you might be like me wondering, could my place be an Airbnb? And if it could, what could it earn? So I was pretty surprised to hear about Lisa in Manitoba, who got the idea to Airbnb the Backyard Guest House of her childhood home. Now, the extra income helps pay her mortgage.

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No, it's quite novel, and what we're going to have is, the company who invents a vaccine is going to allow other companies to use their factories to do the manufacture, so we scale up very quickly to this billions of doses. And that's never been done before, and so we're our foundation because we have a lot of that expertise, people who spent their careers at these private sector companies. We're able to broker through our relationships with the companies and the governments how that works. So for example, two of the companies in India have big capacity, but they're unlikely to invent one of these vaccines, but serum and bioe are these two companies,

and so we're giving money to them and making sure the licensing and cooperation is such that they can latch on to whichever of the other companies' work looks promising and be there to make a lot of the volume. So yes, I'm very pleased with the cooperation. We didn't practice for this the way we should have, either the governments or the private sector, but my days are mostly those conversations, which everybody has a good attitude. Very few people are being greedy about this, most are being willing to do things in a very novel, high-speed way. Now, just follow up on that. It seems to me as an optimist that that could present a new way forward for humanity

for things to work together on things that aren't necessarily COVID-19 related. Is that naive and foolish, or could this be a good opportunity for something like that? Well, it's a little bit naive in that the economic imperative of a coronavirus vaccine is a stronger market signal than you've ever seen for any disease. It's costing economies trillions of dollars. The U.S. alone has put out already three trillion in relief money, and they're talking about additional trillions. So the net gain from bringing this epidemic to an end in economic terms is very clear, whereas a lot of the diseases we need vaccines for are just in poor countries,

or mostly in poor countries, where the rich countries like tuberculosis or malaria is basically not seen in any rich country. So there, the economic imperative isn't great, and that's where our foundation for HIV, we in the U.S. governments are the big funders for malaria. We're the big funder. There is no market signal, and in a way, it's terrible that this disease hit the rich world, but whatever somebody in the rich world gets sick, wow, then resources are put into play in a way that is just incredible.

So I feel like I should probably preface this, but there are some people, you may not be aware of this, there are some people who are wary of vaccines, and there's a possibility that some people might feel wariness toward a COVID vaccine in particular, because everything is being stepped up as quickly as possible. And one of the things that I've run into is this idea that it might not even work, that sometimes you go in for a flu vaccine and you still get the flu that year. Can you kind of talk about how that differs and how it would be more effective than say like your average flu vaccine, how the two are different?

Yeah, there's two problems with the flu vaccine. One is that there are multiple varieties of flu that circulate, and as you get into flu season, we try by going to China where most flus originate to sample what's there and make a two or three component seasonal flu vaccine. But we often miss the strain that is most prevalent during the season, and the way those flu vaccines are made, they're not very effective in elderly people. And that's really bad because the flu mostly kills old people, very similar in the age profile to COVID.

And so here we are in the trials for this vaccine making sure it works well in old people, because otherwise the sickness protection thing is almost useless. But flu is very difficult. It's constantly emerging in new forms and re-assorting. This disease, there's one target. The genetic variation is very, very minor. So the vaccine will be able to target every coronavirus that we've seen. And once we get rid of it, it won't be crossing over into humans on a regular basis.

You know, we could go a long, long time before we would ever see it again. And then we'll have surveillance and catch it when it's small numbers. Now, you know, it's important to talk about vaccines. I think that's the sort of carrot dangling in front of the world. But what about therapeutics? I know that's something that we don't hear enough of probably in the news. Where are we with therapeutics and where can we go with therapeutics? Well, the doctors are way better at treating COVID patients now than at the start.

They're not as overloaded. They realize that you don't use the ventilator nearly as much because it has bad side effects. They use oxygen earlier. They use the chrome position. The two drugs that are being used, Remdesivir, which is an antiviral and Dexamethasone, which was proven out in a trial we funded in the UK, is an immune modulator. There are two other antivirals that are actually as promising as Remdesivir and actually could be used orally, which is much easier.

There's monoclonal antibodies where dozens of companies are working on that. But Regeneron, Eli Lilly, and AstraZeneca have the three that are leading the way there. And by the time we get more antivirals, monoclonal antibodies, and some improved immune modulators, we could cut the death rate by 80 to 90%. And testing therapeutics is easier because you just take a few hundred sick people, and if you're going to have substantial results, you 100 get the intervention, 100 don't, you'll see significant variance between those. And so, yes, the death rate will come down quite a bit well before we get the vaccine out in the large numbers

to stop dropping the case numbers. Bill, you kind of referenced a point in time that is on everyone's mind, but I think seems kind of amorphous, which is the point where we have a viable vaccine and good treatments. What is the world with coronavirus look like after that? Does it just disappear? Does it hit a reservoir? Does it come back seasonally? What is it going to look like? And then how far off are we from that goal of reaching that world? If we get this cheap vaccine, and it's not only safe, but everybody knows that it's safe, so they're willing in large numbers to take the vaccine.

And if we get the generosity that the rich countries are, along with our foundation, are funding the vaccine, so it's available even in the developing countries, we can truly bring this thing to an end, where it won't be coming back, you'll get rid of all the pockets the disease are in, you'll be willing to go to big public events, and then we'll monitor to see if something similar is crossing over and catch that very quickly. We might not hang around with bats quite as much as we do now in these live markets, where this crossover almost certainly took place. But I'm spending a lot of time getting the U.S. to provide money to help buy the vaccine for other countries.

Historically, the U.S. has been super generous. We drove smallpox eradication, we fund the polio effort that's near to completion on HIV and malaria, we've been super generous. Here, the leadership has been distracted and not wanting to talk about the epidemic, so we haven't gotten the money yet, but I'm optimistic that'll get solved by the Congress. Because it's hitting both people, it's hitting both the bleeding hearts who care about human lives, and it's hitting both the hard cases who care about the bottom line, huh? It has something for everybody. The humanitarian argument, the strategic argument of not creating a vacuum for China and others,

and the selfish argument of, hey, we don't want it coming back again and again. You know, countries like Australia or South Korea that did a competent job, even they have found it hard that everybody who's coming into the country potentially can start up a chain of infection again. So, you know, they're doing great, but they have to keep fighting and fighting and doing local shutdowns, whereas if the rest of the world had done what they've done, you know, they could go and have their economy in a normal state. Yeah, you know, you mentioned the live markets and the crossover and sort of the problems with that. What does that future look like and what can we do about it as Americans?

Are we working with China? Are they willing to close these things down? Like, how is all that going to work? Yeah, a lot of species of bats are there south of Wuhan, and, you know, the cross-protection from related coronaviruses may explain why Vietnam, although they've certainly done a good job, you know, they just had their first death. And so coronaviruses do come out, and if you're looking with modern tools, you'll see it when the numbers are very small. So those, you know, making sure the exposures to bats are reduced and that the surveillance is very strong, and then once you see meaningful spread, then kicking up a sort of what I call mega-testing diagnostic capability,

that is all very doable, and so we won't suffer from a coronavirus being widespread like this again. We will really have our act together for a pretty modest level of resources. Chuck, I have one last question. Do you have any more? I got one more, but you go first. Okay, well, my bill was, and I'm presuming here, I hope I'm not overly presuming that it's okay for me to call you Bill. Sure. At this point, okay, I probably should have verified that before, but I think people are, there's like an inherent suspicion or suspiciousness that I think people can kind of lean towards when they encounter a mind-bogglingly wealthy person who wants to help eradicate disease around the world and uses their money for that end.

So what is it that interested you that kind of took you from pioneering computers to pioneering eradicating disease around the world? What was that? Was that Melinda's influence? Was that something that you've always been interested in? What's the deal? Well, like your listeners, I'm curious to understand things. And so as I was starting to wind down and spend a little bit less time on my Microsoft work, I was reading, I was thinking, okay, how can I give this wealth back to society? And I was learning about what kills children. And I was stunned that there were diseases that we had solutions for, we had vaccines for, but millions would die of those diseases because they weren't affordable to the poor countries even though the cost of manufacture was very, very low.

And so I saw that Melinda and I could focus on global health and get the death rate down, which amazingly and counterintuitively reduces population growth because parents, when they know their kids are likely to survive, have less children. And so that quest, which involved creating this gobby organization to help buy the vaccines, overall, the under five death rate has gone from 10% now down to about 5% globally. And so that's mind blowing. It was over 10 million children here, now less than 5 million a year. And we have a clear path with a few new vaccines to get down to 2.5 million. So 2.5%.

And even rich countries are close to 1%. So you're getting pretty close to the kind of equity that any child born anywhere, their life is treated as having value. Now, on this journey, you know, I've gotten to learn about the immune system and meet great scientists. And so I love the work, you know, it gives purpose to how we take the Microsoft money and get it back out to the world because we don't need it for our consumption. And, you know, so this work in partnership with Melinda has been a great joy to me. So I guess in finishing up, I mean, you know, you've been pretty busy being Bill Gates superhero during this time. I'm curious though about, you know, you've been locked down like the rest of us.

What's what is Bill Gates human being been doing? Have you had any fun? What do you guys been doing? What have you been up to? Well, you know, in a way, I don't know what the kids think, but we've got more time with our kids than we would have expected, including one that's at medical school, one that's at University of Chicago in college. And so, you know, lots of family game nights, you know, I'm using the team software from Microsoft and zoom and some of the others. And so I'm giving a lot of feedback to the Microsoft team that now this this has become so mainstream. Let's make it easy to take notes and review the slides and search through a previous meeting to see what was done. You know, so the rate of innovation on the software will be up quite a bit.

You know, it's been simple for me to meet with leaders because they don't expect to show that you're serious that you have to fly all the way there. And even for these African leaders, they're they're the most stuck there have to fly to the US and fly to Europe. So they're they're able to stay in their countries and get more of their work done. So, you know, how once it's all over, we realize, wow, some of those trips are time in the office wasn't necessary. That is pretty fascinating that it's really accelerated rethinking office work and business travel. And we really can save a lot of the overhead from those things. But, you know, I've gotten to read more than normal, you know, less jet lag than normal. Any particular books that you've been that you've enjoyed most?

You know, I was just reading Zeke Emanuel has one about which is the best health system in the world that does a good job of talking about the strengths and weaknesses. You know, where the US has a lot of weaknesses, but has, you know, big chance to to get better. Well, we're working on a stuff you should know board game bill. So we'll make sure the Gates family gets one. Fantastic. I'd love that. Maybe even signed. All right.

Chuck, you got anything else? I got nothing else. Thanks a lot, sir. It's great talking to you again. Yeah. Thank you, Bill. But wait, Bill, do you have anything else? No.

Oh, good. You know, thanks for feeding people's curiosity. You guys do a great job. Hey, well, thank you for saving the world. You're doing a great job, too. Well, since we just made Bill Gates laugh, that's it for short stuff, everybody. The short stuff is out.