Short Stuff: The Return of Bill Gates!

kind of goes in the end. Well, there's fortunately a lot of different vaccine constructs using uh, most of the

approaches that we know. And as we get these out in larger human studies and eventually have a Human Emergency Youth Thought authorization, we'll start to understand for the various candidates how much they prevent disease transmission, how much they prevent often you get sick, whether they work in the elderly, and what type of duration they have, And so they'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 hast 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 you um brought up though, is that we want like all of these different factors that make basically like a perfect vaccine. Um. 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 that magic perfect vaccine that 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 uh, you know, the US has funded a lot of the R and D. Our Foundation and a group were part of called SEPPI is also funded R and D, but well less than what the US itself has done, and that's got a really good pipeline. You know, the astro Seneca probably will come out first, then Johnson and Johnson,

then Novavax, then Sonofie. Those are the ford that are most promising because they're they're clearly low cost Maderna and Visor in that same time frame, but probably pretty expensive and may only end up being used in rich countries. So that's 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 and gauge what type of responses you're getting there. And I have to say that all these vaccines look pretty good. You know, the Nova vacts which just came

out this week, has the best numbers. But uh, you know, we're this kind of respiratory disease. Protecting your lungs is easier than many other vaccination tasks like malaria or hivar or TV. 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 you 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

her immunity where the total number of cases is very small, pretty quickly, probably adding to the US population to the vaccinated would do that. And so that's you know, seventy million people to be vaccinated, and almost all these vaccines unfortunately going to require two doses, so that's a hundred and forty million doses. The various UH 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 five percent of the world's population, so that's a twenty times harder problem, and the rest of the world is not as rich. 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, uh 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, Uh, that's just billions, So you know, it's it's highly leveraged, uh investment. You you, I mean 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. Um, who can't necessarily afford to throw billions of dollars at

this problem. Um, How 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 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 farmer companies to

sell it for lower no cost to other countries. What's the economic to that. Yeah, Typically the vaccine companies for the poorest countries, developing countries that a group called gobby that we support and the US government other government support it does the bind uh for these poor countries. The vaccine manufacturers agree that they're not getting any profit, nor are they getting any recovery for their fixed costs. Their R and D and trial type costs are just getting

uh close to that marginal cost. And that makes sense because they're 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. Uh. Some of the companies have agreed to make no profits, so when they price to the rich in the middle income, they'll just recover their fixed costs. Uh. And the poor countries. It's just

that that marginal cost. A number of these constructs look like they'll be around two dollars per dose. Uh, perhaps even less. Uh. Yeah, many of these constructs are very productive, including the aDNA virus which is astro Centeca and J and J and the subunit protein which is UH includes

Novavax and the Sonofi approaches. There are a name platform which you can think, I'm kind of leaving that out, you know, in the long rum, 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 port portion of it called the lipid, the costs are still higher than these other approaches. So for the big world, I doubt those vaccines uh, which includes Maderna and Visor Bio and tech, I doubt they'll they'll play much of a role. And what you're talking about just now, you you're talking about

different types of vaccines that are being tested. So there's an RNA vaccine that Maderna is working on that UM has never a vaccine has never been produced using RNA, right, that's right. This would be the first one. Can you can you just talk a little bit about how an RNA vaccine differs from you know, saying a dina virus

vaccine or even a flu vaccine. Well, RNA is the name of these molecules that are like the software code that tell yourselves 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 URNA

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 UH is really brilliant and in the future of vaccines, UH this will be a critical way to bank vaccines because the speed and the cost will get figured out and you'll just

have these general factories. Whether it's UH for malaria, or cancer vaccines, and so it's great Maderna and Byron Tech careback. 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. How closely? And I think the answer I want to hear is that we've never seen a response like this as far as sharing of research. But how closely is the international

research community working together? And have we seen anything like this? No, it's quite novel. Um. And what we're gonna have is the company who invents a vaccine is going to allow other companies to use their factories to do the manufacturer. 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 have 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 onto whichever of the other companies work looks promising and be there to 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 uh, you know, my days are mostly those conversations which everybody has a good attitude. Uh. You know, very few people are being greedy about this, most 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 uh COVID nineteen related. Is that is that naive and foolish or or could this be a good opportunity for something like that? Well, it's a little bit naive, and that the economic comparative of a coronavirus vaccine is a stronger market signal than you've ever seen for any disease.

It's costing economies trillions of dollars. It's you know, the US alone has put out already three trillion and relief money, and they're talking about additional trillions, and so the net gain from being 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, are mostly in poor countries where the rich countries, Like tuberculosis or malaria is basically not seen in any rich country,

so they're the economic comparative isn't great. And that's where our foundation, uh you know, for HIV, we and the U S governments are the big funders. For milaria, we're the big funder. There is no market signal and you know, in a way, it's terrible that this disease hit the rich world, but whatever, somebody in the rich world gets sick. Wow, then uh, you know, resources are put into play in

a way that is you know, just incredible. So, um, I should 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 um, there there's a possibility that some people might feel wariness toward covid um vaccine in particular because everything is is being stepped up as quickly as possible. UM. And one of the things that I've run into is

this idea that um, it might not even work. That you know, sometimes you go in for a flu vaccine and you still get the flu that year. Um. Can you kind of talk about how 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 flues originate, to sample what's there and make a two or three components seasonal flu vaccine, but we often miss the strain that UH is most prevalent during a season, and the way those flu vaccines are made, they're not very effective and elderly people. And that's really bad because the flu mostly kills old people very similar

in the age profile two COVID. And so here we are in the trials for this vaccine making sure it works well and old people, because otherwise the sickness protection thing is almost useless. But flu is very difficult. It's constantly emerging in new forms and reassorting 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. Uh. 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 um 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 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 ramdasevere, which is an anti viral, and Dexi methos on, which was proven out in a trial we funded in

the UK is a immune modulator. There are two other anti virals that are actually as promising as ramdasevere and actually could be used orally, which is much easier. There's monoclonal antibodies where uh dozens of companies are working on that, but Regeneran, Eli, Lilly and Astro Seneca have the three that are leading the way there. And you know, by the time we get more anti virals, monclone antibodies and some improved immune modulators, we could cut the death rate

by eight to nine. And testing therapeutics is easier because you just take a few hundred sick people and if you're going to have substantial results, you you know, a hundred at the intervention a hundred don't uh, you'll see, you know, 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. Great um, Bill, you kind of referenced a point in time that is on everyone's mind, but I think it seems kind of amorphous, which is the point where we have viable vaccine and good treatments. What does the world with coronavirus look like after that, does it just like disappeared, does it hit a reservoir, does it come back seasonally? What? What is what is it going to look like? And then how far off are we from that goal of reaching that that world.

If we get this cheap vaccine um and it's not only safe, but everybody uh 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 uh available even in the developing countries, we can truly

bring this into an end where it won't be coming back. Uh, You'll get rid of all the pockets the disease or in you'll be willing to go to big public events and then will monitor to see if it if something similar is crossing over and catch that very quickly. We might not hang around with bats quite as much uh as we do now. Uh these live markets where uh this crossover almost certainly took place. But you know, I'm spending a lot of time getting the US to provide

money to help buy the vaccine for other countries. Historically, the US has been super generous. You know, we 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 epidemics, 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 you care about human lives, and it's hitting both the hard cases you care about the bottom line. Huh, it's 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, South Korea that did a competent job, even they have found it hard that everybody was coming into the country potentially can start up a chain of infection again. So uh, you know, they're doing great, but they have to keep fighting and fighting and and doing local shutdowns. Whereas if if they the rest of the world had done what they've done, you know, they they

could go and 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 um, 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 uh, and you know, the cross protection from related cornervirces may explain why vietnamal

that 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 uh, you know, making sure the exposures to bats are reduced, it 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 and so we won't suffer from a coronavirus being widespread like this again, we will really have our act together for pretty modest level of resources. Chuck, I have one last question. Do you have any anymore? I got one more, but you go first. Okay, well,

well my bill was um, 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 UM, what I think people are there's like an inherent suspicion or suspiciousness that I think people can can kind of lean towards when they encounter a mind bogglingly wealthy person who um, wants to help eradicate disease around the world and uses

their money for that end. Um, So what is it that that interested you that kind of took you from you know, uh, 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? What? What's the deal? Well, like your listeners, I I'm curious to understand things. And so as I was uh starting to wind down, uh 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? Uh? 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 uh, millions would die of those diseases because they weren't affordable to the poor countries, even though the cost of manufacturer 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 encounterintuitively reduces population growth because parents, when they know their kids are likely to survive, have less children. And so that quest, you know, which involved creating this gobby organization to help buy the vaccines. Overall, the under five death rate has gone from ten percent now down to about five globally, and you know, so that's you know,

that's mind blowing. It was over ten million children here now less than then five million a year, and we have a clear path with a few new vaccines to get down to two and a half million two and a half percent. Uh, and even rich countries are close to one percent. So you're getting pretty close to the kind of equity that any child point anywhere, their life is treated as having value. Now on this journey, you you know, I've gotten to learn about the immune system

and meet great scientists, and so I love the work. Uh, 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 me Linda has been a great joy to me. Uh 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 have you guys been doing? What have you been up to? Well, you know, in a way, Uh, 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 uh at University of Chicago and college and so

you know, lots of family game nights. Uh. 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 becomes 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

rated innovation the software will be up to quite a bit. Uh. 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 there they're the most stuck. They 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. Uh. So you know how once it's all over, we realized, Wow, some of

those trips our time in the office wasn't necessary. That is pretty fascinating that it's really accelerated rethinking office work and business travel. Uh. And you know we really can uh save a lot of the overhead from those things. But you know, I've gotten to read more than normal, uh,

you know, less jet legg than normal. Uh. Any particular books that you've been that you've you've enjoyed most Uh you know, I was just reading Zeke Emmanuel 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 weakness is but has you know big chance to to get better? Um, 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? Uh uh, you know. Thanks for feeding people's curiosity. You guys do a great job. Hey, well, thank you for saving the world from doing a great job too. Well. Since we just made Bill Gates lap,

that's it for short stuff. Everybody's short stuff is out. Stuff you Should Know is a production of iHeart Radio's How Stuff Works. For more podcasts for my heart Radio, visit the iHeart Radio app, Apple Podcasts, or wherever you listen to your favorite shows.