The following is a conversation with Vincent Reconyello,
professor of microbiology and immunology at Columbia.
Vincent is one of the best educators in biology
and in general that I've ever had the pleasure
of speaking with.
I highly recommend you check out his This Week
in Virology podcast and watch his introductory lectures
on YouTube.
In particular, the playlist I recommend
is called Virology Lectures 2021.
To support this podcast, please check out the sponsors
in the description.
As a side note, please allow me to say a few words
about the COVID vaccines.
Some people are scared of a virus hurting or killing
somebody they love.
Some are scared of their government betraying them,
their leaders blinded by power and greed.
I have both of these fears.
And two, I'm afraid, as FDR said, of fear itself.
Fear manifests as anger and anger leads to division
in the hands of charismatic leaders
who then manufacture truth in quotes
that maximize controversy and a sense of imminent crisis
that only they can save us from.
And though I'm sometimes mocked for this,
I still believe that love, compassion, empathy
is the way out from this vicious downward spiral
of division.
I personally took the vaccine based
on my understanding of the data,
deciding that for me, the risk of negative effects
from COVID, short-term and long-term,
are far worse than the negative effects
from the mRNA vaccine.
I read, I thought, I decided, for me.
But I never have and never will talk down
to people who don't take the vaccine.
I'm humble enough to know just how little I know,
how wrong I have been and will be
on many of my beliefs and ideas.
I think dogmatic certainty and division
is more destructive in the long term than any virus.
The solution for me personally, like I said,
is to choose empathy and compassion
towards all fellow human beings
no matter who they voted for.
I hope you do the same.
Read, think, and try to imagine
that what you currently think is the truth
may be totally wrong.
This mindset is one that opens you
to discovery, innovation, and wisdom.
I hope my conversation with Vincent Racaniello
is a useful resource for just this kind of exploration.
He doesn't talk down to people
and he's the most knowledgeable virologist
I've ever spoken to.
He has no political agenda,
no desire to mock those who disagree with him.
He just loves biology and explaining
the fundamental mechanisms of how biological systems work.
That's a great person to listen to
and learn from with an open mind.
I hope you join me in doing so
and no matter what, try to put more love
out there in the world.
This is the Lex Friedman podcast
and here is my conversation with Vincent Racaniello.
You mentioned in one of your lectures on virology
that there are more viruses in a liter of coastal seawater
than people on earth.
In the Nature article titled,
Microbiology by Numbers,
it says there are 10 to the 31 viruses on earth.
Also it says that the rate of viral infection
in the ocean stands at 10 to the 23 infections per second.
And these infections are moved 20 to 40%
of all bacterial cells each day.
There's a war going on.
Do you, what do you make of these numbers?
Why are there so many viruses?
So the numbers you're quoting,
they're in my first virology lecture, right?
Cause people don't know these numbers
and they get wow, they get wowed by them.
So I love to give them.
Sorry to interrupt, but as I was saying offline,
you have one of the best introductory lectures
on virology that I've ever seen,
introductory lectures periods.
I highly recommend people find you on YouTube and watch it.
If you're curious at all about viruses,
it, yeah, there's a lot of times throughout watching it,
I felt like, whoa.
Yeah, that's my goal is to,
and that's what my students tell me.
One student once said, every day after every lecture,
I could go home and tell my roommate something
she didn't know and blew her away.
So the number of viruses is really an amazing number.
So that number 10 to the 31 is actually
just the bacterial viruses in the ocean.
So there are viruses that infect everything on the planet,
including bacteria, there are a lot of bacteria in the ocean.
And so 10 to the 31 is from basically particle counts
of seawater all over the world.
So there are more viruses than 10 to the 31,
but just in the ocean.
And that number is so big.
First of all, the mass exceeds that of elephants
on the planet by 1,000 fold.
And if you lined up those viruses end to end,
they would go 200 million light years into space.
It's so big a number, it's amazing.
And then yes, 10 to the 20 some infections per second
of these viruses killing bacteria
and releasing all this organic matter.
And that's part of this,
what we call the biogeochemical pump,
cycling of material in the ocean,
the bacteria die, they start to sink
and then they get metabolized and converted
to compounds that are needed.
A lot of it gets released as carbon dioxide and so forth.
So these are actually really important cycles
that are catalyzed by the virus.
Well, it's so wild that nature has developed
a mechanism for mass murder of bacteria.
That's one way to look at it,
but it's just what happened, right?
It's interesting.
I mean, I wonder what the evolutionary advantage
of such fast cycling of life is.
Is it just an accident of evolution
that viruses are so numerous?
Or is it a feature, not a bug?
So the fast is, it does not all fast,
not all viruses are fast.
Some are 20 minutes per cycle,
some take weeks per cycle.
But that's just per second.
There's so many viruses in the ocean
that that's what you get per second,
no matter how fast the cycle is.
But I look at it this way.
Viruses were probably the first organic entities
to evolve on the planet.
Long ago, billions, billion years ago,
just as the earth cooled and organic molecules began to form.
I think these self, we call them self replicators.
They're just short things that today
would look like RNA,
which is the basis of many viruses, right?
They evolved and they were able to replicate.
Of course, they were just naked molecules.
They had no protection.
And it was just RNA based.
And that's tough because RNA is pretty fragile
in the world and it probably didn't get very big
as a consequence.
But then proteins evolved
and I'm skipping like hundreds of millions of years
of evolution, proteins evolved,
maybe without a cell, maybe with a cell.
But then to make a cell,
there probably were some RNA based cells early on,
but they were pretty simple.
But the cells that we know of today,
even bacteria and single cell eukaryotes,
they have very long DNA genomes.
And you need a lot of DNA to make a complicated cell.
And so we think at some point, the RNA became DNA
and probably one of the earliest enzymes that arose
is the enzyme that could copy that RNA into DNA,
which we now know today as reverse transcriptase,
which my former boss, David Baltimore
and Howard Timmons had co-discovered.
And that enzyme arose and copied RNA to DNA
and then you could build big cells because DNA
can be millions and millions of bases in length.
And RNA, the longest RNA we know of is 40,000 bases,
not much bigger than the SARS-CoV-2.
What would you say is the magic moment along that line?
I saw it was one or two billion,
maybe three billion years it took
to go from bacteria to complex organism.
Like it seems like Earth had a very long time,
like not a very long time without life.
And then a very long time with very primitive life.
Maybe I'm discriminating, calling bacteria primitive life.
People would object to you, doing that for sure.
But it seems like complex organism,
when it starts becoming something like,
I don't know what's a good, not animal like,
but more complexity than just like a single cell.
What do you think is the magic there?
What's the hardest thing?
If you were trying to engineer Earth and build life
and build the simulations,
obviously we're living in a video game, what this is.
So if you were trying to build this video,
what's the hardest part along this evolution path?
So bacteria are mostly single cells.
They do make colonies, they get together in biofilms,
which are really important,
but they're all single bacteria in that.
And the key is making an organism
where cells do different things.
We have skin cells and eye cells and brain cells.
Bacteria never do that.
And the reason is probably energy.
Bacteria can't make enough energy to do that.
And so there was another cell existing at the time,
the archaea.
And the idea is that a bacteria went into an archaea
and became the modern day mitochondria,
the energy factory of the cell.
And that now led that cell develop
into more and more complicated organisms like we have today.
It was all about energy.
So the mitochondria, the energy,
the mitochondria is the magic thing.
I think so.
It's actually not my idea, it's Nick Jones.
Have you heard of Nick Jones?
He's an evolutionary biologist in the UK.
And he's done experimental work on this.
And it's his idea that the defining point was
the ability to make a lot of energy
which a mitochondria can do.
It's basically a whole bacteria inside of a bigger cell
and that becomes what we now call eukaryotes
and that they can get more and more complicated.
So let me bring you back to the viruses.
I wanna finish that story.
Yeah, which points of virus has come along?
So remember, we have these precellular,
they're called precellular replicons, right?
And so we have a precellular stage
where we have these self replicating molecules
and cells arise and then the self replicating molecules
invade the cells, why?
Because it's a hospitable environment.
I mean, they didn't know that.
They just went in and it turned out
it was beneficial for them, so it's stuck.
And they replicate inside the cell now
where they have pools of everything they need.
They get more and more complicated
and then they steal proteins from the cell
to build a protective shell.
And then they can be released as virus particles
are now protected, they can move from host to host.
And because they're at the earliest stages of cellular
evolution, they can diversify to infect anything
that arises.
And that is why I think there's so many of them
and everything on the planet is infected
because the ancestor of everything
was infected many years ago.
So it's easier to steal than to build from scratch.
So like it's easier to sort of break into
somebody else's thing and steal their proteins.
Yes, my colleague, Dixon de Palmier calls viruses safe
crackers.
Safe crackers.
So it's just, from an evolutionary perspective,
it's easier to steal because you can select.
But then you have to figure out mechanisms for stealing,
for breaking into, for cracking the safe.
Well, you don't have to figure out, it just happens, right?
Because molecules are so diverse
that a molecule gets into a cell.
And if there's a protein that sticks to it,
it's gonna stick and that gives an advantage.
There's no, you know, there's no planning,
there's no thinking about it, right?
It just happens.
Oh, we'll return to that.
What, but these numbers are crazy.
So what, as these more complex organisms evolved,
let's take us humans as an example,
should we be afraid of these high numbers?
Should we be worried that there's so many viruses
in the world?
But to a certain extent, I mean, they have, it's twofold.
They're good and bad, right?
Viruses are no, there's no question they can be bad.
We know that because they've infected
and cause disease throughout history.
But we're also, you and I are full of viruses
that don't hurt us at all and probably help us.
And every organism is the same.
So they are clearly beneficial as a consequence.
So I think, so every living thing on the planet
has multiple viruses infecting.
Everything you can see.
And most of them, I think we don't worry about
because they can't infect us.
They're unable.
In fact, now you could actually,
you can actually take your feces and send them to a company
and they will sequence your viruses in your feces for you.
Your fecal viral, right?
And the most common virus in human feces
is a plant virus that infects peppers.
It's called pepper model mosaic virus.
And that's cause people eat a lot of peppers.
And it just passes right through you.
Cabbage is full of viruses from the insects
that walk on the cabbage in the fields.
We eat them, they just pass us.
So I think most of the viruses we don't need to worry about
except when we're talking about species
that are closest to us, mammals, of course.
I think the most numerous ones are the most concerning.
They're viruses like bats, bats are 20% of mammals
and rodents are 40% of mammals.
And we humans live nearby, right?
And we know throughout history,
many viruses have come from bats
and from rodents to people.
No question about it.
So there's a proximity in terms of just living together
and a proximity genetically too.
So it's more like that a virus will jump from a bat
and a rodent.
And birds too.
Birds can give us their viruses that's happened.
Influenza viruses come from birds mainly.
So I think those are the three species,
not species, it's higher than species obviously,
but those are the three I would worry about
in terms of getting their viruses.
And we don't really know what's out there, right?
We have very little clue about what viruses.
And I've for years wanted to capture wild mice
in my backyard and see what viruses they have
because no one knows.
And it's an easy-
We can't ask them.
So you mean map, like is there a way to ask them?
No, I would have to sacrifice them
to take tissue and then bring it in the lab
and do genome sequencing.
So you can do a thorough sequencing
to determine your viruses.
Is there a sufficiently good categorization of viruses
where you'd be-
That's a very good question.
So whenever you do sequence, right?
You get some environmental sample
and you extract nucleic acid and you sequence it.
What you do is you run it past the database.
The gold standard is the GenBank database,
which is maintained here in the US.
And you see if you get any hits.
And then you can say,
ah, look, this sequence is similar to this virus.
And you can classify all the viruses you see.
The problem is 90% of your sequence is dark matter.
It doesn't hit with anything.
It's probably a lot of it is unknown viruses.
And that's gonna be hard to figure out
because someone's gonna have to go after it
and sort it through.
So yes, you can find a lot of viruses.
And the numbers you get are astounding.
You can find thousands of new viruses
just by looking in various life forms.
But there are many more that we don't pick up
because they're not in the database.
Maybe this is a good time to take a quick tangent.
What do you think about AlphaFold too?
I don't know if you've been paying attention to that.
With them deep mind solving the protein folding problem.
And then also releasing,
first of all, open sourcing the code,
which is for me as a software person, I love.
And then second of all, also making like $300,000
in predictions or something like that
for different protein structures and releasing that data.
On the side of, because you're saying there's dark matter.
Is there something, first, what are your general thoughts,
level of excitement about their work?
And second, how can that be applied to viruses?
Do you think we'll be able to explore the dark matter
of virology using machine learning?
Yeah, absolutely.
Because in all this dark sequence,
you can translate it and make a protein.
You can see what a protein looks like.
It has what we call an open reading frame, right?
A start and a stop.
And right now it's just a bunch of amino acids.
But if we could fold it,
maybe the fold would be like something we already know.
Some protein fold, which gives you a lot of clues, right?
Because there are only so many protein folds in biology.
And that dark matter is probably one of them.
So I think that's very exciting because for years,
I followed structural biologists for years.
And in the beginning,
we couldn't even solve structures of viruses.
They're too big.
We could do small molecules like myoglobin.
That was the first one done, took years to do that.
Then as computational power increased,
then they could start to do viruses.
But it took a long time.
X-ray crystallography,
depending on getting crystals of the virus, right?
And now we can do cryoelectron microscopy,
which is much faster.
You could solve a spike of SARS-CoV-2
was solved in two months by Jason McClelland here
in Austin actually at the beginning of the pandemic.
But you're limited.
You can't do huge proteins.
You can only do moderately sized ones.
So, or actually you can do viruses,
but you can't do small proteins.
So that's speeded it up, but it's still too fast
to solve, you get a new protein,
you wanna solve its structure.
So if we could predict it,
and I know from talking to structural biologists,
this has been their holy grail from day one.
They wanna be able to take a sequence of a protein,
put it in a computer and have the structure put out
without having to do all the experiment.
So that's why this is very exciting
that you can predict it.
That mean it's not finished, obviously,
and there's more to do.
But I think it will be a day
where you could take any amino acid sequence
and predict what it's gonna look like.
See, but aren't structural biologists gonna get greedy?
So once you have that,
don't you wanna go more complicated then?
Don't you wanna go,
because that's just the first step, right?
To go from amino acid to structure,
and there's multiple protein interactions.
How do you get to the virus?
Well, so that's what the ultimate goal
of getting a structure is,
that then you can do experiments
and figure out what the structure means, right?
So many, in the old days, structural biology
was a career in itself.
You worked with people who had a system
and just solved proteins for them,
and then you moved on to another one.
You didn't really do any experiments.
The other people got to do
all the interesting experiments.
Now, young structural biologists are multifaceted.
They solve the structure,
and then they say,
what happens if we change this amino acid?
Oh, look, it blocks binding to the receptor.
This must be the receptor-binding interface.
So that's the exciting stuff,
absolutely, is doing the experiment.
Well, I wonder if you can do some kinds of simulations
of different proteins or multi-protein systems
going to war against each other.
Like, to try to figure out,
reinforcement learning is used in AlphaZero,
for example, to learn chess and go,
and that's using the self-play mechanism
where the thing plays against itself.
Sure.
And learns better and better.
Whether you can,
I wonder if you can simulate almost evolution in that way
for primitive biological systems,
have them in simulation, fight each other,
and then see what comes out,
like a super-dangerous virus comes out,
or super, like Chuck Norris type of thing
that defends against the super-dangerous virus,
and it's all in simulation.
So an example would be,
we have all these variants of SARS-CoV-2 arising, right?
Which look to be selected by immune responses.
But we know what amino acids are changing in the spike,
and how they block antibody bonding.
You could simulate that.
You could say, what is the antibody looking at?
Where antibodies bind on proteins are called epitopes, right?
You could map them all and change them in a simulation,
one by one, and go back and forth
between the antibody and the virus.
So all these, evolution is what we call an arms race, right?
The virus changes, and then it evades the host,
and then the host can change.
The host takes longer to change, though, unfortunately.
It takes geological time, but it can,
and then the virus can change,
and it can go back and forth,
and we can see evidence of this in genome sequences
of both viruses and their hosts.
And so you can take a protein in a host
that is a receptor for multiple viruses,
and you can see all the impacts of virus pressure on it,
and you could simulate that for sure.
And that's just one thing that you could do.
You could simulate changes in, say, an enzyme
that makes it resistant to a drug,
and predict all the drug resistance.
But the problem is, people like me,
the experimental virologists,
don't know how to do any of that,
so we need to collaborate with people, I guess.
All with other humans.
We do that, we do that.
But with people from a field that we're not used to,
I suppose people who, would it be AI, I suppose?
Yeah, machine learning people.
Machine learning people, and you would say,
look, this is the biological problem.
Is there a way we can use your tools to attack it?
The problem is those people are antisocial introverts
that have a place like this
and try to hide from other people in the world.
Very difficult to find in the wild.
Okay, so outside of doing amazing, brilliant lectures online,
you host and produce five, I would say, related podcasts,
including my favorite this week in virology,
also this week in parasitism,
this week in microbiology, and so on.
So you're a good person to ask,
what are the categories of small things,
small biological things in this world that can kill you?
Kill us, humans.
You said like most viruses are friendly,
or at least not unfriendly,
but let's look at the unfriendly ones,
in viruses and bacteria and those kinds of things.
When you look at the full spectrum
of things that can kill you,
can you kind of paint a brief picture?
Yeah, I think the big picture is that
the things that can kill you are a minority
of everything that's out there.
And we're talking about molecules.
So we have in us proteins that can kill us,
prions that are just, it's a protein in us,
and if it misfolds,
it makes all of its other copies misfold,
and then you die of a neurological disease.
That's pretty rare.
So there are proteins that are viruses,
and as I said, only certain ones can kill us,
but even if we get those from animals,
it's not straightforward.
If you look at SARS-CoV-2,
this is probably a once in a hundred year pandemic,
I would say, equivalent to 1918 in its devastation,
and in between there have been smaller pandemics
of other viruses, but it doesn't happen all that often.
So we have a lot of viruses,
we have a lot of bacteria of various sorts
that can cause infections in us,
and it's a limited number, right?
You're streptococci and staphylococci and clostridia,
we could go on and on,
but we know how to handle those as long
as we have antimicrobials,
it's just that we abuse them and we get resistance,
so that can be a problem.
Then we have fungi, not mushrooms,
but much smaller fungi that multiply the submicroscopic
or just at the microscopic level,
they can, in dry climates of the US,
you can inhale their spores,
and they can grow in your lung
if you're immunosuppressed and so forth.
So those are the tiny guys,
and then we have parasites,
which we do this week in parasitism,
where single cells, even worms of various sorts,
can invade you and cause all sorts of problems.
How, I was kind of terrified to listen to that podcast.
What's it like?
Well, I mean, what you learn is that you can,
you travel somewhere and you can get infected
and bring it back home.
Yes.
In the US, we do have certain kinds of parasites,
but because of our lifestyle,
we more or less have avoided them.
For example, there is a parasite called toxoplasma,
which is infected most of the world, actually,
because a lot of people like to eat raw meat,
and you would get it from raw meat,
and we're not as fond of that here in the US.
We like to cook our meat,
but that could be a consequence of eating raw meat.
Is that what leads to what is it called, toxoplasmosis?
Yeah, so toxoplasmosis,
it's mainly a big issue is if you're pregnant
and you get toxa, then your fetus
is gonna be very badly malformed.
It's gonna have brain defects and so forth,
and animals can get it as well.
So there are a lot of parasites of that nature,
which you often acquire by food,
eating food of different sorts,
and it usually happens elsewhere.
We just, on this week in parasitism, we do a case.
So Daniel Griffin is a resident physician.
He's a doctor, a real doctor, right?
And every month, he comes up with a case.
Okay, this is a person I saw.
And last month, this young lady had traveled somewhere
and she ate raw fish.
It was somewhere Southeast Asia or something,
and she ended up with red bumps all over her skin,
and it turned out it was a parasite from the fish
that moved around in her.
And very easy to cure.
We have the right doctors and the right drugs,
you can cure all these.
What about diagnosed, like connect the red spots
to the fact that it's a parasite?
Very easy if you have the right diagnostics.
Now Daniel often goes to parts of the world
where they don't have diagnostics,
and he has to use other mechanisms.
He may have to take a bit and look under a microscope,
and then he may not be able to get the drug
depending on where he is.
But often he sees patients who come back to the US
and they get diarrhea or they have a fever,
and he said, where have you been?
And he can put two and two together.
And so we let our listeners do that,
and they all send in guesses,
and it's wonderful to hear them go through this.
So there are a lot of parasites
that can get you.
You have to be careful about eating when you go overseas.
And water too?
Water as well.
And in parts of Africa, there are parasites in the lakes,
and if you go swimming, they can invade you.
And in fact, they can go into your hair follicles
and burrow in and get into your bloodstream.
That's exciting.
So Daniel is interesting,
because he's very adventurous,
and he's not afraid of any of this.
So there's a famous lake in Africa, Lake Malawi,
which harbors a lot of these parasites.
And he said, oh yeah, yeah, I just make sure
I towel off vigorously when I get out.
And get rid of them.
And that was the name of an episode.
But food is-
Towel off vigorously?
You know, sushi, you can get worms from sushi.
And the solution is to freeze it.
And many sushi restaurants now have liquid nitrogen.
They snap freeze their sushi,
and that kills all the parasites.
And a study was actually done in Japan
showing that freezing does not alter the taste of sushi
because it's up here, you see a big industry there.
Wow, that's brilliant.
That's brilliant.
Yeah, I was thinking about,
you know, I'm so boring and bland
that especially when I'm now in Texas here
and I've been eating quite a bit of barbecue,
I realized I really haven't explored the culinary world.
And I've been curious to travel and taste different foods.
Is there something you can say by way of advice?
You know, channeling Daniel, I guess.
If you were to travel in the world,
if eating is the thing that gets you the parasites,
what's the good advice for eating
in strange parts of the world?
Mongolia, India, China,
is there something you could say by way of advice?
I think Daniel would say,
make sure your food is cooked, right?
Cooked, but that's so boring.
Yeah, it's unfortunate.
And he would agree with you
because, you know, many vegetables are delicious.
Salads even are delicious, not cooked,
but they can have parasites in them.
Meats, fish, people like to have uncooked fish.
So if you want to be really safe and boring,
just make sure everything is cooked.
Now we have a case this week on TWIP,
of a young man who went, I forgot where he went,
but he stayed in a hotel.
I think he, oh, Oaxaca, Mexico,
stayed in a hotel.
And he came back with diarrhea and fever.
And he said, I don't know where I stayed in the hotel.
I just ate hotel food, lots of vegetables and fruits.
And probably they weren't washed with clean water, you know?
He got something from that.
The bottom line is most of these infections
with parasites can be diagnosed,
and you can be treated and you'll be fine.
So if you really want to experience the cuisine,
I don't think you should worry about it.
That's what Daniel would say.
Let's return to the basics.
We can then jump around all over the place.
What are the basic principles of virology?
Maybe a good place to start is, what is a virus?
That's great.
I mean, I talk in my first lecture for 20 minutes
before I get to that.
But, and I wonder if I should put it up front,
but it's kind of a boring definition.
So if you do that, first people will turn off.
So first you tell them about all the millions and billions
of viruses around.
So a virus, we have a very specific definition
because it's different from everything else on the planet.
Because first of all, it's a parasite.
Parasite means you take something from someone else.
We have human parasites who take money from others, right?
But in biological terms, a parasite
takes something from the host that the host would otherwise
use energy or some building block or something.
There's never really a symbiotic relationship
between a virus and a host.
Well, there can be.
So that's the dichotomy, I think, is that we define them
as parasites.
Yet, I just told you 20 minutes ago that many viruses
are probably beneficial.
So I think what it means is we, at some point,
we're gonna have to change our definition, right?
Because after all definitions we make are just constructs
that make it easier for us to study,
that not necessarily represent what's right.
Yeah, like Pluto was a planet at first,
and now it's not a planet anymore,
and a lot of people are very upset.
But it's only according to us.
There may be another race living somewhere else
who thinks it's a planet, right?
Well, maybe that's why viruses are attacking humans.
They're very angry, they weren't calling them parasites.
So right now our definition includes parasite
because a virus cannot do anything without a cell.
If this mug were full of viruses,
it would not do anything for years.
It would eventually probably lose its infectivity,
but it's not gonna reproduce here, it needs cells.
And to the first people who discovered viruses,
that was astounding that they didn't just reproduce,
divide on their own like bacteria.
So a virus needs to get inside of a cell,
inside the cell, it can't just hang around on the surface.
It needs to get in in order to make more of itself.
And so we call it an obligate intracellular parasite
because it needs to get in a cell,
and then it takes things from the cell
in the form of all kinds of molecules and processes
and energy and so forth to make new viruses.
Obligate means it's obligated to be inside the cell.
Absolutely, it will not reproduce outside of the cell.
So this mug of viruses can in no way be living,
in my opinion.
However, once it gets inside of a cell,
now the cell is a virus infected cell, it's alive.
So a virus in my view has two phases, right?
It's this non-living particulate phase
that everyone is used to.
I'll send you, you need a virus for your table.
I'll send you a nice model.
I think it would look good here.
Yes, definitely.
You don't have to go with all this other stuff.
Yeah, well, these are all mechanical,
there's no biology here.
So you wouldn't want a virus here?
No, I'd want a virus, of course.
No, I'll send you one, and then you can look at it.
Because now that we have the three-dimensional structure
solved by structural biologists, we take the coordinates
and we put it in a 3D printer
and you can make amazing models, right, of any virus.
And so there's a huge variety of viruses.
Huge, that we know of,
which is only a fraction of what's out there.
What's the category?
So there's RNA, there's DNA viruses, what are those?
What's DNA and RNA?
Two broad categorizations, RNA,
and these are genetic material.
It can be two different chemicals.
So RNA, everything else on the planet besides viruses
is all DNA-based, UNI are DNA-based.
Everything on the planet today is DNA-based,
except some viruses are RNA-based.
And that's because, as I mentioned earlier,
the first life that arose on the planet was RNA-based.
Yeah, so these are like old-school viruses.
These are old-school, we call relics, yeah.
Relics, and this has got a name,
it's called the RNA world, which I think is great.
Is it big still, or are they out of the relics dying out?
Oh, no, the relics, in my opinion,
are the most successful viruses, the RNA viruses.
And SARS-CoV-2 is an RNA virus.
We can talk about why they're so successful.
But you have broadly speaking viruses with RNA,
genetic information, which are relics.
Of course, they're contemporary.
They have adapted to the modern world
and the modern organisms living in it.
And then we have DNA-based viruses,
which are extremely conservative and slow.
They're very successful.
Everyone has a herpes virus infection,
but they don't get the news like the RNA viruses do,
the HIV's and the influenza viruses
and the SARS-CoV-2 viruses.
They get all the press in their RNA-based
because RNA lets you change more so than DNA.
So they evolve much faster, the RNA viruses?
Much faster.
And in fact, when I have an electron evolution,
I don't know if you've listened to that when you should,
it's really, I think it's really interesting.
RNA viruses exist at their error threshold,
which means they can't make any more mutations
when they reproduce, otherwise they're dead.
They would go extinct.
They're evolving at their error threshold.
DNA viruses are hundreds of times lower
than their error thresholds.
And we know this, we can do an experiment to find that out.
Now, why that is is a good question.
But that's the reason why RNA viruses
are far more successful.
They, in fact, many more hosts
and they're very, I would say, slippery.
They can change hosts really quickly
because in any animal, harboring an RNA virus,
like let's say a bat in some cave somewhere,
it's not just one genome.
It's millions of different genomes of all kinds,
all within the framework of say, coronavirus,
but they're all different.
And one genome in there might just be right
for infecting a person if it ever encountered that person.
I mean, that's the thing that-
Or there could be a large number.
This is a tiny fraction, but a large number of them.
And they're all operating at the threshold of error.
That's fascinating.
It's like little startups, little entrepreneurs,
like a startup world.
Yes, and many of them fail.
Yeah, many of them fail.
And then there's the DNA viruses that are like the IBM
and the Google, the big corporations
that become conservative with the bureaucracies
and all that kind of stuff.
So they-
They have a lot of baggage.
Yeah, it's expensive for them to reproduce.
Yeah, and they don't move quickly.
Yes, the RNA viruses are the fast-moving members.
So that's what a virus is.
We call them obviously intercellular parasites.
And then I told you there's DNA and RNA,
but then let's go further.
The nucleic acid's not naked
because naked nucleic acid in the world isn't good.
I mean, it existed in the precellular world,
but there probably weren't a lot of threats to it then.
Naked nucleic acid doesn't last long in the environment.
So they're covered.
The nucleic acid is covered.
It can be covered with a protein shell,
a pure protein shell,
or it can have a membrane around it,
which would be lipids from the host cell.
So lipids, so it's fatty membrane.
Fatty membrane.
So our cells are coated with fatty membranes, right?
Our cells, the outer plasma membrane, right?
That's the same.
The viruses can be too.
So they're kind of like cells,
but without the ability to do the mitochondria stuff.
Some are, they don't have nuclei,
they don't have mitochondria,
but they do have a nucleic acid, they have a membrane,
and then of course, there are spikes in the membrane
that allow them to attach to cells.
And so that completes our two different kinds.
So they all have like attachment mechanisms,
like ways to like keys into the cells.
They all have to get into cells.
There are a couple of exceptions though.
There are viruses of fungi and plants.
So let's do the fungi.
Fungi would be like yeast.
The yeast cell wall is pretty hard to get through.
So viruses typically don't attach to a yeast
and get inside, rather they just live in the yeast forever.
And they multiply as mostly nucleic acids,
and as the yeast divide, they go into the daughter cells,
and that's how they exist.
Plant viruses, also the plant cell wall
would be very hard to get across
with by binding a protein.
So plant viruses get into plants
either by pests that inject them in.
They're sucking sap out
and they inject virus at the same time,
or farmers, they have contaminated farm equipment
and they roll over the plants and introduces viruses.
So those fungi and plant viruses,
they don't have this specific receptor binding
to get them into the cell,
but everything else, yeah,
the virus binds to something on the surface,
very specific, it's taken into the cell,
because that's what cells do.
When things bind their exterior, they take it in,
because in most cases it's good, it's something they need.
And so the virus slips in,
I guess you'd call that a Trojan horse, right?
Trojan horse, it's so hard to not
anthropomorphize this whole thing.
It is hard.
So obviously they don't know any of this.
It's not an actual Trojan horse.
So they're not getting actually tricked
in the way humans trick each other.
No, it's all passive.
And it's just through so many years of evolution,
it's you select something that works and it continues.
And what survives then goes on
with a perhaps a slightly different approach.
I love this idea of passive.
Of course, according to Sam Harris,
so for my sufficiently intelligent alien civilization,
observing humans, our behavior might seem passive too,
because they understand fully exactly what we're doing.
And then there's no free will
and we're all just operating in the same way a cell does,
but just a much higher level of complexity.
Yeah, so I love the distinction between active and passive.
I mean, the point is,
I think anthropomorphizing to a certain extent is fine,
because it helps people understand.
But when you start to say,
I think the virus is doing that
because then you're putting a human lens on it
and you may be wrong.
Because you don't know why things happen for a virus.
So right now we have variants emerging and people say,
well, I think it's because the antibodies
are selecting for variants.
That's a good idea,
but it may not be the only thing that's going on.
You start imagining them coming to the table negotiating.
Yeah, you get into trouble with that.
That's why I tell my students,
be careful about the anthropomorphizing,
because you're gonna apply your values to a virus
and you have different value, you're a human,
and what you think is the reason
for this outcome may not be right.
That's all, just be open-minded about it.
In both directions.
I actually, one of the things that pushed back
on this in the space of robotics,
people, most people in robotics
try to not anthropomorphize.
For example, they don't give a gender or a name to robots.
They really try to see it as a machine.
And to me, that makes sense in one way,
but it totally doesn't make sense in another.
If that robot is to interact,
operate in the human world and interact with humans,
we have to anthropomorphize it
in order to understand as an engineering problem,
how should it operate in a human world?
Now, the difference with viruses,
the scale of operation,
it doesn't make sense to treat them as human-like,
because the scale of operation is much smaller,
but with robots, you're in the same time scale
at the same spatial scale.
But of course, in the movies,
they always give them names and personalities.
Yeah, well, yeah, that's my argument
is we should do the same
when you're trying to solve the engineering problem
of robotics too.
It's not just for the movies.
Well, let me ask you this,
because you've said, controversially, not really,
that viruses are not living.
Defend yourself.
Are viruses alive or not?
So I've seen many people say,
oh, they have to be, they have nucleic acids,
they evolve, they mutate.
That's all true, but they don't do it on their own.
The particles in my mug are just not doing any of that
unless they get into a cell.
So a virus-infected cell is alive.
I totally agree with that,
because in fact, when a virus gets in a cell,
it converts it into a virus-making factory, if you will.
There's no longer a cell.
Some people call it a virus cell.
I don't really like that, but it's fine.
So that's what I'm talking about.
The particle is not alive.
You can have your virus-infected cell as alive,
but the particle, it just would not do anything forever
without getting inside of a cell.
Well, once it's into cells, it is alive then,
but it's no longer a particle.
It's taken apart and nucleic acid is moving around the cell.
It's making proteins.
Eventually it makes new particles.
And then those particles released from the cell,
they're not living anymore.
So I think it's kind of like a spore, a spore of a seed.
Although the seed just doesn't work
because the cells in the seed
have the ability to make their own energy and so forth.
But a bacterial spore, and it's the same thing,
doesn't do anything unless you add water and nutrients
and that starts to divide,
but it doesn't need to get into a cell.
It's very different from a virus.
So that's why the particle.
And when people think of virus,
they're always thinking of the particle.
And that's why I say it can't be alive
because the particle can't do anything on its own.
But if you think of a virus as an organism
with a particle phase in a cell,
then it makes sense to be alive.
And by the way, when you say particle,
you're referring to that structure
that you've been mentioning some parts of membrane and not,
that has been called, what is it, a virion particle?
Virion, so what you should have here, I'll send you one.
And then you can refer to it.
What's the sexiest one to have?
Like what, in terms of particles to have on a table?
Well, fortunately, the ones that you can 3D print.
Oh, they're not going to be, super.
They're the ones that we know the structure's of, right?
So someone sent me last year,
a 3D model of SARS-CoV-2 and it's beautiful.
It's actually cracked open so you can see the RNA
and the spikes are sticking out.
And they even put some antibodies sticking onto the spikes.
And I mean, when I show this on a live stream,
people love this, they go, oh my God, this is beautiful.
And it is, it's absolutely gorgeous.
I have that, I have my virus
that I worked on most of my career polio virus.
I have a 3D model of that,
which I actually just had made, it's gorgeous.
And you can have it made in any color you want, right?
What would you say is the most fascinating,
terrifying, surprising, beautiful virus to you?
So of all the viruses you looked at,
sometimes when you just sit late at night
with a glass of wine looking over the sunset,
which virus do you think about?
So fulfilling all of those adjectives is hard, right?
Fascinating, exciting, terrifying.
Well, the terrifying is an optional one, I think,
because maybe that puts a lot of pressure.
See, terrifying to me,
I'm not terrified because I think we can handle
as most viruses, as you see with this brand new one
that emerged a year ago, we can handle it.
From a virology perspective.
Yeah, I mean, the human perspective
is a different story, right?
That's always an issue, but so I think
there are a couple of different categories of virus.
So we could do the terrifying.
And I think rabies is a terrifying virus
because unless you're vaccinated,
100% certainty you're gonna die.
So you get bitten by a rabid raccoon or bat
or dog, whatever, and there's still 70,000 deaths a year
of rabies throughout the world
because there are a lot of feral dogs running around
that are infected, unless you're vaccinated,
you're gonna die, there's nothing we can do.
But we do have a vaccine,
which we can actually give you even after you've been bitten,
which is the only vaccine that works that way.
It's a therapeutic, right?
It will treat your illness
because the disease takes so long to develop,
eventually you get all kinds of neurological issues
and paralysis and so forth, but it takes time
and you can be vaccinated and it will prevent that
in the meanwhile.
So people always say, what's the most lethal virus?
Is it Ebola?
I said, no, it's actually rabies.
Unless you're vaccinated, it will kill you.
Maybe it's good to linger,
because we'll talk about vaccines a few times today.
It's good to linger on cases where vaccines have clearly,
undoubtedly helped human civilization.
And it seems like rabies is a good example.
Oh, rabies is great because everyone knows
what happens when somebody gets rabies, right?
You have fear of water, hydrophobia,
and your body becomes spastic and stiff and jerks around
and you lose consciousness.
You can't know more.
It's not a fun ride to death.
It's horrible.
It's a horrible way to die.
So I think most people know that.
It's been popularized enough in media, right?
So then nobody would probably object to getting,
oh, I was just bit by this raccoon and it ran off.
Okay, well, we should assume it's rabid.
We should immunize you.
And most people are okay with that
because they know the consequences.
And it's also pretty rare, right?
It's not like something that you're trying to get
into the arms of 250, 300 million Americans.
That's hard, but the few thousand every year, it's easy.
So the transmissibility is difficult, right?
It has to, oh, it's not airborne.
It's not airborne.
It just, you have to be bitten.
Although some people claim you could walk into a cave
and the bats, you know, breathing out rabies virus
could infect you, but I don't really think
that's well substantiated.
I think it's a bite.
How would you do a study on that?
Yeah, it's just very hard to do.
You'd have to collect the vapors in the cave
and show that they're infectious, which,
and by the way, someone emailed me the other day,
you'll like this, they say,
why can't we just immunize all the bats in the world
against these viruses?
And I said, well, how would you do that?
There are caves everywhere, right?
Yeah.
And he said, well, maybe you could just go
and aerosolize them.
Yeah.
It's pretty dangerous.
And then all the bats should have vaccine passports
to make sure that they're all.
Yeah, and I said, you have to get their consent
before you do it.
But we do immunize wildlife against rabies.
We have rabies vaccines for wild animals.
So there are a whole bunch of them that get rabies.
And we put it in bait and drop it from helicopters
in the woods, and it drops down the incidence
of rabies and people.
Wow.
You know, people hiking get bitten and so forth,
it drops the incidence, so we can do that.
I didn't know that.
I was wondering how much medical care we're doing
for animals in the wild,
because I've recently become more and more aware
that animals are living in extreme poverty, right?
Like you don't know, you think like natural, it's great.
You know, like when animals are living on a farm,
it's terrible, but then you also have to compare
to like what life is like in the, or like the zoo.
You have to compare what life is like in the wild.
Well, the life in the wild is very tough, I think.
I mean, most animals have to, the carnivores anyway,
they have to catch their food every day, right?
And then there's the viruses there.
They have viruses as well.
So the rabies immunization is the only one I'm aware of
for wild animals.
We do immunize lots of other animals.
We immunize chickens and pigs and cows, even fish,
farmed fish, we pick each fish up and give it an injection,
you know, when it's a small fish.
But that's mostly so that the farmers get a good yield.
We don't really care about the animals, right?
We want a good yield for market.
And then there's some examples where we immunize animals
to prevent spillovers into people.
So there's a disease called Hendra in Australia,
which was discovered in the 90s.
And it turns out there's, there are bats, fruit bats,
that have this virus and the bats are fine,
but sometimes they're flying into horse stalls
and the horses get infected.
These are in Australia was initially race horses,
which are very expensive, right?
The horses got infected and they died
and the humans who would take care of them would die also.
So now they immunize the horses to prevent the,
well, to save the horses,
probably that's the motivation
because these horses are hundreds of thousands of dollars,
right?
And then the people don't get sick
because the horses don't get sick.
You don't want to immunize all the people
because it's too rare,
but that approach is called one world health approach,
which means everything's connected on the planet.
And we have to think of everything
in the grander scheme, not just us.
Yeah, so you can immunize some things
along the trajectory that a virus would take.
Exactly.
Some living beings.
In the Arabian Peninsula,
they have a MERS coronavirus issue every month.
There are a couple of cases where a camel
will infect a human and the human can get very sick.
It's a respiratory disease, very much like COVID.
And so camels are very common there.
They're raced, they're used as pets, they're eaten.
So there's a lot of human camel contact,
but the number of cases are rare to a month.
So you don't want to immunize all the humans.
So the idea would be to immunize the camels.
So.
I like it.
So, okay, so you put rabies,
but Ebola also is a famously deadly one.
Right.
What is it?
It kills like, I don't know, 50, 60% of it.
50 to 90, but that's in Africa,
where the healthcare isn't great.
What you saw when the cases of Ebola came to the U.S.,
we could take care of it.
We knew how to take care of it.
We had fancy hospitals and so forth,
and now we have a vaccine.
So we can, and the vaccine is really good,
but there are many governments in Africa
that are suspicious of us
and they don't want to use our vaccine.
So there's a vaccine for Ebola.
There is, yeah.
And the effectiveness and safety of it,
to how much is understood.
So this is difficult
because there's not a lot of Ebola, right?
It's not a continuous ongoing thing.
There are sporadic outbreaks here and there.
Of a few thousand people.
At most, at most, usually a few hundred.
And the biggest ever, in fact,
this is why we didn't for years have an Ebola vaccine.
The U.S. military, together with Canada,
developed an Ebola vaccine for service people, right?
They wanted to say, well, we're sending people
into these Ebola areas.
We want a vaccine for them.
So they had developed it through all the preclinical,
which means before it goes into people.
And that stopped because there was no money
to do a phase one and a phase two and a phase three.
In fact, for phase two and three,
you need to have infections going on
because you're looking at how well
the vaccine prevents infections, right?
So then there was a West African outbreak in 2015.
2013, 2015.
The most cases ever, 25,000.
So they got the test of vaccine.
But they only put it in a few thousand people.
It's not like it's been in hundreds of thousands of people
like the COVID vaccines has been.
So it looks like it has high efficacy,
but we'd like to have more data.
Side effects maybe are not so great.
There are a couple of different available vaccines.
Some have been tested more than others.
I would say this would probably not be widely accepted
in the U.S.
But then neither would be something over 50%
deadliness of a virus.
No, I think if you are, in fact, many physicians
work in countries that have Ebola,
so they get vaccinated because they understand the choice.
Yeah, right, it's always about the choice.
So.
So then one more thing to answer the interesting,
what are some of the viruses you really
are fascinated by?
There are a number of viruses that have clearly been shown
to alter host behavior, and that's how they spread.
I think those are fascinating.
For example, there's some viruses of plants
that are spread by aphids.
And the aphid bites the plant,
the virus reproduces in the plant,
and it somehow engineers the plant to give off
volatile organics to attract more aphids,
which will spread the virus.
Isn't that amazing?
Yeah.
So that's altering the behavior.
Might be a Twitter.
Altering because somehow the virus infecting the plant cells
gives off these organics and it attracts aphids.
And furthermore, somehow when the aphid bites,
it tastes horrible.
So they immediately leave with the virus
they've just picked up and go to another plant
to spread it.
So they're attracted and then repulsed at the same time.
And obviously you don't want to anthropomorphize this
like a strategy they're taking on.
Somehow this worked out.
It worked out this way.
It just evolved.
And evolution is sometimes hard to trace, right?
Like Darwin famously said,
he could never figure out how an eye evolved
from a single cell, right?
But it did.
The more complicated, complex,
the holistic organism is that the virus invades,
the less able it is to control that organism, right?
So I wonder if there's viruses that can control human behavior,
to induce more spread of the virus.
Well, I don't see why not.
There's not enough humans I supposed to like evolve through.
Well, we can't do the experiment to test it, right?
We have to observe.
And that's always hard when you're observing
because there's so many things that can confound.
But you look at that.
Yeah, change human behavior, yeah.
I mean, there's so many things that impinge on our behavior.
But yeah, I think it's possible.
I think it's highly possible.
If it does it in a plant,
why not change some other organisms' behavior?
I think it's fine.
Anyway, those fascinate me.
There are lots of examples of those that are fascinating
and how they work people are trying to figure out.
But there's not a lot of money to work on, you know,
insect and plant viruses
unless you're going to the USDA.
So they don't get a lot of work moving forward.
Well, if you understand some of those viruses,
is that transferable to human viruses, that understanding?
I think some of it could be, sure.
I think the general principles, for example,
how does the virus cause volatile organics to be made?
It must be turning on some genes
and you could learn principles from that,
how the virus might do that.
Sure, I think everything is broadly applicable.
So to say it's not useful to study viruses of insects
and plants is just wrong.
Because in science, we probably know this,
maybe in your field it's the same.
If you're curious, you're going to run into interesting things
that you never planned on, right?
That's why people, like you can criticize,
why do we want to go on Mars?
Why do we want to colonize Mars?
Well, it's like, why do you want to go to the moon?
The reality is when you do really difficult things,
yeah, engineering things,
like all these inventions along the way are created.
It's kind of fascinating,
how basically just pick a thing
that everyone can agree is kind of cool
and is really hard and do that.
And then you'll have like thousands of inventions
that have nothing to do with the thing.
That's right.
And I think you should let curious scientists
just follow what they're interested in to a certain extent.
You can't, you know, in science we say
we have translational research where we say,
okay, here's some money,
go cure cancer or diabetes or heart disease, whatever, right?
And that's fine.
But that often doesn't work out very well.
What works better is to say you have a good lab,
you have a good track record,
here's some money or something.
And that's where PCR, CRISPR, recombinant DNA,
all that stuff which has made the field explode,
that's all it came from.
Not from people saying I want to cure genetic diseases
by gene editing,
but by saying what are these repeated things
in this bacterium doing?
Yeah.
Can I ask you a big philosophical question?
So there's these deadly viruses,
they're not very transmissible, Ebola, rabies.
And then there's these less deadly viruses
that are very transmissible, like COVID,
I guess kind of borderline.
But why isn't there super transmissible,
super deadly viruses?
I think if you compare SARS-1 and 2,
you get somewhat of an answer, right?
SARS-1 was more deadly.
In fact, over half of the time when people were infected,
they ended up in the hospital,
because they were that sick.
And then the peak of virus shedding from them
happened long after they went in the hospital.
So it's easy to contain the infection
when you're in a hospital, right?
There was not much pre-symptomatic
or asymptomatic shedding with SARS-1.
And shedding means you become infectious.
So in a respiratory virus,
you inhale the droplets of the virus
and they reproduce in your upper respiratory tract,
what we call the nasopharynx, right?
The nose and going back to that little cavity
just above your mouth.
So the virus reproduces really well.
And then as you talk and sneeze and cough,
you expel droplets and then those are inhaled by other people.
And then they reproduce.
And for SARS-2, we now know there's a lot of reproduction
just before you feel anything, if at all.
So there's a lot of shedding
and transmission before you get symptomatic.
And many people don't ever get symptomatic, right?
So they spread really easily.
So that explains why some viruses
can transmit a lot better than others.
And if one happens to knock you out,
then you're never gonna transmit
because you're in the hospital like SARS-1.
But why can't you have both?
Why can't you just wait a while before you knock you out?
But when you knock you out, it really kills you.
That is a philosophical question, right?
Because we could talk about why we haven't observed it.
I mean, one issue is that if you're killed too quickly
by a highly lethal virus,
you're not gonna transmit it very well, right?
So Ebola can kill you quite rapidly.
And most of the transmission occurs when people
are being cared for at home or in hospitals.
Doctors and nurses get virus, but people walking around,
you're not walking around when you have Ebola, you're too sick.
You know, you have black, bloody diarrhea,
you're vomiting, you're bleeding from your skin
and mucus membranes, you're not walking around,
you're not going to parties.
So I think that's part of it,
that if the infection is too lethal,
you're simply not a good transmitter.
And I think transmission is probably one
of the most powerful selection forces for viruses
because a virus always has to have find a new host.
If it doesn't, it's a startup that fails, right?
If it doesn't find a new host, it's gone.
And so anything that makes the virus transmit better
is gonna help it.
And if killing you, being less lethal is part of that,
that works too.
So there's a strong selection pressure against being lethal.
I think there's a strong selection pressure
against being lethal and being more transmissible.
Those two seem to work in opposite ways.
And now we don't have a lot of data to support this.
This is kind of a thought experiment,
but there is one experiment done in Australia many years ago.
I don't know if you know this, but in the 1800s,
the hunters in Australia imported a rabbit from Europe
so they could hunt it because the native rabbit
in Australia was too fast for them.
They couldn't shoot them.
So they brought in this European rabbit
and they reproduced out of control.
Within a couple of years, they were everywhere,
millions of rabbits and all the watering holes.
And now they had a problem.
So they decided to use a virus
to get rid of these excess rabbits.
And they use a virus, a pox virus called myxoma virus,
which is a natural virus of a different kind of rabbit.
But for these European rabbits, it was quite lethal.
And it's spread by mosquitoes.
So they said, okay, let's release this virus.
And the first year, 99.2% of the rabbits were killed,
but that 0.8% that were left had some form of resistance.
They were variants, you know,
every organism, not just viruses makes mutants
and there were some variants of the rabbits
that could survive infection.
And then in subsequent years, the virus became less lethal
and then the mosquitoes had a better shot
of transmitting it from one rabbit to another
if the rabbit lived longer.
That's the selection probably.
And so in the end, the rabbits lived on,
the virus was there, it evolved to be more transmissible
and less lethal.
So that's the only data.
Life is amazing.
Life on Earth is amazing.
It is, it is.
If you take the time to look at it and see what's happened,
it is amazing.
So it's also humbling that it just makes you realize humans
are just a small part of the picture.
Of course.
And we're wrecking it, aren't we?
Well, I mean, that's not really,
I mean, viruses are wrecking it some ways.
Part of this, we're not really wrecking anything.
It's all part of it.
But you know, when the ways that human exists
encourages viruses to infect us, right?
When we were hunter-gatherers,
living in bands of a hundred people,
very few viruses because it was hard for the virus
to go from one band to another.
And perhaps a hunter would,
one of these humans would get an animal
and bring a virus at the camp and some people would die,
but it would never spread to another.
And then when we started to congregate in cities,
we figured out agriculture and so forth
and how to harvest animals.
Then we could get bigger and bigger populations
and the viruses went crazy.
And they went from animals to us.
So measles went from cows to humans,
when humans learned to domesticate cows
and started gathering in big cities.
Yeah, but now that humans are able to communicate
and travel globally,
the virus has become more and more dangerous, transmissible.
Thereby, if you look at earth as an organism,
thereby pushing humans to be more innovative,
create Alpha-Fol-2 and three and four and five,
create better systems and eventually there's rockets
that keep flying from earth.
And eventually the virus is becoming super dangerous
and threatening all of human civilization,
will force it to become a multi-planetary species
and its organism starts expanding.
So I think it's a feature, not a bug, I don't know.
Well, I think that we have our early,
probably the most of the,
we're studying viruses since 1900, right?
Most of that time was because of diseases they caused.
The first virus is discovered, yellow fever,
virus, smallpox, polio virus, influenza virus.
Those were all because people got sick and they said,
oh, look, this is a virus that's associated with it.
And so we got good at learning how to take care of these
infection making vaccines and so forth over the years.
And it's only in the last 20 years
that we recognize that there are more viruses out there
that are far more interesting, perhaps,
but we've learned how to deal with the bad ones for sure.
So we talked about what is a virus.
We talked about some of the most dangerous
and deadly viruses.
Can we zoom in and talk about COVID-19 virus?
I don't know what your preferred name is, but maybe-
Well, the virus is SARS-CoV-2, which is hard, it's long, right?
And then COVID-19 is the disease.
So you could say the virus of COVID-19, that's fine.
The virus of COVID-19.
But for the purpose of this conversation,
we'll every once in a while just say COVID.
It's fine, no problem.
What is this virus?
From, I don't know how many ways we can talk about it.
I think from a basic structural,
like the variant structure, biological structure perspective,
what is it, what are its variants?
Can you describe the basics
and the important characteristics of the virus?
So viruses are classified by humans
just to make it easier to keep track of them, right?
So this is a coronavirus, which is because
when they were first discovered,
I think the first ones were animal coronaviruses.
They looked at them in the electron microscope
and it looked like the solar corona,
and that's all there is to it.
And I have to say that, early in the outbreak,
the place with the highest seropositivity in the US
for a while, 68% was a working-class neighborhood
in New York City called Corona.
Can you beat that, right?
That's crazy, yeah.
So coronaviruses, they have membranes, right?
We talked about membranes that have spike proteins
in the membrane so they can attach to cells.
And inside, they have RNA.
And they are the viruses with the longest RNA
that we know of.
None other comes close.
For some reason, they're able to maintain 30,000.
So SARS-CoV-2 RNA is 30,000 bases of RNA.
And some of the other coronas are even longer, 40,000.
This is coronas are family of viruses
that included the one you mentioned before, version one.
So SARS-CoV-1, yeah.
CoV-1 and I guess other ones as well.
So the first, we first learned of them in animals.
A lot of animals, pigs and cows and horses
have coronaviruses.
And then in the 60s, we discovered a couple
of human coronaviruses that just cause colds,
very mild colds that you wouldn't even think twice about,
right?
And then suddenly in 2003,
there's this outbreak of severe respiratory disease
in China.
And it started in November
and they didn't tell the world until February.
And that was really bad
because it was already spreading by the time
they told people about it.
But this went to 29 different countries,
only 8,000 people were infected and then it stopped.
And that was the first time we saw
an epidemic coronavirus and what they did afterwards
is they said, okay, it looks like it came
from the meat markets.
They have live meat markets in Guangzhou
in the south of China, where you can go
and pick out an animal and the guy will slaughter it
for you and give it to you.
And then of course there's blood everywhere
and that's how they got infected.
And they figured out that there's this animal
called a palm civet that was the source of virus.
The palm civets are shipped in from the countryside
and the palm civets somehow in the countryside
got it from a bat.
So they went looking in caves in the countryside
and they found in one cave all the viruses
that could make up SARS-1.
And that was 2000, I would say,
took about five, eight years after that outbreak.
So that was the first hint that bats have coronaviruses
that can infect people and cause problems, right?
And after that, we should have been ready.
So didn't they already start developing vaccines
after then?
Yes, so some people started making vaccines.
They tested them in mice, but they never got into people.
And some people started working on antiviral drugs.
Nothing ever came of them because industry,
there's no disease, it's gone.
Why should we make vaccines and drugs and NIH in the US?
You submit a grant and they say,
it's too risky, there's none of this virus around.
So people were really short-sighted
because I always say we could have had antivirals
for this, absolutely, for sure, no question.
In fact, the one antiviral that's in phase three,
it's called molnupiravir,
it's the only one that you can take orally, it's a pill.
It looks really good.
That was developed five years ago,
but never taken into humans, it could have been ready.
So we dropped the ball and then the next decade,
2012, MERS coronavirus comes up in the Arabian Peninsula,
this comes from camels and infects people,
but probably the camels got it from bats originally
some time ago, but that never transmits
from person to person, very rarely.
Every new little outbreak is a new infection from a camel.
So that was 2012.
And now here we are, 2019,
the new outbreak of respiratory disease in China,
and this one really goes all over the world
where SARS-1 could not.
It's a coronavirus, it's different enough from SARS-1
that it has very different properties.
But it still has a membrane,
it still has a very long RNA in the middle,
and then it still has the spike proteins.
That's right.
What are the things that are,
what are the little unique things
that make it that much more effective?
That make it cause a pandemic of millions of people
as opposed to SARS-1.
Well, the genome is 20% different from SARS-1, say,
and in those bases, there's some,
there are things that make it different from SARS-1.
It binds the same receptor, ACE2 on the cell surface,
so that's remarkable.
It has a lot of the same proteins, they look similar.
Like if you look at the structure of the spikes,
they look similar, but there's enough
amino acid differences to make the bylaw.
And what it is, we don't know,
because how do you figure that out?
You need to study animals,
cause you can't infect people.
And the animal models aren't great enough for SARS-1.
So the way you figure that out is you figure out
how those differences, what functional,
like how the difference in the amino acids
lead to functional difference in the virus.
That's right.
Like how it attaches, how it breaks the cell off.
Exactly.
And how the hell do you figure that out?
Like, I guess there's models of interaction.
You need to, first you need an animal
of some kind to infect, right?
You can use mice, people have used ferrets, guinea pigs,
non-human primates, all of the above
and non-human primates are very expensive,
so not many people do that.
And then you can put the virus in the respiratory tract,
but in fact, none of them get sick like people do, you know?
Many people with COVID get a mild disease,
but 20% get a very severe, longer lasting disease
and they can die from it, right?
No animal does that yet.
So we have no insight into what's controlling that.
But if you just want to look at the very first part
of infection and the shedding and the transmission,
you can do it in any one of several animal models.
Ferrets are really good for transmission.
They tend to have nasal structures like humans
and you can put them in cages next to each other
and they'll transmit the virus really nicely.
So you can study that.
But the other thing that's important
that we should mention is how do you manipulate these viruses?
So these are RNA viruses.
You can't manipulate RNA.
We don't know how to do it.
But DNA, because of the recombinant DNA revolution
that occurred in the 70s,
we can change DNA anyway we want.
We can change a single base.
We can cut out bases.
We can put other things in really easily.
And if I may give it a personal aspect,
when I went to MIT as a postdoc in 1979,
David Boothman said, here's what I want you to do.
The moratorium on recombinant DNA experiments on viruses
has just been lifted.
I want you to make a DNA copy of polio
and see if you put that in a cell,
whether it will start an infection.
It's okay.
So I made a DNA copy of polio virus.
It's only 7,500 bases.
It's much smaller than corona.
And I took that DNA and I put it in a piece of DNA
from a bacteria called a plasmid.
And you can grow plasmids and many, many bacteria,
make lots of them and purify the DNA really easily.
And I took that DNA and I sequenced it
because we didn't know the genome sequence
of polio at the time.
And that took me a year, by the way,
because the techniques we had were really archaic
and nowadays you could do it in 15 minutes, right?
It's amazing.
And I took the DNA and put it into cells
and out came polio.
So that's the start.
Now, since then, everybody has taken that technique
and used it for their virus.
You can now do it with SARS-CoV-2.
You make a DNA copy of any RNA virus.
You can modify it and you put it back into cells
and you'll get your modified virus out.
So that's an important part of understanding
the properties of the virus is saying an animal.
By changing the virus, you're changing a DNA copy,
you're making the virus then and putting it into the animal.
Can you clarify?
So even in the RNA virus, you can take and turn it into DNA.
Yes.
And then that allows you to modify it.
Yes.
What's that mapping?
Well, no, no, no.
What's the process of going from RNA to DNA?
Reverse transcription.
That's reverse transcription.
Right.
Also, you actually go into the process
of reverse transcription to do this.
Yes.
Remember, David Baltimore and Howard...
Yes.
...had discovered this enzyme in the 70s
and they got the Nobel Prize for that.
And when I went to David's lab at MIT,
he had the enzyme in the freezer.
He said, here, take this and make a DNA copy of polio.
Yeah, I didn't make the connection
that you can use that kind of thing for an RNA virus.
And then modify it.
See, any DNA virus already exists as DNA,
so you can modify it.
But for RNA viruses, it was difficult.
And so then from that point on, for influenza,
every other RNA virus and coronaviruses,
people made DNA copies and that's what they used
to modify and ask questions about what things are doing.
What's this gene doing?
What if we take it out?
What happens?
Can you do the same thing with COVID?
Of course.
It takes the RNA and then...
Of course.
And in fact, in January 2020,
as soon as the genome sequence was released
from China, the labs all over were synthesizing
this 30,000-base DNA and getting back to...
What can you figure out without infecting anything?
Just turning into, well, the reverse transcription,
turning it to DNA, modifying stuff,
and then putting it into a cell.
What can you figure out from that?
Oh, well, you could, let's say you can cut out a gene.
You see some genes in the sequence.
I don't know what these genes do.
Let's cut them out.
And then you could cut them out of the DNA.
You put the DNA in cells and maybe you get virus out
and you go, oh, clearly that gene's not needed
for the virus to reproduce, at least in cells, right?
Or maybe you take the gene out
and you never get any virus, so it's lethal.
Is there a nice systematic ways of doing this?
Do people kind of automate it?
Absolutely.
And the problem with SARS, the COVID virus,
is it's 30,000 bases, there's a lot of stuff there.
And what makes it more difficult
is that it's been classified as a BSL3 agent,
biosafety level three.
And so not everyone has a lab that's capable of doing that,
so it limits the number of people who can do experiments.
We're lucky to have a few in New York City,
but not every place has them.
So you cannot work with a virus just out on the bench
like we do with many other viruses.
You have to wear a suit and have to have special procedures
and containment and so forth.
So it makes it difficult to do basic experiments
on the virus.
But when it's a pandemic, there's a lot of money,
there's a lot of incentive to work on it harder.
And also you don't need to work on the virus.
You can take bits of it and work,
you could say just the spike, right?
And say, can we make a vaccine with just the spike?
Cause that doesn't require BSL3.
So yes.
So like building a vaccine requires you to figure out
how, or antiviral drugs,
how to attack various structural parts of the virus
and the functional parts of the virus.
Right.
You have to decide on a target.
Yeah.
Like I'm gonna make an antiviral,
what am I gonna target in the virus?
And there are a few things that make more sense than others.
Usually we like to target enzymes.
I don't know if you remember any, your biochemistry,
but you know, enzymes are catalytic.
You don't need a lot of them to do a lot of things.
So they're typically in low concentrations
in a virus infected cell.
So it's easier to inhibit them with a drug.
And the coronas have a couple of enzymes that we can target.
So you have to figure that out ahead of time
and decide what to go after.
And then you can look for drugs that inhibit
what you're interested in.
It's not that hard to do.
There's just something beautiful about biology,
about the mechanisms of biology.
And I kind of regret falling in love with computer science
so much that I left that biology textbook on the show
and left it behind,
but hopefully we'll return to it now
because I think one of the things you learn
even in computer science,
that studying biology and certainly neurobiology,
you get inspired.
Here's a mechanism of incredible complexity
that works really well, is very robust,
is very effective, efficient.
It inspires you to come up with techniques
that you can engineer in the machine.
That's what drives a field forward
when people improvise and come up with new technologies
that really make a difference.
We have a bunch of those now.
What's the difference between the coronavirus family
and the other popular family influenza virus family?
Because you mentioned we should have done a lot more
in terms of vaccine development,
that kind of thing for coronavirus.
But if I were back then, from my understanding,
the thing we should all be afraid of is influenza,
like some strong variants coming out from that family,
that seems like the one that will destroy human civilization
or hurt us really badly.
I don't know if you agree with this sense,
but maybe you can also just clarify
what to use is the difference between the families.
So it's an interesting difference.
They both have membranes, right?
So then they have spike proteins embedded in them for,
and they're different spikes.
In fact, for influenza, they're two main ones.
They're called the HA and the NA.
But what's inside is RNA, but it's very different RNA.
And here we have to explain that.
So viruses with RNA can have three different kinds of RNA.
They can have what we call plus RNA.
They can have minus RNA.
Or they could have plus minus, actually, two strands
hybridized together.
The plus RNA simply means that if you put that plus RNA in a cell,
your cell has ribosomes in it that make the proteins that you need.
The ribosomes will immediately latch onto the plus RNA
and begin to make proteins.
A minus RNA is not the right strand to make proteins.
So it has to be copied first.
And then the plus minus is both together.
So the SARS coronaviruses, all the coronaviruses,
have plus RNA.
So as soon as that RNA gets in the cell,
boom, it starts an infectious cycle.
Same thing with poliovirus, by the way, which I worked on.
Influenza viruses are negative stranded.
So they cannot be translated when they get in the cell.
So that's tough for the virus, because the cell actually
cannot make plus RNA from minus RNA.
It doesn't have the enzyme to do it.
So the virus has to carry it in inside the virus particle.
And then when the minus RNA is in the cell,
the virus enzyme makes plus RNAs, and those get translated.
It's a big difference.
And then in the influenza viruses, not only is it minus RNA,
but it's in pieces.
It's in eight pieces.
We call that segmented, whereas the corona
is in one long piece of RNA.
So they're like floating separately?
So the genes are on separate pieces.
They're all packaged inside that virus
particle of influenza virus.
But they're in pieces.
And why that's important is because if two different influenza
viruses infect the same cell, the pieces as they reproduce
can mix and out can come a virus with a new assortment
of pieces.
And that allows influenza virus to undergo extremely high
frequency evolution.
That's why we get pandemics.
When we have a new flu pandemics,
it's because somewhere in some animal,
two viruses have reassorted and made a new virus
that we hadn't seen before.
So you're talking about kind of biological characteristics.
But what am I incorrect in my intuition
that are from the things I've heard
that the influenza family of viruses is more dangerous?
Like what makes it more dangerous to humans?
Well, it depends on the, there are many flavors or vintages
of influenza virus.
Some are dangerous and some are not, right?
It depends on which one.
Some, like the 1918 apparently was very lethal,
killed a lot of people.
But more contemporary viruses.
We had a pandemic in 2009 of influenza.
There wasn't such a lethal virus.
We don't know exactly why, but it didn't kill that many people.
It transmitted pretty well.
Is that the bird flu one?
They're all deriving.
That one was called swine influenza.
Swine, that's why swine, yeah.
It seemed to have started in a pig, but it had bird,
it had RNAs from bird influenza viruses.
These viruses are all reassortants of different viruses
from pigs and birds and humans.
But influenza can cause pneumonia
and can kill you as does SARS-CoV-2.
So it depends on the virus.
So there is another influenza virus
that's currently circulating.
So right now we have the 2009 pandemic virus
that's still around.
And then the 1968 pandemic virus,
which was the one before 2009,
that one is still around too.
And that's more lethal.
And depending on the season,
some seasons the 2009 virus predominates,
some seasons the 1968.
And when the 68 is around, you get more lethality.
So we're living with the influenza family.
We haven't exterminated them.
Right, we never will, never exterminate them.
Why?
Because every shore bird in the world
is infected with them.
Gulls and turns and ducks and all sorts of things.
Why can't we develop strong vaccines that defend against?
Oh, we could do that, sure.
But that would not eliminate them from humans.
Because even if you had the best vaccine,
you would never get rid of it in people
because there would always be someone
who's not vaccinated or in which the vaccine didn't work.
No vaccine is 100%.
Right.
Well, you just contradicted yourself.
You said the perfect vaccine.
So.
Imperfect, imperfect.
But then you said, like even if you had the perfect,
yeah, some people wouldn't get vaccinated.
But I understand what you mean.
So, but I actually was asking,
how difficult is it to make vaccines like that for,
it seems like it's very difficult to do that
for the influenza virus.
So it's really easy to make an old school vaccine.
So the way the first influenza vaccines were made
was actually Jonas Salk worked on them in the 40s.
You just grow lots of virus
and you grow it in eggs, by the way, chicken eggs.
Nice, literally?
Wait, wait.
Yeah, chicken, embryo needed so they get fertilized
and there's a 10 or 12 day embryo in it
and you put virus in it, it grows up
and then you harvest it.
You get about 10 mls of fluid.
And then you take that,
you treat it with formaldehyde or formalin
and it inactivates the virus.
So it's no longer infectious.
And you just inject that into people.
And that was the first flu vaccine
that was made for the US Army actually.
And then it got moved over to people.
We still use that old school tech today.
So you're taking, can you help me out here?
Okay, so this is a good time to talk about vaccines.
Okay, so you're talking about,
you're taking the actual virus,
you put it in an egg, you let it grow up.
It's very funny that you put it in an egg,
it's very poetic.
And then how do you make it not effective or whatever?
Not infectious.
Not infectious, is that the right term here?
So how do you make it not infectious?
You can treat it with any number of chemicals
that'll disrupt the particle,
so it no longer infects.
So that step of disrupting the particle,
is that very specific to a particular variant particle?
No, the same collection of chemicals
you can use for all kinds of,
and which have been used for SARS-CoV-2 vaccines also.
Same technology.
Okay, so what are, there's several things to ask.
So you call it old school in a way
that's slightly dismissive,
like people talk about Windows 98 or something.
So is there risks involved with it,
or is it just difficult to produce large amounts?
No, it's totally, it's very easy.
And we could do it in cells and culture,
but eggs were convenient.
And in the 1940s, we didn't have cells and culture.
We didn't have to do that,
so we had to use something else.
It's easy to do, but the process of inactivating
the virus with a chemical makes it not the best vaccine
you can make.
The flu vaccines that we have today,
which are mostly based on this inactivation,
is called inactivated virus vaccines.
Also like the kind of thing it presents
to the immune system to train on,
is not close to the actual virus.
Yes, that's what we think.
So that's why probably the flu vaccines
are just not very good.
60% efficiency at the best, right?
Which is not really good.
What does it mean?
What is the measure of efficiency for a vaccine?
Well, it's how it does in the general population
at preventing influenza.
At preventing illness, not infection.
We usually don't measure infection
when we're testing a vaccine.
We just measure sickness.
That's really easy to score, right?
You do a trial and you say, if you feel sick,
give us a call.
We'll tell you what to do.
So yeah, I mean, what's sickness?
Sickness is the presence of symptoms.
So this is good time to say what a symptom is, okay?
A symptom is what you only can feel.
Only you can feel an upset stomach
or a sore throat or that sort of thing.
It's the lived experience of a symptom.
Whereas a sign is something that someone could measure
and tell that you're infected,
like virus in your nasopharynx or something else, right?
Signs and symptoms.
And so in a vaccine trial,
they tell you if you have any of these symptoms
and they give you a paper with the exact symptoms listed
to make sure you're picking them up, right?
So for flu, it would probably be fever, sore throat, cough.
You call them and then they will do a PCR
and make sure you've got flu
and not some other virus that makes similar symptoms.
And then they would say, are you a vaccine
or non-vaccine arm and to count up all the infections
and see how the vaccine did basically.
That's so fascinating because the reporting,
so symptom is what you feel.
Yes, for sure.
And certainly the mind has the ability to conjure up feelings.
Oh yes, absolutely.
And so like culturally, maybe there was a time
in our culture where it was looked down upon
to feel sick or something like that,
like toughen up kind of thing.
And so then you probably have very few symptoms
being reported.
Absolutely, absolutely.
And then now is like much more, I don't know,
perhaps you're much more likely to report symptoms.
Now it's fascinating because then it changes.
Oh, it is definitely a perception
because your symptom may be nothing to me
or vice versa, right?
And so when you're doing this,
it's a little bit of a imprecise science
because and even it's a cultural thing in some countries,
something that would make us feel horrible,
they wouldn't even bother reporting.
No, I didn't have any symptoms.
So it's a little bit imprecise and it clouds the results.
So if you can measure things, it's always better.
But you start out with a symptom.
And if you say, if someone tells you this virus,
20% of the people are asymptomatic.
They don't report symptoms.
That number is probably not as a constant.
It depends where you did the study.
It could be different in China versus South America,
Europe, et cetera, yeah.
I mean, I was trying to fix it.
So I took two shots of the Pfizer vaccine
and I had zero symptoms.
Wow.
So, and I was wondering, well, see,
but that's my feelings, right?
This is not, because I felt fine.
I was waiting.
Did you have pain at the injection site?
No, it was kind of pleasant.
You felt nothing the next day, no?
Nothing.
No, no, no, no, no, no, no, no, no, no, no, no, no, no, no.
But see, like I have an insane sleeping schedule.
I already put myself through crazy stuff.
That said, maybe I was expecting something really bad.
Like I was waiting and therefore didn't feel it.
Then I, but I also got allergy shots
and those I was out all next day,
like exhausted for some reason.
So that gave me like a sense like, okay,
at least sometimes I can feel shitty.
That's good to know.
Sure, sure.
Then when the vaccine, it didn't,
but the question is like, how much does my mind
come into play there?
The expectations of symptoms,
the expectations of not feeling well.
How does that affect the sort of the self-reporting
of the symptoms?
I think it's definitely a variable there,
but there's certainly many people
that don't feel anything after the vaccines.
And there's some that have a whole range of things
like soreness and fever, et cetera.
Yeah.
So, okay, you were talking about
the old school development side, the egg.
Right.
What's better than that?
So then the next generation of vaccines,
which arose in the 50s were what we call
replication competent, where the virus you take
and it's actually reproducing in you.
Yeah, that sounds safe.
And it can be somewhat problematic.
Yes, as you might imagine,
because once you put that virus in you,
you have no more control, right?
It's not like you have a kill switch in it,
which actually would be a great idea to put in.
And like nanobots, what can possibly go wrong?
You could just put something in there
if you added a drug, you would shut it off, right?
And people are thinking about that
because now we're engineering viruses to treat cancers
and other diseases.
And we may want to put kill switches in them
just to make sure they don't run away.
Oh, interesting.
So you can like deploy a drug that binds to this virus
that would shut it off in the body, something like that.
Something like that, yeah.
That would be the idea.
You'd have to engineer it in.
Anyway, the first one was yellow fever vaccine.
That was made because that was a big problem.
And this virus, and the way you do this back in the old day
was empirical.
So Max Tyler, who did the yellow fever vaccine,
he took the virus, which is a human virus, right?
And he infected, I think he used chick embryos.
And he went from one embryo to another
and just kept passing.
He did that hundreds of times.
And every 10 passages, he would take the virus
and put it in a mouse or a monkey, whatever his model was.
And then eventually he got a virus
that didn't cause any disease after 200 in some passages.
And then that was tested in people.
And it became the yellow fever vaccine that we use today.
He selected for mutations that made the virus
not cause disease, but still make an immune response.
So those are called replication competent.
We now have the polio vaccine, which was developed
in the 50s after the yellow fever.
Then we had measles, mumps, rubella.
Those are all replication competent vaccines.
And you mentioned, that's a good idea.
They are all safe vaccines.
The only one that has had an issue
is the polio replication competent vaccine.
It was called Saban vaccine or oral polio virus vaccine.
Because you take it orally, it's a wonderful
because you don't have to inject it.
This is the perfect delivery.
Either intranasal for a respiratory virus
or orally for polio, it goes into your intestines,
it reproduces, and it gives you wonderful protection
against polio.
However, you do shed virus out.
And that virus is no longer a vaccine.
It's reverted genetically in your intestine.
So you can infect others with polio.
Take that virus and it put it into an animal
and give it polio.
And in fact, the parents of some kids
in the 60s and 70s who were immunized got polio
from the vaccine.
The rate was about one and one and a half million cases
of polio.
So it's called vaccine associated polio.
And I always argue that we may not have
picked the right vaccine.
There was a big fight in the US and other countries
between the inactivated polio and the infectious polio
vaccines, which ones we should be using.
Because we found out that the infectious vaccine
actually caused polio.
And eight to 10 kids a year in the US alone
got polio from the vaccine.
Which looking back is really not acceptable in my view,
although the public health community said it was
to get rid of polio.
So now we're close to eradicating polio globally.
But this vaccine derived polio is a problem.
So now we have to go back to the inactivated vaccine,
which is tough because it's injected.
So the basic high level, how vaccines work principle
is you want to deploy something in the body
that's as close to the actual virus as possible,
but doesn't do nearly as much harm.
And there's like a million, not a million,
but there's a bunch of ways you could possibly do that.
So those are two ways.
And now of course we have modern ways.
We can make mRNA vaccines, right?
What are the modern ways?
Did you want to look at mRNA vaccine?
So that's the most modern, but even before mRNA vaccines,
we learned that we could use viruses to deliver
proteins from a virus that you want to prevent.
And so the Ebola vaccine, we took the spike gene
of Ebola virus and put it in a different virus
and we deliver that to people.
And that's called a vector vaccine.
And some of the COVID vaccines are vectors
of different kinds of most famous or adenovirus vectors
carrying the spike gene into the cell.
Can you explain how the vector vaccine works again?
So we take a virus that will infect humans,
but will not make you sick.
In the case of adenovirus,
the years and years of people studying it
has told us what genes you could cut out
and allow the virus to infect the cell,
but not cause any disease.
So instead of doing selection on it,
you actually genetically modify it.
Yes, you modify the vector, yeah.
So you're much more precise about it.
You're very precise.
And then you splice in the gene for the spike
and then you use that to deliver the gene
and it becomes produced as protein
and then you make an immune response.
And vectors the term for this modified.
Right.
So we're now using viruses at our bidding.
We're using them as vectors.
Not just for vaccines.
We can cure monogenic diseases.
That is, if you're born with a genetic disease,
you have a deletion or mutation in a gene, a single gene,
we can give you the regular gene back
using a virus vector.
So, but...
Cancers too.
We can cure cancers with vectors.
Wow.
Really?
Interesting.
Yeah.
I think in 10 to 15 years,
most cancers will be treatable with viruses, yeah.
Wow.
And not only can we put things in the vector
to kill the tumor,
we can target the vector to the tumor specifically
in a number of ways.
And that makes it less toxic, right?
It doesn't infect all your other cells.
But it takes time to develop a vector for a particular thing
because it requires a deep understanding.
Yeah.
In fact, we have about a dozen different virus vectors
that have been studied for 20 years.
And those are the set of vaccine vectors that we're using.
So it includes adenovirus, vesicular stomatitis virus,
which is a cousin of rabies,
but doesn't make people sick.
Influenza virus is being used as a vector
and even measles virus.
So we're familiar with how to modify those to be vectors
and those are being used for COVID vaccines.
And then of course we have the new,
the new is just the nucleic acid vaccines.
So years ago, people said,
why can't we just inject DNA into people?
Take the spike and put it in a DNA and inject it.
So people tried many, many different vaccines.
And in fact, there are no human licensed vaccines
that are DNA vaccines.
Although there is a West Nile vaccine for horses
that's a DNA based vaccine.
So if you have a horse, you can give it this vaccine,
but no human.
Can you clarify, does a DNA vaccine
only work for DNA viruses?
No, it can work for DNA or RNA.
Because remember, if for an RNA virus,
we can make a DNA copy of it.
And it will still, when you put that DNA in a cell,
it goes into the nucleus.
Okay, right.
So it's, you're just skipping a step.
And eventually you get proteins.
For RNA vaccines, you're giving, okay, I got it.
So those didn't work for human vaccines.
And there were many HIV, AIDS vaccine trials
that used DNA vaccines, didn't work.
And then a number of years ago,
people started thinking, how about RNA?
RNA vaccines.
And I first heard this.
I saw what?
I've worked with RNA my whole career.
It's so fragile.
If you look at it the wrong way, it breaks.
I mean, that's being facetious, right?
But you have to be very careful
because your hands are full of enzymes
that will degrade RNA.
So I thought, how could this possibly work
injecting it into someone's?
It's an example of I was skeptical and I was wrong.
It turns out that if you modify the RNA properly
and protect it in a lipid capsule,
it actually works as a vaccine.
And people were working on this years
before COVID came around.
They were doing experimental mRNA vaccines.
And there were a couple of companies
that were working on it.
And so at the beginning of 2020, they said, let's try it.
And I was skeptical, frankly,
because I just thought RNA would be too labile,
but I was wrong.
So this is, as we're saying offline,
one of the great things about you is you're able to say
when you were wrong about intuitions you've had in the past,
which is a beautiful thing for a scientist.
But I still think it's very surprising
that something like that works, right?
I am surprised.
So you're just launching RNA in a protective membrane.
And then now, one thing is surprising
that the RNA sort of lasts long enough, right?
That's right.
In its structure.
But then the other thing is why does it work
that that's a good training ground for the immune system?
Because is that obvious?
Well, I don't think it's obvious to most people.
And it's worth going into because it's really interesting.
I mean, first of all, they wrap the RNA in fats,
in lipid membranes, right?
And the particular formulation,
they test for years to make sure it's stable,
it lasts a long time after it's injected.
And the two companies that make the current COVID vaccines,
Moderna and Pfizer,
they have different lipid formulations to get to the same.
So that's a real part of it.
And it's not simple.
There are quite a few different lipids
that they put into this coding.
And they test to see how long they protect the RNA
after it's injected, say, into a mouse,
how long does it last?
And the way it works is these apparently,
these lipid nanoparticles,
they get injected into your muscle,
they bump into cells and they get taken up.
So lipid fat is sticky.
It's greasy, we like to say.
And so your cells are covered with the greasy membrane also.
So when these lipid nanoparticles bump into them,
they stick and they eventually get taken up.
And they figured this out right at the beginning.
If we put RNA in a lipid nanoparticle,
will it get taken up into a cell?
And the answer was yes, it was just,
let's try it and it worked.
So it's basically experiment,
it's not like some deep understanding of biology,
it's experimentally speaking, it just seems to work.
Yeah, well, they had some idea that lipids
would target this to a cell membrane.
And remember, there's no receptor involved.
Like the virus has a specific protein
that attaches to a receptor.
It's not efficient enough to just bump around
and get into a cell.
That's what these things are doing.
And they probably optimize the lipids
to get more efficient uptake.
But it's not as efficient as a virus
would be to get into a cell.
So you have no specific,
I mean, which is why it's surprising
that you can crack into the safe with a hammer
or with some fat.
I mean, that's kind of surprising.
It's kind of amazing that it works.
But so maybe let's try to talk about this.
So one of the hesitancies around vaccines
or basically around any new technology
is the fact that mRNA is a new idea.
And it's an idea that was shrouded
in some skepticism, as you said,
by the scientific community.
Because it's a cool new technology,
surprising that it works.
What's your intuition?
I think one nice way to approach this is
try to play devil's advocate and say both sides.
One side is why your intuition says
that it's safe for humans.
And what arguments can you see
if you could steal man and argument
why it's unsafe for humans?
Or not unsafe for humans,
but the hesitancy to take an mRNA vaccine is justified.
So many people are afraid because it's new technology
and they feel it hasn't been tested.
I mean, in theory, what could go wrong?
This is the nice thing about mRNA
is that it doesn't last forever
as opposed to DNA, which doesn't last forever,
but it can last a lot longer
and it could even go into your DNA, right?
So mRNA has a shorter lifetime,
maybe days after it's injected into your arm,
then it's gone.
So that's a good thing
because it's not gonna be around forever.
So that would say, okay,
so it's sticking around for your lifetime is not happening,
but what else could happen?
Well, let's see, the protein that's made,
could that be an issue?
And again, proteins don't last forever.
They have a finite longevity in the body.
And this one also lasts perhaps at the best a few weeks.
Now, this is a protein that's made after the RNA
gets into the cell.
Yeah, so the lipid nanoparticles taken up into a cell
and the mRNA is translated and you get protein made.
And there's also a question,
and I'm sorry to interrupt,
where in the body, so because it's not well-targeted
or I don't know if it's supposed to be targeted,
but it can go throughout the body,
that's one of the concerns.
So it's injected deep into your deltoid muscle,
right here, shoulder.
And the idea is not to put it in a blood vessel,
otherwise it would then for sure circulate everywhere.
So they go deep in a blood vessel
and it's locally injected.
And they did, before this even went into people,
they did experiments in mice
where they gave them a thousand times higher concentrations
than they would ever give to people.
And then when you do that, it can go everywhere basically.
You can find these nanoparticles
in every tissue of the mouse.
But that's at a thousand-fold higher concentration, right?
So I think at the levels that we're using in people,
most of it's staying in the muscle,
but sure, small amounts go elsewhere.
And could there be a lot of harm caused if it goes elsewhere?
Like let's say ridiculously high quantities.
I'm trying to understand what is the damage
that could be done from an RNA just floating about?
So the RNA itself is not gonna be a problem,
it's the protein that is encoded in it, right?
This is a viral RNA which has no sequence in us.
So there's nothing that it could do.
It's the protein that I would say you could ask,
what is that gonna do?
And the one property we know about the spike
is that it can cause fusion of cells, right?
That's how the virus gets in in the beginning.
The spike attaches to the cell by this H2 receptor
and it causes the virus and the cell to fuse.
And that's how the RNA gets out of the particle.
But so wait, I'm a bit confused.
So with this mRNA vaccine with the lipids and the RNA,
there's no spike, right?
The mRNA codes for the spike.
Oh, the mRNA codes, so it creates the spike.
Creates a spike.
And so that spike could cause fusion of cells.
Yes, except they modified the spike so it wouldn't.
Got it.
They made two amino acid changes in the spike
so it would not fuse.
So they understand enough
which amino acids are responsible for the fusion.
That's right.
Interesting.
This is so cool.
So they could modify it.
So now it's not gonna cause fusion,
so that's not an issue.
It's called the pre-fusion stabilized spike.
Cool.
So the spike when it binds ACE2,
that top fulls off and the part of the spike
that causes fusion is now exposed.
And that doesn't happen in this mRNA vaccine.
So those are the things that could have happened,
but I think they're ruled out by what we've just said.
But there's no better test than putting it into people, right?
And doing phase one, phase two, and phase three
and increasing numbers of people and asking,
what do we see?
Do we have any concerns?
And so now it's been in many millions of people
and we don't see,
most of the effects you see in a vaccine,
you see in the first couple of months,
things like the myocarditis with some of the vaccines,
the clotting issues with the AstraZeneca vaccine,
Guillain-Barre, you see those relatively quickly.
And we've seen small numbers of those occur,
but other things we haven't seen
and you never say never, right?
Right, so I mean, this is fascinating, right?
It's like I drink, I put Splenda in my coffee
and has supposedly no calories, but it tastes really good.
And despite what like rumors and blogs and so on,
I have not seen good medical evidence
that is harmful to you, but it's like it tastes too good.
So I'm thinking like,
there's gotta be long-term consequences,
but it's very difficult to understand
what the long-term consequences are.
And there's this kind of like distant fear
or anxiety about it.
Like this thing tastes too good, it's too good to be true,
there's gotta be, there's no free launch in this world.
This is the kind of feeling that people have
about the long-term effects of the vaccine.
That you mentioned that there's some intuition
about near-term effects that you want to remove
like the diffusion of cells and all those kinds of things,
but they think, okay, this travels to other cells
in the body, this travels to neurons
or that kind of stuff.
And then what kind of effect does that have long-term
that's yet to be discovered?
What do you make, I mean, for this vaccine,
but in general in science about making statements
about long-term negative effects.
Is that something that weighs heavy on you?
Is that something that can kind of escape
through just large-scale experimentation
with animals and humans?
Well, if you're really,
if you're concerned about long-term,
then you have to do a long-term experiment, right?
And maybe you don't see something for 50, 60 years.
So if someone says to you,
there are no long-term effects of the COVID vaccines,
they can't say that
because they haven't done the long experiment, right?
There's always the possibility, but you have to weigh it.
It's always, there's no free lunch, right?
There's always a risk-benefit calculation you have to make.
You can have the study, it goes for 50 years
and then decide, but I guess what you're doing
is just like we said, I forget with which one,
with polio, with rabies, I forget,
but you're weighing the side effects of the vaccine
versus the effects of the virus.
And like both of them, you don't know long-term effects,
but you're building up intuition as you study,
which what are the long-term effects?
Like there's a huge number of people that have,
like I don't wanna say experts
because I don't like the word,
but people have studied it long enough
to where they build up intuition.
They don't know for sure.
There's basic science being done, there's basic studies.
We start to build up an intuition
of what might be a problem down the line
and what is not, biologically speaking.
And so given that map, considering the virus,
there seems to be a lot of evidence for COVID
having negative effects on all aspects of the body,
and not just even respiratory, which is kind of interesting.
So the cognitive stuff, that's terrifying.
All kinds of systems evolve.
And then you look at the same thing with the vaccine,
and there seems to be less of that.
But of course you don't know
if it's some kind of dormant thing that's just going to-
You won't know.
You have to make a judgment
and for a lot of people, they can't, right?
Because they don't have the tools to make the judgment.
I totally understand that.
And we have let people down a few times in medicine, right?
And I know two very specific examples.
The first polio vaccine ever made.
The Salk vaccine was released in 1955.
Immediately, within months,
a few hundred cases of paralysis in kids who got it
because it was not properly inactivated.
Now you have to understand,
parents were dying for a polio vaccine
because kids were getting paralyzed every summer,
30,000 kids a year.
And so they went and took it.
They took the word of the medical establishment
that it was safe, and it wasn't.
Big let down.
Never going to forget something.
Although I think a lot of people today
don't aren't aware of that.
I think that was a big problem that's everlasting.
Then the attenuated vaccine that we talked about,
the infectious, causing polio.
Yet parents continued to bring their kids to be vaccinated
because they were said, this is the right thing to do.
And I have to say, I was involved in several lawsuits
where parents of a kid who got paralyzed
from the polio vaccine decided to sue the manufacturer
and get some money for their kid.
And so they got mad.
And I think you could not,
the first issue could have been prevented,
could have been prevented by inactivating it properly.
I think the company just did the wrong thing.
The second we had evidence for,
and we should probably have not used that vaccine any longer,
but I think that destroys public confidence.
But those are, that's the minority of cases.
This minority, this is a very rare event, yeah.
But nevertheless, science as an institution didn't make
corrections in that case.
No, they didn't.
And so what do you make of that?
I mean, it's very unfortunate
that those few things can destroy trust.
But I don't think that lasts till today.
I think today is a different era, right?
And most people don't know about those stories.
I tell them to you because that's what could happen.
I think it could happen today.
If you look at the history of the polio vaccine,
the US Public Health Service wanted kids to be vaccinated.
So they did things that probably weren't correct
to get the vaccine back online, right?
But they did it and they pushed it through.
So the question is, what do we do today?
So I can look at, as we just said,
I can look at what might happen
and I can make reasonable decisions
about the likelihood of them happening.
And I can also say, I don't wanna get COVID of any kind
because I've seen how nasty it can be.
And I decide, I'm taking the risk,
whatever small of a long-term effect,
I'm gonna take the risk.
My family took the risk and many other people did.
Both of a vaccine.
Of getting vaccinated, because I think it's very small.
But I understand where people can't make that decision.
And that begs the question, what would they need
to make a decision?
So if you're concerned about an effect in 40 years,
we're not gonna know for 40 years.
Yeah, so I think if I were to speak,
because I talked to, like I mentioned offline
to Joe Rogan and his podcast yesterday,
I talked to him all the time about this.
I think the concern is less about the long-term effects, like on paper.
It's more about the, like people like Anthony Fauci
and people at the top are simply misrepresenting the data
or like are not actually being transparent,
not collecting the data properly,
not reporting on the data properly,
not being transparent, not representing the uncertainties,
not openly saying they were wrong two months ago.
Like in a way that's not like dramatic,
but revealing the basic process of science
when you have to do your best under uncertainty,
just also just being inauthentic.
There's a sense, especially with like a younger generation now,
there's a certain way on the internet,
like the internet can smell bullshit,
much better than previous generations could.
And so they see there's a kind of inauthenticity
that comes with being like representing authority.
Like I am a scientist, I'm an expert, I have a PhD,
I have four decades of work,
therefore everyone should listen to me.
And somehow that maps to this feeling of, well, what are they hiding?
If they're speaking from authority like this,
if everyone is in agreement like this,
that means they all have emails between each other.
They said, we're gonna tell this,
this is the message we're gonna tell the public.
Then what is the truth, the actual truth?
Maybe there's a much bigger uncertainty.
Maybe there's dead people in the basement
that they're hiding from bad mRNA vaccine experiments.
Maybe they're, and then the conspiracy theories
start to grow naturally
when there's this kind of mistrust of that.
So it's less about kind of like a deep concern
about long-term effects.
It's a concern about long-term effects
if we find out that there's some secret stuff
that we're not being told.
It all runs on that.
So I put the blame not on the data,
but basically on the leaders and the communicators
of the science at the top.
Well, to that I would say,
all the data, as far as I know, are made public.
So you can dive into it.
And I know a lot of people ask me questions,
and I just say it's right here in the data.
And I know a lot of people can't do that.
They can't dive into it.
But that's one solution for people who are able.
Now, you could argue, well, maybe they've left data out.
Well, then not even I can help
because then they're hiding it from me too.
And I think that's highly unlikely.
I think for the most part,
the FDA requires the release
of all the clinical trial data, right?
So this clinical trial data, that's one thing.
So that's the data that we should be focusing on, right?
So there's a lot of different data sets here.
So there's preclinical data,
which is everything that was done in the lab
before this vaccine ever went into a human arm.
It's all the cell culture work
that we talked about a little, experiments in animals.
All of that is publicly accessible.
Most of it gets published.
And then there's the initial drug filing,
which is huge, the books have died.
You can get that and look at it, right?
This is me sort of asking sort of difficult questions here.
It's okay.
So there's a lot of money to be made by makers of the vaccine.
So for these companies,
and obviously there's a distress of those folks too.
They've done a lot of really good things in this world,
but the incentives are such
that you wanna sweep stuff under the rug
if you're not 100% pure in your ethics.
And how hard is it for that data to be fabricated,
manipulated, like what's your intuition
for the pre-trial stuff?
I think when you start fabricating,
then you get inconsistencies,
which are pretty easy to pick up.
When you're talking about some large scale things of this nature.
Because then you can look through the data very,
you're gonna, I mean, we require looking very carefully,
but you'll see inconsistencies from one trial to another.
And that may ring a bell that something's been done.
Yeah.
It's like the moon landing thing.
I think sometimes like going to the moon
is easier than faking it, right?
In the sense it might be easier to do a large scale trial
and get an effective vaccine versus faking it.
But you know, when you brought up the for-profit issue,
I think that is always been an issue.
I've always felt that having your health depend
on for-profit industry may not be the best solution.
And I don't know how else to do it.
People tell me I'm a dreamer,
that thinking that all medicines could be non-profit,
but I also think that the world should have one health system
that takes care of everyone, right?
Because there are some countries that can't
and other countries haven't access like us.
So I wish we could do that.
Well, the argument is the speed of which the vaccines
for COVID were produced would never happen
in a non-profit system,
would never happen in a non-capitalist system.
Oh, I could set up a vaccine production institute
in the US that would get the vaccines done
because you just need to put money into it.
That's what made these vaccines get done.
Money, they poured billions of dollars
and they got it done quickly.
But if I set up a non-profit institutes of vaccines
throughout the US, staffed with really talented people,
pay them well, keep them motivated,
you'll get your vaccines.
No, but that's the thing with capitalism
is that the selection of who to hire,
like when you say good people,
capitalism has a machine that fires people
who are not good and selects people that are good.
Coming from the Soviet Union,
the dream of communism is similar to what you're saying,
broadly defy.
It certainly doesn't work in the broads,
the question of whether it works in the healthcare space.
There is some aspect to the machine of capitalism
being the most effective way to select for good people
to effectively produce the thing.
But then of course, a lot of people would argue
that even the current healthcare is not with regulations.
There's some weird mix
where there's a lot of opportunities for inefficiencies.
There's a lot of opportunities for bureaucracy.
So you have like the worst of all the world.
Can't there be some intermediate that works?
Because I mean, the other issue that we have mentioned
is that politics gets thrown into this
and that really messes up
and it should never be mixed with healthcare,
but it is because a lot of funding comes from the government.
So that's another confounding factor.
But I really think I could make a vaccine institute
that if someone didn't do well, I'd fire them.
No, you're not gonna stay if you can't do your job
and do it well, you don't give them incentives,
but it doesn't have to be the two extremes, I think.
There has to be a solution
that people don't have this mistrust
for a company making huge profits off of a drug.
But you know what?
It's funny, it seems that vaccines and antivirals
bear the brunt of this criticism,
yet there are many other pharmaceuticals
that people rely on of all sorts.
They don't seem to question and have issues with those
and they have far more side effects than vaccines.
It's very strange how we're picking that way.
But I should also say that if you have one big vaccine
institute, one of the other like sets
of vaccine conspiracies, I mean,
I would say they're a little farther out
into the wild set of ideas.
But there's one way to control the populace
is by injecting substances into them, right?
People, I mean, part of that funny enough
is probably has to do with needles
versus something you put in your mouth.
But there's something about the government,
especially when it's government mandated,
injection of a substance into you.
I don't care what the science says,
if it's 100% effective, 100% safe,
there's a natural distrust of what,
like even if this is effective and safe,
giving the government power to do this,
aren't they gonna start getting ideas down the line
for, you know.
I think that they can barely govern.
I don't think they're gonna do that,
but you don't have to take,
unless you're a federal employee,
you don't have to take a COVID vaccine.
Yeah, but that's, that largely has to do,
not largely, but there is an individualistic
spirit, you know, to the American people.
There's this, like, you're not gonna take my gun away
from me, you're not going,
and I think that, you know,
that's something that makes America what it is.
Just coming from the Soviet Union,
there's a power to sort of resisting
the overreach of government.
That's quite interesting,
because I'm a believer, I hope that it's possible
to have, to strive towards a government
that works extremely well.
I think at its best, a government represents the people
and functions in a similar way that you're mentioning,
but that, like, pushback,
even if it turns into conspiracy theory sometimes,
I think is actually healthy in the long arc of history.
It can be frustrating sometimes,
but that mechanism of pushing back against power,
against authority, it can be healthy.
I agree, I think it's fine to question the vaccines.
What I have issue with is that many people put it out
in correct information,
and I'm not sure what their motivations are,
and it's very hard to fight that,
because then it's my word versus theirs,
and I'm happy to talk with people
about any of their concerns,
but if you start getting into the stuff
that just isn't true, then we have a problem.
The thing I struggle with is conspiracy theories,
whatever language you want to use,
but sort of ideas that challenge the mainstream,
quote, unquote, narrative.
Given our current social media and internet,
like the way it operates,
they can become viral much easier.
There's something much more compelling about them.
Like, I have a secret about the way things really work.
That becomes viral, and that's very frustrating,
because then you're not having a conversation
on level ground.
When you're trying to present scientific ideas,
and then there's conspiracy theories,
the conspiracy theories become viral much faster,
and then you're not just having a discussion on level ground.
That's the frustrating part,
that it's not an even discussion.
Can I just say one more thing?
So, I mean, the internet is here to stay,
so we're gonna have to figure out how to deal with it, right?
But from my perspective,
I was skeptical that these mRNA vaccines,
that any COVID vaccine would be ready within a year.
That's amazing. Me too.
Plus, the way I look at the mRNA vaccine as a scientist,
it's G-wiz to me.
It's amazing that it worked,
and I think the data are great, so I want it.
As a scientist, I want it.
One of the really sad things, again,
with me too, as a scientist or as an admirer of science is,
I don't know if it's politics,
but one of the sad things to me about the previous year
is that I wasn't free to celebrate
the incredible accomplishment of science with the vaccines.
I was very skeptical as possible
to develop a vaccine so quickly.
So, it's unfortunate that we can't celebrate
how amazing humans are to come up with this vaccine.
Now, this vaccine might have long-term effects.
That doesn't mean this is not incredible.
Why couldn't you celebrate?
Because I would love to inspire the world
with the amazing things science can do.
And when you say something about the vaccines,
they're not listening to the science.
A lot of people are not listening to the science.
What they hear is, oh, you're a Republican
or you're a Democrat,
and you're doing some kind of signaling.
No, I think that the vaccine,
you're talking about injecting something into you,
and maybe you're right that the rhetoric is like,
you better take this or you're dumb.
It's not the right approach.
I've seen, actually, it's kind of interesting.
I've seen both sides kind of imply that.
So, the people who are against the vaccine
are dumb for not trusting science,
and the people who are for the vaccine
are called dumb for trusting science,
the scientific institutions.
And nobody wins, yeah.
And they both kind of have a point.
Because you can always,
it's like a glass half full or half empty
because you can always look at science
from a perspective of certain individuals
that don't represent perhaps the not greatest leaders,
almost like political leaders.
There's a lot of,
I've, yesterday went on a whole rant against,
I said a lot of positive things about Anthony Fauci
before I went on a rant against him.
Because ultimately, I think he failed as a leader,
and I know it's very difficult to be a leader,
but I still wanted to hold him accountable for that
as a great communicator of science and as a great leader.
But what do you think he'd do, right?
I'm curious.
So the core of the problem is the several characteristics
of the way he was communicating to the public.
So one is the general inauthenticity.
Two is a thing that it's very hard to put into words,
but there are certain ways of speaking to people
that sounds like you're hiding something from them.
That sounds like you're full of shit.
That's the authenticity piece.
It sounds like you're not really speaking
to the full truth of what you know,
and that you did some shady shit in your past
that you're trying to hide.
So that's a way of communicating
that I think the internet and people in general
are becoming much better at detecting.
Yeah, as you said, they're good BS detectors.
Yeah, good BS detectors.
But contributing to that is speaking from authority.
Speaking with authority and confidence
where neither is deserved.
So first of all, nobody's an authority on this new virus.
We're facing a deadly pandemic
and especially in the early stages,
it was unclear how deadly it would be.
It was unclear, probably still unclear,
fully how it's transmitted,
the full dynamics of the virus,
the full understanding of which solutions work and not,
how well masks of different kinds work,
how easy or difficult it is to create tests,
how many months or years it's gonna take
to create a vaccine,
how well in history or currently do quarantine methods
or lockdown methods work,
what are the different data mechanisms
that are data collection mechanisms
that are being implemented?
What are the clear plans they need to happen?
What the epidemiology that's happening,
what is the uncertainty around that?
Then there's the geopolitical stuff with China.
I personally believe there should have been
much more openness about the origins of the virus,
whether a leak from a lab or not.
I think communicating that you're open to these ideas
is actually the way to get people to trust you,
that you're legitimately open to ideas
that are very unpleasant that go against the mainstream.
Showing that openness is going to get people
to trust you when you finally decrease
the variance in your uncertainty,
like decrease uncertainty and have,
we still have a lot of uncertainty,
but this is the best course of action.
Vaccines still have a lot of uncertainty around them.
mRNA is a new technology,
but we have increasing amounts of data,
and here's the data sources,
and laying them out in a very clear way
of this is the best course of action that we have now.
We don't know if it's the perfect course of action,
but it's by far the best course of action,
and that would come from a leader
that has earned the capital of trust from people.
I mean, I think in recent history, the worst pandemic
is 1918 flu, right?
But that's mainly because we didn't know what to do.
We didn't have many tools at our disposal.
And that was tied up with World War I.
That's right, that's right.
So the leadership there, I mean.
But I don't know what is a lot of deaths, right?
And any one person is someone's family,
so to them it's a lot, right?
But that logic, we don't apply that logic generally,
because there's a lot of people suffering
and dying throughout the world,
and we turn the other way all the time.
And that's the story of history.
So saying you all of a sudden.
Well, bothers me though.
I mean, personally, I don't like anyone dying anywhere,
but especially considering what technology
we're able to muster, yet we still kill each other.
It's just dichotomy to me.
Yeah, but I mean, this is the, what is it, Paul Farmer?
There's these great stories.
I mean, that's the burden of being in healthcare,
being a doctor, is you have to help.
You can't help but help a person in front of you
who's hurting.
Sure.
But you also are burdened by the knowledge
that you helping them, you spending money
and effort and time on them,
means you're not going to help others.
And you cannot possibly allocate
that amount of time to everybody.
So you're choosing which person lives
and which person dies.
Sure.
And you're doing so,
the reason you're helping the person in front of you
is because they're in front of you.
And so the reason right now we care a lot about COVID
is because the eye of the world has turned to COVID,
but we're not seeing all the other atrocities
going on in the world.
They're not necessarily related to deaths.
They're related to suffering, human suffering,
which you could argue is worse than death.
For long suffering.
Yeah, of course.
So there's all of these questions.
And the fundamental question here
is are we overreacting to COVID in our policies?
So this is the, when we turn our eye
and care about this particular thing and not other things,
are we dismissing the pain that business owners
who've lost their businesses are going to feel?
And then the long talking about long COVID,
the long term economic effects
on the millions of people that will suffer,
that suffer financially,
but also suffer from their dreams being completely collapsed.
So a lot of people seek gain meaning from work.
And if you take away that work,
there's anger that can be born, there's pain.
And so what does that lead to?
That can lead to the rising up of charismatic leaders
that channel that anger towards destructive things.
That's been done throughout history.
So you have to balance that with the policies
that you have in COVID.
And then, I mean, very much my main opposition
to Fauci is not on the details, but the final result,
which is I just observe
that there's a significant decrease in trust in science
as not the institution,
but the various sort of mechanisms of science.
I think science is both beautiful and powerful
and the reason why we have so many amazing things
and such a high quality of life and distrust in that.
The thing we need now to get out of all the troubles we're in,
continue getting out of the troubles we're in is science,
the scientific process broadly defined like innovation,
technological innovation, scientific innovation,
all of that distrust in that is totally the wrong thing we need.
And so anybody who causes a distrust in science to me,
carries the responsibility of that.
And because of the response, I mean, should be fired,
should be or at least openly have to carry the burden of that,
of having caused of that kind of level of mistrust.
Now, it may be unfair to place it on any one individual,
but you have to, I think in your pocket said the buck stops at the top,
like the leaders have to care.
There's a clear leader here, yes, absolutely.
So even if it's not directly his fault,
he has to carry the price of that.
Do you think we should at this point say,
okay, we have vaccines,
you can decide whether you take them or not, let's move forward?
Maybe you can help me understand this because it seems like,
why is that not the right solution?
Completely open society.
The vaccines, at least in the United States,
as I understand, are widely available.
So this is the American way.
You have the decision to make.
If you have conditions that make you worried to get COVID
and go to the hospital, then you should get vaccinated.
Because here's the data that shows
that it's much less likely for you to die if you get vaccinated.
If you don't want to get vaccinated because you're worried
about a long-term effects of vaccine that you don't have to,
but then you suffer the consequences of that, and that's it.
So here's what I think is driving.
I think it's all about kids because they're going to go back
to school in the fall and many of them can't be vaccinated.
So if they get infected, they do have less frequency of disease,
but it's not zero.
They do get sick, and they can have long-term consequences.
And at that age, it would be a shame, right?
And not even their choice.
They can't decide to get vaccinated or not
because they can't have access to it.
So I think that's what would drive my efforts to try
and get more people, at least in schools, vaccinated.
But I might be wrong.
It may not be that.
Can you kind of dig into that a little bit?
So you're saying that there should be an effort
for increased vaccinations of kids going to school,
just not for societal benefit, but for the benefit
of each individual kid, right?
So right now, kids under 12, right, are not yet vaccinated.
Is that correct?
Yeah, I think so.
And it's not going to be in time for school opening
that they get vaccinated.
And then I suppose the teachers are all going to be vaccinated.
Makes sense for them to do that.
But I'm just worried the kids are going
to be transmitting it amongst them.
And many states don't allow mask mandate in school.
So I think that's what's driving the larger narrative
in the US, to protect kids.
It's kind of what I hear from Daniel Griffin,
because increasing numbers of kids
are being admitted to hospitals now,
because they're becoming the major unvaccinated population.
They're hanging out over the summer,
and that's just going to get worse in the fall.
And so you could have a lot of kids with long COVID
and disabled their entire lives, right?
So and of course, hearing from people who are vaccine hesitant,
I hear exactly the kids' statement,
but they're saying they don't want the long vaccine,
the long-term effects of the vaccine to affect the kids.
That's the of this new vaccine.
Which I would say is, as I said before, you can't say never.
But we do know that long COVID exists.
We don't know for how long, because we've only looked out
six or eight months.
We know that exists.
And the frequency is increasing.
It certainly exists in young kids.
And we have no idea about long vaccine effects.
So I think they have to make their decision based on that.
But yeah.
But your question is, why don't we just open up society?
Say, here we have these vaccines,
if you want to protect yourself.
I think it's mainly the school that's driving
the whole narrative.
That's my opinion.
In which direction not to open up or?
No, to open up, but to try and get, you know,
their efforts at the federal level
to get people vaccinated, right?
But see, how high are the risk for kids?
I mean, my understanding was it's, I mean, yes, it's non-zero,
but it's very low for any.
But what is the numbers?
Now, 70,000 hospitalizations so far in kids as of last week.
So yes, it's low.
But polio was low.
Polio was 20,000, 30,000 kids a year paralyzed.
And well, many people have actually
argued that that vaccine wasn't necessary, you know?
It wasn't a substantial enough health problem.
But paralyze is different than hospital.
So what does hospitalized mean?
Long COVID.
But that's the long COVID question.
I mean, this is the open question.
What is long COVID in kids?
What is that?
Well, a lot of the same issues, cognitive issues, motor
issues, respiratory, GI dysfunction.
How long?
We don't know.
I mean, it could end in a year.
As you know, there are other post-acute infectious
sequelae that we know about.
You know, chronic fatigue, ME-CFS,
is thought to be a post-infectious sequelae, which
has gone for many decades now in many millions of people.
This could be another one of those.
So I'm just saying it might be worth airing on the side of not
letting the kids get infected.
Yeah, but well, I'm trying to keep an open mind here
and I appreciate you doing the same.
Of course, I lean on definitely not requiring people
to get vaccinated, but I do think getting vaccinated
is just the wiser choice of looking at all
the different trajectories before us.
Getting vaccinated seems like, from the data,
it seems like the obvious choice, frankly.
But I'm also trying to keep an open mind.
There's some things in the past that seemed obvious
would turn out to be completely wrong.
So I'm trying to keep an open mind here.
So for example, one of the things
I'd love to get your thoughts on this is antiviral ideas.
So ideas outside of the vaccine.
So Ivermectin, something that Brett Weinstein and a few others
have been talking about.
There's been a few studies.
Some of them have been shown not to be very good studies.
But nevertheless, there seems to be some promise.
And I wanted to talk to Brett about this particular topic
for two reasons.
One, I was really bothered by censorship of this.
That's a whole other topic.
I'm bothered by censorship.
There's a gray area, of course.
But it just feels like that should not
have been censored from YouTube, like discussions
of Ivermectin.
We can set that aside.
The other thing, I was bothered by the lack of open mindedness
on exploring things like Ivermectin in the early days,
especially when at least I thought the vaccine would
take a long time.
I mean, it's not just Ivermectin.
It's really seriously, at a large scale,
rigorously exploring the effectiveness of masks.
And the big one for me is testing.
Like the fact that that wasn't explored aggressively
to lead to mass manufacture in like May 2020 is absurd.
Anyway, so I was bothered by these solutions not
being explored and not by now having really good Ivermectin
studies.
So can I talk about Ivermectin?
Yeah, I would love that, yeah.
So full disclosure, my wife worked on Ivermectin at Merck
for 20 years.
OK, so they just want people to know.
But I don't talk to her all the time about it.
Anyway, she hasn't been at Merck for a long time.
As you know, Ivermectin is a very safe drug
used to treat certain parasitic infections, right?
And it is approved.
It's amazing.
You can take one dose a year and be protected
against river blindness in Africa and certain parts of Africa.
It's remarkably effective.
And so it's quite a safe drug at the doses that are approved.
Now, early last year a study was done,
I believe in Australia, which showed in cells in the lab,
if you infect with SARS-CoV-2 and then put Ivermectin in,
it would inhibit the virus production substantially.
It was quite clear, right?
But the concentrations they were using were rather high
and could not be achieved by the approved dosing.
So you would need to do a dosing study to make sure it's safe.
And the reason is that Ivermectin binds to receptors
in your brain, and it can have high doses.
A lot of some people take high doses inappropriately,
and they have neurological consequences.
So if you needed 10 times more Ivermectin,
you'd have to make sure it would be safe.
So this is a question of safety, too.
Right.
So I think it has always been the case
that it should have been properly studied, but it wasn't.
There are lots of trials here and there,
lots of improperly controlled trials
where someone would just treat some patients and say,
hey, they all did fine, but have no control arm.
And there were some controlled trials,
but they were very small.
So right now, a 4,000-person trial is enrolling
to test in a randomly controlled trial setting
whether it works or not.
There's still plenty of cases that you can do that,
so you can ask whether there are any side effects.
I think that's completely fine.
And if it says it works, then we should use it.
In the meantime, I always tell people,
if you want to use Ivermectin, you can do it off-label.
It's FDA-approved.
And if your physician says, I'm going to give you this off-label,
I don't have any objection, but I don't know if it's going to work.
Now, a friend of ours last week in New Jersey got COVID.
He went to his local hospital, and their regimen
was Remdesivir, dexamethasone, Ivermectin.
That's what they do for every COVID patient.
They just give it to them automatically.
And so he recovered.
So who's to say it was or was not Ivermectin, right?
So I don't have any strong ideological opposition.
And I just think it should be tested
for what you want to use it for.
And that's being done, and I think that's fine.
Is it strange to you that Ivermectin or other things
like it weren't tested aggressively in the beginning?
From a broad scientific community aspect,
I can be a little bit conspiratorial,
and this is what people talk about with Ivermectin,
is with the vaccines, there's quite a lot of money to be made.
With Ivermectin, there's not as much money to be made.
Is that too conspiratorial?
Why didn't we try more solutions in the beginning?
Well, all the money was put into vaccines, right?
Very little was put into antivirals,
because the decision was made at a very high level,
probably involving Dr. Fauci.
We're going to put $24 billion into vaccines, right?
And I think part of the reasoning
is they give you years' worth of protection,
whereas an antiviral works, and you
have to keep dosing and so forth.
But Ivermectin is not trivial in this.
I agree it should have been tested early on,
but we had a really bad experience with hydroxychloroquine,
which we can talk about too.
Ivermectin is very hard to synthesize.
Most drugs, you synthesize chemically.
You devise a formulation and a synthesis,
and they do it.
They scale it up, and it's fine.
Ivermectin is really hard, and so what they do instead
is they take the culture of the bacterium that makes it,
and they grow it up, and they ferment it,
and then they purify it.
And Merck owns the bacteria.
A number of years ago, two employees of Merck
stole it and left the company and tried to mark it,
and they were arrested, and they got put in jail.
So they protect it very carefully.
So you can't just make it.
If you do, it's incredibly expensive.
And now India, it's very cheap apparently.
They use it quite liberally there,
and I don't know how they're making it.
Maybe they've licensed it from Merck and so forth,
but that's why it hasn't been tested more widely, I think.
There's complexities in terms of getting a lot of it
and manufacturing a lot of it.
Yes.
So what was the other, the hydroxychloroquine?
So hydroxychloroquine was also shown early on
to inhibit virus in cell culture.
And that's not surprising, hydroxychloroquine,
of course, is used for malaria.
And what it does, when your cell takes up things
from the plasma membrane, including viruses,
it goes through a pathway called the endocytic pathway,
which involves a vesicle moving through the cell.
And as it moves through the cell, it's pH drops.
And that lets a lot of viruses out actually,
and hydroxychloroquine blocks that.
So it blocks infection with a lot of viruses.
So the problem with those early studies that were published
is that they were done in kidney cells and culture,
where the only way the virus can get in
is through the endosome.
And hydroxychloroquine inhibits that,
and that's why it inhibits in kidney cells and culture.
But lung cells and respiratory cells of humans
where the virus reproduces can get in two different ways.
It can get in from this endocytic pathway,
which is inhibited by hydroxychloroquine,
or it can get in at the cell surface,
which is not inhibited by hydroxychloroquine.
So when you treat patients, it has no effect in the lung
because the virus can just bypass it.
And all the usage initially were based on the studies
done in kidney cells and culture.
So that was just wrong, scientifically incorrect.
Yet it drove a lot of.
And today, many people still think
they should be taking it.
So that not panning out kind of resulted
in a loss of optimism about other similar things panning out.
Well, that and many other repurposed drugs were tried.
A lot of HIV antivirals were tried.
I think the problem with hydroxychloroquine
influenced the ivermectin narrative.
People thought that data was being hidden
about hydroxychloroquine.
So they said, well, they must be doing the same thing
with ivermectin.
But with hydroxychloroquine, it just scientifically
could not work as an antiviral.
The other problem that is more broad that is important
to point out is that when you have COVID
and you need an antiviral, it's usually
because you can't breathe and you go in a hospital.
Because if you're mildly ill, you're
never going to go to your doctor and ask for an antiviral.
And the problem is when you can't breathe,
it's no longer a viral issue.
It is now an inflammatory issue.
And no antiviral in the world is going to help you.
So if that's why remdesivir doesn't work very well,
because it's mainly given intravenously to people
who go in a hospital, if you get ivermectin in the hospital,
it's not going to do anything for reducing virus.
Because by that time, you have very little virus to begin with.
You have an inflammatory problem that you
need to treat in other ways.
So this is why a lot of the antivirals failed,
because they're used too late.
What you need is a pill you take on that first positive test
when you have a scratchy throat.
You get a PCR in 15 minutes, I'm positive, take a pill, boom.
That's going to inhibit it.
If you wait till you can't breathe,
and that's why the monoclonals even don't work
if you're in a hospital that well, because it's too late.
And the approach now is if you're in a high risk group,
if you're over 65, if you are obese or have diabetes
or any other comorbidities, your first sign
of a scratchy throat positive, you get monoclonals.
Then they might help you.
But if you wait till you go in a hospital, it's too late.
Because the viral curve drops.
After that first symptom, within three days,
you're no longer shedding enough virus to transmit.
It drops really quickly.
So that's the reason a lot of these antivirals failed,
because they were tested in hospitalized patients.
And we have nothing but Remdesivir now, unfortunately.
So it was the wrong approach.
We should have been giving it to people
who just tested positive from the start.
Or just even for preventative and see.
You could do that too.
But I have to say, the other issue is,
this molupiravir is a drug in phase three now.
It's an oral antiviral that looks good.
If we go ahead with just one,
we're going to get resistance within a few months,
and it will be useless.
We need to have at least two or three drugs
that we can give in combinations.
And we know that, because that's what took care of HIV.
That's what took care of HCV, hepatitis C virus.
It really reduces the emergence of resistance.
Joe Rogan got quite a bit of heat recently
about mentioning a paper and a broader idea,
which I don't think is that controversial.
But maybe we can expand on it.
And the idea is that vaccines
create selective pressure for a virus to mutate
and for variants to form.
First of all, from a biological perspective,
can you explain this process?
And from a societal perspective,
what are we supposed to do about that?
So let's get the terminology right.
So as we talked about earlier,
viruses are always mutating.
So no vaccine or no drug makes a virus mutate.
That's the wrong perspective.
We should look at it.
What the immune response is putting pressure,
selection pressure on the virus.
And if there's one particle with the right mutation
that can escape the antibody, that will emerge, right?
So that's what happens with influenza virus.
We vaccinate every year
and there are not a lot of people that get infected
so they get natural immunity.
And then the virus is incredibly varied.
It mutates like crazy.
And there's in some person somewhere,
there's one variant that escapes the antibody
which has been induced either by infection or vaccination.
It can be both.
And that drives the emergence of the new variants
so the next year we need to change the vaccine.
So I would say both natural infection and vaccination
sure select for variants.
Absolutely, there's no question
because they're inducing immunity.
Now, what happened last year was at the beginning of 2020,
very few people in the world were immune
as the virus first started spreading.
But you can see in the sequences of those isolates
from the beginning of 2020,
you can see all of the changes that are now present
in the variants of concern at very, very low frequencies.
They were already there
but there was no selection for them to emerge.
Until November, when we now had many millions of people
who had mostly been infected but also some vaccinated,
then we saw the alpha variant emerge in England
probably because of immune selection.
Now the virus that had the change that evaded the antibody
had an advantage
and that virus drove through the population.
So that's what we're seeing.
All these variants are simply antigenic selection.
So the variants, the mutations that are at the core
of these quote unquote variants,
they were always there all along the vaccine
or the infections did not create them.
No, the infections don't create them, they're selected.
It's like the vaccine wipe out a lot of the variants
and then by making your body immune to them.
And so, but some of them survive.
Yeah, exactly.
And then there's another tree that's built
and it's unclear what that tree leads to.
I mean, it could make things much worse or much better
and we don't know.
Well, with flu, we see year after year, the virus changes,
we change the vaccine, we deal with it,
we change it again, there's an unending series.
But see, that's a very different story.
If do you think COVID will be with some likelihood
like the flu, whereas basically variants
will never be able to eradicate it.
It will never eradicate it in any case, ever.
Well, come up with a vaccine that makes you immune
to enough variants where there's not enough
evolutionary like room.
Well, if you cut down the number of infections,
then you reduce the diversity, sure, right?
The problem is if, let's say you're a cynic
and you say, well, vaccination is just selecting
for variants, so let's stop it.
But then you're gonna have infection
and that's gonna select for variants.
And there, you're more likely to get very sick
because we know the vaccines are really good
at preventing you from dying.
So that's why it still makes sense to use vaccines
because they prevent you from dying.
That's the bottom line.
But can we ever make a vaccine that deals with all variants?
Absolutely.
And the reason I say that is because people
who get naturally infected with SARS-CoV-2,
they develop COVID, they recover.
If you give them one vaccine dose,
they make an immune response that handles
all the variants that are around right now.
All of them, much better than people
who've gotten two doses of vaccine.
For some reason, their immune response
is suddenly broadened after the infection vaccination
and they can handle all the variants
that we know of so far.
So that tells me we can devise a strategy
to do the same thing with a vaccine
that makes a really broad vaccine
that'll handle all the variants.
Well, you actually, on the virology blog,
I don't know if you're the author of that,
but the blog, yes, but there's a particular post
that's talking about reporting on a paper
that makes a match strategy.
Oh yes, that's one of my co-writers, Trudy Ray.
Yeah, that's an interesting idea
that there are some early evidence now
that mixing and matching vaccines,
like one shot of Pfizer and one of Moderna or something,
that creates a much better immunity
than does two shots of Pfizer.
I think that's worth exploring, absolutely.
And this is relevant.
What we're doing with influenza,
instead of having to vaccinate people every year,
why can't we devise a vaccine
which you'd get once in your lifetime
or maybe once every 10 years, okay?
So the spike of influenza, it's a long protein,
kind of like the spike of SARS-CoV-2,
it's stuck in the virus membrane.
And the very tip, that's the part that changes every year.
This is where the antibodies bind.
But the stem doesn't change.
And if you make antibodies to the stem,
they can also prevent infection.
It's just that when people are infected
or with the current vaccines,
they don't make many antibodies to that stem part.
But we're trying to figure out how to make those
and we think they would be broadly protective
and you'd never be able to or more rarely be able to
have a variant emerge that escaped it.
And I think we can do the same thing with coronavirus too,
for sure.
Can I ask you about testing?
Sure.
Sure.
So you mentioned PCR, what kind of tests are there?
The antigen test, what are your thoughts on each?
Maybe this is a good place to also mention like viral load.
And the history of the virus as it passes through your body
in terms of what's being tested for
and all those kinds of things.
So the first tests that were developed were PCR,
polymerase chain reaction.
They're basically nucleic acid amplification tests.
And they were very first ones.
They stuck the swab all the way up into your brain almost.
I had that done a couple of weeks ago.
Oh my gosh, it's really nasty.
But now they do an interior nary swab.
They get a bunch of cells and some mucus
which has virus and parts of virus sticking in a test tube
and then they run a reaction,
which by the way involves reverse transcriptase
because it converts the viral RNA to DNA
and then you amplify it.
And you can specify what part of the viral RNA
you wanna amplify.
And then a machine will detect it
and it can be done in 15 minutes.
But you're detecting pieces of RNA, not infectious virus.
So we're measuring viral RNA loads, right?
And a common mistake that many people who should know better
physicians and scientists of all kinds,
they think that indicates how much virus you have.
It doesn't.
It's a diagnostic of whether you have bits of RNA in you.
And it probably means you're infected,
but you can't use it to shed light on what's going on.
And I'll tell you why in a bit,
but first we have to explain some other things.
So until you get to about a million copies of RNA,
so you can measure the copy number in this test,
this PCR test.
It's a number called CT or cycle threshold.
The test, the way the machine works, it goes through cycles
and every cycle it amplifies what you put in.
And the more cycles you need to see something,
that means there's not a lot of RNA there.
So if you do a test and you have a cycle threshold of 35,
you have very little RNA in you.
Contrary, if you have a cycle threshold of 10,
you have a ton of RNA and you only took 10 cycles
to detect it.
And you can extrapolate from that number,
the number of copies you have per sample, say per swab.
And if you don't have a million, you're not infectious.
You're not gonna infect anyone.
So in the early days, no matter what PCR result you had,
they would quarantine you.
And that was wrong because you're not shedding,
you don't need to be quarantined,
but wasn't thought through properly, right?
That's where you had like 14 days or something like that.
14 days, which is now we know is too long
because you don't shed for that long in a normal infection.
Now it's 10 days should be fine.
So what happens is you get infected,
you don't know it, of course,
the virus starts to grow very quickly.
And within four or five days,
you reach a peak of shedding,
you're making a lot of RNA
and you may be asymptomatic,
you're shedding, you can infect others,
and then you may or may not have your symptom onset.
So you shed for a couple of days before symptom onset
and then within three days, four days,
the viral RNA crashes and you're no longer shedding,
you're no longer transmitting.
So that's the one kind of test we have.
It can tell you if you're infected at the moment,
but it won't tell you
if you're gonna be infected tomorrow, right?
Because if you're negative today,
you could be positive tomorrow.
You just might be in a different part
of the incubation period, right?
So that's one test been used the most.
You can now get 15 minute versions of them
in a walk-in or whatever, fine.
Then there are antigen tests,
which look for the proteins that the virus is making.
So as it's reproducing in your nose,
it's not only making genomes, it's making proteins.
And so these you can buy in the drugstore.
And these would have been great if they had,
Michael Minna last year had the idea
that if we could make a little stick,
a little piece of paper that you would suck on
and it would tell you if you're infected or not,
if this could cost less than a buck,
everybody could test themselves.
Which they can cost less than a buck, by the way.
Yeah, but they were never made, right?
Yeah, they're never mass manufactured.
So his idea is to do like daily tests.
So there's-
Yeah, daily and then the kid's going to school,
he's positive or she's positive.
Well, if it's cheap enough, you just take another test
because they have a certain error frequency.
If it's positive twice, you stay home
and the next day you try again.
And I think this would have revolutionized
because the PCR tests are more expensive at the time
and they take longer to do and so forth.
But that never happened.
But now we do have $20 binacks now
and others that you can buy and people buy them and-
See, but that can still happen, right?
And this is the very frustrating thing to me
because I'm worried about variants,
but I'm also worried about future
and much more deadly pandemics.
I know we kind of said, yes, COVID and lots of deaths,
but like it could be a lot worse too.
So I'm thinking what is going to be
the right response for the future pandemic of its kind?
And what's the right response for continued number of variants
and some of the variants might be deadlier
or more transmissible?
Well, the antigen tests will pick up the variants.
That's not a question.
The PCR may be influenced by changes,
but you can quickly adapt the primers that you use.
But that's what I mean, like to me,
all these discussions about vaccines and so on.
Vaccines, we got very lucky that they took so little time.
Right.
And you have to be aware, no matter what,
that there's hesitancy with the vaccines in this country.
Before, I mean, yeah, that's a reality.
You can't just be like magically saying that-
That's right.
You're going to overcome that.
And I don't think there's any hesitancy
and cheap tests at home.
I agree, I think if someone,
so the question is if someone tested positive,
would they stay home?
That's the question.
What if their job depends on them going in?
I mean, that's-
Well, you have to look at sort of aggregate,
how many people would decide.
And I think, again, a lot of that is in leadership,
but I think a lot of them,
I would say most people would stay home.
I think that Mina had the idea
and it would have changed the whole situation for sure.
If it could have been made when we talked to him
last spring, I think, or summer,
we would have gotten around a lot of the issues
that we're in today
because I think people would have stayed home
and not transmitted.
And I think it's still valuable to this day.
In the fall, if we don't have vaccine uptake,
we could just test kids every day and get her
and keep them home when they're infected.
It cuts, it's, and we don't have it.
But I think, and I'm not privy to what was going on,
but I don't think a lot of emphasis
was put on testing early on.
You know, the CDC developed the first one,
it was flawed, they had to recall the kids.
I mean, there's a fiasco.
They should have had 100 companies
making the tests initially, right?
So for the future, I think what we have learned
is we need to have a rapid antigen test
right off the bat that's doable.
You can't do it in a day like you can for PCR
because you need to make antibodies
to the protein that you're looking for
and you need to do those in animals,
but you can do it in weeks
and we should be ready for that.
Yeah, because, I mean, to me, that's obvious.
That's obviously the best solution.
Second to that, if we understood how well masks work.
Like maybe let me ask you this question.
Let's put masks aside.
How will do we understand how COVID is transmitted?
There's droplets of different sizes, aerosols,
tiny, tiny droplets.
It seems like that's a very difficult thing
to understand thoroughly.
So it seems like it's transmitted both ways.
It's unclear how exactly.
So how much do we understand
and why is it so difficult to understand it fully?
I think it's clear that it's transmitted
through the air mostly.
It's not touching.
We thought initially it would be a lot of touch,
but very little of that.
It's through the air and when you talk,
mainly when you talk, you expel a lot of droplets, right?
Even the plosives that your foam thing here
are meant to pee, right?
That you send out little sprays
and those have viruses in them.
And the big drops fall to the ground
and the little ones can go 100 feet or more, right?
But the little ones also have less virus in them.
So I'm not sure, well, we certainly do not know
how much virus you need to be infected,
but it's probably at least several thousand particles,
if not more.
And it could be that for most people,
the tiny droplets don't have enough virus
to infect someone else.
But there's one observation about this virus
that's really interesting.
And that is that 80% of transmissions
are done by 20% of the people, of the infected people.
Not every infected person transmits.
That's been borne out in multiple studies.
And in fact, there's a study at University of Colorado
where they quantified the viral RNA loads
and all the swabs that had been done of students
for like a six month period.
And most of the infectious virus,
most of the RNA copies were found in
15 to 20% of the people.
The rest had really low and that's probably
why they don't transmit.
So those are the ones that might get enough virus
in the tiny droplets to be able to infect someone
at a distance.
And I think that's entirely possible.
Why is it hard to study?
You can't do it in real life
because you don't know who's infected.
And if you do, there's not a controlled environment
to measure droplets and so forth.
You'd have to do it in a laboratory situation.
If you use an animal, you just don't know
what the relevance of that is to people.
You'd have to use human and do challenge experiments
and we don't do that at this point,
at least not for this virus.
So that's why it's hard to know what's going on.
So we have to make inferences
from epidemiological associations
where you're studying say transmission in a household
where people are stuck in the same rooms together
and you can get an idea of what kind of droplets
we're involved in.
So that makes it much harder too
if you're leaning on epidemiological stuff
as opposed to like biophysics or something
like the mechanic.
Very hard.
So that makes it really hard
to then develop solutions like masks
to ask the question, how well do masks work?
Because then to answer that question,
you can lean on epidemiological stuff again,
like looking at populations that wear masks
or just don't wear masks.
As opposed to actually saying,
like from an engineering perspective,
like what kind of material and what kind of tightness
by which amount decreases the viral load
that's received on the other end.
But some experiments have been done with masks
and just droplets with no virus in them, right?
And you can measure the efficiency
of different mask materials at keeping those in.
So if I say that this mask stops 70%
of this or larger size droplet,
that leads to this percent decreased transmission.
And also on both the generation
and the receiving end and the giving end.
So how well do masks protect you from others?
How well do you do mask protect others from you?
Like all of those things seem like
they could be more rigorously studied.
There's no doubt about it.
And now is the time because once this is over,
nobody's gonna do it.
Nobody's gonna care, right?
But it seems like to me, so tests is one thing,
but masks, like the good mask,
whatever the good means, whatever that means,
like some level of quality of material on your face,
if it's shown to actually like thoroughly shown
to work well, that seems like an obvious solution
to reopen society with,
if you have a good understanding of how well they work.
Because if you don't have a good understanding,
if there's a lot of uncertainty, that's when you get,
and you have people speaking from authority,
that's when you start getting the politicization
of the solution.
Of course, of course.
No, the data, there are some data.
Most, they're mostly epidemiological
and they show some effect in some countries, right?
But they could be way better.
Yeah.
And, but the fact that they're not perfect,
then people take advantage of and say,
well, look, they don't work that well,
so I'm not gonna wear it.
I think as you said, people can use it as an excuse.
But even if it works, so Daniel always says it,
a mask will cut down transmission by 50 to 60%.
And then distance will do another 30%.
Yeah, those numbers are made up though.
I mean, they're not made up, but they're estimates.
Absolutely.
And many of them are made based on models, right?
We will make this model and let's say the mask
cuts down this much, what will be the effect on,
I mean, yeah, they're models and it's for the same reason.
I don't believe the transmission of the variants
because it's all based on statistical models as well,
not biological experiments done in the lab.
So that in that sense, vaccine date
is much better than mask date.
For sure, for sure.
So my problem with the mask date,
which I always thought was fascinating,
I stopped talking about it.
I was in the paper about masks.
I stopped talking about it because what started happening
is mask created assholes on both sides.
The people that were like in Silicon Valley,
the friends of mine that were wearing masks,
the way they look at others who don't is like.
Well, that's a whole nother issue, right?
Yeah, I understand.
That happens when you don't have solid science.
Understood.
They now start judging you like you're a lesser human being.
You're not only dumb, but you're almost like evil.
You're doing bad for society by not wearing a mask.
And then the people looking in the other way
are seeing you for the asshole that you're being
for judging them unrightly.
So they almost wanna say F you by not wearing the mask.
And there's this division that's created
that was heartbreaking to me
because masks like testing is a solution
that was available early on.
And if understood well, it could be deployed in a mass scale.
And it seems like there's some historical evidence
for other viruses where it does very well.
That's correct.
And so like the fact that this was politicized,
yeah, was a little bit heartbreaking.
You can find in the literature studies,
mostly of healthcare workers and influenza,
where you can actually, because you see the people every day
that can sample them,
you can actually see what masking does.
And some of them show an effect and others do not.
Then that's the problem.
Like any trial, sometimes if it's not big enough
and then people latch onto that, see,
it doesn't really work.
But I think the main issue is that in January,
both CDC and WHO said masks don't work, don't use them.
That was the kiss of death for masks
because when they then changed their mind,
they didn't say we screwed up.
They just said wear masks.
If they had said we made a mistake, we were wrong,
I think more people would have worn masks, but they didn't.
And like you said, admitting you're wrong
is like a real big part of it.
And I also think almost the better way
is not just saying you're kind of saying you're wrong,
but in January saying,
like revealing the uncertainty under which we operate.
Like actually like reveal what was done
with the Spanish flu at the beginning
of the previous century
because there's a lot of mass controversy then too.
It went back and forth
and that was actually the source of a lot
of distrust there too.
So, and then look at influenza,
like how is it effective with that?
And just reveal this, we don't know,
but with some probability,
this is the best option we got currently.
And then in a month or two, adjust it saying that,
you know what are like the uncertainty decreased
a little bit, we have a better idea.
Like that was an incorrect estimate,
but reveal that you're struggling.
It's not like this weird binary clock
that goes one direction or the other.
You're struggling with uncertainty.
And like trusting, people maybe criticize me sometimes
of this, but I think most people are actually intelligent.
Like trusting the public to be intelligent with,
if you give them, if you have transparent
and give them information in a real authentic way,
like don't look like you're hiding something.
I think they're intelligent enough
to use that data to make decisions.
It's the same thing as with the testing,
is if you put that power in the people's hands
to know if they're sick or not,
they're gonna make unmasked the right decision, I think.
The masks and the testing has been a bit heartbreaking.
I think that's a good point though,
that most people don't seem to have an objection to testing.
It's a good point.
Yes.
And then obviously Makamina makes that point brilliantly.
And still there's very little excitement around that.
But he said he was going to do it.
I don't understand.
I mean, I haven't spoken to him since then.
So I don't know why.
He's pushing it.
Well, I mean, but he can't do it alone.
He has to get, so one of the resistances,
FDA doesn't like cheap things.
Yeah.
They don't want to approve it.
So it makes the mass manufacture,
like with emergency exceptions,
all those kinds of things, very difficult.
And then there's not much money to be made on it
without that.
I don't know.
I think there's just economic pressures against it.
And because so much investment was placed on the vaccines,
and obviously there's an incentive mechanism there
where the company's lobbyists and all those,
there's this machine that says,
arguing for tests is difficult
because the thing that's worked for most severe viruses
in the past is vaccines.
Now we have vaccines, why the hell would you need tests?
At that time, like why the hell do you need tests
when we can be working on vaccines?
It seems like the obvious thing to be working
is the vaccines from their perspective.
But it's not obvious at all to me.
I think you should have both.
I think have vaccines and good testing
and that covers you really well
because you're always gonna have people
who don't get vaccinated.
I don't know if you've been paying attention to this.
There's a guy named Brett Weinstein
and there's a guy named Sam Harris.
They have good representation,
I would say of two sides of a perspective on the vaccine.
So from Sam Harris's perspective,
it's obvious that everybody should get vaccinated
and it's irresponsible to not get vaccinated.
I think he represents a lot of people's belief in that.
And then Brett talks a lot about hivermectin
but also talks about hesitancy towards the vaccine
for people who are healthy,
who are people who are younger, that kind of thing.
And saying we should consider longterm effects of the vaccine
in making this calculation.
What do you make about this conversation?
Some of it happens on Twitter,
some of it happens in the space of podcasts.
Do you pay attention to this kind of thing?
What's your role in this?
What do you hope is the way to resolve this conversation?
Do you think it's healthy?
Well, a conversation is always healthy
but to make definitive statements is not
because it suggests you have information that you don't have.
So we talked about longterm effects.
I think you need to balance those
versus longterm effects of the disease
and you can make your decision.
I don't think you need to tell everybody to get vaccinated.
I think you need to present the case.
You say here we made good vaccines,
here the safety profile,
here's the risk-benefit balance and you should decide.
You're a smart person, you should decide.
Now, companies are gonna do differently, right?
Companies may say you have to be vaccinated to work here.
My employer, Columbia, said we have to be vaccinated
to work in the fall and if you wanna be a student,
you have to be vaccinated.
So you decide whether you wanna go or not.
But the idea that you should make a decision
based on longterm effects, there is no evidence, right?
So how can you make a decision
where you don't have evidence?
Whereas we do have evidence
that there are longterm effects of getting COVID.
So I don't think that's a fair argument
and it just makes people scared to say that.
But on the other hand, for some of the say it's a no-brainer
and to denigrate people for not being vaccinated,
that's not the approach either
because they're gonna dig in and say,
I'm not doing this because you tell me to, right?
I think the middle ground is to say,
take a bit of both and say,
here are the potential issues and here are the benefits
and this is what I would do
and you have to just decide on your own.
I'd leave it to them.
I say, you decide and if you don't want to, you know,
it's up to you, you don't have to get vaccinated
and you'll probably get infected at some point
and maybe you'll be okay.
But here's the best available data
and it looks like the vaccines are pretty damn smart solution.
They seem to work.
I think you tell people what you did
and present both sides calmly
and I think digging in, you know, as like in a debate,
I don't think that's terribly useful.
So that's my view.
I mean, people come to me all the time
and ask me, I'm worried, what should I do?
And I said, what are you worried about?
Let's talk about it and go through it calmly.
And if they want to still take ivermectin,
I said, it's fine, it's your choice and I have a problem
with that.
I love that.
I love that's the way you think.
People should definitely listen to this week in virology
and follow your work is brilliant.
I've been really enjoying it lately.
It's like, it's my favorite way to stay in touch
with the happenings of COVID.
Obviously you put in a lot of other stuff in there, but.
We used to do other viruses before COVID.
It was quite interesting.
And I'm trying to slip other viruses in
because I think they're informative in many ways
and we're gonna do more and more of that.
But I have to say, I canceled,
usually I record on Tuesday and Friday
and I canceled today so I could be with you.
Huge honor, I appreciate that.
No, no, it's fine.
I think a couple of other people
were gonna be away anyway, so.
So I do a lot of different pods.
They're all on YouTube and I also do a live stream
on Wednesday nights on YouTube, which you can find.
And that's where people can come and ask questions.
We don't have an agenda, we just start
and by 30 minutes in, there's 700 people
with questions that I can't even get through
because there's so many of them.
And I'm actually astounded that so many people
are have really good questions.
Most of them are reasonable and they come back every week.
So it's a great, it's turning into a great forum
to have a nice discussion.
And the YouTube channel is called what?
So you could search for my name,
which is Vincent Radkin Yellow, it'll turn up
or my handle on YouTube is ProfVRR, P-R-O-F-V-R-R.
Have you read The Plague by Camus by any chance?
Years ago, years ago, I have to read it again.
That's really relevant.
Let me ask you a question about it.
It describes a town that's overtaken by a plague
and it's blocked off from the rest of the world
and it kind of reveals the best, the worst of human nature.
That's like how people respond to that,
sort of the encroaching that their own mortality,
their own death and the horizon.
I think one of the messages in the book
that ultimately like love for others.
So it's like a lot of people want to become isolated
and they hide from each other,
but ultimately the thing that saves you is love,
which is one of the things of just watching this pandemic,
you know, with the distance, with the masks,
that's all fine,
but there's a distancing from people
of that attention, the breaking
of the common humanity between people.
That's one of the reasons I,
when I came to Austin earlier this year just to visit,
I fell in love with the city
because even with the masks and the distance,
there was still a camaraderie,
like I don't know, just a love for each other,
just a kindness towards each other.
And that's what I took away from the plague.
Mostly it's told the story of the doctor
who basically gives in
and just gives himself as a service to others.
And that love is the thing that liberates him
from his own conception of mortality.
The fact that he's here, he's going to die.
What do you think about this, the effect of the virus?
We talked a lot about biology,
but the effect of the virus
and the fabric of the common humanity that connects us.
Well, that's what a pandemic does.
It really cuts that, right?
Because small outbreaks are local,
they don't have global effects,
but when you have something this big
where pretty much nobody escapes
and not just making people sick,
it changes your life, right?
People lose jobs, they change jobs,
they move somewhere else,
they have all kinds of disruptions,
kids can't go to school, really shows you.
I mean, I always like to say
a tiny virus can bring earth to its knees.
A tiny virus that you can't even see them,
that most people don't even think about most of the time.
And the real effect is not just sickness,
it's what it does to people
because in the end we are animals
and most animals like each other
and they interact, they have great social structures
and that makes them do well.
I guess the exception is people in AI, right?
They could be on their own.
Well, that's why you build robots that you fall in love with.
That's right.
And so I think when a,
the real story is what it does to society for sure,
which has ramifications way beyond
the number of people dying and the vaccines
and the tests and all of that.
And this one has really made a big rupture
and you could tell not now so much,
I think being out and about now,
things look pretty normal except,
for some people wearing masks,
you would never know.
I mean, the airport this morning was completely jammed.
People going, and they're all on vacation,
they're all wearing shorts, right?
So they're back to normal, it's August.
But last year was really different in New York
where you're used to lots of people on the street,
it was eerie, it was just quiet.
But under it all, people are still,
most people help each other when they have to, right?
Most people are willing to,
if something happens to someone to reach out and help them,
there are always exceptions where people are mean
and that's just the way animals are.
We're not the only ones that can be mean to our own species.
But I think most of the motivation for everything
that was done is to help other people.
I mean, I do think that the vaccine manufacturers,
maybe not the leaders, but the people working in the labs
really wanted to get this out quickly and help people, right?
I think at every level, people who are contributing
really wanted to help other people
and feel proud that they're able to do that.
So I view it as, we're never gonna be 100% good
because animals are not.
Evolution made us, I mean, we're lucky.
We somehow rose above by having incredible brain
and so forth, but a lot of our base instincts are animals
and they chase each other and have alpha males
and all that stuff.
And we always have a little bit of that in us,
but we do have some humanity
that this really ripped up, it really did.
And I think for me, someone who studied,
viruses for over 40 years, it's just amazing
that an invisible thing can do that, right?
It goes back to the thing you found fascinating,
which is a virus affecting human behavior
or behavior of the organism.
Yes, so humans can make weapons and do harm
and you can see that, but this you can't even see.
You can't, and look what it has done.
And it'll do it again, there'll be more.
I just, I wish we would be more prepared
because we know what to do.
We know we should be making antivirals vaccines masks,
testing masks, making test modalities
that we can really quickly redesign.
But after SARS-1, all that went out the door.
People didn't do anything
and that's why we're in this situation.
So, people ask me this all the time,
are we gonna be ready for the next one?
And I always say, we should be.
We have all the information we need to know what to do.
But somehow, I think people forget.
That said, sometimes we really step up
when the tragedy is right in front of us.
We do.
On the catastrophic.
So, I don't know, somehow humans have still survived.
The fact that we had nuclear weapons for so many decades
and we're still not blowing each other up,
whether by terrorists or by nation, is-
It's amazing.
It's quite surprising.
That's always, after reading the Pentagon Papers,
it's even more amazing, right?
So, I don't know how we do it.
I tend to believe there's that at the surface,
you notice the greed, the corruption, the evil,
but the core of human nature, the human spirit,
is one in the scientific realm is curiosity
and more deeply is kindness, compassion
and wanting to do good for the world.
I believe that desire to do good outpowers
all the other stuff by a large amount.
And that's why we don't, we have not yet destroyed ourselves.
We kind of, there's a lot of bickering.
There's a lot of wars on the surface, but underneath it all,
there's this ocean of love for each other.
I mean, I think there's an evolutionary advantage to that.
And it would be a good explanation
why we still haven't destroyed ourselves.
Oh, we had so many opportunities.
If you look at all the wars in history, so many.
I was just, my son was telling me
about the Ottoman Empire, right?
I mean, it's just, war after war.
And then other countries splitting up countries
with no regard to who's living where, right?
It's just, how can these people do this?
Yeah, it's fascinating.
Human history is fascinating.
And we're still young as a species.
We have a lot more time to go
and a lot more ways to destroy ourselves.
Do you have advice, like you said,
you have many decades of research
and incredible career and life.
Do you have advice for young people about career,
about life, people in high school, people in college,
of how to live a life that can be proud of?
So what I like to do is tell people, don't plan it
because I didn't plan anything.
Everything I did was one step at a time.
You don't have to plan.
I just found things that were interesting to me.
And so my father was a doctor
and he wanted me to be a doctor,
but I was not interested in taking care of people.
I learned that, but I couldn't say no to him.
So I was a biology major in college and I graduated
and I didn't have anything to do.
So I liked science.
So I got a job in a lab and it was very exciting.
And that led to everything else
that I've done one step at a time.
And I think the most important thing you can do,
whether two important things,
you could be really curious all the time.
You mentioned curiosity.
I think curiosity is essential.
You have to be curious about everything.
And if you are, you're never gonna be bored.
And so people who say they're bored,
I say, you are not curious.
You should just think about things
and say, look at something and say, how does that work?
Or what is it doing and how do they get there?
And you'll never be bored.
And the other thing is when you find something,
which may take time, it's fine.
You have to be passionate about it.
You have to put everything into it.
And that's what I did with viruses.
So I think they're amazing.
And I tell my classes, I love viruses.
They're amazing.
And people think I'm morbid
because obviously they kill people
and I shouldn't love something that,
but that's not the point.
That's not what I mean.
I love them in the way they have emerged
and how they work and so forth
and all that we don't know about them.
So you need to be curious and passionate
and don't plan too much.
And just find something that you don't call a job.
Because someone said on the live stream last week,
I wish I had a job I liked as much as you.
I said, it's not a job.
I never looked at it as a job.
It's my vocation.
It's my passion.
If it's a job, then you're not gonna like it.
Yeah, something that doesn't feel like a job.
So you said viruses are kind of passive,
non-living, you could say.
Or even cells are passive.
And humans are kind of active.
We seem to be making our own decisions.
So let me ask you the why question.
What do you think is the meaning of this life of ours?
Oh, there's no meaning.
It just happened.
It's an accident.
I think there's no life elsewhere
because this was just a rare accident that happened
and the right conditions.
I mean, people all think I'm wrong
because there are billions and billions of stars out there.
So there's a lot of opportunity.
There's no meaning.
It's just a, what do they call it?
A perfect storm of events
that led to molecules being formed and eventually,
I mean, it took a long time for life to evolve, right?
But it's just driven by conditions.
If something emerged that worked,
it would then go on to the next step.
There's no meaning other than that.
The only difference is that we,
I don't think many other animals can probably,
we have the ability, we're sentient, right?
We can influence what happens to us.
We can take medicines, right?
We can alter what would normally happen to us
so we can remove some of the selection pressure.
But I think everything else on the planet just goes,
looks for food and give a lot of offspring
so you can perpetuate.
It's just a natural biological function.
Yeah, they're much more directly concerned with survival.
I think humans are able to contemplate their mortality.
We can see that even if we're okay today,
we're eventually going to die
and we really don't like that.
So we try to come up with ways
to push that deadline farther and farther away.
Well, we have really,
I mean, we used to die in our 30s, right?
Now it's 70s, 80s.
Well, most of us used to die in the first few weeks.
That's true.
Yeah, infant death.
I always tell people the only thing that's 100% is death.
It's the only thing in the world that's 100%.
Do you think about your own mortality?
Yeah, I never think about it.
I'm just enjoying day to day.
And I don't think about it.
Really, you work on viruses.
You don't contemplate your own mortality
given the deadliness of the virus around us.
I never thought COVID would kill me.
No, I never was afraid of that, not at all.
I've mostly feared for other people getting sick,
especially people who could die of it
and want that to happen to them.
But I always thought that,
it's obviously not a realistic viewpoint not to be worried
because many people are,
but I've been relatively healthy.
They should sequence my genome
because it works really well and have a good immune system.
Maybe you'd be the first immortal person.
I don't think so.
There's gotta be a first.
I don't think so.
I think that biologically, you just can't,
you know, the ends of our chromosomes
keep getting shorter and shorter
and that's eventually what kills us.
So we just can't keep going on.
But that's fine, I don't need to.
I understand from the vampires
that it's not good to live forever.
I guess make the most of the time you got.
That's the, bacteria live a much shorter time.
So we got that on bacteria.
Bacteria are just, you know, little bags of chemicals
that split.
So they have no, they have no stake in the matter at all.
It doesn't bother.
And I think that you have to go a long ways
before you get into some kind of consciousness, but.
Yes, weird that this bag of chemicals
has a stake in the matter.
Like our human body is a consciousness is a weird thing.
Not just in us, but they make half of the oxygen
on the planet.
20% of the oxygen comes from bacteria.
And they made, in the beginning of Earth,
they made enough oxygen to start oxygenation going,
life going.
I mean, it's, they have an incredible role.
It's all an accident.
Just happen.
Well, Vincent, like I told you, I'm a huge fan.
It's a big honor that you were talking with me today.
Thank you so much for coming down.
Thank you for spending so much time with me.
And thank you for everything you do in terms of educating
about viruses, about biology, microbiology
and everything else.
I can't wait.
Everybody should check out Vincent's YouTube,
watch his lectures, listen to the podcast.
It's truly incredible.
Thank you so much for talking, Davidson.
My pleasure.
Thanks for listening to this conversation
with Vincent Racaniello.
To support this podcast,
please check out our sponsors in the description.
And now let me leave you with some words
from Isaac Asimov.
The saddest aspect of life right now
is that science gathers knowledge
faster than society gathers wisdom.
Thank you for listening and hope to see you next time.