Short Stuff: The Return of Bill Gates!

Our old pal Bill Gates is back for a very special short stuff where we talk all about Covid vaccines and therapeutics.

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Episode Transcript

Speaker 1 (00:04):
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. Uh, thanks for coming back and
joining us, Bill to talk about COVID and vaccines and therapeutics,
and uh, you know, we've got a short window here,
so let's dive right in. And I guess my first

(00:25):
question is, let's just kind a level said 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 uh, most of the
approaches that we know. And as we get these out

(00:45):
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,

(01:05):
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

(01:26):
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

(01:46):
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

(02:08):
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,

(02:32):
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

(02:53):
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

(03:15):
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

(03:40):
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

(04:03):
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

(04:26):
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,

(04:51):
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

(05:15):
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

(05:35):
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.

(05:57):
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.

(06:19):
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

(06:40):
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

(07:04):
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

(07:27):
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

(07:48):
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,

(08:13):
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

(08:35):
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

(08:56):
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

(09:18):
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

(09:40):
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

(10:03):
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

(10:25):
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

(10:45):
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

(11:06):
we will be right back with Bill Gates. How closely?

(11:28):
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

(11:51):
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

(12:15):
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

(12:37):
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

(13:02):
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

(13:25):
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.

(13:50):
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

(14:13):
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

(14:35):
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,

(15:02):
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.

(15:25):
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

(15:48):
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

(16:09):
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

(16:34):
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

(16:55):
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,

(17:22):
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

(17:45):
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

(18:06):
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,

(18:28):
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

(18:52):
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

(19:14):
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.

(19:35):
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

(19:57):
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

(20:20):
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

(20:43):
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

(21:06):
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

(21:27):
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,

(21:47):
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

(22:10):
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

(22:32):
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

(22:54):
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

(23:18):
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,

(23:41):
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

(24:03):
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

(24:26):
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,

(24:51):
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,

(25:13):
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

(25:35):
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

(25:57):
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

(26:21):
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

(26:41):
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?

(27:02):
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,

(27:22):
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

(27:44):
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

(28:06):
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

(28:31):
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

(28:52):
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

(29:14):
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

(29:35):
job too. Well. Since we just made Bill Gates lap,
that's it for short stuff. Everybody's short stuff is out.
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