back to index

Vincent Racaniello: Viruses and Vaccines | Lex Fridman Podcast #216


small model | large model

link |
00:00:00.000
The following is a conversation with Vincent Recaniello,
link |
00:00:03.400
professor of microbiology and immunology at Columbia.
link |
00:00:08.120
Vincent is one of the best educators in biology
link |
00:00:10.840
and in general that I've ever had
link |
00:00:12.520
the pleasure of speaking with.
link |
00:00:14.360
I highly recommend you check out
link |
00:00:16.120
his This Week in Virology podcast
link |
00:00:19.040
and watch his introductory lectures on YouTube.
link |
00:00:22.520
In particular, the playlist I recommend
link |
00:00:24.920
is called Virology Lectures 2021.
link |
00:00:28.720
To support this podcast,
link |
00:00:30.040
please check out the sponsors in the description.
link |
00:00:33.640
As a side note, please allow me to say
link |
00:00:35.800
a few words about the COVID vaccines.
link |
00:00:38.320
Some people are scared of a virus hurting
link |
00:00:41.000
or killing somebody they love.
link |
00:00:43.280
Some are scared of their government betraying them,
link |
00:00:46.720
their leaders blinded by power and greed.
link |
00:00:50.360
I have both of these fears.
link |
00:00:52.160
And two, I'm afraid, as FDR said, of fear itself.
link |
00:00:57.160
Fear manifests as anger and anger leads to division
link |
00:01:01.120
in the hands of charismatic leaders
link |
00:01:03.200
who then manufacture truth in quotes
link |
00:01:06.600
that maximize controversy and a sense of imminent crisis
link |
00:01:10.160
that only they can save us from.
link |
00:01:13.160
And though I'm sometimes mocked for this,
link |
00:01:15.920
I still believe that love, compassion, empathy
link |
00:01:20.520
is the way out from this vicious downward spiral of division.
link |
00:01:24.240
I personally took the vaccine
link |
00:01:26.240
based on my understanding of the data,
link |
00:01:28.520
deciding that for me, the risk of negative effects
link |
00:01:30.880
from COVID, short term and long term,
link |
00:01:33.840
are far worse than the negative effects
link |
00:01:36.200
from the mRNA vaccine.
link |
00:01:38.640
I read, I thought, I decided, for me.
link |
00:01:43.480
But I never have and never will talk down to people
link |
00:01:47.280
who don't take the vaccine.
link |
00:01:49.160
I'm humble enough to know just how little I know,
link |
00:01:52.480
how wrong I have been and will be
link |
00:01:55.480
on many of my beliefs and ideas.
link |
00:01:58.160
I think dogmatic certainty and division
link |
00:02:01.080
is more destructive in the long term than any virus.
link |
00:02:04.720
The solution for me personally, like I said,
link |
00:02:07.520
is to choose empathy and compassion
link |
00:02:09.600
towards all fellow human beings,
link |
00:02:12.360
no matter who they voted for.
link |
00:02:14.760
I hope you do the same.
link |
00:02:16.400
Read, think, and try to imagine
link |
00:02:19.880
that what you currently think is the truth
link |
00:02:22.840
may be totally wrong.
link |
00:02:24.760
This mindset is one that opens you to discovery,
link |
00:02:27.760
innovation, and wisdom.
link |
00:02:30.400
I hope my conversation with Vincent Racanello
link |
00:02:33.040
is a useful resource for just this kind of exploration.
link |
00:02:36.080
He doesn't talk down to people
link |
00:02:37.920
and he's the most knowledgeable virologist
link |
00:02:40.400
I've ever spoken to.
link |
00:02:42.040
He has no political agenda,
link |
00:02:43.960
no desire to mock those who disagree with him.
link |
00:02:47.200
He just loves biology
link |
00:02:49.000
and explaining the fundamental mechanisms
link |
00:02:51.280
of how biological systems work.
link |
00:02:54.040
That's a great person to listen to
link |
00:02:55.720
and learn from with an open mind.
link |
00:02:58.040
I hope you join me in doing so,
link |
00:02:59.880
and no matter what,
link |
00:03:01.120
try to put more love out there in the world.
link |
00:03:04.720
This is the Lex Friedman Podcast
link |
00:03:06.560
and here is my conversation with Vincent Racanello.
link |
00:03:11.280
You mentioned in one of your lectures on virology
link |
00:03:14.480
that there are more viruses
link |
00:03:16.040
in a leader of coastal seawater
link |
00:03:17.880
than people on earth.
link |
00:03:20.560
In the Nature article titled Microbiology by Numbers,
link |
00:03:25.560
it says there are 10 to the 31 viruses on earth.
link |
00:03:29.600
Also it says that the rate of viral infection
link |
00:03:33.600
in the ocean stands at 10 to the 23 infections per second.
link |
00:03:39.200
And these infections remove 20 to 40%
link |
00:03:42.440
of all bacterial cells each day.
link |
00:03:45.160
There's a war going on.
link |
00:03:47.200
Do you, what do you make of these numbers?
link |
00:03:49.360
Or why are there so many viruses?
link |
00:03:52.400
So the numbers you're quoting,
link |
00:03:54.600
they're in my first virology lecture, right?
link |
00:03:57.920
Because people don't know these numbers
link |
00:04:00.720
and they get, whoa, they get wild by them.
link |
00:04:02.560
So I love to give them.
link |
00:04:04.160
So the way, sorry to interrupt.
link |
00:04:06.280
As I was saying offline,
link |
00:04:08.680
you have one of the best introductory lectures on virology
link |
00:04:12.320
that I've ever seen, introductory lectures, period.
link |
00:04:14.760
So I highly recommend people
link |
00:04:16.680
find you on YouTube and watch it
link |
00:04:18.440
if you're curious at all about viruses.
link |
00:04:20.480
It, yeah, there's a lot of times throughout watching it,
link |
00:04:24.920
I felt like, whoa.
link |
00:04:26.480
Yeah, that's my goal is to work.
link |
00:04:28.280
And that's what my students tell me.
link |
00:04:29.800
One student once said, every day after every lecture,
link |
00:04:33.240
I could go home and tell my roommate something
link |
00:04:35.960
she didn't know and blew her away.
link |
00:04:38.840
So the number of viruses is really an amazing number.
link |
00:04:42.080
So that number 10 to the 31 is actually
link |
00:04:45.200
just the bacterial viruses in the ocean.
link |
00:04:48.800
So there are viruses that infect everything
link |
00:04:50.880
on the planet, including bacteria.
link |
00:04:52.400
There are a lot of bacteria in the ocean.
link |
00:04:54.720
And so 10 to the 31 is from basically particle counts
link |
00:04:58.280
of seawater all over the world.
link |
00:05:00.200
So there are more viruses than 10 to the 31,
link |
00:05:02.560
but just in the ocean.
link |
00:05:04.240
And that number is so big.
link |
00:05:06.920
First of all, the mass exceeds that of elephants
link |
00:05:10.320
on the planet by a thousand fold.
link |
00:05:12.040
And if you lined up those viruses end to end,
link |
00:05:15.840
they would go 200 million light years into space.
link |
00:05:19.720
It's so big a number.
link |
00:05:21.600
It's amazing.
link |
00:05:23.000
And then yes, 10 to the 20 some infections per second
link |
00:05:27.560
of these viruses killing bacteria
link |
00:05:30.240
and releasing all this organic matter.
link |
00:05:32.680
And that's part of this, what we call
link |
00:05:35.040
the biogeochemical pump, cycling of material in the ocean.
link |
00:05:39.680
The bacteria die, they start to sink
link |
00:05:42.600
and then they get metabolized
link |
00:05:45.120
and converted to compounds that are needed.
link |
00:05:48.200
A lot of it gets released as carbon dioxide and so forth.
link |
00:05:50.960
So these are actually really important cycles
link |
00:05:52.800
that are catalyzed by the virus.
link |
00:05:54.480
Well, it's so wild that nature has developed
link |
00:05:56.320
a mechanism for mass murder of bacteria.
link |
00:05:59.680
That's one way to look at it,
link |
00:06:00.840
but it's just what happened, right?
link |
00:06:02.840
It's interesting.
link |
00:06:03.680
I mean, I wonder what the evolutionary advantage
link |
00:06:06.400
of like such fast cycling of life is.
link |
00:06:10.800
Is it just an accident of evolution
link |
00:06:13.360
that viruses are so numerous
link |
00:06:16.200
or is it a feature and not a bug?
link |
00:06:20.800
So the fast is, it's not all fast.
link |
00:06:25.320
Not all viruses are fast.
link |
00:06:26.640
Some are 20 minutes per cycle.
link |
00:06:28.720
Some take weeks per cycle, but that's just per second.
link |
00:06:33.720
There's so many viruses in the ocean
link |
00:06:35.640
that that's what you get per second,
link |
00:06:36.920
no matter how fast the cycle is.
link |
00:06:39.280
But I look at it this way.
link |
00:06:41.760
Viruses were probably the first organic entities
link |
00:06:46.000
to evolve on the planet.
link |
00:06:48.200
Long ago, billion years ago,
link |
00:06:50.840
just as the earth cooled
link |
00:06:52.080
and organic molecules began to form,
link |
00:06:55.480
I think these self, we call them self replicators.
link |
00:07:00.480
They're just short things that today,
link |
00:07:02.720
would look like RNA, which is the basis of many viruses.
link |
00:07:07.720
They evolved and they were able to replicate.
link |
00:07:09.960
Of course, they were just naked molecules.
link |
00:07:12.400
They had no protection and it was just RNA based.
link |
00:07:16.320
And that's tough because RNA is pretty fragile in the world.
link |
00:07:20.560
And it probably didn't get very big as a consequence.
link |
00:07:24.760
But then proteins evolved and I'm skipping like hundreds
link |
00:07:28.920
of millions of years of evolution.
link |
00:07:30.400
Proteins evolved, maybe without a cell, maybe with a cell.
link |
00:07:35.400
But then to make a cell,
link |
00:07:38.240
there probably were some RNA based cells early on,
link |
00:07:40.800
but they were pretty simple.
link |
00:07:42.240
But the cells that we know of today,
link |
00:07:43.840
even bacteria and single celled eukaryotes,
link |
00:07:48.360
they have very long DNA genomes.
link |
00:07:50.720
And you need a lot of DNA to make a complicated cell.
link |
00:07:54.360
And so we think at some point, the RNA became DNA.
link |
00:07:59.360
And probably one of the earliest enzymes that arose
link |
00:08:04.080
is the enzyme that could copy that RNA into DNA,
link |
00:08:06.480
which we now know today as reverse transcriptase,
link |
00:08:09.040
which my former boss, David Baltimore
link |
00:08:11.560
and Howard Temin co discovered.
link |
00:08:14.160
And that enzyme arose and copied RNA to DNA.
link |
00:08:19.400
And then you could build big cells with DNA
link |
00:08:22.080
because DNA can be millions and millions of bases
link |
00:08:24.600
in length and RNA, the longest RNA we know of
link |
00:08:27.720
is 40,000 bases, not much bigger than the SARS CoV2.
link |
00:08:32.880
What would you say is the magic moment along that line?
link |
00:08:36.200
I saw it was one or two billion,
link |
00:08:39.920
maybe three billion years it took
link |
00:08:43.840
to go from bacteria to complex organism.
link |
00:08:49.240
It seems like Earth had a very long time,
link |
00:08:52.800
not a very long time without life,
link |
00:08:54.800
and then a very long time with very primitive life.
link |
00:08:59.920
Maybe I'm discriminating, calling bacteria primitive life.
link |
00:09:03.200
People would object to you doing that for sure.
link |
00:09:06.240
But it seems like complex organism
link |
00:09:07.800
when it starts becoming something like,
link |
00:09:11.040
I don't know what's a good, not animal like,
link |
00:09:13.320
but more complexity than just like a single cell.
link |
00:09:17.800
What do you think is the magic there?
link |
00:09:20.040
What's the hardest thing?
link |
00:09:21.000
If you were trying to engineer Earth and build life
link |
00:09:23.600
and build the simulations,
link |
00:09:25.080
obviously we're living in a video game, what this is.
link |
00:09:27.880
So if you were trying to build this video game,
link |
00:09:29.160
what's the hardest part along this evolution?
link |
00:09:32.080
Bacteria are mostly single cells.
link |
00:09:36.080
They do make colonies.
link |
00:09:37.520
They get together in biofilms, which are really important.
link |
00:09:41.160
But they're all single bacteria in that.
link |
00:09:43.840
And the key is making an organism
link |
00:09:46.760
where cells do different things.
link |
00:09:49.360
We have skin cells and eye cells and brain cells.
link |
00:09:51.760
Bacteria never do that.
link |
00:09:53.320
And the reason is probably energy.
link |
00:09:55.520
Bacteria can't make enough energy to do that.
link |
00:09:58.920
And so there was another cell
link |
00:10:02.600
existing at the time, the archaea.
link |
00:10:06.120
And the idea is that a bacteria went into an archaea
link |
00:10:10.160
and became the modern day mitochondria,
link |
00:10:13.120
the energy factory of the cell.
link |
00:10:14.960
And that now led that cell
link |
00:10:17.480
develop into more and more complicated organisms
link |
00:10:19.880
like we have today.
link |
00:10:20.720
It was all about energy.
link |
00:10:21.800
So the mitochondria, the energy,
link |
00:10:24.520
the mitochondria is the magic thing.
link |
00:10:26.440
I think so.
link |
00:10:27.280
It's just actually not my idea.
link |
00:10:28.720
It's Nick Jones.
link |
00:10:29.560
Have you heard of Nick Jones?
link |
00:10:30.600
He's an evolutionary biologist in the UK.
link |
00:10:33.480
And he's done experimental work on this.
link |
00:10:36.400
And it's his idea that the defining point
link |
00:10:39.440
was the ability to make a lot of energy,
link |
00:10:41.840
which a mitochondria can do.
link |
00:10:43.080
It's basically a whole bacteria inside of a bigger cell.
link |
00:10:46.240
And that becomes what we now call eukaryotes
link |
00:10:48.240
and that they can get more and more complicated.
link |
00:10:51.640
So let me bring you back to the viruses.
link |
00:10:53.200
I wanna finish that story.
link |
00:10:54.320
Yeah, which points of viruses come along?
link |
00:10:56.280
So remember, we have these precellular,
link |
00:10:58.800
they're called precellular replicons, right?
link |
00:11:01.480
And so we have a precellular stage
link |
00:11:05.240
where we have these self replicating molecules
link |
00:11:08.720
and then cells arise.
link |
00:11:10.600
And then the self replicating molecules invade the cells.
link |
00:11:15.720
Why?
link |
00:11:16.560
Because it's a hospitable environment.
link |
00:11:17.960
I mean, they didn't know that.
link |
00:11:19.240
They just went in and it turned out
link |
00:11:20.560
it was beneficial for them, so it stuck.
link |
00:11:23.480
And they replicate inside the cell now
link |
00:11:25.600
where they have pools of everything they need.
link |
00:11:27.480
They get more and more complicated.
link |
00:11:29.240
And then they steal proteins from the cell
link |
00:11:31.880
to build a protective shell.
link |
00:11:34.240
And then they can be released as virus particles.
link |
00:11:36.920
They're now protected.
link |
00:11:37.840
They can move from host to host.
link |
00:11:39.920
And because they're at the earliest stages
link |
00:11:43.560
of cellular evolution, they can diversify
link |
00:11:46.680
to infect anything that arises.
link |
00:11:48.400
And that is why I think there's so many of them
link |
00:11:52.320
and everything on the planet is infected
link |
00:11:54.560
because the ancestor of everything
link |
00:11:56.080
was infected many years ago.
link |
00:11:57.480
So it's easier to steal than to build from scratch.
link |
00:12:01.680
So it's easier to sort of break into somebody else's thing
link |
00:12:05.280
and steal their proteins.
link |
00:12:06.400
Yes.
link |
00:12:07.520
My colleague, Dixon de Palmier, calls viruses safe crackers.
link |
00:12:11.360
Safe crackers.
link |
00:12:12.680
So it's just, from an evolutionary perspective,
link |
00:12:15.800
it's easier to steal because you can select.
link |
00:12:20.720
But then you have to figure out mechanisms for stealing,
link |
00:12:23.320
for breaking into, for cracking the state.
link |
00:12:25.640
Well, you don't have to figure out.
link |
00:12:26.920
It just happens, right?
link |
00:12:28.560
Because molecules are so diverse
link |
00:12:30.920
that a molecule gets into a cell
link |
00:12:33.360
and if there's a protein that sticks to it,
link |
00:12:35.760
it's gonna stick and that gives an advantage.
link |
00:12:39.400
There's no planning.
link |
00:12:41.120
There's no thinking about it, right?
link |
00:12:43.040
It just happens.
link |
00:12:44.960
Oh, we'll return to that.
link |
00:12:46.240
Ha ha ha ha ha.
link |
00:12:48.280
What, but these numbers are crazy.
link |
00:12:50.840
So what, as these more complex organisms evolved,
link |
00:12:55.880
let's take us humans as an example,
link |
00:12:58.960
should we be afraid of these high numbers?
link |
00:13:01.360
Should we be worried
link |
00:13:02.320
that there's so many viruses in the world?
link |
00:13:05.240
Well, to a certain extent.
link |
00:13:06.280
I mean, they have, it's twofold.
link |
00:13:08.200
They're good and bad, right?
link |
00:13:09.280
Viruses are no, there was no question they can be bad.
link |
00:13:12.000
We know that because they've infected
link |
00:13:14.040
and caused disease throughout history,
link |
00:13:15.480
but we're also, you and I are full of viruses
link |
00:13:17.880
that don't hurt us at all and probably help us
link |
00:13:20.200
and every organism is the same.
link |
00:13:22.000
So they are clearly beneficial as a consequence.
link |
00:13:25.880
So I think, so every living thing on the planet
link |
00:13:31.000
has multiple viruses infecting everything you can see.
link |
00:13:35.760
And most of them I think we don't worry about
link |
00:13:39.560
because they can't infect us.
link |
00:13:41.320
They're unable.
link |
00:13:42.160
In fact, now you can actually take your feces
link |
00:13:45.960
and send them to a company
link |
00:13:47.000
and they will sequence your viruses in your feces for you,
link |
00:13:49.960
your fecal virome, right?
link |
00:13:52.200
And the most common virus in human feces
link |
00:13:57.680
is a plant virus that infects peppers.
link |
00:14:00.480
It's called pepper model mosaic virus.
link |
00:14:03.120
And that's because people eat a lot of peppers
link |
00:14:05.040
and it just passes right through you.
link |
00:14:06.680
Cabbage is full of viruses from the insects
link |
00:14:09.160
that walk on the cabbage in the fields.
link |
00:14:10.880
We eat them, they just pass us.
link |
00:14:13.120
So I think most of the viruses we don't need to worry about
link |
00:14:16.360
except when we're talking about species
link |
00:14:19.480
that are closest to us, mammals, of course.
link |
00:14:23.160
And I think the most numerous ones
link |
00:14:25.320
are the most concerning, they're viruses like bats.
link |
00:14:28.320
Bats are 20% of mammals and rodents are 40% of mammals.
link |
00:14:33.480
And we humans live nearby, right?
link |
00:14:37.080
And we know throughout history,
link |
00:14:38.600
many viruses have come from bats and from rodents to people,
link |
00:14:41.440
no question about it.
link |
00:14:42.280
So there's a proximity in terms of just living together
link |
00:14:44.600
and a proximity genetically too.
link |
00:14:46.240
So it's more likely that a virus will jump
link |
00:14:48.800
from a bat and a rodent.
link |
00:14:49.880
And birds too.
link |
00:14:50.880
Birds can give us their viruses that's happened.
link |
00:14:53.880
Influenza viruses come from birds mainly.
link |
00:14:57.080
So I think those are the three species,
link |
00:15:00.640
not species, it's higher than species obviously,
link |
00:15:02.680
but those are the three I would worry about
link |
00:15:04.240
in terms of getting their viruses.
link |
00:15:05.960
And we don't really know what's out there, right?
link |
00:15:09.520
We have very little clue about what viruses,
link |
00:15:12.480
and I've for years wanted to capture wild mice
link |
00:15:16.480
in my backyard and see what viruses they have
link |
00:15:18.640
because no one knows.
link |
00:15:20.960
And it's an easy.
link |
00:15:21.800
We can't ask them, so you mean map,
link |
00:15:23.760
like is there a way?
link |
00:15:24.600
I can't ask them, yeah.
link |
00:15:25.440
No, I would have to sacrifice them and take tissue
link |
00:15:27.640
and then bring it in the lab and do genome sequencing.
link |
00:15:30.120
So you can do a thorough sequencing
link |
00:15:32.160
to determine which viruses.
link |
00:15:33.800
Is there a sufficiently good categorization of viruses
link |
00:15:37.400
where you'd be?
link |
00:15:38.240
That's a very good question.
link |
00:15:40.080
So whenever you do sequence, right?
link |
00:15:42.640
You get some environmental sample
link |
00:15:44.160
and you extract nucleic acid and you sequence it.
link |
00:15:47.120
What you do is you run it past the database.
link |
00:15:49.680
The gold standard is the GenBank database
link |
00:15:52.120
which is maintained here in the US.
link |
00:15:54.360
And you see if you get any hits.
link |
00:15:56.600
And then you can say, ah, look,
link |
00:15:58.560
this sequence is similar to this virus.
link |
00:16:01.080
And you can classify all the viruses you see.
link |
00:16:03.560
The problem is 90% of your sequence is dark matter.
link |
00:16:09.200
It doesn't hit with anything.
link |
00:16:11.120
It's probably a lot of it is unknown viruses.
link |
00:16:14.480
And that's gonna be hard to figure out
link |
00:16:16.080
because someone's gonna have to go after it
link |
00:16:17.640
and sort it through.
link |
00:16:18.960
So yes, you can find a lot of viruses
link |
00:16:21.600
and the numbers you get are astounding.
link |
00:16:22.960
You can find thousands of new viruses
link |
00:16:25.200
just by looking in various life forms.
link |
00:16:28.160
But there are many more that we don't pick up
link |
00:16:30.400
because they're not in the database.
link |
00:16:32.200
Maybe this is a good time to take a quick tangent.
link |
00:16:36.120
What do you think about Alpha Fold 2?
link |
00:16:38.000
I don't know if you've been paying attention to that.
link |
00:16:40.280
With them DeepMind solving the protein folding problem
link |
00:16:44.200
and then also releasing, first of all,
link |
00:16:47.800
open sourcing the code, which is for me
link |
00:16:49.960
as a software person, I love.
link |
00:16:52.240
And then second of all, also making like 300,000 predictions
link |
00:16:57.000
or something like that for different protein structures
link |
00:17:00.040
and releasing that data.
link |
00:17:01.760
Yeah.
link |
00:17:03.520
On the side of,
link |
00:17:04.360
because you're saying there's dark matter.
link |
00:17:06.840
Right.
link |
00:17:07.680
Is there something, first, what are your general thoughts,
link |
00:17:12.920
level of excitement about their work?
link |
00:17:15.920
And second, how can that be applied to viruses?
link |
00:17:19.400
Do you think we'll be able to explore
link |
00:17:20.800
the dark matter of virology using machine learning?
link |
00:17:24.520
Absolutely.
link |
00:17:25.360
Because in all this dark sequence,
link |
00:17:26.800
you can translate it and make a protein.
link |
00:17:29.880
You can see what a protein looks like.
link |
00:17:31.480
It has what we call an open reading frame, right?
link |
00:17:34.000
A start and a stop.
link |
00:17:35.280
And right now it's just a bunch of amino acids,
link |
00:17:37.520
but if we could fold it,
link |
00:17:39.800
maybe the fold would be like something we already know,
link |
00:17:43.200
some protein fold, which gives you a lot of clues, right?
link |
00:17:46.480
Because there are only so many protein folds in biology
link |
00:17:49.640
and that dark matter is probably one of them.
link |
00:17:52.600
So I think that's very exciting because for years,
link |
00:17:55.200
I've followed structural biologists for years
link |
00:17:59.560
and in the beginning,
link |
00:18:01.960
we couldn't even solve structures of viruses, they're too big.
link |
00:18:04.480
We could do small molecules like myoglobin,
link |
00:18:06.760
that was the first one done, took years to do that.
link |
00:18:09.400
Then as computational power increased,
link |
00:18:13.040
then they could start to do viruses,
link |
00:18:14.720
but it took a long time.
link |
00:18:16.760
X ray crystallography,
link |
00:18:18.400
depending on getting crystals of the virus, right?
link |
00:18:21.520
And now we can do cryo electron microscopy,
link |
00:18:24.440
which is much faster.
link |
00:18:26.360
You could solve,
link |
00:18:27.240
the spike of SARS COVID 2 was solved in two months
link |
00:18:29.680
by Jason McClelland here in Austin actually
link |
00:18:32.520
at the beginning of the pandemic,
link |
00:18:34.840
but you're limited, you can't do huge proteins.
link |
00:18:38.720
You can only do moderately sized ones.
link |
00:18:41.960
So, or actually you can do viruses,
link |
00:18:45.440
but you can't do small proteins.
link |
00:18:47.000
So that's speeded it up, but it's still too fast to solve.
link |
00:18:50.720
You get a new protein, you wanna solve its structure.
link |
00:18:52.720
So if we could predict it,
link |
00:18:53.840
and I know from talking to structural biologists,
link |
00:18:55.960
this has been their holy grail from day one.
link |
00:18:58.280
They wanna be able to take a sequence of a protein,
link |
00:19:00.880
put it in a computer and have the structure put out
link |
00:19:03.320
without having to do all the experiment.
link |
00:19:05.200
So that's why this is very exciting
link |
00:19:06.840
that you can predict it.
link |
00:19:08.560
That mean it's not finished obviously,
link |
00:19:10.800
and there's more to do,
link |
00:19:11.840
but I think it will be a day
link |
00:19:12.960
where you could take any amino acid sequence
link |
00:19:15.540
and predict what it's gonna look like.
link |
00:19:17.360
See, but like aren't structural biologists
link |
00:19:19.520
gonna get greedy?
link |
00:19:20.400
So once you have that,
link |
00:19:21.720
don't you wanna go more complicated then?
link |
00:19:24.040
Don't you wanna go,
link |
00:19:25.440
because that's just the first step, right?
link |
00:19:27.680
You go from amino acid to the structure,
link |
00:19:29.480
then there's like multiple protein interactions.
link |
00:19:32.120
Like how do you get to the virus?
link |
00:19:34.400
Well, so that's what the ultimate goal
link |
00:19:37.020
of getting a structure is that then you can do experiments
link |
00:19:39.700
and figure out what the structure means, right?
link |
00:19:42.400
So many, in the old days,
link |
00:19:44.880
structural biology was a career in itself.
link |
00:19:48.160
You worked with people who had a system
link |
00:19:50.000
and just solve proteins for them,
link |
00:19:51.360
and then you moved on to another one.
link |
00:19:52.520
You didn't really do any experiments.
link |
00:19:54.200
The other people got to do all the interesting experiments.
link |
00:19:57.000
Now, young structural biologists are multifaceted.
link |
00:20:02.300
They solve the structure,
link |
00:20:03.640
and then they say,
link |
00:20:04.480
what happens if we change this amino acid?
link |
00:20:06.520
Oh, look, it blocks binding to the receptor.
link |
00:20:09.000
This must be the receptor binding interface.
link |
00:20:11.240
So that's the exciting stuff, absolutely,
link |
00:20:13.400
is doing the experiment.
link |
00:20:14.480
Well, I wonder if you can do some kinds of like simulations
link |
00:20:18.780
of like, you know, different proteins
link |
00:20:22.240
or multi protein systems going to war against each other,
link |
00:20:27.640
like to try to figure out, you know,
link |
00:20:31.400
reinforcement learning is used in alpha zero, for example,
link |
00:20:35.360
to learn chess and go,
link |
00:20:37.120
and that's using the self play mechanism
link |
00:20:39.200
where the thing plays against itself
link |
00:20:41.360
and learns better and better.
link |
00:20:42.760
Whether you can, I wonder if you can simulate
link |
00:20:45.080
almost evolution in that way
link |
00:20:46.680
for primitive biological systems,
link |
00:20:49.560
have them in simulation, fight each other,
link |
00:20:52.600
and then see what comes out,
link |
00:20:53.640
like a super dangerous virus comes out
link |
00:20:55.680
or super like Chuck Norris type of thing
link |
00:20:58.480
that defends against the super dangerous virus,
link |
00:21:00.640
and it's all in simulation.
link |
00:21:01.840
So an example would be,
link |
00:21:03.680
we have all these variants of SARS COVID 2 arising, right?
link |
00:21:07.840
Which look to be selected by immune responses,
link |
00:21:13.080
but we know what amino acids are changing in the spike
link |
00:21:17.280
and how they block antibody binding.
link |
00:21:19.080
You could simulate that.
link |
00:21:20.360
You could say, what is the antibody looking at?
link |
00:21:24.960
Where antibodies bind on proteins are called epitopes, right?
link |
00:21:28.040
You could map them all and change them in a simulation
link |
00:21:30.400
one by one and go back and forth
link |
00:21:32.120
between the antibody and the virus.
link |
00:21:33.800
So all these, evolution is what we call an arms race, right?
link |
00:21:38.400
The virus changes and then it evades the host
link |
00:21:41.600
and then the host can change.
link |
00:21:43.240
The host takes longer to change though, unfortunately.
link |
00:21:45.240
It takes geological time, but it can.
link |
00:21:47.960
And then the virus can change
link |
00:21:49.640
and it can go back and forth.
link |
00:21:50.600
And we can see evidence of this in genome sequences
link |
00:21:54.360
of both viruses and their hosts.
link |
00:21:56.240
And so you can take a protein in a host
link |
00:22:00.040
that is a receptor for multiple viruses
link |
00:22:02.720
and you can see all the impacts of virus pressure on it.
link |
00:22:05.720
And you could simulate that for sure.
link |
00:22:07.280
And that's just one thing that you could do.
link |
00:22:09.000
You could simulate changes in say an enzyme
link |
00:22:13.680
that makes it resistant to a drug
link |
00:22:15.120
and predict all the drug resistance.
link |
00:22:18.240
But the problem is people like me,
link |
00:22:21.280
the experimental virologists
link |
00:22:22.800
don't know how to do any of that.
link |
00:22:24.040
So we need to collaborate with people, I guess.
link |
00:22:27.720
Oh, with other humans.
link |
00:22:29.680
We do that, we do that.
link |
00:22:31.480
But with people from a field that we're not used to,
link |
00:22:35.720
I suppose people who, would it be AI, I suppose?
link |
00:22:39.160
Yeah, machine learning people.
link |
00:22:40.000
Machine learning people.
link |
00:22:41.320
And you would say, look, this is the biological problem.
link |
00:22:44.400
Is there a way we can use your tools to attack it?
link |
00:22:46.960
The problem is those people are antisocial introverts
link |
00:22:51.680
that have a place like this
link |
00:22:55.160
and try to hide from other people in the world.
link |
00:22:57.200
Very difficult to find in the wild.
link |
00:23:00.120
Okay, so outside of doing amazing brilliant lectures online,
link |
00:23:04.960
you host and produce five, I would say, related podcasts,
link |
00:23:09.960
including my favorite, This Week in Virology,
link |
00:23:13.600
also This Week in Parasitism,
link |
00:23:16.280
This Week in Microbiology, and so on.
link |
00:23:18.640
So you're a good person to ask,
link |
00:23:21.080
what are the categories of small things,
link |
00:23:23.960
small biological things in this world that can kill you,
link |
00:23:27.320
kill us humans?
link |
00:23:30.120
Let's look, you said like most viruses are friendly
link |
00:23:33.360
or at least not unfriendly.
link |
00:23:35.840
But let's look at the unfriendly ones.
link |
00:23:38.960
And viruses and bacteria and those kinds of things.
link |
00:23:42.160
When you look at the full spectrum of things
link |
00:23:43.960
that can kill you, can you kind of paint a brief picture?
link |
00:23:47.240
Yeah, I think the big picture is that
link |
00:23:50.720
the things that can kill you are a minority
link |
00:23:52.720
of everything that's out there.
link |
00:23:54.320
And we're talking about molecules.
link |
00:23:57.240
So we have in us proteins that can kill us.
link |
00:24:01.320
Preons that are just, it's a protein in us.
link |
00:24:04.560
And if it misfolds, it makes all of its other copies misfold
link |
00:24:08.680
and then you die of a neurological disease.
link |
00:24:11.680
That's pretty rare.
link |
00:24:13.840
So there are proteins, there are viruses.
link |
00:24:16.480
And as I said, only certain ones can kill us.
link |
00:24:20.200
But even if we get those from animals,
link |
00:24:22.960
it's not straightforward.
link |
00:24:24.440
If you look at SARS CoV2, right?
link |
00:24:26.760
This is probably a once in a hundred year pandemic,
link |
00:24:29.880
I would say, equivalent to 1918 in its devastation.
link |
00:24:34.760
And in between there have been smaller pandemics
link |
00:24:36.560
of other viruses, but it doesn't happen all that often.
link |
00:24:39.600
So we have a lot of viruses.
link |
00:24:40.560
We have a lot of bacteria of various sorts
link |
00:24:43.600
that can cause infections in us.
link |
00:24:46.240
And it's a limited number, right?
link |
00:24:49.240
You're streptococci and staphylococci and clostridia.
link |
00:24:52.680
We could go on and on, but we know how to handle those.
link |
00:24:56.360
As long as we have antimicrobials,
link |
00:24:58.280
it's just that we abuse them and we get resistant.
link |
00:25:00.360
So that can be a problem.
link |
00:25:02.120
Then we have fungi, not mushrooms,
link |
00:25:04.840
but much smaller fungi that multiply sub microscopic
link |
00:25:09.440
or just at the microscopic level.
link |
00:25:11.400
They can, in dry climates of the US,
link |
00:25:13.920
you can inhale their spores and they can grow in your lung
link |
00:25:16.280
if you're immunosuppressed and so forth.
link |
00:25:18.800
So those are the tiny guys.
link |
00:25:21.080
And then we have parasites,
link |
00:25:22.320
which we do this week in parasitism,
link |
00:25:24.960
where single cells, even worms of various sorts
link |
00:25:30.040
can invade you and cause all sorts of problems.
link |
00:25:33.640
How, I was like kind of terrified to listen to that podcast.
link |
00:25:37.200
What's it like?
link |
00:25:39.720
Well, I mean, what you learn is that you can,
link |
00:25:45.200
you travel somewhere and you can get infected
link |
00:25:47.200
and bring it back home.
link |
00:25:48.720
Here in the US, we do have certain kinds of parasites,
link |
00:25:52.640
but because of our lifestyle,
link |
00:25:55.000
we more or less have avoided them.
link |
00:25:56.560
For example, there's a parasite called toxoplasma,
link |
00:26:00.440
which is infected most of the world, actually,
link |
00:26:03.960
because a lot of people like to eat raw meat
link |
00:26:06.160
and you would get it from raw meat.
link |
00:26:08.400
And we're not as fond of that here in the US.
link |
00:26:12.320
We like to cook our meat,
link |
00:26:13.320
but that could be a consequence of eating raw meat.
link |
00:26:16.440
Is that what leads to, what is it called, toxoplasmosis?
link |
00:26:19.840
Yeah, so toxoplasmosis, it's mainly,
link |
00:26:25.560
a big issue is if you're pregnant and you get toxo,
link |
00:26:28.400
then your fetus is gonna be very badly malformed.
link |
00:26:32.520
It's gonna have brain defects and so forth.
link |
00:26:36.240
And animals can get it as well.
link |
00:26:39.480
So there are a lot of parasites of that nature,
link |
00:26:41.280
which you often acquire by food,
link |
00:26:43.280
eating food of different sorts.
link |
00:26:45.000
And it usually happens elsewhere.
link |
00:26:47.560
On This Week in Parasitism, we do a case.
link |
00:26:50.840
So Daniel Griffin is our resident physician.
link |
00:26:54.320
He's a doctor, a real doctor, right?
link |
00:26:56.480
And every month, he comes up with a case.
link |
00:26:58.640
Okay, this is a person I saw.
link |
00:27:00.880
And last month, this young lady had traveled somewhere
link |
00:27:04.960
and she ate raw fish.
link |
00:27:09.600
It was somewhere Southeast Asia or something.
link |
00:27:11.920
And she ended up with red bumps all over her skin.
link |
00:27:15.880
And it turned out it was a parasite from the fish
link |
00:27:17.720
that moved around in her and very easy to cure.
link |
00:27:21.720
We have, if the right doctors and the right drugs,
link |
00:27:23.720
you can cure all these things.
link |
00:27:24.640
What about diagnose, like connect the red spots
link |
00:27:27.600
to the fact that it's a parasite?
link |
00:27:28.760
It's very easy if you have the right diagnostics.
link |
00:27:31.240
Now, Daniel often goes to parts of the world
link |
00:27:33.080
where they don't have diagnostics
link |
00:27:34.560
and he has to use other mechanisms.
link |
00:27:37.240
He may have to take a bit and look at it under a microscope.
link |
00:27:40.320
And then he may not be able to get the drug
link |
00:27:41.960
depending on where he is.
link |
00:27:43.840
But often he sees patients who come back to the US
link |
00:27:47.160
and they get diarrhea or they have a fever.
link |
00:27:49.640
And he said, where have you been?
link |
00:27:50.720
And he can put two and two together.
link |
00:27:52.200
And so we let our listeners do that.
link |
00:27:53.800
And they all send in guesses.
link |
00:27:55.240
And it's wonderful to hear them go through this.
link |
00:27:57.840
So there are a lot of parasites that can get you.
link |
00:28:00.760
You have to be careful about eating when you go overseas.
link |
00:28:03.360
And water too?
link |
00:28:04.640
Water as well.
link |
00:28:05.520
And in parts of Africa, there are parasites in the lakes
link |
00:28:09.200
that if you go swimming, they can invade you.
link |
00:28:11.840
And in fact, they can go into your hair follicles
link |
00:28:14.080
and burrow in and get into your bloodstream.
link |
00:28:15.960
That's exciting.
link |
00:28:16.960
So Daniel is interesting because he's very adventurous
link |
00:28:20.320
and he's not afraid of any of this.
link |
00:28:22.800
So there's a famous lake in Africa, Lake Malawi,
link |
00:28:26.040
which harbors a lot of these parasites.
link |
00:28:28.480
And he said, oh yeah, yeah, I just make sure
link |
00:28:30.280
I towel off vigorously when I get out and get rid of them.
link |
00:28:34.840
And that was the name of an episode.
link |
00:28:37.160
But food is, sushi, you can get worms from sushi.
link |
00:28:43.400
And the solution is to freeze it.
link |
00:28:46.800
And many sushi restaurants now have liquid nitrogen.
link |
00:28:49.880
They snap freeze their sushi and that kills all the parasites.
link |
00:28:53.000
And a study was actually done in Japan
link |
00:28:56.400
showing that freezing does not alter the taste of sushi
link |
00:28:59.240
because it's up, you see a big industry there.
link |
00:29:01.680
Wow, that's brilliant.
link |
00:29:03.240
That's brilliant.
link |
00:29:04.440
Yeah, I was thinking about, I'm so boring and bland
link |
00:29:10.560
that especially when I am now in Texas here
link |
00:29:12.640
and I've been eating quite a bit of barbecue,
link |
00:29:14.280
I realized I really haven't explored the culinary world.
link |
00:29:18.960
And I've been curious to travel and taste different foods.
link |
00:29:22.280
Is there something you could say by way of advice,
link |
00:29:26.680
channeling Daniel, I guess, if you were to travel
link |
00:29:30.160
in the world, if eating is the thing
link |
00:29:32.600
that gets you the parasites,
link |
00:29:34.560
what's a good advice for eating
link |
00:29:37.040
in strange parts of the world, Mongolia, India, China?
link |
00:29:41.760
Is there something you could say by way of advice?
link |
00:29:43.840
I think Daniel would say,
link |
00:29:45.200
make sure your food is cooked, right?
link |
00:29:47.520
Cooked, but that's so boring.
link |
00:29:49.040
Yeah, it's unfortunate.
link |
00:29:50.440
And he would agree with you
link |
00:29:52.200
because many vegetables are delicious.
link |
00:29:55.520
Salads even are delicious, not cooked,
link |
00:29:57.840
but they can have parasites in them.
link |
00:29:59.520
Meats, fish, people like to have uncooked fish.
link |
00:30:04.280
So if you wanna be really safe and boring,
link |
00:30:06.060
just make sure everything is cooked.
link |
00:30:07.920
And now we have a case this week on TWIP
link |
00:30:11.000
of a young man who went, I forgot where he went,
link |
00:30:14.200
but he stayed in a hotel.
link |
00:30:15.600
I think, oh, Oaxaca, Mexico.
link |
00:30:18.080
Stayed in a hotel.
link |
00:30:20.480
And he came back with diarrhea and fever.
link |
00:30:23.740
And he said, I don't know where, I stayed in the hotel.
link |
00:30:26.520
I just ate hotel food, lots of vegetables and fruits,
link |
00:30:30.000
and probably they weren't washed with clean water.
link |
00:30:32.960
He got something from that.
link |
00:30:34.840
The bottom line is most of these infections
link |
00:30:38.480
with parasites can be diagnosed,
link |
00:30:40.180
and you can be treated, and you'll be fine.
link |
00:30:42.680
So if you really wanna experience the cuisine,
link |
00:30:47.520
I don't think you should worry about it.
link |
00:30:49.240
That's what Daniel would say.
link |
00:30:50.680
Let's return to the basics.
link |
00:30:51.960
We can then jump around all over the place.
link |
00:30:54.840
What are the basic principles of virology?
link |
00:30:58.720
Maybe a good place to start is what is a virus?
link |
00:31:02.120
That's great.
link |
00:31:03.600
I mean, I talk in my first lecture for 20 minutes
link |
00:31:05.840
before I get to that.
link |
00:31:07.520
But, and I wonder if I should put it up front,
link |
00:31:10.060
but it's kind of a boring definition.
link |
00:31:12.100
So if you do that first, people will turn off.
link |
00:31:14.840
So first you tell them about all the millions and billions
link |
00:31:17.600
of viruses around.
link |
00:31:18.920
So a virus, we have a very specific definition
link |
00:31:22.720
because it's different from everything else on the planet.
link |
00:31:26.400
Because first of all, it's a parasite.
link |
00:31:28.960
It takes, a parasite means you take something
link |
00:31:32.060
from someone else.
link |
00:31:33.920
We have human parasites who take money from others, right?
link |
00:31:36.840
But in biological terms, a parasite takes something
link |
00:31:40.880
from the host that the host would otherwise use energy
link |
00:31:44.280
or some building block or something.
link |
00:31:46.200
There's never really a symbiotic relationship
link |
00:31:48.560
between a virus and a host.
link |
00:31:50.440
Well, there can be.
link |
00:31:52.000
So that's the dichotomy I think is that we define them
link |
00:31:54.640
as parasites, yet I just told you 20 minutes ago
link |
00:31:58.720
that many viruses are probably beneficial.
link |
00:32:01.520
So I think what it means is we, at some point
link |
00:32:04.480
we're gonna have to change our definition, right?
link |
00:32:06.800
Because after all, definitions we make are just constructs
link |
00:32:12.000
that make it easy for us to study,
link |
00:32:14.140
that don't necessarily represent what's right.
link |
00:32:16.760
Yeah, like Pluto was a planet at first
link |
00:32:20.420
and now it's not a planet anymore
link |
00:32:21.680
and a lot of people are very upset.
link |
00:32:23.360
But it's only according to us.
link |
00:32:24.700
There may be another race living somewhere else
link |
00:32:27.020
who thinks it's a planet, right?
link |
00:32:28.500
Well, maybe that's why viruses are attacking humans.
link |
00:32:30.680
They're very angry.
link |
00:32:31.560
They're calling them parasites.
link |
00:32:33.980
So right now our definition includes parasite
link |
00:32:38.000
because a virus cannot do anything without a cell.
link |
00:32:41.400
If this mug were full of viruses,
link |
00:32:44.040
it would not do anything for years.
link |
00:32:46.360
It would eventually probably lose its infectivity,
link |
00:32:49.040
but it's not gonna reproduce here, it needs cells.
link |
00:32:52.040
And to the first people who discovered viruses,
link |
00:32:54.240
that was astounding that they didn't just reproduce,
link |
00:32:57.360
divide on their own like bacteria.
link |
00:32:59.640
So a virus needs to get inside of a cell,
link |
00:33:02.640
inside the cell, it can't just hang around on the surface.
link |
00:33:05.520
It needs to get in in order to make more of itself.
link |
00:33:09.200
And so we call it an obligate intracellular parasite
link |
00:33:13.080
because it needs to get in a cell
link |
00:33:15.060
and then it takes things from the cell
link |
00:33:17.320
in the form of all kinds of molecules
link |
00:33:19.280
and processes and energy and so forth to make new viruses.
link |
00:33:23.640
Obligate means it's obligated to be inside the cell.
link |
00:33:26.240
Absolutely, it will not reproduce outside of the cell.
link |
00:33:30.800
So this mug of viruses can in no way be living,
link |
00:33:35.880
in my opinion.
link |
00:33:36.920
However, once it gets inside of a cell,
link |
00:33:39.160
now the cell is a virus infected cell, it's alive.
link |
00:33:42.320
So a virus, in my view, has two phases, right?
link |
00:33:45.360
It's this nonliving particulate phase
link |
00:33:48.200
that everyone is used to.
link |
00:33:50.600
I'll send you, you need a virus for your table.
link |
00:33:52.720
I'll send you a nice model.
link |
00:33:54.560
I think it would look good here.
link |
00:33:55.400
Which, yes, definitely.
link |
00:33:56.240
You don't have to go with all this other stuff.
link |
00:33:57.800
Yeah, well, these are all mechanical.
link |
00:33:59.560
There's no biology here.
link |
00:34:01.240
So you wouldn't want a virus here?
link |
00:34:02.480
No, I'd want a virus, of course.
link |
00:34:04.000
No, I'll send you one and then you can look at it.
link |
00:34:06.840
Because now that we have the three dimensional structures
link |
00:34:09.920
solved by structural biologists,
link |
00:34:12.600
we take the coordinates and we put it in a 3D printer
link |
00:34:14.720
and you can make amazing models, right?
link |
00:34:18.040
Of any virus.
link |
00:34:18.880
And so there's a huge variety of viruses?
link |
00:34:21.520
Huge, that we know of,
link |
00:34:23.320
which is only a fraction of what's out there.
link |
00:34:24.840
What's the categories?
link |
00:34:25.800
So there's RNA, there's DNA viruses.
link |
00:34:27.840
What are those, what's DNA and RNA?
link |
00:34:30.240
Two broad categorizations.
link |
00:34:33.920
RNA, these are genetic material.
link |
00:34:37.080
Can be two different chemicals.
link |
00:34:39.200
So RNA, everything else on the planet besides viruses
link |
00:34:43.120
is all DNA based.
link |
00:34:44.120
You and I are DNA based.
link |
00:34:45.280
Everything on the planet today is DNA based,
link |
00:34:47.320
except some viruses are RNA based.
link |
00:34:50.200
And that's because, as I mentioned earlier,
link |
00:34:53.120
the first life that arose on the planet was RNA based.
link |
00:34:57.240
Yeah, so these are like old school viruses.
link |
00:34:59.480
These are old school.
link |
00:35:00.600
We call relics, yeah.
link |
00:35:02.560
Relics, and this has got a name,
link |
00:35:04.480
it's called the RNA world, which I think is great.
link |
00:35:06.760
Is it big still, or are the relics dying out?
link |
00:35:09.640
Oh no, the relics, in my opinion,
link |
00:35:11.520
are the most successful viruses, the RNA viruses.
link |
00:35:14.880
And SARS CoV2 is an RNA virus.
link |
00:35:16.680
We can talk about why they're so successful.
link |
00:35:19.040
But you have, broadly speaking, viruses with RNA,
link |
00:35:22.720
genetic information, which are relics.
link |
00:35:24.920
Of course, they're contemporary.
link |
00:35:26.440
They have adapted to the modern world
link |
00:35:28.920
and the modern organisms living in it.
link |
00:35:31.160
And then we have DNA based viruses,
link |
00:35:33.240
which are extremely conservative and slow.
link |
00:35:36.440
They're very successful.
link |
00:35:37.800
Everyone has a herpes virus infection,
link |
00:35:40.040
but they don't get the news like the RNA viruses do.
link |
00:35:44.520
The HIVs and the influenza viruses
link |
00:35:46.800
and the SARS Coronaviruses, they get all the press
link |
00:35:49.880
and they're RNA based, because RNA lets you change
link |
00:35:52.880
more so than DNA.
link |
00:35:54.400
So they evolve much faster, the RNA viruses.
link |
00:35:57.240
Much faster.
link |
00:35:58.320
And in fact, I have an lecture on evolution.
link |
00:36:01.920
I don't know if you've listened to that one.
link |
00:36:03.800
You should, it's really, I think it's really interesting.
link |
00:36:07.760
RNA viruses exist at their error threshold,
link |
00:36:13.720
which means they can't make any more mutations
link |
00:36:17.120
when they reproduce, otherwise they're dead.
link |
00:36:19.560
They would go extinct.
link |
00:36:20.880
They're evolving at their error threshold.
link |
00:36:23.600
DNA viruses are hundreds of times lower
link |
00:36:26.280
than their error thresholds.
link |
00:36:28.400
And we know this, we can do an experiment to find that out.
link |
00:36:31.120
Now, why that is, is a good question,
link |
00:36:33.560
but that's the reason why RNA viruses
link |
00:36:38.240
are far more successful.
link |
00:36:39.400
They infect many more hosts and they're very,
link |
00:36:42.920
I would say slippery.
link |
00:36:44.120
They can change hosts really quickly,
link |
00:36:46.440
because in any animal harboring an RNA virus,
link |
00:36:50.440
like let's say a bat in some cave somewhere,
link |
00:36:52.960
it's not just one genome.
link |
00:36:55.160
It's millions of different genomes of all kinds,
link |
00:36:58.680
all within the framework of, say, coronavirus,
link |
00:37:01.240
but they're all different.
link |
00:37:02.600
And one genome in there might just be right
link |
00:37:04.760
for infecting a person if it ever encountered that person.
link |
00:37:08.200
I mean, that's the thing that.
link |
00:37:09.400
Or there could be a large number.
link |
00:37:11.240
This is a tiny fraction, but a large number of them.
link |
00:37:15.000
And they're all operating at the threshold of error.
link |
00:37:18.280
That's fascinating.
link |
00:37:19.120
It's like little, like it's like startups,
link |
00:37:21.560
little entrepreneurs, like a startup world.
link |
00:37:23.840
Yes, and many of them fail.
link |
00:37:25.160
Yeah, many of them fail.
link |
00:37:26.000
Many of the changes fail.
link |
00:37:26.840
And then there's the DNA viruses that are like the IBM
link |
00:37:29.200
and the Google. Exactly, exactly.
link |
00:37:30.520
The big corporations.
link |
00:37:31.720
That's very good, I like that.
link |
00:37:32.560
They become conservative with the bureaucracies
link |
00:37:34.120
and all that kind of stuff, so they.
link |
00:37:34.960
And a lot of baggage.
link |
00:37:36.240
Yeah, yeah, it's expensive for them to reproduce, yeah.
link |
00:37:39.440
And they don't move quickly.
link |
00:37:40.480
Yes, the RNA viruses are the fast moving members.
link |
00:37:43.760
So that's what a virus is.
link |
00:37:45.400
We call them ovulated intracellular parasites.
link |
00:37:48.840
And then I told you there's DNA and RNA,
link |
00:37:50.760
but then let's go further.
link |
00:37:52.880
The nucleic acid is not naked.
link |
00:37:56.120
Because naked nucleic acid in the world isn't good.
link |
00:37:59.800
I mean, it existed in the precellular world,
link |
00:38:03.440
but there probably weren't a lot of threats to it then.
link |
00:38:07.080
Naked nucleic acid doesn't last long in the environment.
link |
00:38:09.640
So they're covered, the nucleic acid is covered.
link |
00:38:12.120
It can be covered with a protein shell,
link |
00:38:13.920
a pure protein shell, or it can have a membrane around it,
link |
00:38:18.920
which would be lipids from the host cell.
link |
00:38:22.360
So lipids, so it's a fatty membrane.
link |
00:38:26.160
Fatty membrane, yeah, so our cells
link |
00:38:27.760
are coated with fatty membranes, right?
link |
00:38:30.440
Our cells, the outer plasma membrane, right?
link |
00:38:32.480
That's the same.
link |
00:38:33.320
Viruses can be too.
link |
00:38:34.320
So they're kind of like cells,
link |
00:38:35.720
but without the ability to do the mitochondria stuff.
link |
00:38:38.600
Some are, they don't have nuclei,
link |
00:38:41.120
they don't have mitochondria.
link |
00:38:42.760
But they do have a nucleic acid, they have a membrane,
link |
00:38:45.960
and then of course there's spikes in the membrane
link |
00:38:48.600
that allow them to attach to cells.
link |
00:38:51.200
And so that completes our two different kinds.
link |
00:38:53.320
So they have, they all have like attachment mechanisms,
link |
00:38:55.720
like ways to, like keys into the cell.
link |
00:38:59.240
They all have to get into cells.
link |
00:39:01.280
There are a couple of exceptions though.
link |
00:39:05.160
There are viruses of fungi and plants.
link |
00:39:10.560
So let's do the fungi.
link |
00:39:11.920
Fungi would be like yeast.
link |
00:39:13.520
The yeast cell wall is pretty hard to get through.
link |
00:39:17.960
So viruses typically don't attach to a yeast
link |
00:39:21.200
and get inside.
link |
00:39:22.040
Rather, they just live in the yeast forever.
link |
00:39:24.880
And they multiply as mostly nucleic acids,
link |
00:39:27.920
and as the yeast divide, they go into the daughter cells.
link |
00:39:30.600
And that's how they exist.
link |
00:39:31.840
Plant viruses, also the plant cell wall
link |
00:39:34.920
would be very hard to get across by binding a protein.
link |
00:39:39.760
So plant viruses get into plants either by
link |
00:39:43.280
pests that inject them in, they're sucking sap out,
link |
00:39:48.440
and they inject virus at the same time.
link |
00:39:49.920
Or farmers, they have contaminated farm equipment
link |
00:39:52.600
and they roll over the plants and introduces viruses.
link |
00:39:55.800
So those fungi and plant viruses,
link |
00:39:57.680
they don't have this specific receptor binding
link |
00:40:00.520
to get them into the cell.
link |
00:40:01.480
But everything else, yeah, the virus binds
link |
00:40:03.560
to something on the surface, very specific.
link |
00:40:05.360
It's taken into the cell because that's what cells do.
link |
00:40:09.000
When things bind their exterior, they take it in.
link |
00:40:12.600
Because in most cases, it's good.
link |
00:40:14.280
It's something they need.
link |
00:40:15.800
And so the virus slips in.
link |
00:40:17.200
I guess you'd call that a Trojan horse, right?
link |
00:40:19.200
Trojan horse.
link |
00:40:20.040
It's so hard to not anthropomorphize this whole thing.
link |
00:40:23.280
It is hard.
link |
00:40:24.160
So obviously, they don't know any of this.
link |
00:40:26.960
It's not an actual Trojan horse.
link |
00:40:29.400
So they're not getting actually tricked
link |
00:40:32.760
in the way humans trick each other.
link |
00:40:34.600
No, it's all passive.
link |
00:40:35.720
And it's just through so many years of evolution,
link |
00:40:38.600
you select something that works, and it continues.
link |
00:40:42.920
And what survives then goes on
link |
00:40:44.920
with perhaps a slightly different approach.
link |
00:40:48.280
I love this idea of passive.
link |
00:40:49.720
Of course, according to Sam Harris,
link |
00:40:52.040
so for my sufficiently intelligent alien civilization
link |
00:40:54.840
observing humans, our behavior might seem passive too
link |
00:40:58.080
because they understand fully exactly what we're doing.
link |
00:41:00.800
And then there's no free will,
link |
00:41:02.200
and we're all just operating in the same way.
link |
00:41:04.040
Could be.
link |
00:41:04.880
A cell does, but just a much higher level of complexity.
link |
00:41:07.760
Yeah, so I love the distinction between active and passive.
link |
00:41:11.760
I mean, the point is, I think anthropomorphizing
link |
00:41:14.760
to a certain extent is fine
link |
00:41:15.880
because it helps people understand.
link |
00:41:17.800
But when you start to say,
link |
00:41:19.520
I think the virus is doing that
link |
00:41:21.040
because then you're putting a human lens on it,
link |
00:41:24.640
and you may be wrong.
link |
00:41:26.200
Yeah.
link |
00:41:27.040
Because you don't know why things happen for a virus.
link |
00:41:30.880
So right now, we have variants emerging,
link |
00:41:33.400
and people say, well, I think it's because the antibodies
link |
00:41:35.920
are selecting for variants.
link |
00:41:38.120
That's a good idea,
link |
00:41:39.080
but it may not be the only thing that's going on.
link |
00:41:41.440
You start imagining them coming to the table negotiating.
link |
00:41:45.760
Yeah, you get into trouble with that.
link |
00:41:47.920
That's why I tell my students,
link |
00:41:49.320
be careful about the anthropomorphizing
link |
00:41:51.720
because you're gonna apply your values to a virus,
link |
00:41:55.880
and you have different values.
link |
00:41:57.040
You're a human, and you have,
link |
00:41:58.920
what you think is the reason for this outcome
link |
00:42:01.200
may not be right, that's all.
link |
00:42:02.280
Just be open minded about it.
link |
00:42:04.160
In both directions.
link |
00:42:05.120
I actually, one of the things that pushed back
link |
00:42:07.680
on this in the space of robotics,
link |
00:42:10.360
people, most people in robotics
link |
00:42:12.280
try to not anthropomorphize.
link |
00:42:14.560
For example, they don't give a gender or a name to robots.
link |
00:42:17.480
They really try to see it as a machine.
link |
00:42:20.000
And to me, that makes sense in one way,
link |
00:42:23.840
but it totally doesn't make sense in another.
link |
00:42:25.440
If that robot is to interact,
link |
00:42:27.600
operate in the human world and interact with humans,
link |
00:42:30.720
we have to anthropomorphize it
link |
00:42:33.880
in order to understand, as an engineering problem,
link |
00:42:38.880
how should it operate in a human world?
link |
00:42:42.080
Now, the difference with viruses, the scale of operation,
link |
00:42:46.000
it doesn't make sense to treat them as humanlike
link |
00:42:49.240
because the scale of operations is much smaller.
link |
00:42:51.560
But with robots, you're in the same time scale,
link |
00:42:54.240
the same spatial scale.
link |
00:42:55.280
Of course, in the movies,
link |
00:42:56.240
they always give them names and personalities, right?
link |
00:42:58.480
Yeah, well, yeah, that's the,
link |
00:43:00.400
but that's my argument is we should do the same
link |
00:43:02.960
when you're trying to solve
link |
00:43:03.920
the engineering problem of robotics too.
link |
00:43:06.280
It's not just for the movies.
link |
00:43:07.760
Well, let me ask you this,
link |
00:43:08.800
because you've said, controversially, not really,
link |
00:43:12.280
that viruses are not living.
link |
00:43:17.160
Defend yourself.
link |
00:43:19.360
Are viruses alive or not?
link |
00:43:20.600
So I've seen many people say, oh, they have to be,
link |
00:43:22.880
they have nucleic acids, they evolve, they mutate.
link |
00:43:27.160
That's all true, but they don't do it on their own.
link |
00:43:29.560
The particles in my mug are just not doing any of that
link |
00:43:32.200
unless they get into a cell.
link |
00:43:33.960
So a virus infected cell is alive.
link |
00:43:36.200
I totally agree with that,
link |
00:43:37.800
because in fact, when a virus gets in a cell,
link |
00:43:40.800
it converts it into a virus making factory, if you will.
link |
00:43:45.280
It's no longer a cell.
link |
00:43:47.240
Some people call it a viro cell.
link |
00:43:48.920
I don't really like that, but it's fine.
link |
00:43:51.200
So that's what I'm talking about.
link |
00:43:53.000
The particle is not alive.
link |
00:43:54.840
You can have your virus infected cell as alive,
link |
00:43:57.760
but the particle, it just would not do anything forever
link |
00:44:02.160
without getting inside of a cell.
link |
00:44:03.840
But once it's in a cell, it is alive then,
link |
00:44:07.040
but it's no longer a particle.
link |
00:44:08.200
It's taken apart and nucleic acid is moving
link |
00:44:10.720
around the cell, it's making proteins.
link |
00:44:12.920
Eventually it makes new particles.
link |
00:44:14.080
And then those particles released from the cell,
link |
00:44:16.440
they're not living anymore.
link |
00:44:17.960
So it's kind of, I think it's kind of like a spore,
link |
00:44:21.320
a spore of a, or a seed.
link |
00:44:25.200
Although the seed just doesn't work because the seeds,
link |
00:44:28.120
the cells in the seed have the ability
link |
00:44:29.840
to make their own energy and so forth.
link |
00:44:31.920
But a bacterial spore, and it's the same thing,
link |
00:44:34.400
doesn't do anything unless you add water and nutrients
link |
00:44:36.520
and then it starts to divide.
link |
00:44:37.560
But it doesn't need to get into a cell.
link |
00:44:39.040
It's very different from a virus.
link |
00:44:40.640
So that's why the particle.
link |
00:44:42.440
And when people think of virus,
link |
00:44:45.280
they're always thinking of the particle.
link |
00:44:47.320
And that's why I say it can't be alive
link |
00:44:49.240
because the particle can't do anything on its own.
link |
00:44:51.320
But if you think of a virus as an organism
link |
00:44:53.360
with a particle phase in a cell,
link |
00:44:55.880
then it makes sense to be alive.
link |
00:44:58.360
And by the way, when you say particle,
link |
00:44:59.880
you're referring to that structure
link |
00:45:01.160
that you've been mentioning,
link |
00:45:02.000
some parts of the membrane and not,
link |
00:45:03.440
that's been called, what is that,
link |
00:45:05.600
a virion particle or something?
link |
00:45:06.800
Virion.
link |
00:45:07.640
So it's what you should have here.
link |
00:45:09.120
I'll send you one.
link |
00:45:10.280
And then you can refer to it.
link |
00:45:11.720
What's the sexiest one to have?
link |
00:45:13.640
Like what, in terms of particles to have on a table?
link |
00:45:17.920
Well, unfortunately, the ones that you can 3D print.
link |
00:45:21.400
Oh, they're not going to be super.
link |
00:45:23.520
They're the ones that we know the structures of, right?
link |
00:45:26.360
So someone sent me last year
link |
00:45:29.200
a 3D model of SARS CoV2, and it's beautiful.
link |
00:45:32.000
It's actually cracked open so you can see the RNA
link |
00:45:34.720
and the spikes are sticking out.
link |
00:45:36.960
And they even put some antibodies sticking onto the spikes.
link |
00:45:39.760
And I mean, when I show this on a live stream,
link |
00:45:42.760
people love this.
link |
00:45:43.600
They go, oh my God, that's beautiful.
link |
00:45:45.080
It is, it's absolutely gorgeous.
link |
00:45:46.640
I have that.
link |
00:45:47.480
I have my virus that I worked on
link |
00:45:49.520
most of my career, poliovirus.
link |
00:45:50.840
I have a 3D model of that, which I actually just had made.
link |
00:45:54.200
It's gorgeous.
link |
00:45:55.040
And you can have it made in any color you want, right?
link |
00:45:57.600
What would you say is the most fascinating,
link |
00:46:01.480
terrifying, surprising, beautiful virus to you?
link |
00:46:05.120
So of all the viruses you looked at,
link |
00:46:08.400
sometimes when you just sit late at night
link |
00:46:10.920
with a glass of wine looking over the sunset,
link |
00:46:13.960
which virus do you think about?
link |
00:46:16.240
So fulfilling all of those adjectives is hard, right?
link |
00:46:21.280
Fascinating, exciting, terrifying.
link |
00:46:24.920
Well, the terrifying is an optional one, I think,
link |
00:46:27.120
because maybe that puts a lot of pressure.
link |
00:46:30.200
See, terrifying, to me, I'm not terrified
link |
00:46:34.240
because I think we can handle most viruses.
link |
00:46:37.560
As you see with this brand new one that emerged a year ago,
link |
00:46:40.720
we can handle it.
link |
00:46:42.400
From a virology perspective.
link |
00:46:44.120
Yeah, I mean, the human perspective
link |
00:46:45.600
is a different story, right?
link |
00:46:46.840
That's always an issue.
link |
00:46:47.840
But so I think there are a couple of different categories
link |
00:46:55.120
of virus.
link |
00:46:55.960
You could do the terrifying,
link |
00:46:57.400
and I think rabies is a terrifying virus
link |
00:47:00.080
because unless you're vaccinated,
link |
00:47:02.360
100% certainty you're gonna die.
link |
00:47:05.920
So you get bitten by a rabid raccoon or bat or dog, whatever,
link |
00:47:11.000
and there's still 70,000 deaths a year of rabies
link |
00:47:15.600
throughout the world because there are a lot of feral dogs
link |
00:47:17.480
running around that are infected.
link |
00:47:19.080
Unless you're vaccinated, you're gonna die.
link |
00:47:21.720
There's nothing we can do.
link |
00:47:23.120
But we do have a vaccine
link |
00:47:24.480
which we can actually give you
link |
00:47:26.440
even after you've been bitten,
link |
00:47:27.800
which is the only vaccine that works that way.
link |
00:47:31.120
It's a therapeutic, right?
link |
00:47:32.880
It will treat your illness
link |
00:47:34.840
because the disease takes so long to develop.
link |
00:47:38.720
Eventually, you get all kinds of neurological issues
link |
00:47:41.240
and paralysis and so forth, but it takes time,
link |
00:47:44.800
and you can be vaccinated.
link |
00:47:45.960
It will prevent that in the meanwhile.
link |
00:47:47.440
So people always say,
link |
00:47:48.400
what's the most lethal virus?
link |
00:47:50.280
Is it Ebola?
link |
00:47:51.120
I said, no, it's actually rabies.
link |
00:47:53.600
Unless you're vaccinated, it will kill you.
link |
00:47:56.000
Maybe it's good to linger,
link |
00:47:57.800
because we'll talk about vaccines a few times today.
link |
00:48:01.160
It's good to linger on cases
link |
00:48:04.240
where vaccines have clearly,
link |
00:48:09.040
undoubtedly helped human civilization.
link |
00:48:12.280
And it seems like rabies is a good example.
link |
00:48:15.400
Oh, rabies is great because everyone knows what happens
link |
00:48:19.000
when somebody gets rabies, right?
link |
00:48:21.400
You have fear of water, hydrophobia.
link |
00:48:26.160
Your body becomes spastic and stiff and jerks around,
link |
00:48:31.320
and you lose consciousness.
link |
00:48:33.600
You can't, no more.
link |
00:48:35.520
It's not a fun ride to death.
link |
00:48:36.640
It's horrible.
link |
00:48:37.480
It's a horrible way to die.
link |
00:48:39.200
So I think most people know that.
link |
00:48:40.880
It's been popularized enough in media, right?
link |
00:48:44.080
So that nobody would probably object to getting,
link |
00:48:47.060
oh, I was just bit by this raccoon and it ran off.
link |
00:48:51.000
Okay, well, we should assume it's rabid.
link |
00:48:53.000
We should immunize you.
link |
00:48:54.200
And most people are okay with that,
link |
00:48:56.320
because they know the consequences.
link |
00:48:57.560
And it's also pretty rare, right?
link |
00:48:59.880
It's not like something that you're trying to get
link |
00:49:02.120
into the arms of 250, 300 million Americans.
link |
00:49:06.920
That's hard.
link |
00:49:07.920
But the few thousand every year, it's easy.
link |
00:49:11.680
So the transmissibility is difficult, right?
link |
00:49:13.800
It has to, oh, it's not airborne.
link |
00:49:16.640
It's not airborne.
link |
00:49:17.480
It's just you have to be bitten.
link |
00:49:19.880
Although some people claim you could walk into a cave
link |
00:49:24.760
and the bats breathing out rabies virus could infect you,
link |
00:49:28.340
but I don't really think that's well substantiated.
link |
00:49:32.600
I think it's a bite.
link |
00:49:33.440
How would you do a study on that?
link |
00:49:34.800
Yeah, it's very hard to do.
link |
00:49:36.360
You'd have to collect the vapors in the cave
link |
00:49:38.440
and show that they're infectious, which,
link |
00:49:40.760
and by the way, someone emailed me the other day.
link |
00:49:43.200
You'll like this.
link |
00:49:44.260
They say, why can't we just immunize
link |
00:49:45.760
all the bats in the world against these viruses?
link |
00:49:49.280
And I said, well, how would you do that?
link |
00:49:50.500
There are caves everywhere, right?
link |
00:49:52.320
Yeah.
link |
00:49:53.240
He said, well, maybe you could just go and aerosolize.
link |
00:49:56.580
Yeah.
link |
00:49:57.420
It's pretty dangerous.
link |
00:49:58.440
And then all the bats should have vaccine passports
link |
00:50:01.480
to make sure that they're all.
link |
00:50:02.320
Yeah, and I said, you have to get their consent
link |
00:50:03.840
before you do it.
link |
00:50:05.340
But we do immunize wildlife against rabies.
link |
00:50:12.060
We have rabies vaccines for wild animals.
link |
00:50:15.040
There are a whole bunch of them that get rabies.
link |
00:50:17.400
And we put it in bait
link |
00:50:19.760
and drop it from helicopters in the woods
link |
00:50:21.560
and it drops down the incidence of rabies in people.
link |
00:50:25.160
People hiking, get bitten and so forth,
link |
00:50:27.120
it drops the incidence.
link |
00:50:28.000
So we can do that.
link |
00:50:29.000
I didn't know that.
link |
00:50:30.320
I always wondered how much medical care
link |
00:50:32.200
are we doing for animals in the wild
link |
00:50:34.020
because I've recently become more and more aware
link |
00:50:37.480
that animals are living in extreme poverty, right?
link |
00:50:42.000
Like you don't know, you think like natural, it's great.
link |
00:50:45.360
Like when animals are living on a farm, it's terrible.
link |
00:50:51.800
But then you also have to compare to like
link |
00:50:53.720
what life is like in the, or like the zoo.
link |
00:50:56.320
You have to compare what life is like in the wild.
link |
00:50:58.760
Well, the life in the wild is very tough, I think.
link |
00:51:01.600
Most animals have to, well, the carnivores anyway,
link |
00:51:03.760
they have to catch their food every day, right?
link |
00:51:06.160
And then there's the viruses there.
link |
00:51:08.200
Yeah, viruses as well.
link |
00:51:09.200
So the rabies immunization is the only one I'm aware of
link |
00:51:14.200
for wild animals.
link |
00:51:17.480
We do immunize lots of other animals.
link |
00:51:20.640
So we immunize chickens and pigs and cows,
link |
00:51:24.960
even fish, farmed fish.
link |
00:51:26.600
We pick each fish up and give it an injection,
link |
00:51:30.080
you know, when it's a small fish.
link |
00:51:32.520
But that's mostly so that the farmers get a good yield.
link |
00:51:36.220
We don't really care about the animals, right?
link |
00:51:38.400
We want a good yield for market.
link |
00:51:41.040
And then there's some examples where we immunize animals
link |
00:51:46.080
to prevent spillovers into people.
link |
00:51:50.000
So there's a disease called Hendra in Australia,
link |
00:51:53.360
which was discovered in the 90s.
link |
00:51:57.560
And it turns out that there are bats, fruit bats,
link |
00:51:59.720
that have this virus, and the bats are fine,
link |
00:52:02.460
but sometimes they fly into horse stalls
link |
00:52:05.180
and the horses get infected.
link |
00:52:06.720
In Australia, it was initially racehorses,
link |
00:52:09.040
which are very expensive, right?
link |
00:52:11.240
The horses got infected and they died,
link |
00:52:12.880
and the humans who would take care of them would die also.
link |
00:52:15.080
So now they immunize the horses to prevent the,
link |
00:52:19.280
well, to save the horses.
link |
00:52:20.400
Probably that's the motivation,
link |
00:52:21.600
because these horses are hundreds of thousands of dollars,
link |
00:52:23.880
right?
link |
00:52:24.720
And then the people don't get sick
link |
00:52:25.800
because the horses don't get sick.
link |
00:52:27.440
You don't want to immunize all the people
link |
00:52:29.360
because it's too rare.
link |
00:52:30.360
But that approach is called the one world health approach,
link |
00:52:33.960
which means everything's connected on the planet.
link |
00:52:37.240
And we have to think of everything in the grander scheme,
link |
00:52:39.320
not just us.
link |
00:52:40.960
Yeah, so you can immunize some things
link |
00:52:42.920
along the trajectory that a virus would take.
link |
00:52:45.000
Exactly.
link |
00:52:45.840
Some living beings.
link |
00:52:48.240
In the Arabian Peninsula,
link |
00:52:49.880
they have a MERS coronavirus issue every month.
link |
00:52:52.640
There are a couple of cases where a camel
link |
00:52:55.840
will infect a human, and the human can get very sick.
link |
00:52:59.200
It's a respiratory disease, very much like COVID.
link |
00:53:03.200
And so camels are very common there.
link |
00:53:05.840
They're raced, they're used as pets, they're eaten.
link |
00:53:10.520
So there's a lot of human camel contact.
link |
00:53:12.560
But the number of cases are rare, two a month.
link |
00:53:15.120
So you don't want to immunize all the humans.
link |
00:53:16.760
So the idea would be to immunize the camels.
link |
00:53:20.320
So.
link |
00:53:21.160
I like it.
link |
00:53:22.000
So, okay, so you put rabies.
link |
00:53:23.720
But Ebola also is a famously deadly one.
link |
00:53:30.120
What is it?
link |
00:53:30.960
It kills like, I don't know, 50%, 60% of its.
link |
00:53:33.240
It could be 50 to 90, but that's in Africa,
link |
00:53:37.120
where the healthcare isn't great.
link |
00:53:38.840
You saw when the cases of Ebola came to the U.S.,
link |
00:53:42.880
we could take care of it.
link |
00:53:43.800
We knew how to take care of it.
link |
00:53:45.160
We had fancy hospitals and so forth,
link |
00:53:46.800
and now we have a vaccine, so we can.
link |
00:53:49.960
And the vaccine is really good,
link |
00:53:52.280
but there are many governments in Africa
link |
00:53:54.960
that are suspicious of us,
link |
00:53:56.960
and they don't want to use our vaccine, so they.
link |
00:53:58.960
So there's a vaccine for Ebola.
link |
00:54:00.640
There is, yeah.
link |
00:54:01.480
And the effectiveness and safety of it,
link |
00:54:04.520
to how much is understood.
link |
00:54:06.400
So this is difficult,
link |
00:54:08.480
because there's not a lot of Ebola, right?
link |
00:54:11.880
It's not a continuous, ongoing thing.
link |
00:54:14.040
There are sporadic outbreaks here and there.
link |
00:54:16.560
Of a few thousand people.
link |
00:54:17.640
At most, at most, usually a few hundred.
link |
00:54:19.840
And the biggest ever, in fact,
link |
00:54:23.000
this is why we didn't for years have an Ebola vaccine.
link |
00:54:25.440
The U.S. military, together with Canada,
link |
00:54:27.880
developed an Ebola vaccine for service people, right?
link |
00:54:30.560
They wanted to say, well, we're sending people
link |
00:54:32.120
into these Ebola areas, we want a vaccine for them.
link |
00:54:34.680
So they had developed it through all the preclinical,
link |
00:54:38.120
which means before it goes into people.
link |
00:54:40.960
And that stopped, because there was no money
link |
00:54:43.240
to do a phase one and a phase two and a phase three.
link |
00:54:46.320
In fact, for phase two and three,
link |
00:54:47.800
you need to have infections going on,
link |
00:54:49.480
because you're looking at how well
link |
00:54:50.760
the vaccine prevents infections, right?
link |
00:54:52.960
So then there was a West African outbreak in 2015.
link |
00:54:57.000
2013, 2015.
link |
00:54:58.680
The most cases ever, 25,000.
link |
00:55:00.720
So they got to test the vaccine.
link |
00:55:03.640
But they only put it in a few thousand people.
link |
00:55:07.400
It's not like it's been in hundreds of thousands of people
link |
00:55:10.480
like the COVID vaccines has been.
link |
00:55:12.080
So it looks like it has high efficacy.
link |
00:55:16.600
But we'd like to have more data.
link |
00:55:18.560
Side effects maybe are not so great.
link |
00:55:21.440
There are a couple of different available vaccines.
link |
00:55:23.560
Some have been tested more than others.
link |
00:55:25.840
I would say this would probably not be widely accepted
link |
00:55:29.760
in the US.
link |
00:55:31.440
But then neither would be something over 50%
link |
00:55:36.840
deadliness of a virus.
link |
00:55:38.440
No, I think if you were, in fact, many physicians
link |
00:55:41.240
work in countries that have Ebola,
link |
00:55:43.280
so they get vaccinated, because they understand the choice.
link |
00:55:45.960
Yeah, right, it's always about the choice.
link |
00:55:48.480
So.
link |
00:55:49.400
So then one more thing.
link |
00:55:50.680
To answer the interesting,
link |
00:55:53.200
what are some of the viruses you really are fascinated by?
link |
00:55:57.000
There are a number of viruses that have clearly been shown
link |
00:56:01.240
to alter host behavior, and that's how they spread.
link |
00:56:04.600
I think those are fascinating.
link |
00:56:05.840
For example, there are some viruses of plants
link |
00:56:11.080
that are spread by aphids.
link |
00:56:14.920
And the aphid bites the plant,
link |
00:56:16.760
the virus reproduces in the plant,
link |
00:56:18.880
and it somehow engineers the plant
link |
00:56:21.640
to give off volatile organics to attract more aphids,
link |
00:56:26.440
which will spread the virus.
link |
00:56:30.080
Isn't that amazing?
link |
00:56:31.440
Yeah.
link |
00:56:32.280
So that's altering the behavior.
link |
00:56:35.080
Altering because somehow the virus infecting the plant cells
link |
00:56:38.640
gives off these organics and attracts aphids.
link |
00:56:40.760
And furthermore, somehow when the aphid bites,
link |
00:56:44.720
it tastes horrible.
link |
00:56:46.280
So they immediately leave with the virus
link |
00:56:48.400
they've just picked up and go to another plant to spread it.
link |
00:56:51.240
So they're attracted and then repulsed at the same time.
link |
00:56:53.760
And obviously you don't want to anthropomorphize this
link |
00:56:55.920
like a strategy they're taking on.
link |
00:56:57.560
Somehow this worked out.
link |
00:56:58.680
It worked out this way.
link |
00:56:59.840
It just evolved.
link |
00:57:00.680
And you know, evolution is sometimes hard to trace, right?
link |
00:57:04.280
Like Darwin famously said,
link |
00:57:06.320
he could never figure out how an eye evolved
link |
00:57:08.240
from a single cell, right?
link |
00:57:09.320
But it did.
link |
00:57:11.160
The more complicated, complex the holistic organism is
link |
00:57:16.120
that the virus invades,
link |
00:57:18.120
the less able it is to control that organism, right?
link |
00:57:21.360
So I wonder if there's viruses
link |
00:57:22.600
that can control human behavior,
link |
00:57:26.800
you know, to induce more spread of the virus.
link |
00:57:32.880
Well, I don't see why not.
link |
00:57:34.320
There's not enough humans
link |
00:57:35.160
that's supposed to like evolve through.
link |
00:57:37.080
Well, we can't do the experiment to test it, right?
link |
00:57:39.240
We have to observe.
link |
00:57:40.080
And that's always hard when you're observing
link |
00:57:41.720
because there's so many things that can confound
link |
00:57:45.040
what you're looking at.
link |
00:57:45.880
Yeah, change human behavior, yeah.
link |
00:57:47.520
I mean, there's so many things that impinge on our behavior,
link |
00:57:50.360
but yeah, I think it's possible.
link |
00:57:54.960
I think it's highly possible.
link |
00:57:56.520
If it does it in a plant,
link |
00:57:58.000
why not change some other organism's behavior?
link |
00:58:00.800
I think it's fine.
link |
00:58:01.640
Anyway, those fascinate me.
link |
00:58:02.480
There are lots of examples of those that are fascinating
link |
00:58:06.080
and how they work, people are trying to figure out.
link |
00:58:08.840
But there's not a lot of money to work on, you know,
link |
00:58:10.680
insect and plant viruses unless you're going to the USDA.
link |
00:58:13.560
So they don't get a lot of work moving forward.
link |
00:58:17.120
Well, is there, if you understand some of those viruses,
link |
00:58:19.800
is that transferable to human viruses, that understanding?
link |
00:58:23.760
I think some of it could be, sure.
link |
00:58:25.560
I think the general principles, for example,
link |
00:58:28.160
how does the virus cause volatile organics to be made?
link |
00:58:32.280
It must be turning on some genes
link |
00:58:34.960
and you could learn principles from that,
link |
00:58:37.400
how the virus might do that.
link |
00:58:38.720
Sure, I think everything is broadly applicable.
link |
00:58:41.320
So to say it's not useful to study viruses of insects
link |
00:58:46.200
and plants is just wrong because in science,
link |
00:58:49.280
we probably know this, maybe in your field it's the same.
link |
00:58:52.880
If you're curious, you're going to run into interesting
link |
00:58:55.040
things that you never planned on, right?
link |
00:58:57.160
That's why people like, you can criticize,
link |
00:58:59.680
why do we want to go on Mars?
link |
00:59:01.280
Why do we want to colonize Mars?
link |
00:59:03.560
Well, it's like, why do you want to go to the moon?
link |
00:59:06.600
The reality is when you do really difficult things,
link |
00:59:10.520
engineering things, like all these inventions
link |
00:59:13.080
along the way are created.
link |
00:59:14.320
It's kind of fascinating.
link |
00:59:16.080
Basically just pick a thing that everyone can agree
link |
00:59:21.120
is kind of cool and is really hard and do that.
link |
00:59:24.440
And then you'll have like thousands of inventions
link |
00:59:26.920
that have nothing to do with the thing.
link |
00:59:28.200
That's right.
link |
00:59:29.040
I think you should let curious scientists
link |
00:59:32.040
just follow what they're interested in
link |
00:59:34.440
to a certain extent.
link |
00:59:35.280
You can't, in science we say we have translational research
link |
00:59:38.880
where we say, okay, here's some money,
link |
00:59:40.200
go cure cancer or diabetes or heart disease, whatever.
link |
00:59:43.600
And that's fine.
link |
00:59:44.520
But that often doesn't work out very well.
link |
00:59:46.680
What works better is to say, you have a good lab,
link |
00:59:49.840
you have a good track record,
link |
00:59:50.800
here's some money, here's something.
link |
00:59:52.960
And that's where PCR, CRISPR, recombinant DNA,
link |
00:59:56.840
all that stuff which has made the field explode,
link |
00:59:59.840
that's all it came from.
link |
01:00:00.760
Not from people saying, I want to cure genetic diseases
link |
01:00:04.280
by gene editing, but by saying,
link |
01:00:05.840
what are these repeated things in this bacterium doing?
link |
01:00:09.800
Yep.
link |
01:00:11.120
Can I ask you a big philosophical question?
link |
01:00:14.640
So there's these deadly viruses
link |
01:00:17.200
that are not very transmissible, Ebola, rabies.
link |
01:00:21.520
And then there's these less deadly viruses
link |
01:00:23.800
that are very transmissible, like COVID,
link |
01:00:29.200
I guess kind of borderline.
link |
01:00:31.000
But why isn't there super transmissible,
link |
01:00:35.560
super deadly viruses?
link |
01:00:38.360
I think if you compare SARS one and two,
link |
01:00:40.360
you get somewhat of an answer, right?
link |
01:00:42.600
SARS one was more deadly.
link |
01:00:45.560
In fact, over half of the time when people were infected,
link |
01:00:50.400
they ended up in the hospital because they were that sick.
link |
01:00:53.440
And then the peak of virus shedding from them
link |
01:00:57.400
happened long after they went in the hospital.
link |
01:00:59.640
So it's easy to contain the infection
link |
01:01:02.760
when you're in a hospital, right?
link |
01:01:04.640
There was not much pre symptomatic
link |
01:01:07.480
or asymptomatic shedding with SARS one.
link |
01:01:11.360
And shedding means you become infectious.
link |
01:01:14.000
So in a respiratory virus,
link |
01:01:16.040
you inhale the droplets with the virus
link |
01:01:18.160
and they reproduce in your upper respiratory tract,
link |
01:01:20.840
what we call the nasopharynx, right?
link |
01:01:22.920
The nose and going back to that little cavity
link |
01:01:24.880
just above your mouth.
link |
01:01:27.000
So the virus reproduces really well.
link |
01:01:28.440
And then as you talk and sneeze and cough,
link |
01:01:30.120
you expel droplets and then those are inhaled
link |
01:01:32.560
by other people and then they reproduce.
link |
01:01:35.160
And for SARS two, we now know there's a lot of reproduction
link |
01:01:39.640
just before you feel anything, if at all.
link |
01:01:42.320
So there's a lot of shedding and transmission
link |
01:01:45.560
before you get symptomatic.
link |
01:01:47.680
And as many people don't ever get symptomatic, right?
link |
01:01:50.200
So they spread really easily.
link |
01:01:52.840
So that explains why some viruses can transmit
link |
01:01:55.960
a lot better than others.
link |
01:01:57.360
And if one happens to knock you out,
link |
01:02:00.040
then you're never gonna transmit
link |
01:02:01.400
because you're in the hospital like SARS one.
link |
01:02:03.400
But why can't you have both?
link |
01:02:05.840
Why can't you just wait a while before it knocks you out
link |
01:02:08.680
but when it knocks you out, it really kills you?
link |
01:02:10.800
That is a philosophical question, right?
link |
01:02:13.200
Because we could talk about why we haven't observed it.
link |
01:02:16.640
I mean, one issue is that if you're killed too quickly
link |
01:02:23.480
by a highly lethal virus,
link |
01:02:25.840
you're not gonna transmit it very well, right?
link |
01:02:27.920
So Ebola can kill you quite rapidly.
link |
01:02:31.040
And most of the transmission occurs when people
link |
01:02:35.840
are being cared for at home or in hospitals.
link |
01:02:38.640
The doctors and nurses get the virus,
link |
01:02:40.440
but people walking around, you're not walking around
link |
01:02:42.880
when you have Ebola, you're too sick.
link |
01:02:45.160
You know, you have black, bloody diarrhea,
link |
01:02:47.360
you're vomiting, you're bleeding from your skin
link |
01:02:51.680
and mucous membranes, you're not walking around,
link |
01:02:54.360
you're not going to parties.
link |
01:02:55.440
So I think that's part of it,
link |
01:02:57.920
that if the infection is too lethal,
link |
01:03:00.400
you're simply not a good transmitter.
link |
01:03:02.520
And I think transmission is probably one
link |
01:03:05.880
of the most powerful selection forces for viruses
link |
01:03:09.720
because a virus always has to find a new host.
link |
01:03:12.720
If it doesn't, it's a startup that fails, right?
link |
01:03:16.400
If it doesn't find a new host, it's gone.
link |
01:03:18.560
And so anything that makes the virus transmit better
link |
01:03:22.520
is gonna help it.
link |
01:03:23.600
And if killing you, being less lethal is part of that,
link |
01:03:27.480
that works too.
link |
01:03:28.360
So there's a strong selection pressure
link |
01:03:30.720
against being lethal.
link |
01:03:32.360
I think there's a strong selection pressure
link |
01:03:34.880
against being lethal and being more transmissible.
link |
01:03:38.680
Those two seem to work in opposite ways.
link |
01:03:41.600
And now we don't have a lot of data to support this.
link |
01:03:43.440
This is kind of a thought experiment,
link |
01:03:46.520
but there is one experiment done in Australia
link |
01:03:50.560
many years ago.
link |
01:03:51.840
I don't know if you know this, but in the 1800s,
link |
01:03:54.720
the hunters in Australia imported a rabbit from Europe
link |
01:03:57.400
so they could hunt it because the native rabbit
link |
01:04:00.560
in Australia was too fast for them.
link |
01:04:02.000
They couldn't shoot them.
link |
01:04:03.440
So they brought in this European rabbit
link |
01:04:05.560
and they reproduced out of control.
link |
01:04:07.800
Within a couple of years, they were everywhere,
link |
01:04:10.320
millions of rabbits in all the watering holes.
link |
01:04:13.440
And now they had a problem.
link |
01:04:14.960
So they decided to use a virus
link |
01:04:16.520
to get rid of these excess rabbits.
link |
01:04:19.120
And they used a virus, a pox virus called myxoma virus,
link |
01:04:22.880
which is a natural virus of a different kind of rabbit.
link |
01:04:26.240
But for these European rabbits, it was quite lethal
link |
01:04:28.640
and it's spread by mosquitoes.
link |
01:04:30.080
So they said, okay, let's release this virus.
link |
01:04:33.840
And the first year, 99.2% of the rabbits were killed,
link |
01:04:40.320
but that 0.8% that were left had some form of resistance.
link |
01:04:45.120
They were variants.
link |
01:04:46.360
Every organism, not just viruses, makes mutants.
link |
01:04:49.040
And there were some variants of the rabbits
link |
01:04:51.000
that could survive infection.
link |
01:04:52.760
And then in subsequent years, the virus became less lethal.
link |
01:04:56.560
And then the mosquitoes had a better shot
link |
01:04:59.120
of transmitting it from one rabbit to another
link |
01:05:01.120
if the rabbit lived longer.
link |
01:05:02.320
That's the selection probably.
link |
01:05:04.200
And so in the end, the rabbits lived on.
link |
01:05:06.520
The virus was there.
link |
01:05:07.480
It evolved to be more transmissible and less lethal.
link |
01:05:11.440
So that's the only.
link |
01:05:12.280
Life is amazing.
link |
01:05:13.160
That's the only data. Life on Earth is amazing.
link |
01:05:15.080
It is, it is.
link |
01:05:15.920
If you take the time to look at it and see what's happened,
link |
01:05:19.440
it is amazing.
link |
01:05:20.760
It's also humbling that it just makes you realize
link |
01:05:22.720
humans are just a small part of the picture.
link |
01:05:25.280
Of course.
link |
01:05:26.360
And we're wrecking it, aren't we?
link |
01:05:28.320
Well, I mean, we're not really.
link |
01:05:32.520
I mean, viruses are wrecking it some ways.
link |
01:05:35.400
We're not really wrecking anything.
link |
01:05:36.880
It's all part of it.
link |
01:05:38.240
But you know, when the ways that humans exist
link |
01:05:41.480
encourages viruses to infect us, right?
link |
01:05:43.960
When we were hunter gatherers,
link |
01:05:45.840
living in bands of 100 people, very few viruses
link |
01:05:49.640
because it was hard for the virus to go
link |
01:05:51.760
from one band to another.
link |
01:05:53.200
And perhaps a hunter would, one of these humans
link |
01:05:55.840
would get an animal and bring a virus into camp
link |
01:05:58.600
and some people would die,
link |
01:05:59.560
but it would never spread to another.
link |
01:06:02.160
And then when we started to congregate in cities,
link |
01:06:04.480
we figured out agriculture and so forth
link |
01:06:06.640
and how to harvest animals,
link |
01:06:07.760
then we could get bigger and bigger populations
link |
01:06:09.480
and the viruses went crazy.
link |
01:06:10.960
And they went from animals to us.
link |
01:06:12.560
So measles went from cows to humans
link |
01:06:15.120
when humans learned to domesticate cows
link |
01:06:17.480
and started gathering in big cities.
link |
01:06:20.680
Yeah, but now that humans are able to communicate
link |
01:06:24.880
and travel globally,
link |
01:06:26.960
the viruses become more and more dangerous, transmissible.
link |
01:06:31.760
Thereby, if you look at earth as an organism,
link |
01:06:33.960
thereby pushing humans to be more innovative,
link |
01:06:36.800
create alpha fold two and three and four and five,
link |
01:06:39.600
create better systems and eventually there's rockets
link |
01:06:41.800
that keep flying from earth.
link |
01:06:43.960
And eventually the virus is becoming super dangerous
link |
01:06:47.480
and threatening all of human civilization,
link |
01:06:49.680
will force it to become a multi planetary species
link |
01:06:52.520
and its organism starts expanding.
link |
01:06:54.520
So I think it's a feature, not a bug, I don't know.
link |
01:06:57.520
Well, I think that we have our early,
link |
01:07:00.720
probably the most of the,
link |
01:07:03.120
we're studying viruses since 1900, right?
link |
01:07:06.120
Most of that time was because of diseases they caused.
link |
01:07:09.680
The first viruses discovered, yellow fever,
link |
01:07:12.920
virus, smallpox, polio virus, influenza virus,
link |
01:07:17.920
those were all because people got sick and they said,
link |
01:07:21.520
oh, look, this is a virus that's associated with it.
link |
01:07:24.560
And so we got good at learning how to take care
link |
01:07:28.840
of these infections, making vaccines and so forth
link |
01:07:31.040
over the years and it's only in the last 20 years
link |
01:07:33.240
that we recognize that there are more viruses out there
link |
01:07:36.120
that are far more interesting, perhaps,
link |
01:07:38.240
but we've learned how to deal with the bad ones for sure.
link |
01:07:41.120
So we talked about what is a virus.
link |
01:07:43.480
We talked about some of the most dangerous
link |
01:07:45.560
and deadly viruses.
link |
01:07:47.080
Can we zoom in and talk about COVID 19 virus?
link |
01:07:51.320
Sure.
link |
01:07:52.160
I don't know what your preferred name is, but maybe for this.
link |
01:07:54.400
Right, the virus is SARS CoV2, which is hard, it's long,
link |
01:07:58.360
and then COVID 19 is the disease.
link |
01:08:00.440
So you could say the virus of COVID 19, that's fine.
link |
01:08:03.280
The virus of COVID 19.
link |
01:08:04.680
But for the purpose of this conversation,
link |
01:08:06.240
we'll every once in a while just say COVID.
link |
01:08:08.320
It's fine, no problem.
link |
01:08:10.480
What is this virus from,
link |
01:08:14.280
I don't know how many ways we can talk about it.
link |
01:08:16.640
I think from a basic structural,
link |
01:08:19.680
like the variant structure,
link |
01:08:22.960
biological structure perspective, what is it?
link |
01:08:25.920
What are its variants?
link |
01:08:28.080
Can you describe the basics,
link |
01:08:30.080
the important characteristics of the virus?
link |
01:08:32.040
So viruses are classified by humans
link |
01:08:35.020
just to make it easier to keep track of them, right?
link |
01:08:38.280
So this is a coronavirus, which is because
link |
01:08:42.340
when they were first discovered,
link |
01:08:45.160
I think the first ones were animal coronaviruses.
link |
01:08:48.280
They looked at them in the electron microscope
link |
01:08:50.440
and it looked like the solar corona,
link |
01:08:51.960
and that's all there is to it.
link |
01:08:53.480
And I have to say that early in the outbreak,
link |
01:08:56.320
the place with the highest seropositivity in the US,
link |
01:09:00.240
for a while, 68% was a working class neighborhood
link |
01:09:03.800
in New York City called corona.
link |
01:09:06.520
Can you beat that, right?
link |
01:09:08.120
That's crazy, yeah.
link |
01:09:09.600
So coronaviruses, they have membranes, right?
link |
01:09:12.220
We talked about membranes,
link |
01:09:13.160
they have spike proteins in the membrane,
link |
01:09:15.000
so they can attach to cells.
link |
01:09:16.320
And inside, they have RNA.
link |
01:09:19.040
And they are the viruses with the longest RNA
link |
01:09:22.000
that we know of.
link |
01:09:23.400
None other comes close.
link |
01:09:25.120
For some reason, they're able to maintain 30,000,
link |
01:09:29.640
so SARS, COVID, two RNAs, 30,000 bases of RNA,
link |
01:09:33.860
and some of the other coronas are even longer, 40,000.
link |
01:09:37.240
This is a, coronas are family of viruses
link |
01:09:40.920
that included the one you mentioned before, version one.
link |
01:09:46.320
So SARS, COVID one, yeah.
link |
01:09:47.800
COVID one, and I guess other ones as well.
link |
01:09:49.640
So the first, we first learned of them in animals,
link |
01:09:52.520
a lot of animals, pigs, and cows,
link |
01:09:56.360
and horses have coronaviruses.
link |
01:09:58.240
And then in the 60s, we discovered
link |
01:10:01.440
a couple of human coronaviruses that just cause colds,
link |
01:10:05.220
very mild colds that you wouldn't even think twice about.
link |
01:10:08.920
And then suddenly, in 2003, there's this outbreak
link |
01:10:14.160
of severe respiratory disease in China.
link |
01:10:18.600
And it started in November,
link |
01:10:21.560
and they didn't tell the world until February.
link |
01:10:24.000
And that was really bad, because it was already spreading
link |
01:10:27.220
by the time they told people about it.
link |
01:10:30.080
But this went to 29 different countries.
link |
01:10:34.600
Only 8,000 people were infected, and then it stopped.
link |
01:10:37.480
And that was the first time we saw an epidemic coronavirus.
link |
01:10:43.060
And what they did afterwards is they said,
link |
01:10:45.780
okay, it looks like it came from the meat markets.
link |
01:10:48.380
They have live meat markets in Guangzhou,
link |
01:10:50.620
in the south of China, where you can go
link |
01:10:53.220
and pick out an animal and the guy will slaughter it for you
link |
01:10:56.440
and give it to you, and then of course,
link |
01:10:57.780
there's blood everywhere, and that's how they got infected.
link |
01:11:00.580
And they figured out that there's this animal
link |
01:11:02.760
called a palm civet, that was the source of virus.
link |
01:11:05.780
The palm civets are shipped in from the countryside,
link |
01:11:08.460
and the palm civets somehow in the countryside
link |
01:11:10.660
got it from a bat.
link |
01:11:11.700
So they went looking in caves in the countryside,
link |
01:11:13.900
and they found in one cave all the viruses
link |
01:11:16.860
that could make up SARS 1.
link |
01:11:19.140
And that was 2000, and I would say,
link |
01:11:21.620
took about five, eight years after that outbreak.
link |
01:11:24.340
So that was the first hint that bats have coronaviruses
link |
01:11:30.040
that can infect people and cause problems, right?
link |
01:11:32.940
And after that, we should have been ready.
link |
01:11:35.620
So didn't they already start developing
link |
01:11:37.580
vaccines after then? Yes.
link |
01:11:38.860
So some people started making vaccines.
link |
01:11:41.300
They tested them in mice, but they never got into people.
link |
01:11:46.780
And some people started working on antiviral drugs.
link |
01:11:50.860
Nothing ever came of them because, you know,
link |
01:11:54.140
industry, there's no disease, it's gone.
link |
01:11:57.460
Why should we make vaccines and drugs?
link |
01:11:59.420
And NIH in the US, you submit a grant,
link |
01:12:02.540
and they say, ah, it's too risky.
link |
01:12:03.960
There's none of this virus around.
link |
01:12:05.520
So people were really shortsighted because I always say,
link |
01:12:08.180
we could have had antivirals for this, absolutely, for sure.
link |
01:12:13.060
No question.
link |
01:12:14.260
In fact, the one antiviral that's in phase three,
link |
01:12:17.180
it's called molnupiravir.
link |
01:12:20.220
It's the only one that you can take orally.
link |
01:12:22.260
It's a pill.
link |
01:12:23.100
It looks really good.
link |
01:12:24.220
That was developed five years ago,
link |
01:12:26.340
but never taken into humans.
link |
01:12:27.980
It could have been ready.
link |
01:12:29.340
So we dropped the ball, and then the next decade, 2012,
link |
01:12:33.940
MERS coronavirus comes up in the Arabian Peninsula.
link |
01:12:38.900
This comes from camels and infects people,
link |
01:12:41.580
but probably the camels got it from bats originally
link |
01:12:44.820
some time ago.
link |
01:12:46.260
But that never transmits from person to person, very rarely.
link |
01:12:50.580
Every new little outbreak is a new infection from a camel.
link |
01:12:55.460
So that was 2012, and now here we are, 2019,
link |
01:12:59.260
the new outbreak of respiratory disease in China.
link |
01:13:02.680
And this one really goes all over the world
link |
01:13:06.420
where SARS1 could not.
link |
01:13:07.780
It's a coronavirus.
link |
01:13:09.380
It's different enough from SARS1
link |
01:13:11.100
that it has very different properties.
link |
01:13:12.940
Causes a lot.
link |
01:13:13.780
But it still has a membrane.
link |
01:13:14.620
It still has a very long RNA in the middle,
link |
01:13:17.820
and then it still has the spike proteins.
link |
01:13:19.900
That's right.
link |
01:13:20.740
What are the things that are,
link |
01:13:22.460
what are the little unique things
link |
01:13:24.780
that make it that much more effective?
link |
01:13:27.740
That make it cause a pandemic of millions of people
link |
01:13:30.940
as opposed to SARS1?
link |
01:13:32.500
Well, the genome is 20% different from SARS1, say.
link |
01:13:38.540
And in those bases, there's some,
link |
01:13:40.300
there are things that make it different from SARS1.
link |
01:13:42.900
It binds the same receptor, ACE2, on the cell surface.
link |
01:13:45.580
So that's remarkable.
link |
01:13:48.020
It has a lot of the same proteins.
link |
01:13:50.100
They look similar.
link |
01:13:50.980
Like if you look at the structure of the spikes,
link |
01:13:53.100
they look similar,
link |
01:13:54.660
but there's enough amino acid differences
link |
01:13:57.020
to make the bio.
link |
01:13:58.500
And what it is, we don't know,
link |
01:14:00.060
because how do you figure that out?
link |
01:14:03.200
You need to study animals,
link |
01:14:04.900
because you can't infect people.
link |
01:14:06.700
And the animal models aren't great.
link |
01:14:10.220
So the way you figure that out
link |
01:14:11.600
is you figure out how those differences,
link |
01:14:14.980
what functional,
link |
01:14:16.780
like how the difference in the amino acids
link |
01:14:18.540
lead to functional difference of the virus.
link |
01:14:20.860
That's right.
link |
01:14:21.700
Like how it attaches, how it breaks the cell wall.
link |
01:14:23.180
Exactly.
link |
01:14:24.020
And how the hell do you figure that out?
link |
01:14:25.700
Like, I guess there's models of interaction.
link |
01:14:29.980
First, you need an animal of some kind to infect, right?
link |
01:14:33.180
You can use mice.
link |
01:14:34.920
People have used ferrets, guinea pigs,
link |
01:14:38.660
nonhuman primates,
link |
01:14:40.820
all of the above.
link |
01:14:41.780
Nonhuman primates are very expensive,
link |
01:14:43.260
so not many people do that.
link |
01:14:45.740
And then you can put the virus in the respiratory tract.
link |
01:14:48.500
But in fact, none of them get sick like people do.
link |
01:14:52.720
Many people with COVID get a mild disease,
link |
01:14:55.580
but 20% get a very severe, longer lasting disease.
link |
01:14:59.620
They can die from it, right?
link |
01:15:00.780
No animal does that yet.
link |
01:15:03.020
So we have no insight into what's controlling that.
link |
01:15:05.460
But if you just wanna look at the very first part
link |
01:15:07.500
of infection and the shedding and the transmission,
link |
01:15:10.880
you can do it in any one of several animal models.
link |
01:15:14.620
Ferrets are really good for transmission.
link |
01:15:16.660
They tend to have nasal structures like humans
link |
01:15:19.620
and you can put them in cages next to each other
link |
01:15:22.780
and they'll transmit the virus really nicely.
link |
01:15:24.900
So you can study that.
link |
01:15:26.620
But the other thing that's important that we should mention
link |
01:15:29.740
is how do you manipulate these viruses?
link |
01:15:34.100
So these are RNA viruses.
link |
01:15:36.680
You can't manipulate RNA.
link |
01:15:38.740
We don't know how to do it.
link |
01:15:40.820
But DNA, because of the recombinant DNA revolution
link |
01:15:45.740
that occurred in the 70s,
link |
01:15:47.980
we can change DNA any way we want.
link |
01:15:51.460
We can change a single base, we can cut out bases,
link |
01:15:53.680
we can put other things in really easily.
link |
01:15:56.960
And if I may give it a personal aspect,
link |
01:16:01.680
when I went to MIT as a postdoc in 1979,
link |
01:16:05.820
David Baltimore said, here's what I want you to do.
link |
01:16:09.020
The moratorium on recombinant DNA experiments
link |
01:16:12.580
on viruses has just been lifted.
link |
01:16:14.740
I want you to make a DNA copy of polio
link |
01:16:18.180
and see if you put that in a cell
link |
01:16:19.820
whether it will start an infection.
link |
01:16:21.600
It's okay.
link |
01:16:24.440
So I made a DNA copy of polio virus.
link |
01:16:27.280
It's only 7,500 bases.
link |
01:16:29.360
It's much smaller than corona.
link |
01:16:31.760
And I took that DNA and I put it in a piece of DNA
link |
01:16:35.560
from a bacteria called a plasmid.
link |
01:16:37.960
And you can grow plasmids in many, many bacteria,
link |
01:16:41.440
make lots of them and purify the DNA really easily.
link |
01:16:44.600
And I took that DNA and I sequenced it
link |
01:16:48.680
because we didn't know the genome sequence
link |
01:16:50.880
of polio at the time.
link |
01:16:52.680
And that took me a year by the way,
link |
01:16:54.640
because the techniques we had were really archaic
link |
01:16:57.280
and nowadays you could do it in 15 minutes, right?
link |
01:17:00.000
It's amazing.
link |
01:17:01.520
And I took the DNA, I put it into cells and out came polio.
link |
01:17:06.800
So that's the start.
link |
01:17:07.980
Now, since then everybody has taken that technique
link |
01:17:10.720
and used it for their virus.
link |
01:17:11.720
You can now do it with SARS CoV2.
link |
01:17:13.180
You make a DNA copy of any RNA virus,
link |
01:17:16.000
you can modify it and you put it back into cells
link |
01:17:19.040
and you'll get your modified virus out.
link |
01:17:21.440
So that's an important part of understanding
link |
01:17:23.780
the properties of the virus as, say, in an animal.
link |
01:17:26.620
By changing the virus, you're changing a DNA copy,
link |
01:17:28.840
you're making the virus then and putting it into the animal.
link |
01:17:32.500
Can you clarify, so even in the RNA virus,
link |
01:17:35.360
you can take and turn it into DNA?
link |
01:17:38.040
Yes.
link |
01:17:38.880
And then that allows you to modify it.
link |
01:17:41.000
Yes.
link |
01:17:41.840
What's that mapping?
link |
01:17:44.240
Well, no, no, no, what's the process
link |
01:17:46.000
of going from RNA to DNA?
link |
01:17:48.320
Reverse transcription.
link |
01:17:49.680
That's reverse transcription.
link |
01:17:50.680
Right.
link |
01:17:51.520
Oh, so you actually go through the process
link |
01:17:53.120
of reverse transcription to do this?
link |
01:17:54.720
Yes.
link |
01:17:55.540
Remember, David Baltimore and Howard had discovered
link |
01:17:58.400
this enzyme in the 70s.
link |
01:18:00.080
They got the Nobel Prize for that.
link |
01:18:01.720
And when I went to David's lab at MIT,
link |
01:18:04.560
he had the enzyme in the freezer.
link |
01:18:06.360
He said, here, take this and make a DNA copy of polio.
link |
01:18:08.760
Yeah, I didn't make the connection
link |
01:18:10.160
that you can use that kind of thing for an RNA virus.
link |
01:18:14.000
And so that's.
link |
01:18:14.840
And then modify it.
link |
01:18:15.880
See, any DNA virus already exists as DNA.
link |
01:18:18.200
So you can modify it.
link |
01:18:19.760
But for RNA viruses, it was difficult.
link |
01:18:22.280
And so then from that point on, for influenza,
link |
01:18:25.640
every other RNA virus and coronaviruses,
link |
01:18:28.000
people made DNA copies.
link |
01:18:29.840
And that's what they use to modify
link |
01:18:31.520
and ask questions about what things are doing, right?
link |
01:18:34.600
What's this gene doing?
link |
01:18:35.560
What if we take it out?
link |
01:18:36.400
What happened?
link |
01:18:37.220
Can you do the same thing with COVID?
link |
01:18:39.560
Is take the RNA and then.
link |
01:18:41.160
Of course.
link |
01:18:42.000
And in fact, in January 2020,
link |
01:18:44.160
as soon as the genome sequence was released from China,
link |
01:18:47.600
the labs all over were synthesizing this 30,000 base DNA
link |
01:18:52.760
and getting virus.
link |
01:18:54.320
What can you figure out without infecting anything?
link |
01:18:58.280
Just turning into, with the reverse transcription,
link |
01:19:01.720
turning into DNA, modifying stuff,
link |
01:19:03.560
and then putting it into a cell.
link |
01:19:05.520
What can you figure out from that?
link |
01:19:08.360
Oh, well, you could, let's say you can cut out a gene.
link |
01:19:11.640
You see some genes in the sequence.
link |
01:19:13.280
I don't know what these genes do.
link |
01:19:14.720
Let's cut them out.
link |
01:19:16.040
And then you could cut them out of the DNA.
link |
01:19:18.840
You put the DNA in cells and maybe you get virus out.
link |
01:19:22.080
And you go, oh, clearly that gene's not needed
link |
01:19:25.440
for the virus to reproduce, at least in cells, right?
link |
01:19:27.820
Or maybe you take the gene out
link |
01:19:29.200
and you never get any virus, so it's lethal.
link |
01:19:31.600
Is there a nice systematic ways of doing this?
link |
01:19:33.520
Do people kind of automate it?
link |
01:19:35.480
Absolutely.
link |
01:19:36.320
And we, I mean, the problem with SARS, the COVID virus,
link |
01:19:41.080
is it's 30,000 bases, a lot of stuff there.
link |
01:19:44.460
And what makes it more difficult is that you have to,
link |
01:19:48.480
it's been classified as a BSL3 agent, biosafety level three.
link |
01:19:55.600
And so not everyone has a lab that's capable of doing that.
link |
01:19:58.960
So it limits the number of people who can do experiments.
link |
01:20:02.760
You know, we're lucky to have a few in New York City,
link |
01:20:05.720
but not every place has them.
link |
01:20:07.520
So you cannot work with a virus just out on the bench
link |
01:20:11.520
like we do with many other viruses.
link |
01:20:13.040
You have to wear a suit and have to have special procedures
link |
01:20:15.800
and containment and so forth.
link |
01:20:16.920
So it makes it difficult to do basic experiments
link |
01:20:19.240
on the virus.
link |
01:20:20.080
But when it's a pandemic, there's a lot of money,
link |
01:20:22.800
there's a lot of incentive to work on it harder.
link |
01:20:25.600
And also you don't need to work on the virus.
link |
01:20:27.360
You can take bits of it and work.
link |
01:20:29.280
You could take, say, just the spike, right?
link |
01:20:31.200
And say, can we make a vaccine with just the spike?
link |
01:20:33.880
Because that doesn't require BSL3, so yes.
link |
01:20:36.800
So like building a vaccine requires you to figure out
link |
01:20:40.480
how, or antiviral drugs, how to attack various structural
link |
01:20:44.680
parts of the virus and the functional parts of the virus.
link |
01:20:47.040
Right.
link |
01:20:47.880
You have to decide on a target.
link |
01:20:50.040
Yeah.
link |
01:20:50.880
Like, I'm gonna make an antiviral,
link |
01:20:52.360
what am I gonna target in the virus?
link |
01:20:55.480
And there are a few things that make more sense than others.
link |
01:21:00.440
Usually we like to target enzymes.
link |
01:21:03.400
I don't know if you remember your biochemistry,
link |
01:21:05.560
but enzymes are catalytic.
link |
01:21:07.840
You don't need a lot of them to do a lot of things.
link |
01:21:10.480
So they're typically in low concentrations
link |
01:21:12.880
in a virus infected cell.
link |
01:21:14.360
So it's easier to inhibit them with a drug.
link |
01:21:17.120
And the coronas have a couple of enzymes that we can target.
link |
01:21:20.920
So you have to figure that out ahead of time
link |
01:21:23.640
and decide what to go after.
link |
01:21:25.080
And then you can look for drugs that inhibit
link |
01:21:27.320
what you're interested in.
link |
01:21:28.400
It's not that hard to do.
link |
01:21:31.200
There's just something beautiful about biology,
link |
01:21:34.040
about the mechanisms of biology.
link |
01:21:36.080
And I kind of regret falling in love
link |
01:21:40.040
with computer science so much
link |
01:21:41.840
that I left that biology textbook on the show
link |
01:21:46.280
and left it behind.
link |
01:21:47.360
But hopefully we'll return to it now
link |
01:21:49.480
because I think one of the things you learn
link |
01:21:51.920
even in computer science that studying biology
link |
01:21:56.040
and certainly neurobiology,
link |
01:22:00.080
you get inspired.
link |
01:22:02.760
Here's a mechanism of incredible complexity
link |
01:22:05.160
that works really well, is very robust,
link |
01:22:07.520
is very effective, efficient.
link |
01:22:09.520
It inspires you to come up with techniques
link |
01:22:11.800
that you can engineer in the machine.
link |
01:22:13.760
That's what drives a field forward
link |
01:22:15.760
when people improvise and come up with new technologies
link |
01:22:21.280
that really make a difference.
link |
01:22:22.720
And we have a bunch of those now.
link |
01:22:25.240
What's the difference between the coronavirus family
link |
01:22:28.440
and the other popular family, influenza virus family?
link |
01:22:33.200
I mean, if I were, because you mentioned
link |
01:22:37.320
we should have done a lot more
link |
01:22:38.480
in terms of vaccine development,
link |
01:22:39.920
that kind of thing for coronaviruses.
link |
01:22:42.320
But if I were back then, from my understanding,
link |
01:22:46.440
the thing we should all be afraid of is influenza,
link |
01:22:49.840
like some strong variants coming out from that family.
link |
01:22:53.840
That seems like the one that will destroy human civilization
link |
01:22:57.880
or hurt us really badly.
link |
01:23:00.240
I don't know if you agree with this sense,
link |
01:23:02.520
but maybe you can also just clarify
link |
01:23:06.520
what to use as the difference between the families.
link |
01:23:09.560
So it's an interesting difference.
link |
01:23:11.000
They both have membranes, right?
link |
01:23:14.440
So then they have spike proteins embedded in them.
link |
01:23:19.000
And they're different spikes.
link |
01:23:20.720
In fact, for influenza, there are two main ones.
link |
01:23:24.240
They're called the HA and the NA.
link |
01:23:27.200
But what's inside is RNA,
link |
01:23:30.840
but it's very different RNA.
link |
01:23:33.560
And here we have to explain that.
link |
01:23:35.640
So viruses with RNA can have three different kinds of RNA.
link |
01:23:42.080
They can have what we call plus RNA.
link |
01:23:45.480
They can have minus RNA,
link |
01:23:48.160
or they could have plus minus,
link |
01:23:49.800
actually two strands hybridized together.
link |
01:23:54.480
The plus RNA simply means that
link |
01:23:58.440
if you put that plus RNA in a cell,
link |
01:24:01.800
you know, your cell has ribosomes in it
link |
01:24:03.640
that make the proteins that you need.
link |
01:24:05.720
The ribosomes will immediately latch onto the plus RNA
link |
01:24:08.560
and begin to make proteins.
link |
01:24:11.280
A minus RNA is not the right strand to make proteins.
link |
01:24:15.280
So it has to be copied first.
link |
01:24:17.160
And then the plus minus is both together.
link |
01:24:19.560
So the SARS coronaviruses,
link |
01:24:22.520
all the coronaviruses have plus RNA.
link |
01:24:25.240
So as soon as that RNA gets in the cell,
link |
01:24:26.800
boom, it starts an infectious cycle.
link |
01:24:28.440
Same thing with poliovirus, by the way, which I worked on.
link |
01:24:31.280
Influenza viruses are negative stranded.
link |
01:24:34.920
So they cannot be translated when they get in the cell.
link |
01:24:37.800
So that's tough for the virus
link |
01:24:40.040
because the cell actually cannot make plus RNA
link |
01:24:45.720
from minus RNA.
link |
01:24:47.000
It doesn't have the enzyme to do it.
link |
01:24:49.160
So the virus has to carry it in inside the virus particle.
link |
01:24:53.600
And then when the minus RNA is in the cell,
link |
01:24:55.600
the virus enzyme makes plus RNAs and those get translated.
link |
01:24:59.440
So it's a big difference.
link |
01:25:00.320
And then in the influenza viruses,
link |
01:25:03.400
not only is it minus RNA, but it's in pieces.
link |
01:25:07.040
It's in eight pieces.
link |
01:25:09.460
We call that segmented,
link |
01:25:10.880
whereas the corona is in one long piece of RNA.
link |
01:25:14.880
So they're like floating separately?
link |
01:25:17.880
Yeah, so the genes are on separate pieces.
link |
01:25:19.580
They're all packaged inside that virus particle
link |
01:25:21.800
of influenza virus, but they're in pieces.
link |
01:25:23.760
And why that's important
link |
01:25:25.480
is because if two different influenza viruses
link |
01:25:29.320
infect the same cell,
link |
01:25:31.520
the pieces as they reproduce can mix
link |
01:25:33.760
and out can come a virus with a new assortment of pieces.
link |
01:25:38.200
And that allows influenza virus
link |
01:25:40.240
to undergo extremely high frequency evolution.
link |
01:25:43.840
That's why we get pandemics.
link |
01:25:45.640
When we have a new flu pandemics
link |
01:25:47.040
is because somewhere in some animal,
link |
01:25:49.960
two viruses have reassorted
link |
01:25:51.880
and made a new virus that we hadn't seen before.
link |
01:25:54.400
So you're talking about kind of biological characteristics,
link |
01:26:00.720
but what am I incorrect in my intuition
link |
01:26:03.640
that are from the things I've heard
link |
01:26:05.680
that the influenza family viruses is more dangerous?
link |
01:26:09.880
Like what makes it more dangerous to humans?
link |
01:26:14.880
Well, it depends on the,
link |
01:26:16.080
there are many flavors or vintages of influenza virus.
link |
01:26:19.400
Some are dangerous and some are not, right?
link |
01:26:21.200
It depends on which one.
link |
01:26:22.560
Some like the 1918 apparently was very lethal,
link |
01:26:26.360
killed a lot of people.
link |
01:26:28.280
But more contemporary viruses,
link |
01:26:30.080
we had a pandemic in 2009 of influenza.
link |
01:26:35.800
That wasn't such a lethal virus.
link |
01:26:39.280
We don't know exactly why,
link |
01:26:40.640
but it didn't kill that many people.
link |
01:26:42.280
It transmitted pretty well.
link |
01:26:43.760
Is that the bird flu one?
link |
01:26:45.200
They're all deriving.
link |
01:26:47.600
That one was called swine influenza.
link |
01:26:49.720
Swine, that's right, swine, yeah.
link |
01:26:50.560
It seemed to have started in a pig,
link |
01:26:52.280
but it had bird, it had RNAs from bird influenza viruses.
link |
01:26:57.040
These viruses are all reassortants of different viruses
link |
01:27:00.600
from pigs and birds and humans.
link |
01:27:04.920
But influenza can cause pneumonia
link |
01:27:07.120
and can kill you as does SARS COVID too.
link |
01:27:09.960
So it depends on the virus.
link |
01:27:11.520
So there is another influenza virus
link |
01:27:13.640
that's currently circulating.
link |
01:27:14.960
So right now we have the 2009 pandemic virus
link |
01:27:18.600
that's still around.
link |
01:27:20.040
And then the 1968 pandemic virus,
link |
01:27:23.840
which was the one before 2009,
link |
01:27:25.760
that one is still around too.
link |
01:27:27.400
And that's more lethal.
link |
01:27:29.080
And depending on the season,
link |
01:27:30.360
some seasons the 2009 virus predominates,
link |
01:27:33.800
some seasons the 1968.
link |
01:27:36.200
And when the 68 is around, you get more lethality.
link |
01:27:38.800
So we're living with an influenza family.
link |
01:27:41.680
We haven't exterminated them.
link |
01:27:43.960
Right, we never will, never exterminate them.
link |
01:27:46.280
Why?
link |
01:27:47.120
Because every shorebird in the world is infected with them.
link |
01:27:51.080
Gulls and terns and ducks and all sorts of things.
link |
01:27:54.760
Why can't we develop strong vaccines that defend against?
link |
01:27:59.440
Oh, we could do that, sure.
link |
01:28:02.160
But that would not eliminate them from humans.
link |
01:28:04.880
Even if you had the best vaccine,
link |
01:28:06.760
you would never get rid of it in people
link |
01:28:08.840
because there would always be someone who's not vaccinated
link |
01:28:12.080
or in which the vaccine didn't work.
link |
01:28:14.400
No vaccine is 100%.
link |
01:28:16.600
So.
link |
01:28:17.440
Well, you just contradicted yourself.
link |
01:28:18.680
You said the perfect vaccine.
link |
01:28:21.080
So.
link |
01:28:21.920
Imperfect, imperfect.
link |
01:28:23.160
But then you said, like, even if you had the perfect,
link |
01:28:26.640
yeah, some people wouldn't get vaccinated.
link |
01:28:28.960
But I understand what you mean.
link |
01:28:30.440
But I actually was asking how difficult is it
link |
01:28:32.640
to make vaccines like that for,
link |
01:28:35.200
it seems like it's very difficult to do that
link |
01:28:36.920
for the influenza virus.
link |
01:28:38.840
So it's really easy to make an old school vaccine.
link |
01:28:42.960
So the way the first influenza vaccines were made
link |
01:28:47.480
was actually Jonas Salk worked on them in the 40s.
link |
01:28:51.040
You just grow lots of virus
link |
01:28:53.240
and you grow it in eggs, by the way, chicken eggs.
link |
01:28:55.920
Nice.
link |
01:28:56.920
Literally?
link |
01:28:57.880
Wait, wait.
link |
01:28:58.720
Yeah, chicken, embryonated.
link |
01:28:59.760
So they get fertilized and there's a 10 or 12 day embryo
link |
01:29:02.760
in it and you put virus in it, it grows up
link |
01:29:04.880
and then you harvest it.
link |
01:29:05.720
You get about 10 mls of fluid.
link |
01:29:08.440
And then you take that,
link |
01:29:09.560
you treat it with formaldehyde or formalin
link |
01:29:12.400
and it inactivates the virus so it's no longer infectious.
link |
01:29:16.560
And you just inject that into people.
link |
01:29:18.440
And that was the first flu vaccine.
link |
01:29:19.840
It was made for the US Army actually.
link |
01:29:22.160
And then it got moved over to people.
link |
01:29:24.200
We still use that old school tech today.
link |
01:29:27.360
So you're taking, can you help me out here?
link |
01:29:30.640
Okay, so this is a good time to talk about vaccines.
link |
01:29:34.440
Okay, so you're talking about,
link |
01:29:36.960
you're taking the actual virus,
link |
01:29:39.160
you put it in an egg, you let it grow up.
link |
01:29:42.520
It's very funny that you put it in an egg.
link |
01:29:44.120
It's very poetic.
link |
01:29:46.720
And then how do you make it not infection,
link |
01:29:52.680
not effective or whatever?
link |
01:29:53.920
Not infectious.
link |
01:29:54.760
Not infectious, is that the right term here?
link |
01:29:56.640
Yeah.
link |
01:29:57.480
So how do you make it not infectious?
link |
01:29:58.920
You can treat it with any number of chemicals
link |
01:30:02.000
that'll disrupt the particle so it no longer infects.
link |
01:30:05.400
So that step of disrupting the particle
link |
01:30:09.040
is that very specific to a particular variant particle?
link |
01:30:12.880
No, the same collection of chemicals
link |
01:30:14.840
you can use for all kinds of,
link |
01:30:16.240
and which have been used for SARS CoV2 vaccines also.
link |
01:30:19.600
Same technology.
link |
01:30:20.440
Okay, so what are, there's several things to ask.
link |
01:30:23.600
So you called it old school in a way
link |
01:30:25.280
that's slightly dismissive,
link |
01:30:27.560
like people talk about Windows 98 or something.
link |
01:30:29.960
So is there risks involved with it?
link |
01:30:34.760
Or is it just difficult to produce large amounts?
link |
01:30:37.320
No, it's only, it's,
link |
01:30:38.800
it's very easy.
link |
01:30:40.080
I mean, you could do it in cells and culture,
link |
01:30:41.600
but eggs were convenient.
link |
01:30:43.000
And in the 1940s, we didn't have cells and culture.
link |
01:30:46.240
We didn't know how to do that.
link |
01:30:47.240
So we had to use something else.
link |
01:30:49.680
It's easy to do,
link |
01:30:52.280
but the process of inactivating the virus with a chemical
link |
01:30:56.920
makes it not the best vaccine you can make.
link |
01:30:59.920
The flu vaccines that we have today,
link |
01:31:02.440
which are mostly based on this inactivation,
link |
01:31:05.680
is called inactivated virus vaccines.
link |
01:31:08.480
Oh, so like the kind of thing
link |
01:31:12.280
it presents to the immune system to train on
link |
01:31:14.920
is not close to the actual virus.
link |
01:31:19.520
Yes, that's what we think.
link |
01:31:20.480
So that's why probably the flu vaccines
link |
01:31:22.360
are just not very good, you know?
link |
01:31:24.880
60% efficiency at the best, right?
link |
01:31:29.000
Which is not really good.
link |
01:31:30.040
What does it mean?
link |
01:31:31.160
What is the measure of efficiency for a vaccine?
link |
01:31:33.920
Well, it's how it does in the general population
link |
01:31:37.440
at preventing influenza.
link |
01:31:38.800
At preventing?
link |
01:31:40.760
Illness, not infection.
link |
01:31:41.880
We usually don't measure infection
link |
01:31:44.800
when we're testing a vaccine.
link |
01:31:46.040
We just measure sickness.
link |
01:31:47.640
That's really easy to score, right?
link |
01:31:50.200
You do a trial and you say,
link |
01:31:52.040
if you feel sick, give us a call.
link |
01:31:53.840
We'll tell you what to do.
link |
01:31:55.280
So yeah, I mean, what's sickness?
link |
01:31:58.040
Sickness is the presence of symptoms?
link |
01:32:01.520
So this is good time to say what a symptom is, okay?
link |
01:32:04.920
A symptom is what you only can feel.
link |
01:32:08.880
Only you can feel an upset stomach
link |
01:32:11.560
or a sore throat or that sort of thing.
link |
01:32:13.320
It's the lived experience of a symptom.
link |
01:32:15.160
Whereas a sign is something that someone could measure
link |
01:32:19.040
and tell that you're infected,
link |
01:32:20.480
like virus in your nasopharynx or something else, right?
link |
01:32:26.040
Signs and symptoms.
link |
01:32:27.080
And so in a vaccine trial, they tell you,
link |
01:32:30.040
well, if you have any of these symptoms,
link |
01:32:31.800
they give you a paper with the exact symptoms listed
link |
01:32:35.040
to make sure you're picking them up, right?
link |
01:32:36.840
So for flu, it would probably be fever, sore throat, cough.
link |
01:32:41.480
You call them and then they will do a PCR,
link |
01:32:44.160
make sure you've got flu and not some other virus
link |
01:32:46.560
that makes similar symptoms.
link |
01:32:49.000
And then they would say, are you a vaccine or non vaccine arm
link |
01:32:53.760
and count up all the infections
link |
01:32:55.760
and see how the vaccine did, basically.
link |
01:32:57.680
That's so fascinating because the reporting,
link |
01:33:02.080
so symptom is what you feel.
link |
01:33:03.760
Yes, for sure.
link |
01:33:04.600
And certainly the mind has a ability to conjure up feelings.
link |
01:33:10.120
Oh yes, absolutely.
link |
01:33:11.800
And so like culturally, maybe there was a time
link |
01:33:16.080
in our culture where it was looked down upon
link |
01:33:20.440
to feel sick or something like that,
link |
01:33:23.480
like toughen up kind of thing.
link |
01:33:25.080
And so then you probably have very few symptoms
link |
01:33:28.560
being reported.
link |
01:33:29.480
Absolutely, absolutely.
link |
01:33:30.960
And now is like much more, I don't know,
link |
01:33:36.000
perhaps you're much more likely to report symptoms.
link |
01:33:37.880
Now it's fascinating because then it changes.
link |
01:33:40.800
Oh, it is definitely a perception because for,
link |
01:33:43.280
your symptom may be nothing to me or vice versa, right?
link |
01:33:46.080
And so when you're doing this,
link |
01:33:47.480
it's a little bit of a imprecise science because,
link |
01:33:52.080
and even it's a cultural thing in some countries,
link |
01:33:56.160
something that would make us feel horrible,
link |
01:33:57.800
they wouldn't even bother reporting.
link |
01:33:59.200
No, I didn't have any symptoms.
link |
01:34:00.440
So it's a little bit imprecise and it clouds the results.
link |
01:34:03.400
So if you can measure things, it's always better,
link |
01:34:05.800
but you start out with a symptom.
link |
01:34:07.720
And if you say, if someone tells you this virus,
link |
01:34:11.120
20% of the people are asymptomatic,
link |
01:34:15.720
they don't report symptoms,
link |
01:34:19.400
that number is probably not a constant.
link |
01:34:21.960
It depends where you did the study.
link |
01:34:24.200
It could be different in China versus South America,
link |
01:34:26.880
Europe, et cetera, yeah.
link |
01:34:28.400
I mean, I was trying to figure,
link |
01:34:29.560
so I took two shots of the Pfizer vaccine
link |
01:34:32.400
and I had zero symptoms.
link |
01:34:34.560
Wow.
link |
01:34:35.400
So, and I was wondering, well, see,
link |
01:34:37.160
but that's my feelings, right?
link |
01:34:38.760
This is not, because I felt fine, I was waiting.
link |
01:34:42.040
Did you have pain at the injection site?
link |
01:34:46.160
No, it was kind of pleasant.
link |
01:34:48.360
You felt nothing the next day, no?
link |
01:34:50.280
Nothing, no tiredness, no exhaustion, no.
link |
01:34:54.520
But see, like I have an insane sleeping schedule.
link |
01:34:56.720
I already put myself through crazy stuff.
link |
01:34:59.280
That said, maybe I was expecting something really bad.
link |
01:35:03.280
Like I was waiting and therefore didn't feel it.
link |
01:35:06.760
But I also got allergy shots
link |
01:35:11.120
and those, I was out all next day,
link |
01:35:14.600
like exhausted for some reason.
link |
01:35:16.400
So that gave me like a sense like, okay,
link |
01:35:20.600
at least sometimes I can feel shitty.
link |
01:35:22.640
That's good to know.
link |
01:35:24.440
Sure, sure.
link |
01:35:25.280
And then with the vaccine it didn't,
link |
01:35:27.160
but the question is like,
link |
01:35:29.000
how much does my mind come into play there?
link |
01:35:32.560
The expectations of symptoms,
link |
01:35:35.920
the expectations of not feeling well,
link |
01:35:39.280
how does that affect the sort of the self reporting
link |
01:35:41.280
of the symptoms?
link |
01:35:42.120
I think it's definitely a variable there,
link |
01:35:44.560
but there's certainly many people that don't feel anything
link |
01:35:47.560
after the vaccines.
link |
01:35:48.440
And there's some that have a whole range of things
link |
01:35:51.980
like soreness and fever, et cetera, yeah.
link |
01:35:54.920
So okay, you were talking about the old school development
link |
01:35:57.040
inside the egg.
link |
01:35:58.560
Right.
link |
01:35:59.400
What's better than that?
link |
01:36:02.000
So then the next generation of vaccines
link |
01:36:04.420
which arose in the 50s were what we call
link |
01:36:07.840
replication competent, where the virus you take
link |
01:36:11.440
and it's actually reproducing in you.
link |
01:36:13.920
Yeah, that sounds safe.
link |
01:36:16.040
And it can be somewhat problematic, yes,
link |
01:36:19.040
as you might imagine,
link |
01:36:20.080
because once you put that virus in you,
link |
01:36:22.320
you have no more control, right?
link |
01:36:24.120
It's not like you have a kill switch in it,
link |
01:36:25.720
which actually would be a great idea to put in.
link |
01:36:29.960
Like nanobots, what can possibly go wrong?
link |
01:36:32.200
No, you could just put something in there.
link |
01:36:34.200
If you added a drug, you would shut it off, right?
link |
01:36:37.880
And people are thinking about that
link |
01:36:39.880
because now we're engineering viruses to treat cancers
link |
01:36:43.560
and other diseases and we may wanna put kill switches
link |
01:36:46.680
in them just to make sure they don't run away.
link |
01:36:48.560
Oh, interesting, so you can deploy a drug
link |
01:36:50.360
that binds to this virus that would shut it off
link |
01:36:54.960
in the body, something like that.
link |
01:36:56.480
Something like that, yeah, that would be the idea.
link |
01:36:58.620
You'd have to engineer it in.
link |
01:36:59.880
Anyway, these were, the first one was yellow fever vaccine
link |
01:37:03.580
that was made because that was a big problem.
link |
01:37:06.220
And this virus, and the way you do this,
link |
01:37:09.640
back in the old day was empirical.
link |
01:37:12.640
So Max Tyler, who did the yellow fever vaccine,
link |
01:37:15.280
he took the virus, which is a human virus, right?
link |
01:37:19.640
And he infected, I think he used chick embryos.
link |
01:37:24.980
And he went from one embryo to another and just kept passing
link |
01:37:27.340
and he did that hundreds of times.
link |
01:37:29.320
And every 10 passages, he would take the virus
link |
01:37:32.680
and put it in a mouse or a monkey, whatever his model was.
link |
01:37:36.560
And then eventually he got a virus
link |
01:37:38.040
that didn't cause any disease after 200 and some passages.
link |
01:37:41.880
And then that was tested in people
link |
01:37:43.840
and it became the yellow fever vaccine that we use today.
link |
01:37:46.800
He selected for mutations that made the virus
link |
01:37:50.420
not cause disease, but still make an immune response.
link |
01:37:55.420
So those are called replication competent.
link |
01:37:57.620
We now have the polio vaccine,
link |
01:37:59.480
which was developed in the 50s after the yellow fever.
link |
01:38:03.160
Then we had measles, mumps, rubella.
link |
01:38:05.440
Those are all replication competent vaccines.
link |
01:38:09.160
And you mentioned is that's a good idea.
link |
01:38:12.400
They are all safe vaccines.
link |
01:38:15.460
The only one that has had an issue
link |
01:38:18.440
is the polio replication competent vaccine.
link |
01:38:21.360
It was called Sabin vaccine or oral polio virus vaccine
link |
01:38:25.960
because you take it orally, it's wonderful
link |
01:38:29.720
because you don't have to inject it.
link |
01:38:31.420
This is the perfect delivery.
link |
01:38:34.280
Either intranasal for a respiratory virus
link |
01:38:37.000
or orally for polio goes into your intestines.
link |
01:38:39.040
It reproduces and it gives you wonderful protection
link |
01:38:42.920
against polio.
link |
01:38:45.280
However, you do shed virus out
link |
01:38:49.000
and that virus is no longer a vaccine.
link |
01:38:52.760
It's reverted genetically in your intestine.
link |
01:38:55.600
So you can infect others with polio.
link |
01:38:57.440
Take that virus and put it into an animal and give it polio.
link |
01:39:00.500
And in fact, the parents of some kids in the 60s and 70s
link |
01:39:05.720
who were immunized got polio from the vaccine.
link |
01:39:08.340
The rate was about one and one and a half million
link |
01:39:12.400
cases of polio.
link |
01:39:13.760
So it's called vaccine associated polio.
link |
01:39:15.360
And I always argue that
link |
01:39:18.040
we may not have picked the right vaccine.
link |
01:39:21.180
There was a big fight in the US and other countries
link |
01:39:25.440
between the inactivated polio
link |
01:39:27.560
and the infectious polio vaccines,
link |
01:39:29.800
which ones we should be using
link |
01:39:31.560
because we found out that the infectious vaccine
link |
01:39:33.980
actually caused polio.
link |
01:39:35.280
And eight to 10 kids a year in the US alone
link |
01:39:38.040
got polio from the vaccine,
link |
01:39:39.800
which looking back is really not acceptable in my view,
link |
01:39:43.520
although the public health community said it was
link |
01:39:46.060
to get rid of polio.
link |
01:39:47.560
So now we're close to eradicating polio globally,
link |
01:39:53.120
but this vaccine derived polio is a problem.
link |
01:39:55.960
So now we have to go back to the inactivated vaccine,
link |
01:39:59.200
which is tough because it's injected.
link |
01:40:01.440
So, okay, so the basic high level,
link |
01:40:05.000
how vaccines work principle is
link |
01:40:09.360
you want to deploy something in the body
link |
01:40:11.200
that's as close to the actual virus as possible,
link |
01:40:13.880
but doesn't do nearly as much harm.
link |
01:40:15.880
And there's like a million, not a million,
link |
01:40:17.840
but there's a bunch of ways you could possibly do that.
link |
01:40:19.640
So those are two ways.
link |
01:40:20.600
And now of course we have modern ways
link |
01:40:22.020
we can make mRNA vaccines, right?
link |
01:40:25.680
What are the modern ways?
link |
01:40:26.800
I did, you wanna look, mRNA vaccine.
link |
01:40:29.160
So that's one of the, that's the most modern,
link |
01:40:31.140
but even before mRNA vaccines,
link |
01:40:33.160
we learned that we could use viruses
link |
01:40:36.080
to deliver proteins from a virus that you wanna prevent.
link |
01:40:41.640
And so the Ebola vaccine,
link |
01:40:43.960
we took the spike gene of Ebola virus
link |
01:40:46.560
and put it in a different virus
link |
01:40:47.980
and we deliver that to people
link |
01:40:49.560
and that's called a vector vaccine.
link |
01:40:52.000
And some of the COVID vaccines are vectors
link |
01:40:54.560
of different kinds of most famous are adenovirus vectors
link |
01:40:57.680
carrying the spike gene into the cell.
link |
01:41:00.440
Can you explain how the vector vaccine works again?
link |
01:41:03.320
So we have, we take a virus that will infect humans
link |
01:41:09.160
but will not make you sick.
link |
01:41:11.480
In the case of adenovirus,
link |
01:41:13.480
the years and years of people studying it
link |
01:41:16.000
has told us what genes you could cut out
link |
01:41:18.720
and allow the virus to infect the cell
link |
01:41:20.960
but not cause any disease.
link |
01:41:22.120
So instead of doing selection on it,
link |
01:41:24.480
you actually genetically modify it.
link |
01:41:27.400
Yes, you modify the vector, yeah.
link |
01:41:29.160
So you're much more precise about it.
link |
01:41:30.640
You're very precise
link |
01:41:31.480
and then you splice in the gene for the spike
link |
01:41:34.880
and then you use that to deliver the gene
link |
01:41:37.640
and it becomes produced as protein
link |
01:41:39.680
and then you make an immune response.
link |
01:41:40.920
And vector is the term for this modified.
link |
01:41:43.200
Right, so we're now using viruses at our bidding.
link |
01:41:47.880
We're using them as vectors, not just for vaccines.
link |
01:41:50.180
We can cure monogenic diseases.
link |
01:41:52.380
That is if you have, if you're born with a genetic disease,
link |
01:41:55.560
you have a deletion or a mutation in a gene,
link |
01:41:57.840
single gene, we can give you the regular gene back
link |
01:42:01.960
using a virus vector.
link |
01:42:03.720
So cancers too, we can cure cancers with vectors.
link |
01:42:07.180
Wow, really?
link |
01:42:09.920
Interesting. Yeah.
link |
01:42:10.880
I think in 10 to 15 years,
link |
01:42:12.540
most cancers will be treatable with viruses, yeah.
link |
01:42:15.920
Wow.
link |
01:42:16.760
And not only can we put things in the vector
link |
01:42:19.640
to kill the tumor,
link |
01:42:21.080
we can target the vector to the tumor specifically
link |
01:42:25.360
in a number of ways.
link |
01:42:26.840
And that makes it less toxic, right?
link |
01:42:28.200
It doesn't infect all your other cells.
link |
01:42:31.100
But it takes time to develop a vector for a particular thing
link |
01:42:34.800
because it requires a deep understanding.
link |
01:42:37.560
Yeah, in fact, we have about a dozen different virus vectors
link |
01:42:40.880
that have been studied for 20 years.
link |
01:42:42.900
And those are the set of vaccine vectors that we're using.
link |
01:42:46.320
So it includes adenovirus, vesicular stomatitis virus,
link |
01:42:50.760
which is a cousin of rabies, but doesn't make people sick.
link |
01:42:54.200
Influenza virus is being used as a vector
link |
01:42:57.600
and even measles virus.
link |
01:43:00.200
So we're familiar with how to modify those to be vectors
link |
01:43:04.080
and those are being used for COVID vaccines.
link |
01:43:07.400
And then of course we have the newest,
link |
01:43:10.560
which is the nucleic acid vaccines.
link |
01:43:12.540
So years ago, people said,
link |
01:43:15.220
why can't we just inject DNA into people?
link |
01:43:18.960
Take the spike and put it in a DNA and inject it.
link |
01:43:22.320
So people tried many, many different vaccines.
link |
01:43:25.240
And in fact, there are no human licensed vaccines
link |
01:43:28.240
that are DNA vaccines.
link |
01:43:29.440
Although there is a West Nile vaccine for horses
link |
01:43:33.040
that's a DNA based vaccine.
link |
01:43:35.880
So if you have a horse, you can give it this vaccine,
link |
01:43:38.120
but no human.
link |
01:43:38.960
Can you clarify, does a DNA vaccine
link |
01:43:42.560
only work for DNA viruses?
link |
01:43:44.860
No, it can work for DNA or RNA.
link |
01:43:46.800
Because remember, for an RNA virus,
link |
01:43:48.360
we can make a DNA copy of it.
link |
01:43:50.700
And it will still, when you put that DNA in a cell,
link |
01:43:53.760
it goes into the nucleus.
link |
01:43:55.440
Okay, right.
link |
01:43:56.680
So it's, you're just skipping a step.
link |
01:43:58.440
You get proteins.
link |
01:43:59.280
For RNA vaccines, you're giving, okay, I got it.
link |
01:44:02.080
So those didn't work for human vaccines.
link |
01:44:04.260
And there were many HIV AIDS vaccine trials
link |
01:44:07.280
that used DNA vaccines, didn't work.
link |
01:44:10.820
And then a number of years ago,
link |
01:44:13.320
people started thinking, how about RNA, RNA vaccines?
link |
01:44:17.800
And I first heard this, I thought, what?
link |
01:44:20.280
I've worked with RNA my whole career.
link |
01:44:22.320
It's so fragile.
link |
01:44:24.280
If you look at it the wrong way, it breaks.
link |
01:44:27.600
I mean, that's being facetious, right?
link |
01:44:29.780
But you have to be very careful
link |
01:44:31.600
because your hands are full of enzymes
link |
01:44:34.540
that will degrade RNA.
link |
01:44:37.360
So I thought, how could this possibly work,
link |
01:44:38.860
injecting it into someone's?
link |
01:44:40.160
It's an example of I was skeptical and I was wrong.
link |
01:44:43.920
It turns out that if you modify the RNA properly
link |
01:44:47.160
and protect it in a lipid capsule,
link |
01:44:50.400
it actually works as a vaccine.
link |
01:44:52.920
And people were working on this years
link |
01:44:54.920
before COVID came around.
link |
01:44:57.060
They were doing experimental mRNA vaccines
link |
01:45:00.280
and there were a couple of companies
link |
01:45:01.480
that were working on it.
link |
01:45:02.500
And so at the beginning of 2020, they said, let's try it.
link |
01:45:07.440
And I was skeptical, frankly,
link |
01:45:09.680
because I just thought RNA would be too labile,
link |
01:45:12.120
but I was wrong.
link |
01:45:13.600
So this is, as we're saying offline, one of the great things
link |
01:45:17.600
about you is you're able to say when you're wrong
link |
01:45:20.600
about intuitions you've had in the past,
link |
01:45:22.320
which is a beautiful thing for a scientist.
link |
01:45:25.140
But I still think it's very surprising
link |
01:45:28.120
that something like that works, right?
link |
01:45:30.120
Yeah, I am surprised.
link |
01:45:31.400
So you're just launching RNA in a protective membrane.
link |
01:45:36.200
And then now one thing is surprising
link |
01:45:39.800
that the RNA sort of lasts long enough in its structure.
link |
01:45:45.720
But then the other thing is why does it work
link |
01:45:50.440
that that's a good training ground for the immune system?
link |
01:45:56.760
Is that obvious that that should work?
link |
01:45:59.800
I don't think it's obvious to most people
link |
01:46:01.260
and it's worth going into it
link |
01:46:03.040
because it's really interesting.
link |
01:46:04.560
I mean, first of all, they wrap the RNA in fats,
link |
01:46:09.040
in lipid membranes, right?
link |
01:46:10.560
And the particular formulation they test for years
link |
01:46:14.160
to make sure it's stable,
link |
01:46:16.040
it lasts a long time after it's injected.
link |
01:46:17.960
And the two companies that make the current COVID vaccines,
link |
01:46:22.120
right, Moderna and Pfizer,
link |
01:46:23.240
they have different lipid formulations to get to the same.
link |
01:46:26.660
So that's a real part of it.
link |
01:46:29.040
And it's not simple.
link |
01:46:30.220
There are quite a few different lipids
link |
01:46:31.880
that they put into this coding.
link |
01:46:34.080
And they test to see how long they protect the RNA
link |
01:46:37.040
after it's injected, say, into a mouse,
link |
01:46:39.160
how long does it last?
link |
01:46:40.620
And the way it works is these,
link |
01:46:43.320
apparently these lipid nanoparticles,
link |
01:46:46.160
they get injected into your muscle,
link |
01:46:48.800
they bump into cells and they get taken up.
link |
01:46:52.120
So lipid fat is sticky.
link |
01:46:56.960
It's greasy, we like to say.
link |
01:46:59.880
And so your cells are covered with a greasy membrane also.
link |
01:47:03.680
So when these lipid nanoparticles bump into them,
link |
01:47:06.560
they stick and they eventually get taken up.
link |
01:47:08.360
And they figured this out right at the beginning.
link |
01:47:11.240
If we put RNA in a lipid nanoparticle,
link |
01:47:13.720
will it get taken up into a cell?
link |
01:47:15.240
And the answer was yes, it was just let's try it.
link |
01:47:17.960
And it worked.
link |
01:47:18.800
So it's basically experiment.
link |
01:47:20.340
It's not like some deep understanding of biology.
link |
01:47:22.640
It's experimentally speaking, it just seems to work.
link |
01:47:25.480
Yeah, well, they had some idea
link |
01:47:26.800
that lipids would target this to a cell membrane.
link |
01:47:30.440
And remember, there's no receptor involved.
link |
01:47:33.880
Like the virus has a specific protein
link |
01:47:36.900
that attaches to a receptor.
link |
01:47:39.240
It's not efficient enough to just bump around
link |
01:47:41.640
and get into a cell.
link |
01:47:43.240
That's what these things are doing.
link |
01:47:44.920
And they probably optimize the lipids
link |
01:47:47.240
to get more efficient uptake.
link |
01:47:49.780
But it's not as efficient as a virus would be
link |
01:47:51.920
to get into a cell.
link |
01:47:52.760
Right, so you have no specific,
link |
01:47:54.480
I mean, which is why it's surprising
link |
01:47:57.600
that you can crack into the safe with a hammer.
link |
01:48:02.600
Or with some fat.
link |
01:48:06.080
I mean, that's kind of surprising.
link |
01:48:08.840
It's kind of amazing that it works.
link |
01:48:11.920
But so maybe let's try to talk about this.
link |
01:48:17.360
So one of the hesitancies around vaccines
link |
01:48:22.560
or basically around any new technology
link |
01:48:24.680
is the fact that mRNA is a new idea.
link |
01:48:28.600
And it's an idea that was shrouded in some skepticism,
link |
01:48:32.200
as you said, by the scientific community.
link |
01:48:35.320
Because it's a cool new technology.
link |
01:48:40.240
Surprising that it works.
link |
01:48:42.560
What's your intuition?
link |
01:48:44.400
I think one nice way to approach this
link |
01:48:46.400
is try to play devil's advocate and say both sides.
link |
01:48:53.040
One side is why your intuition says
link |
01:48:56.160
that it's safe for humans.
link |
01:48:59.080
And what arguments can you see if you could steal man
link |
01:49:03.520
and argument why it's unsafe for humans.
link |
01:49:06.680
Or not unsafe for humans,
link |
01:49:09.340
but the hesitancy to take an mRNA vaccine is justified.
link |
01:49:15.160
So many people are afraid because it's new technology
link |
01:49:19.520
and they feel it hasn't been tested.
link |
01:49:22.280
I mean, in theory, what could go wrong?
link |
01:49:25.160
This is the nice thing about mRNA
link |
01:49:29.040
is that it doesn't last forever.
link |
01:49:32.300
As opposed to DNA, which doesn't last forever,
link |
01:49:35.020
but it can last a lot longer.
link |
01:49:38.180
And it could even go into your DNA, right?
link |
01:49:41.680
So mRNA has a shorter lifetime,
link |
01:49:44.340
maybe days after it's injected into your arm,
link |
01:49:47.300
then it's gone.
link |
01:49:48.720
So that's a good thing
link |
01:49:49.740
because it's not gonna be around forever.
link |
01:49:53.000
So that would say, okay, so it's sticking around
link |
01:49:56.640
for your lifetime is not happening.
link |
01:49:58.300
But what else could happen?
link |
01:50:00.000
Well, let's see the protein that's made,
link |
01:50:03.100
could that be an issue?
link |
01:50:05.240
And again, proteins don't last forever.
link |
01:50:08.980
They have a finite longevity in the body.
link |
01:50:12.500
And this one also lasts perhaps at the best a few weeks.
link |
01:50:17.440
Now this is a protein that's made
link |
01:50:18.880
after the RNA gets into the cell.
link |
01:50:22.060
Yeah, so the lipid nanoparticles taken up into a cell
link |
01:50:25.060
and the mRNA is translated and you get protein made.
link |
01:50:27.860
And there's also a question, I'm sorry to interrupt,
link |
01:50:30.280
where in the body, so because it's not well targeted,
link |
01:50:35.100
or I don't know if it's supposed to be targeted,
link |
01:50:38.320
but it can go throughout the body,
link |
01:50:39.920
that's one of the concerns.
link |
01:50:40.760
Right, so it's injected deep into your deltoid muscle,
link |
01:50:43.660
right here, shoulder.
link |
01:50:46.100
And the idea is not to put it in a blood vessel,
link |
01:50:49.780
otherwise it would then for sure circulate everywhere.
link |
01:50:52.400
So they go deep in a blood vessel and it's locally injected.
link |
01:50:57.200
And they did, before this even went into people,
link |
01:51:00.380
they did experiments in mice
link |
01:51:01.820
where they gave them a thousand times higher concentrations
link |
01:51:05.060
than they would ever give to people.
link |
01:51:06.860
And then when you do that, it can go everywhere basically.
link |
01:51:09.340
You can find these nanoparticles
link |
01:51:11.320
in every tissue of the mouse.
link |
01:51:14.080
But that's at a thousand fold higher concentration, right?
link |
01:51:17.200
So I think at the levels that we're using in people,
link |
01:51:21.180
most of it's staying in the muscle,
link |
01:51:22.520
but sure, small amounts go elsewhere.
link |
01:51:25.620
Could there be a lot of harm caused if it goes elsewhere?
link |
01:51:30.460
Like let's say ridiculously high quantities.
link |
01:51:33.140
I'm trying to understand what is the damage
link |
01:51:35.500
that could be done from an RNA just floating about.
link |
01:51:39.420
So the RNA itself is not gonna be a problem,
link |
01:51:41.260
it's the protein that is encoded in it, right?
link |
01:51:43.940
This is a viral RNA which has no sequence in us,
link |
01:51:48.820
so there's nothing that it could do.
link |
01:51:50.540
It's the protein that I would say you could ask,
link |
01:51:54.040
what is that gonna do?
link |
01:51:56.160
And the one property we know about the spike
link |
01:52:01.740
is that it can cause fusion of cells, right?
link |
01:52:06.740
That's how the virus gets in in the beginning.
link |
01:52:09.280
The spike attaches to the cell by this H2 receptor
link |
01:52:14.520
and it causes the virus and the cell to fuse.
link |
01:52:19.180
And that's how the RNA gets out of the particle.
link |
01:52:21.060
But so wait, I'm a bit confused.
link |
01:52:24.100
So with this mRNA vaccine with the lipids and the RNA,
link |
01:52:28.580
there's no spike, right?
link |
01:52:30.700
The mRNA codes for the spike.
link |
01:52:33.100
Oh, the mRNA codes, so it creates the spike.
link |
01:52:35.860
Creates a spike.
link |
01:52:36.700
And so that spike could cause fusion of cells.
link |
01:52:39.260
Yes, except they modified the spike so it wouldn't.
link |
01:52:44.240
Got it.
link |
01:52:45.080
They made two amino acid changes in the spike
link |
01:52:46.420
so it would not fuse.
link |
01:52:47.260
So they understand enough which amino acids
link |
01:52:49.540
are responsible for the fusion.
link |
01:52:51.100
That's right.
link |
01:52:51.940
Interesting.
link |
01:52:52.760
This is so cool.
link |
01:52:53.600
So they could modify it.
link |
01:52:54.440
So now it's not gonna cause fusion, so that's not an issue.
link |
01:52:57.140
It's called the prefusion stabilized spike.
link |
01:53:00.980
Cool.
link |
01:53:01.820
So the spike, when it binds ACE2,
link |
01:53:04.160
that top falls off and the part of the spike
link |
01:53:07.720
that causes fusion is now exposed.
link |
01:53:09.300
And that doesn't happen in this mRNA vaccine.
link |
01:53:11.980
So those are the things that could have happened,
link |
01:53:14.900
but I think they're ruled out by what we've just said.
link |
01:53:18.340
But there's no better test
link |
01:53:19.700
than putting it into people, right?
link |
01:53:22.300
And doing phase one, phase two, and phase three,
link |
01:53:25.060
and increasing numbers of people and asking,
link |
01:53:27.620
what do we see?
link |
01:53:28.860
Do we have any concerns?
link |
01:53:30.860
And so now it's been in many millions of people
link |
01:53:35.260
and we don't see most of the effects you see in a vaccine,
link |
01:53:40.820
you see in the first couple of months.
link |
01:53:43.180
Things like the myocarditis with some of the vaccines,
link |
01:53:46.060
the clotting issues with the AstraZeneca vaccine,
link |
01:53:49.300
Guillain Barre, you see those relatively quickly.
link |
01:53:54.860
And we've seen small numbers of those occur,
link |
01:53:58.300
but other things we haven't seen,
link |
01:54:01.460
and you never say never, right?
link |
01:54:04.820
Right, so I mean, this is fascinating, right?
link |
01:54:07.780
It's like I drink, I put Splenda in my coffee
link |
01:54:12.780
and it has supposedly no calories,
link |
01:54:20.460
but it tastes really good.
link |
01:54:22.340
And despite what like rumors and blogs and so on,
link |
01:54:26.140
I have not seen good medical evidence
link |
01:54:28.900
that is harmful to you, but it's like, it tastes too good.
link |
01:54:33.560
So I'm thinking like,
link |
01:54:35.420
there's gotta be longterm consequences,
link |
01:54:37.740
but it's very difficult to understand
link |
01:54:40.020
what the longterm consequences are.
link |
01:54:43.100
And there's this kind of like distant fear
link |
01:54:47.660
or anxiety about it.
link |
01:54:49.540
Like this thing tastes too good, it's too good to be true.
link |
01:54:53.020
There's gotta be, there's no free lunch in this world.
link |
01:54:55.700
This is the kind of feeling that people have
link |
01:54:57.820
about the longterm effects of the vaccine,
link |
01:55:01.660
that you mentioned that there's some intuition
link |
01:55:04.420
about near term effects that you want to remove,
link |
01:55:09.000
like the diffusion of cells and all those kinds of things,
link |
01:55:11.500
but they think, okay,
link |
01:55:12.860
this travels to other cells in the body,
link |
01:55:14.860
this travels to neurons or that kind of stuff.
link |
01:55:18.660
And then what kind of effect does that have longterm
link |
01:55:20.700
that's yet to be discovered?
link |
01:55:22.680
What do you make me for this vaccine,
link |
01:55:25.140
but in general in science about making statements
link |
01:55:28.240
about longterm negative effects?
link |
01:55:32.260
Is that something that weighs heavy on you?
link |
01:55:34.500
Is that something we can kind of escape
link |
01:55:36.440
through just large scale experimentation
link |
01:55:39.020
with animals and humans?
link |
01:55:41.300
Well, if you're really, if you're concerned about longterm,
link |
01:55:44.220
then you have to do a longterm experiment, right?
link |
01:55:46.700
And maybe you don't see something for 50, 60 years.
link |
01:55:50.580
So if someone says to you,
link |
01:55:53.060
there are no longterm effects of the COVID vaccines,
link |
01:55:56.620
they can't say that
link |
01:55:57.460
because they haven't done the long experiment, right?
link |
01:56:00.280
There's always the possibility, but you have to weigh it.
link |
01:56:02.820
It's always, there's no free lunch, right?
link |
01:56:06.120
There's always a risk benefit calculation you have to make.
link |
01:56:10.300
You can have the study, it goes 50 years and then decide,
link |
01:56:14.060
but I guess what you're doing is just like we said,
link |
01:56:19.080
I forget which one, with polio, with rabies, I forget,
link |
01:56:22.200
but you're weighing the side effects.
link |
01:56:25.460
Yeah, polio, right.
link |
01:56:26.460
The vaccine versus the effects of the virus.
link |
01:56:31.100
And like both of them, you don't know longterm effects,
link |
01:56:34.540
but you're building up intuition as you study,
link |
01:56:38.620
which what are the longterm effects?
link |
01:56:41.140
Like there's a huge number of people,
link |
01:56:46.140
like that have like, I don't want to say experts
link |
01:56:51.460
because I don't like the word,
link |
01:56:52.420
but people have studied it long enough
link |
01:56:54.460
to where they build up intuition.
link |
01:56:56.260
They don't know for sure.
link |
01:56:57.780
There's basic science being done, there's basic studies.
link |
01:57:00.580
But you start to build up an intuition of what might be
link |
01:57:05.880
a problem down the line and what is not,
link |
01:57:08.580
biologically speaking.
link |
01:57:09.980
And so given that map, then considering the virus,
link |
01:57:14.260
there seems to be a lot of evidence for COVID
link |
01:57:16.800
having negative effects on all aspects of the body,
link |
01:57:21.820
not just even respiratory, which is kind of interesting.
link |
01:57:24.860
So the cognitive stuff is terrifying.
link |
01:57:27.060
All kinds of systems evolve, yes.
link |
01:57:28.940
And then you look at the same thing with the vaccine
link |
01:57:32.380
and there seems to be less of that.
link |
01:57:34.700
But of course you don't know
link |
01:57:36.340
if it's some kind of dormant thing that's just going to.
link |
01:57:39.260
You won't know.
link |
01:57:40.380
You have to make a judgment.
link |
01:57:42.580
And for a lot of people they can't, right?
link |
01:57:44.900
Because they don't have the tools to make the judgment.
link |
01:57:47.580
I totally understand that.
link |
01:57:49.340
And we have let people down a few times in medicine, right?
link |
01:57:54.340
And I know two very specific examples.
link |
01:57:57.820
The first polio vaccine ever made,
link |
01:58:00.580
the Salk vaccine was released in 1955.
link |
01:58:04.460
Immediately within months,
link |
01:58:06.420
a few hundred cases of paralysis in kids who got it
link |
01:58:09.460
because it was not properly inactivated.
link |
01:58:14.180
Now you have to understand,
link |
01:58:15.340
parents were dying for a polio vaccine
link |
01:58:17.820
because kids were getting paralyzed every summer,
link |
01:58:20.020
30,000 kids a year.
link |
01:58:22.340
And so they went and took it.
link |
01:58:24.860
They took the word of the medical establishment
link |
01:58:27.060
that it was safe and it wasn't.
link |
01:58:29.580
Big letdown, never going to forget something.
link |
01:58:31.980
Although I think a lot of people today aren't aware of that.
link |
01:58:36.020
I think that was a big problem that's everlasting.
link |
01:58:38.220
Then the attenuated vaccine that we talked about,
link |
01:58:42.060
the infectious causing polio.
link |
01:58:45.900
Yet parents continued to bring their kids to be vaccinated
link |
01:58:49.940
because they were said,
link |
01:58:50.780
this is the right thing to do.
link |
01:58:52.380
And I have to say,
link |
01:58:53.220
I was involved in several lawsuits
link |
01:58:55.020
where parents of a kid who got paralyzed
link |
01:58:58.420
from the polio vaccine decided to sue the manufacturer
link |
01:59:01.860
and get some money for their kid.
link |
01:59:04.620
And so they got mad.
link |
01:59:07.020
And I think you could not...
link |
01:59:11.620
The first issue could have been prevented,
link |
01:59:15.780
could have been prevented by inactivating it properly.
link |
01:59:18.540
I think the company just did the wrong thing.
link |
01:59:21.180
The second we had evidence for,
link |
01:59:23.220
and we should probably have not used that vaccine any longer,
link |
01:59:25.900
but I think that destroys public confidence.
link |
01:59:28.180
But those aren't...
link |
01:59:29.220
They're not long term.
link |
01:59:30.060
That's a minority of cases.
link |
01:59:30.900
This is a minority.
link |
01:59:31.740
This is a very rare event, yeah.
link |
01:59:32.580
But nevertheless,
link |
01:59:33.420
science as an institution didn't make corrections
link |
01:59:38.700
in that case.
link |
01:59:39.540
No, they didn't.
link |
01:59:40.380
And so what do you make of that?
link |
01:59:44.580
I mean, it's very unfortunate
link |
01:59:45.980
that those few things can destroy trust.
link |
01:59:49.460
But I don't think that lasts till today.
link |
01:59:51.140
I think today is a different era, right?
link |
01:59:53.660
And most people don't know about those stories.
link |
01:59:55.340
I tell them to you because that's what could happen.
link |
01:59:58.900
I think it could happen today.
link |
02:00:01.340
If you look at the history of the polio vaccine,
link |
02:00:06.620
the US Public Health Service wanted kids to be vaccinated.
link |
02:00:10.820
So they did things that probably weren't correct
link |
02:00:13.500
to get the vaccine back online.
link |
02:00:15.740
Right?
link |
02:00:16.580
But they did it and they pushed it through.
link |
02:00:20.300
So the question is, what do we do today?
link |
02:00:23.660
So I can look at, as we just said,
link |
02:00:27.300
I can look at what might happen
link |
02:00:29.100
and I can make reasonable decisions
link |
02:00:33.300
about the likelihood of them happening.
link |
02:00:35.060
And I can also say, I don't wanna get COVID of any kind
link |
02:00:38.940
because I've seen how nasty it can be.
link |
02:00:41.700
And I decide I'm taking the risk,
link |
02:00:44.020
whatever small of a long term effect,
link |
02:00:46.060
I'm gonna take the risk.
link |
02:00:47.020
My family took the risk and many other people did.
link |
02:00:49.980
Of a vaccine.
link |
02:00:50.900
Of getting vaccinated.
link |
02:00:52.460
Because I think it's very small.
link |
02:00:53.980
But I understand where people can't make that decision.
link |
02:00:56.900
And that begs the question,
link |
02:00:58.380
what would they need to make a decision?
link |
02:01:01.260
So if you're concerned about an effect in 40 years,
link |
02:01:06.820
we're not gonna know for 40 years.
link |
02:01:09.180
Yeah, so I think if I were to speak,
link |
02:01:11.020
because I talked to, like I mentioned offline to Joe Rogan
link |
02:01:14.820
and his podcast yesterday,
link |
02:01:15.980
I talked to him all the time about this.
link |
02:01:18.780
I think the concern is less about the long term effects
link |
02:01:27.260
like on paper.
link |
02:01:28.460
It's more about the, like people like Anthony Fauci
link |
02:01:34.540
and people at the top are simply misrepresenting the data
link |
02:01:39.140
or like are not accurately being transparent.
link |
02:01:42.980
Not collecting the data properly.
link |
02:01:45.020
Not reporting on the data properly.
link |
02:01:46.820
Not being transparent.
link |
02:01:48.300
Not representing the uncertainties.
link |
02:01:50.380
Not openly saying they were wrong two months ago.
link |
02:01:55.780
Like in a way that's not like dramatic,
link |
02:01:58.100
but revealing the basic process of science
link |
02:02:00.980
when you have to do your best under uncertainty.
link |
02:02:03.740
Just also just being inauthentic.
link |
02:02:06.060
There's a sense, especially with like a younger generation
link |
02:02:09.500
now, there's a certain way on the internet.
link |
02:02:11.700
Like the internet can smell bullshit
link |
02:02:14.260
much better than previous generations could.
link |
02:02:16.900
And so they see there's a kind of inauthenticity
link |
02:02:21.740
that comes with being like representing authority.
link |
02:02:26.420
Like I am a scientist.
link |
02:02:27.980
I'm an expert.
link |
02:02:29.020
I have a PhD.
link |
02:02:30.460
I have four decades of work.
link |
02:02:31.900
Therefore everyone should listen to me.
link |
02:02:34.020
And somehow that maps to this feeling of,
link |
02:02:38.940
well, what are they hiding?
link |
02:02:40.740
If they're speaking from authority like this,
link |
02:02:43.100
if everyone is in agreement like this,
link |
02:02:45.740
that means they all have emails between each other.
link |
02:02:48.180
They said, we're gonna tell this.
link |
02:02:49.500
This is the message we're gonna tell the public.
link |
02:02:51.860
Then what is the truth, the actual truth?
link |
02:02:54.860
Maybe there's a much bigger uncertainty.
link |
02:02:57.220
Maybe there's dead people in the basement
link |
02:02:59.980
that they're hiding from bad mRNA vaccine experiments.
link |
02:03:03.860
Maybe they're, and then the conspiracy theory
link |
02:03:06.660
starts to grow naturally
link |
02:03:09.140
when there's this kind of mistrust of that.
link |
02:03:11.860
So it's less about kind of like a deep concern
link |
02:03:17.180
about longterm effects.
link |
02:03:18.980
It's a concern about longterm effects
link |
02:03:24.660
if we find out that there's some secret stuff
link |
02:03:27.100
that we're not being told.
link |
02:03:28.420
It all lands on that.
link |
02:03:30.060
So what the heck, I mean, so I put the blame
link |
02:03:32.380
not on the data, but basically on the leaders
link |
02:03:35.580
and the communicators of the science at the top.
link |
02:03:39.260
Well, to that I would say all the data,
link |
02:03:43.780
as far as I know, are made public.
link |
02:03:47.060
So you can dive into it.
link |
02:03:48.780
And I know a lot of people ask me questions
link |
02:03:51.540
and I just say, it's right here in the data.
link |
02:03:54.180
And I know a lot of people can't do that.
link |
02:03:55.820
They can't dive into it.
link |
02:03:57.460
But that's one solution for people who are able.
link |
02:04:00.340
Now you could argue, well,
link |
02:04:01.860
maybe they've left data out.
link |
02:04:03.460
Well, then not even I can help
link |
02:04:05.460
because then they're hiding it from me too.
link |
02:04:07.180
And I think that's highly unlikely.
link |
02:04:08.580
I think for the most part,
link |
02:04:09.940
the FDA requires the release
link |
02:04:11.860
of all the clinical trial data, right?
link |
02:04:14.260
So, okay, so this clinical trial data, that's one thing.
link |
02:04:17.600
So that's the data that we should be focusing on, right?
link |
02:04:20.180
So there's a lot of different data sets here.
link |
02:04:24.180
So there's preclinical data,
link |
02:04:25.700
which is everything that was done in the lab
link |
02:04:28.260
before this vaccine ever went into a human arm.
link |
02:04:30.900
It's all the cell culture work
link |
02:04:32.260
that we talked about a little, experiments in animals.
link |
02:04:35.900
All of that is publicly accessible.
link |
02:04:38.380
Most of it gets published.
link |
02:04:39.980
And then there's the initial drug filing,
link |
02:04:42.580
which is huge, the books of,
link |
02:04:45.060
you can get that and look at it, right?
link |
02:04:46.980
This is me sort of asking sort of difficult questions here.
link |
02:04:49.820
It's okay.
link |
02:04:51.980
So there's a lot of money to be made by makers of the vaccine.
link |
02:04:56.060
So for these companies, and obviously there's a distrust
link |
02:05:00.940
of those folks too.
link |
02:05:02.460
They've done a lot of really good things in this world,
link |
02:05:04.540
but the incentives are such
link |
02:05:07.380
that you wanna sweep stuff under the rug
link |
02:05:09.940
if you're not 100% pure in your ethics.
link |
02:05:15.420
And how hard is it for that data to be fabricated,
link |
02:05:21.140
manipulated, like what's your intuition
link |
02:05:24.540
for the pre trial stuff?
link |
02:05:26.100
I think when you start fabricating,
link |
02:05:29.020
then you get inconsistencies,
link |
02:05:31.380
which are pretty easy to pick up.
link |
02:05:34.380
When you're talking about some large scale things
link |
02:05:36.700
of this nature.
link |
02:05:38.020
Because then you can look through the data very,
link |
02:05:40.940
you're gonna, I mean, we require looking very carefully,
link |
02:05:43.660
but you will see inconsistencies from one trial to another.
link |
02:05:46.860
And that might ring a bell that something's been done.
link |
02:05:50.740
Yeah, it's like the moon landing thing.
link |
02:05:55.180
Sometimes like going to the moon is easier than faking it.
link |
02:05:58.380
Right.
link |
02:06:00.100
In the sense it might be easier to do a large scale trial
link |
02:06:03.380
and get an effective vaccine versus faking it.
link |
02:06:05.940
But when you brought up the for profit issue,
link |
02:06:08.340
I think that is always been an issue.
link |
02:06:11.460
I've always felt that having your health depend
link |
02:06:15.780
on for profit industry may not be the best solution.
link |
02:06:20.820
And I don't know how else to do it.
link |
02:06:23.180
People tell me I'm a dreamer that thinking that,
link |
02:06:26.540
all medicines could be nonprofit.
link |
02:06:28.300
But I also think that the world should have one health
link |
02:06:30.980
system that takes care of everyone, right?
link |
02:06:32.780
Because there's some countries that can't
link |
02:06:34.700
and other countries have an excess like us.
link |
02:06:37.580
So I wish we could do that.
link |
02:06:40.220
Well, the argument is the speed of which the vaccines
link |
02:06:44.140
for COVID were produced would never happen
link |
02:06:47.420
in a nonprofit system,
link |
02:06:49.180
would never happen in a non capitalist system.
link |
02:06:51.700
Oh, I could set up a vaccine production institute
link |
02:06:56.060
in the US that would get the vaccines done
link |
02:06:58.860
because you just need to put money into it.
link |
02:07:00.860
That's what made these vaccines get done money.
link |
02:07:03.540
They poured billions of dollars and they got it done quickly.
link |
02:07:06.900
But if I set up a nonprofit institutes of vaccines
link |
02:07:09.700
throughout the US staffed with really talented people,
link |
02:07:12.500
pay them well, keep them motivated,
link |
02:07:15.020
you'll get your vaccine.
link |
02:07:15.860
No, but that's the thing with capitalism is that
link |
02:07:19.940
the selection of who to hire a good,
link |
02:07:22.820
when you say good people,
link |
02:07:24.940
capitalism has a machine that fires people
link |
02:07:28.140
who are not good and selects people that are good.
link |
02:07:30.900
Coming from the Soviet Union,
link |
02:07:32.660
the dream of communism is similar
link |
02:07:35.020
to what you're saying broadly defined.
link |
02:07:37.340
It certainly doesn't work in the broads.
link |
02:07:40.020
The question of whether it works in the healthcare space,
link |
02:07:45.820
there is some aspect to the machine of capitalism
link |
02:07:49.500
being the most effective way to select for good people
link |
02:07:53.020
and to effectively produce the thing.
link |
02:07:56.100
But then of course, a lot of people would argue
link |
02:07:58.500
the current, even the current healthcare is not
link |
02:08:01.140
with like regulations, there's some weird mix
link |
02:08:03.620
where there's a lot of opportunities for inefficiencies.
link |
02:08:07.060
There's a lot of opportunities for bureaucracy.
link |
02:08:09.020
So you have like the worst of all worlds.
link |
02:08:11.820
Can't there be some intermediate that works
link |
02:08:13.980
because I mean, the other issue that we haven't mentioned
link |
02:08:17.260
is that politics gets thrown into this
link |
02:08:19.220
and that really messes up
link |
02:08:21.380
and it should never be mixed with healthcare,
link |
02:08:22.980
but it is because a lot of funding comes from the government
link |
02:08:26.820
so that's another confounding factor.
link |
02:08:29.300
But I really think I could make a vaccine institute
link |
02:08:33.660
that if someone didn't do well, I'd fire them.
link |
02:08:36.620
No, you're not gonna stay if you can't do your job
link |
02:08:39.100
and do it well, you don't give them incentives,
link |
02:08:41.380
but it doesn't have to be the two extremes I think.
link |
02:08:44.700
There has to be a solution that people don't have
link |
02:08:47.740
this mistrust for a company making huge profits
link |
02:08:51.580
off of a drug.
link |
02:08:52.460
But you know what, it's funny,
link |
02:08:55.340
it seems that vaccines and antivirals bear the brunt
link |
02:08:58.300
of this criticism yet there are many other pharmaceuticals
link |
02:09:01.380
that people rely on of all sorts.
link |
02:09:04.380
They don't seem to question and have issues
link |
02:09:06.400
with those and they have far more side effects than vaccines.
link |
02:09:09.180
It's a very strange how we're picking that way,
link |
02:09:11.900
but I should also say that if you have one big
link |
02:09:17.420
vaccine institute, one of the other sets
link |
02:09:22.220
of vaccine conspiracies, I mean, I would say they're
link |
02:09:28.420
a little farther out into the wild side of ideas,
link |
02:09:32.460
but there's one way to control the populace
link |
02:09:37.220
is by injecting substances into them, right?
link |
02:09:41.140
People, I mean, part of that, funny enough,
link |
02:09:44.860
it probably has to do with needles
link |
02:09:46.180
versus something you put in your mouth,
link |
02:09:48.940
but there's something about the government,
link |
02:09:50.820
especially when it's government mandated injection
link |
02:09:53.580
of a substance into you.
link |
02:09:54.960
I don't care what the science says,
link |
02:09:57.780
if it's 100% effective, 100% safe,
link |
02:10:00.940
there's a natural distrust of what,
link |
02:10:03.980
like even if this is effective and safe,
link |
02:10:08.660
giving the government power to do this,
link |
02:10:11.980
aren't they gonna start getting ideas down the line for,
link |
02:10:15.080
you know.
link |
02:10:17.920
I think that they can barely govern.
link |
02:10:20.760
I don't think they're gonna do that,
link |
02:10:22.220
but you don't have to take, unless you're a federal employee,
link |
02:10:25.980
you don't have to take a COVID vaccine.
link |
02:10:27.900
Yeah, but that largely has to do, not largely,
link |
02:10:32.980
but there is an individualistic spirit
link |
02:10:39.740
to the American people.
link |
02:10:41.420
There's this, like, you're not gonna take my gun away
link |
02:10:44.400
from me, you're not going, and I think that,
link |
02:10:52.420
that's something that makes America what it is.
link |
02:10:56.060
Just coming from the Soviet Union,
link |
02:10:57.500
there's a power to sort of resisting
link |
02:10:59.940
the overreach of government.
link |
02:11:01.720
That's quite interesting, because I'm a believer,
link |
02:11:04.440
I hope that it's possible to have,
link |
02:11:08.020
to strive towards a government that works extremely well.
link |
02:11:11.600
I think at its best, a government represents the people
link |
02:11:14.860
and functions in the similar way that you're mentioning,
link |
02:11:17.880
but that, like, pushback,
link |
02:11:20.140
even if it turns into conspiracy theory sometimes,
link |
02:11:22.580
I think is actually healthy in the long arc of history.
link |
02:11:25.980
It can be frustrating sometimes,
link |
02:11:28.100
but that mechanism of pushing back against power,
link |
02:11:30.900
against authority, can be healthy.
link |
02:11:32.980
I agree, I think it's fine to question the vaccines.
link |
02:11:36.500
What I have issue with is that many people
link |
02:11:40.140
put out incorrect information,
link |
02:11:43.180
and I'm not sure what their motivations are,
link |
02:11:45.380
and it's very hard to fight that,
link |
02:11:47.020
because then it's my word versus theirs,
link |
02:11:50.100
and I'm happy to talk with people
link |
02:11:52.340
about any of their concerns,
link |
02:11:54.300
but if you start getting into the stuff
link |
02:11:56.700
that just isn't true, then we have a problem.
link |
02:11:59.260
The thing I struggle with is conspiracy theories,
link |
02:12:03.340
whatever language you want to use,
link |
02:12:04.660
but sort of ideas that challenge
link |
02:12:09.360
the mainstream quote unquote narrative,
link |
02:12:13.600
given our current social media and internet,
link |
02:12:16.180
like the way it operates,
link |
02:12:17.820
they can become viral much easier.
link |
02:12:20.340
There's something much more compelling about them.
link |
02:12:22.700
Like I have a secret about the way things really work.
link |
02:12:27.760
That becomes viral, and that's very frustrating,
link |
02:12:30.200
because then you're not having
link |
02:12:31.740
a conversation on level ground.
link |
02:12:36.140
When you're trying to present scientific ideas,
link |
02:12:38.280
and then there's conspiracy theories,
link |
02:12:39.820
the conspiracy theories become viral much faster,
link |
02:12:42.780
and then you're not just having a discussion
link |
02:12:44.820
on level ground.
link |
02:12:47.980
That's the frustrating part,
link |
02:12:49.180
that it's not an even discussion.
link |
02:12:51.880
Can I just say one more thing?
link |
02:12:53.580
I mean, the internet is here to stay,
link |
02:12:54.860
so we're gonna have to figure out
link |
02:12:56.140
how to deal with it, right?
link |
02:12:57.300
But from my perspective,
link |
02:12:59.340
I was skeptical that any COVID vaccine
link |
02:13:03.020
would be ready within a year.
link |
02:13:05.860
That's amazing.
link |
02:13:07.020
Plus, the way I look at the mRNA vaccine as a scientist,
link |
02:13:12.340
it's gee whiz to me.
link |
02:13:13.900
It's amazing that it worked,
link |
02:13:15.560
and I think the data are great, so I want it.
link |
02:13:19.980
As a scientist, I want it.
link |
02:13:21.260
One of the really sad things, again,
link |
02:13:23.140
with me, too, as a scientist or as an admirer of science,
link |
02:13:29.780
I don't know if it's politics,
link |
02:13:31.260
but one of the sad things to me about the previous year
link |
02:13:34.940
is that I wasn't free to celebrate
link |
02:13:38.440
the incredible accomplishment of science with the vaccines.
link |
02:13:42.380
I was very skeptical that it's possible
link |
02:13:44.140
to develop a vaccine so quickly.
link |
02:13:47.660
So it's unfortunate that we can't celebrate
link |
02:13:50.740
how amazing humans are to come up with this vaccine.
link |
02:13:54.100
Now, this vaccine might have long term effects.
link |
02:13:57.300
That doesn't mean this is not incredible.
link |
02:14:00.180
Why couldn't you celebrate?
link |
02:14:06.580
Because I would love to inspire the world
link |
02:14:08.620
with the amazing things science can do.
link |
02:14:11.340
And when you say something about the vaccines,
link |
02:14:14.000
they're not listening to the science.
link |
02:14:15.660
A lot of people are not listening to the science.
link |
02:14:17.440
What they hear is, oh, you're a Republican
link |
02:14:22.440
or you're a Democrat, and you're social signaling,
link |
02:14:25.220
doing some kind of signaling.
link |
02:14:26.700
No, I think that the vaccine,
link |
02:14:27.820
you're talking about injecting something into you,
link |
02:14:30.640
and maybe you're right that the rhetoric is like,
link |
02:14:33.740
you better take this or you're dumb.
link |
02:14:37.140
It's not the right approach.
link |
02:14:38.460
I've seen, actually, it's kind of interesting.
link |
02:14:40.220
I've seen both sides kind of imply that.
link |
02:14:42.940
So the people who are against the vaccine
link |
02:14:48.940
are dumb for not trusting science,
link |
02:14:52.260
and the people who are for the vaccine
link |
02:14:55.680
are called dumb for trusting science,
link |
02:14:59.380
the scientific institution.
link |
02:15:00.220
And nobody wins, yeah.
link |
02:15:01.820
And they both kind of have a point.
link |
02:15:03.960
Like, because you can always,
link |
02:15:07.740
it's like, is the glass half full or half empty?
link |
02:15:10.260
Because you can always look at, like, science
link |
02:15:15.420
from a perspective of certain individuals
link |
02:15:18.160
that don't represent, perhaps, the not greatest leaders,
link |
02:15:23.580
almost like political leaders.
link |
02:15:25.380
There's a lot of, you know,
link |
02:15:27.620
yesterday I went on a whole rant against,
link |
02:15:31.380
I said a lot of positive things about Anthony Fauci
link |
02:15:34.140
before I went on a rant against him.
link |
02:15:36.140
Because ultimately, you know,
link |
02:15:40.020
I think he failed as a leader,
link |
02:15:41.980
and I know it's very difficult to be a leader,
link |
02:15:44.260
but I still wanted to hold him accountable for that
link |
02:15:47.340
as a great communicator of science and as a great leader.
link |
02:15:50.700
What do you think he didn't do right?
link |
02:15:52.300
I'm curious.
link |
02:15:55.060
So the core of the problem is the several characteristics
link |
02:16:00.060
of the way he was communicating to the public.
link |
02:16:06.540
So one is the general inauthenticity.
link |
02:16:10.340
Two is a thing that, it's very hard to put into words,
link |
02:16:14.500
but there's certain ways of speaking to people
link |
02:16:18.700
that sounds like you're hiding something from them.
link |
02:16:21.740
That sounds like you're full of shit.
link |
02:16:23.980
That's the authenticity piece.
link |
02:16:25.500
Like, it sounds like you're not really speaking
link |
02:16:30.620
to the full truth of what you know
link |
02:16:34.460
and that you did some shady shit in your past
link |
02:16:38.420
that you're trying to hide.
link |
02:16:40.860
So that's a way of communicating
link |
02:16:42.820
that I think the internet and people in general
link |
02:16:45.020
are becoming much better at detecting.
link |
02:16:46.780
Yeah, it's like you said, they're good BS detectors.
link |
02:16:48.620
Yeah, good BS detectors.
link |
02:16:51.500
But contributing to that is speaking from authority,
link |
02:16:55.380
speaking with authority and confidence
link |
02:17:01.540
where neither is deserved.
link |
02:17:04.500
So first of all, nobody's an authority on this new virus.
link |
02:17:10.140
We're facing a deadly pandemic,
link |
02:17:12.220
and especially in the early stages,
link |
02:17:15.260
it was unclear how deadly it would be.
link |
02:17:17.540
It was unclear, probably still unclear,
link |
02:17:19.660
fully how it's transmitted.
link |
02:17:22.140
The full dynamics of the virus,
link |
02:17:24.420
the full understanding of which solutions work and not,
link |
02:17:28.540
how well masks of different kinds work,
link |
02:17:31.220
how easy or difficult it is to create tests,
link |
02:17:34.260
how many months or years it's gonna take
link |
02:17:36.500
to create a vaccine,
link |
02:17:38.780
how well in history or currently do quarantine methods
link |
02:17:43.140
or lockdown methods work,
link |
02:17:45.620
what are the different data mechanisms
link |
02:17:48.060
that are data collection mechanisms
link |
02:17:50.740
that are being implemented,
link |
02:17:52.060
what are the clear plans that need to happen,
link |
02:17:55.660
what the epidemiology that's happening,
link |
02:17:58.340
what is the uncertainty around that?
link |
02:18:02.340
Then there's the geopolitical stuff with China.
link |
02:18:09.140
I personally believe there should have been
link |
02:18:11.460
much more openness about the origins of the virus,
link |
02:18:15.300
whether they're leaked from a lab or not.
link |
02:18:17.100
I think communicating that you're open to these ideas
link |
02:18:21.180
is actually the way to get people to trust you,
link |
02:18:25.340
that you are legitimately open to ideas
link |
02:18:28.220
that are very unpleasant, that go against the mainstream.
link |
02:18:32.540
Showing that openness is going to get people to trust you
link |
02:18:35.740
when you finally decrease the variance in your uncertainty,
link |
02:18:40.980
like decrease uncertainty and have,
link |
02:18:42.820
we still have a lot of uncertainty,
link |
02:18:44.420
but this is the best course of action.
link |
02:18:46.460
Vaccines still have a lot of uncertainty around them.
link |
02:18:49.660
mRNA is a new technology,
link |
02:18:51.260
but we have increasing amounts of data,
link |
02:18:53.300
and here's the data sources,
link |
02:18:54.940
and laying them out in a very clear way
link |
02:18:58.740
of this is the best course of action that we have now.
link |
02:19:01.260
We don't know if it's the perfect course of action,
link |
02:19:04.060
but it's by far the best course of action.
link |
02:19:06.420
And that would come from a leader
link |
02:19:09.460
that has earned the capital of trust from people.
link |
02:19:13.060
I mean, I think in recent history,
link |
02:19:15.900
the worst pandemic is 1918 flu, right?
link |
02:19:19.740
But that's mainly because we didn't know what to do.
link |
02:19:22.540
We didn't have many tools at our disposal.
link |
02:19:24.420
And that was tied up with World War I.
link |
02:19:26.420
That's right, that's right.
link |
02:19:27.900
So the leadership there, I mean.
link |
02:19:30.300
But I don't know what is a lot of deaths, right?
link |
02:19:32.820
And any one person is someone's family,
link |
02:19:35.420
so to them it's a lot, right?
link |
02:19:37.420
But that logic, we don't apply that logic generally,
link |
02:19:41.740
because there's a lot of people suffering
link |
02:19:43.420
and dying throughout the world,
link |
02:19:44.860
and we turn the other way all the time.
link |
02:19:47.780
And that's the story of history.
link |
02:19:49.100
So saying you all of a sudden.
link |
02:19:51.580
What bothers me though, I mean, personally,
link |
02:19:53.780
I don't like anyone dying anywhere,
link |
02:19:56.180
but, and especially considering what technology
link |
02:20:00.100
we're able to muster, yet we still kill each other.
link |
02:20:02.340
It's just a dichotomy to me.
link |
02:20:04.500
Yeah, but I mean, this is the, what is it, Paul Farmer?
link |
02:20:08.940
There's these great stories.
link |
02:20:10.140
I mean, that's the,
link |
02:20:11.380
that's the burden of being in healthcare,
link |
02:20:17.460
being a doctor, is you have to help.
link |
02:20:23.060
You can't help but help a person in front of you
link |
02:20:25.260
who's hurting, but you also are burdened
link |
02:20:28.580
by the knowledge that you helping them,
link |
02:20:31.420
you spending money and effort and time on them,
link |
02:20:34.860
means you're not going to help others,
link |
02:20:36.860
and you cannot possibly allocate
link |
02:20:38.540
that amount of time to everybody.
link |
02:20:40.220
So you're choosing which person lives and which person dies.
link |
02:20:44.060
And you're doing so,
link |
02:20:45.420
the reason you're helping the person in front of you
link |
02:20:47.740
is because they're in front of you.
link |
02:20:49.460
And so the reason right now we care a lot about COVID
link |
02:20:53.260
is because the eye of the world has turned to COVID,
link |
02:20:56.620
but we're not seeing all the other atrocities
link |
02:20:59.300
going on in the world.
link |
02:21:00.460
They're not necessarily related to deaths,
link |
02:21:02.780
they're related to suffering, human suffering,
link |
02:21:05.260
which you could argue is worse than death,
link |
02:21:07.420
prolonged suffering.
link |
02:21:08.660
So there's all of these questions.
link |
02:21:11.620
And the fundamental question here is,
link |
02:21:15.740
are we overreacting to COVID in our policies?
link |
02:21:19.340
So this is the, when we turn our eye
link |
02:21:23.700
and care about this particular thing and not other things,
link |
02:21:26.900
are we dismissing the pain that business owners
link |
02:21:29.180
who've lost their businesses are going to feel?
link |
02:21:31.660
And then the long, talking about long COVID,
link |
02:21:35.660
the long term effects, economic effects on the millions
link |
02:21:39.380
of people that will suffer, that suffer financially,
link |
02:21:42.460
but also suffer from their dreams
link |
02:21:44.820
being completely collapsed.
link |
02:21:46.660
So a lot of people seek gain meaning from work.
link |
02:21:50.700
And if you take away that work,
link |
02:21:52.820
there's anger that can be born, there's pain.
link |
02:21:55.660
And so what does that lead to?
link |
02:21:57.180
That can lead to the rising up of charismatic leaders
link |
02:22:01.860
that channel that anger towards destructive things.
link |
02:22:05.100
That's been done throughout history.
link |
02:22:06.700
So you have to balance that with the policies
link |
02:22:10.220
that you have in COVID.
link |
02:22:12.060
And then, I mean, very much my main opposition
link |
02:22:16.220
to Fauci is not on the details, but the final result,
link |
02:22:20.700
which is I just observe that there's a significant decrease
link |
02:22:25.020
in trust in science as a, not the institution,
link |
02:22:30.500
but the very sort of mechanisms of science.
link |
02:22:32.700
I think science is both beautiful and powerful.
link |
02:22:35.860
And the reason why we have so many amazing things
link |
02:22:38.220
and such a high quality of life.
link |
02:22:40.460
And distrust in that, that the thing we need now
link |
02:22:44.020
to get out of all the troubles we're in,
link |
02:22:46.580
continue getting out of the troubles we're in is science,
link |
02:22:49.660
the scientific process, broadly defined like innovation,
link |
02:22:53.300
technological innovation, scientific innovation,
link |
02:22:55.660
all of that, distrust in that is totally
link |
02:23:00.860
the wrong thing we need.
link |
02:23:02.460
And so anybody who gets in,
link |
02:23:04.780
who causes a distrust in science to me,
link |
02:23:12.220
carries the responsibility of that
link |
02:23:14.220
and should be in, because the response,
link |
02:23:16.980
I mean, should be fired, should be,
link |
02:23:20.060
or at least openly have to carry the burden of that,
link |
02:23:24.380
of having caused of that kind of level of mistrust.
link |
02:23:27.460
Now, it's maybe unfair to place it on any one individual,
link |
02:23:30.460
but you have to, I think in your pocket said,
link |
02:23:34.060
the buck stops at the top, like the leaders have to.
link |
02:23:37.660
No, no, there's a clear leader here, yes, absolutely.
link |
02:23:40.980
So even if it's not directly his fault,
link |
02:23:44.060
he has to carry the price of that.
link |
02:23:48.340
Do you think we should at this point say,
link |
02:23:50.900
okay, we have vaccines,
link |
02:23:53.420
you can decide whether you take them or not,
link |
02:23:55.420
let's move forward?
link |
02:23:57.420
Maybe you can help me understand this,
link |
02:23:59.180
because it seems like, why is that not the right solution?
link |
02:24:04.540
Completely open society, the vaccines,
link |
02:24:07.220
at least in the United States,
link |
02:24:09.780
as I understand are widely available.
link |
02:24:14.140
So this is the American way, you have the decision to make.
link |
02:24:18.340
If you have conditions that make you worried to get COVID
link |
02:24:23.260
and go to the hospital, then you should get vaccinated
link |
02:24:26.180
because here's the data that shows
link |
02:24:27.820
that it's much less likely for you to die
link |
02:24:31.980
if you get vaccinated,
link |
02:24:34.260
if you don't want to get vaccinated
link |
02:24:35.780
because you're worried about longterm effects of vaccine
link |
02:24:39.300
that you don't have to,
link |
02:24:40.340
but then you suffer the consequences of that,
link |
02:24:43.100
and that's it.
link |
02:24:44.420
So here's what I think is driving,
link |
02:24:47.260
I think it's all about kids,
link |
02:24:50.220
because they're gonna go back to school in the fall
link |
02:24:51.940
and many of them can't be vaccinated.
link |
02:24:53.980
So if they get infected, they do have less frequency
link |
02:24:59.060
of disease, but it's not zero.
link |
02:25:01.260
They do get sick and they can have longterm consequences.
link |
02:25:04.740
And at that age, it would be a shame, right?
link |
02:25:09.340
And not even their choice,
link |
02:25:10.620
they can't decide to get vaccinated or not
link |
02:25:13.460
because they can't have access to it.
link |
02:25:15.220
So I think that's what would drive my efforts
link |
02:25:19.380
to try and get more people, at least in schools, vaccinated,
link |
02:25:22.540
but I might be wrong, it may not be that.
link |
02:25:24.660
So can you kind of dig into that a little bit?
link |
02:25:26.540
So there's,
link |
02:25:30.740
so you're saying that there should be an effort
link |
02:25:33.260
for increased vaccinations of kids going to school,
link |
02:25:37.620
just not for societal benefit,
link |
02:25:39.900
but for the benefit of each individual kid, right?
link |
02:25:42.260
So right now, kids under 12, right,
link |
02:25:46.140
are not yet vaccinated, is that correct?
link |
02:25:48.540
Yeah, I think so.
link |
02:25:49.940
And it's not gonna be in time for school opening
link |
02:25:53.420
that they get vaccinated.
link |
02:25:56.700
And then, I suppose the teachers
link |
02:25:59.700
are all gonna be vaccinated,
link |
02:26:01.380
makes sense for them to do that,
link |
02:26:02.780
but I'm just worried the kids
link |
02:26:04.100
are gonna be transmitting it amongst them
link |
02:26:05.980
and many states don't allow mask mandate in school.
link |
02:26:08.900
So I think that's what's driving the larger narrative
link |
02:26:14.060
in the US to protect kids.
link |
02:26:16.740
It's kind of what I hear from Daniel Griffin,
link |
02:26:18.940
because increasing numbers of kids
link |
02:26:21.620
are being admitted to hospitals now,
link |
02:26:23.980
because they're becoming the major unvaccinated population.
link |
02:26:28.260
They're hanging out over the summer
link |
02:26:29.620
and that's just gonna get worse in the fall.
link |
02:26:32.260
And so you could have a lot of kids with long COVID
link |
02:26:35.380
and disabled their entire lives, right, so.
link |
02:26:38.300
And of course, hearing from people who are vaccine hesitant,
link |
02:26:42.060
I hear exactly the kids statement,
link |
02:26:44.820
but they're saying they don't want
link |
02:26:47.100
the long term effects of the vaccine to affect the kids.
link |
02:26:53.220
That's of this new vaccine.
link |
02:26:56.020
Which I would say is, as I said before,
link |
02:26:58.620
you can't say never,
link |
02:27:00.620
but we do know that long COVID exists.
link |
02:27:05.900
We don't know for how long,
link |
02:27:06.860
because we've only looked out six or eight months.
link |
02:27:09.300
We know that exists and the frequency is increasing.
link |
02:27:12.380
It certainly exists in young kids
link |
02:27:14.260
and we have no idea about long vaccine effects.
link |
02:27:16.540
So I think they have to make their decision based on that.
link |
02:27:22.820
But yeah.
link |
02:27:24.420
But your question is why don't we just open up society,
link |
02:27:28.180
say here we have these vaccines
link |
02:27:29.580
if you wanna protect yourself.
link |
02:27:30.780
I think it's mainly the school
link |
02:27:32.140
that's driving the whole narrative, that's my opinion.
link |
02:27:35.300
In which direction, not to open up or?
link |
02:27:37.740
No, to open up, but to try and get their efforts
link |
02:27:41.380
at the federal level to get people vaccinated, right?
link |
02:27:43.940
But see, how high are the risks for kids?
link |
02:27:45.940
I mean, my understanding was it's,
link |
02:27:48.060
I mean, yes, it's nonzero, but it's very low.
link |
02:27:52.220
But what is the numbers?
link |
02:27:53.620
Now, 70,000 hospitalizations so far
link |
02:27:57.660
in kids as of last week.
link |
02:27:59.740
So yes, it's low, but polio was low.
link |
02:28:05.380
Polio was 20, 30,000 kids a year paralyzed.
link |
02:28:08.740
And well, many people have actually argued
link |
02:28:11.460
that that vaccine wasn't necessary.
link |
02:28:13.540
Now, that wasn't a substantial enough health problem.
link |
02:28:17.300
But paralyzed is different than hospital.
link |
02:28:18.980
So what does hospitalized mean?
link |
02:28:20.860
Long COVID.
link |
02:28:21.700
But this is the long COVID question.
link |
02:28:23.060
I mean, this is the open question.
link |
02:28:24.540
It was long COVID in kids.
link |
02:28:26.420
What is that?
link |
02:28:27.820
Well, a lot of the same issues,
link |
02:28:30.660
cognitive issues, motor issues,
link |
02:28:34.180
respiratory, GI dysfunction.
link |
02:28:37.700
How long?
link |
02:28:39.300
We don't know.
link |
02:28:41.100
I mean, it could end in a year.
link |
02:28:43.260
As you know, there are other post acute infectious sequelae
link |
02:28:47.460
that we know about.
link |
02:28:48.660
Chronic fatigue, ME, CFS is thought
link |
02:28:51.420
to be a post infectious sequelae,
link |
02:28:53.220
which has gone for many decades now
link |
02:28:55.140
in many millions of people.
link |
02:28:56.540
This could be another one of those.
link |
02:28:58.740
So I'm just saying it might be worth erring
link |
02:29:02.060
on the side of not letting the kids get infected.
link |
02:29:05.860
Yeah, well, I'm trying to keep an open mind here
link |
02:29:09.860
and I appreciate you doing the same.
link |
02:29:12.060
Of course, I lean on definitely not requiring people
link |
02:29:18.500
to get vaccinated,
link |
02:29:19.340
but I do think getting vaccinated
link |
02:29:21.540
is just the wiser choice,
link |
02:29:24.980
looking at all the different trajectories before us.
link |
02:29:28.460
Getting vaccinated seems like from the data,
link |
02:29:33.220
it seems like the obvious choice, frankly.
link |
02:29:35.500
But I'm also trying to keep an open mind
link |
02:29:38.100
because some things in the past that seemed obvious
link |
02:29:40.100
would turn out to be completely wrong.
link |
02:29:42.100
So I'm trying to keep an open mind here.
link |
02:29:44.820
So for example, one of the things,
link |
02:29:48.100
I'd love to get your thoughts on this is antiviral ideas.
link |
02:29:52.980
So ideas outside of the vaccine.
link |
02:29:56.020
So ivermectin, something that Brett Weinstein
link |
02:30:00.380
and a few others have been talking about.
link |
02:30:02.100
There's been a few studies.
link |
02:30:03.180
Some of them have been shown not to be very good studies,
link |
02:30:07.100
but nevertheless, there seems to be some promise.
link |
02:30:11.460
And I wanted to talk to Brett
link |
02:30:14.500
about this particular topic for two reasons.
link |
02:30:17.300
One, I was really bothered by censorship of this.
link |
02:30:19.940
That's a whole nother topic.
link |
02:30:22.060
I just, I'm bothered by censorship.
link |
02:30:25.940
There's a gray area, of course,
link |
02:30:28.700
but it just feels like that should not have been censored
link |
02:30:32.180
from YouTube, like discussions of ivermectin.
link |
02:30:34.900
We can set that aside.
link |
02:30:36.740
The other thing I was bothered by
link |
02:30:39.260
the lack of open mindedness
link |
02:30:42.100
on exploring things like ivermectin in the early days,
link |
02:30:46.780
especially when at least I thought
link |
02:30:49.140
the vaccine would take a long time.
link |
02:30:51.660
I mean, it's not just ivermectin.
link |
02:30:53.140
It's really seriously at a large scale,
link |
02:30:57.500
rigorously exploring the effectiveness of masks.
link |
02:31:01.340
And the big one for me is testing.
link |
02:31:03.700
Like the fact that that wasn't explored aggressively
link |
02:31:07.020
to lead to mass manufacturing like May, 2020 is absurd.
link |
02:31:11.500
Anyway, so I was bothered by these solutions
link |
02:31:14.780
not being explored and not by now
link |
02:31:16.860
having really good ivermectin studies.
link |
02:31:19.620
Can I talk about ivermectin?
link |
02:31:20.980
Yeah, I would love that, yeah.
link |
02:31:21.820
Sure, so full disclosure,
link |
02:31:23.060
my wife worked on ivermectin at Merck for 20 years.
link |
02:31:26.580
Okay, so they just want people to know,
link |
02:31:30.940
but I don't talk to her all the time about it.
link |
02:31:34.580
And anyway, she hasn't been at Merck for a long time.
link |
02:31:37.220
As you know, ivermectin is a very safe drug
link |
02:31:39.900
used to treat certain parasitic infections, right?
link |
02:31:43.580
And it is approved, it's amazing.
link |
02:31:47.300
You can take one dose a year
link |
02:31:48.660
and be protected against river blindness in Africa
link |
02:31:51.660
and certain parts of Africa.
link |
02:31:52.700
It's remarkably effective.
link |
02:31:54.660
And so it's quite a safe drug
link |
02:31:57.820
at the doses that are approved.
link |
02:32:01.260
Now, early last year, a study was done,
link |
02:32:04.500
I believe in Australia, which showed in cells in the lab,
link |
02:32:07.380
if you infect with SARS CoV2 and then put ivermectin in,
link |
02:32:11.100
it would inhibit the virus production substantially.
link |
02:32:13.860
It was quite clear, right?
link |
02:32:16.020
But the concentrations they were using were rather high
link |
02:32:19.660
and could not be achieved by the approved dosing.
link |
02:32:24.660
So you would need to do a dosing study
link |
02:32:27.860
to make sure it's safe.
link |
02:32:28.700
And the reason is that ivermectin binds to receptors
link |
02:32:32.060
in your brain and it can have high doses.
link |
02:32:34.300
So some people take high doses inappropriately
link |
02:32:37.500
and they have neurological consequences.
link |
02:32:39.660
So if you needed 10 times more ivermectin,
link |
02:32:42.660
you'd have to make sure it would be safe in people.
link |
02:32:44.980
So this is a question of safety too.
link |
02:32:46.460
Right, so I think it has always been the case
link |
02:32:51.340
that it should have been properly studied, but it wasn't.
link |
02:32:54.580
There were lots of trials here and there,
link |
02:32:56.140
lots of improperly controlled trials
link |
02:32:58.700
where someone would just treat some patients
link |
02:33:00.780
and say, hey, they all did fine, but have no control arm.
link |
02:33:03.780
And there were some controlled trials,
link |
02:33:05.260
but they were very small.
link |
02:33:06.500
So right now, a 4,000 person trial is enrolling
link |
02:33:12.660
to test in a randomly controlled trial setting,
link |
02:33:16.660
whether it works or not.
link |
02:33:17.820
There's still plenty of cases that you can do that.
link |
02:33:20.340
So you can ask whether there are any side effects.
link |
02:33:23.060
I think that's completely fine.
link |
02:33:25.020
And if it says it works, then we should use it.
link |
02:33:28.540
In the meantime, I always tell people,
link |
02:33:31.340
if you wanna use ivermectin, you can do it off label.
link |
02:33:33.820
It's FDA approved.
link |
02:33:35.700
And if your physician says,
link |
02:33:36.780
I'm gonna give you this off label,
link |
02:33:38.740
I don't have any objection,
link |
02:33:41.580
but I don't know if it's gonna work.
link |
02:33:43.780
Now, a friend of ours last week in New Jersey got COVID.
link |
02:33:49.260
He went to his local hospital
link |
02:33:50.540
and their regimen was remdesivir, dexamethasone, ivermectin.
link |
02:33:56.580
It's written, that's what they do for every COVID patient.
link |
02:33:59.140
They just give it to them automatically.
link |
02:34:01.140
And so he recovered.
link |
02:34:04.300
So who's to say it was or was not ivermectin, right?
link |
02:34:08.320
So I don't have any strong ideological opposition.
link |
02:34:12.820
I just think it should be tested
link |
02:34:14.620
for what you wanna use it for.
link |
02:34:16.660
And that's being done, and I think that's fine.
link |
02:34:19.260
Is it strange to you that ivermectin
link |
02:34:23.500
or other things like it
link |
02:34:24.780
weren't tested aggressively in the beginning?
link |
02:34:27.660
From a broad scientific community aspect,
link |
02:34:33.940
I can be a little bit conspiratorial,
link |
02:34:35.980
and this is what people talk about with ivermectin,
link |
02:34:39.060
is with the vaccines,
link |
02:34:40.420
there's quite a lot of money to be made.
link |
02:34:42.700
With ivermectin, there's not as much money to be made.
link |
02:34:45.660
Is that too conspiratorial?
link |
02:34:48.380
Like why didn't we try more solutions in the beginning?
link |
02:34:51.500
Well, all the money was put into vaccines, right?
link |
02:34:55.580
Very little was put into antivirals,
link |
02:34:57.340
because the decision was made at a very high level,
link |
02:34:59.520
probably involving Dr. Fauci.
link |
02:35:01.620
We're gonna put 24 billion into vaccines, right?
link |
02:35:06.220
And I think part of the reasoning is
link |
02:35:08.020
they give you years worth of protection,
link |
02:35:10.100
whereas an antiviral works
link |
02:35:11.380
and you have to keep dosing and so forth.
link |
02:35:13.240
But ivermectin is not trivial in this.
link |
02:35:16.000
I agree, it should have been tested early on,
link |
02:35:18.620
but we had a really bad experience with hydroxychloroquine,
link |
02:35:21.820
which we can talk about too.
link |
02:35:25.380
Ivermectin is very hard to synthesize.
link |
02:35:28.740
Most drugs, you synthesize chemically.
link |
02:35:31.620
You devise a formulation and a synthesis,
link |
02:35:34.660
and they do it, they scale it up, and it's fine.
link |
02:35:36.660
Ivermectin is really hard.
link |
02:35:38.340
And so what they do instead is they take the culture
link |
02:35:41.540
of the bacterium that makes it,
link |
02:35:43.820
and they grow it up, and they ferment it,
link |
02:35:45.420
and then they purify it.
link |
02:35:47.180
And Merck owns the bacteria.
link |
02:35:51.380
A number of years ago, two employees of Merck stole it
link |
02:35:55.420
and left the company and tried to market it,
link |
02:35:58.140
and they were arrested and they got put in jail.
link |
02:35:59.980
So they protect it very carefully.
link |
02:36:02.740
So you can't just make it.
link |
02:36:05.580
If you do, it's incredibly expensive.
link |
02:36:07.660
And now India, it's very cheap apparently.
link |
02:36:10.140
They use it quite liberally there,
link |
02:36:12.540
and I don't know how they're making it.
link |
02:36:14.420
Maybe they've licensed it from Merck and so forth.
link |
02:36:16.660
But that's why it hasn't been tested more widely, I think.
link |
02:36:21.620
There's complexities in terms of getting a lot of it
link |
02:36:24.140
and manufacturing a lot of it.
link |
02:36:25.420
Yes. Okay.
link |
02:36:26.420
So what was the hydroxychloroquine?
link |
02:36:28.420
So hydroxychloroquine was also shown early on
link |
02:36:32.300
to inhibit virus in cell culture.
link |
02:36:36.240
And that's not surprising.
link |
02:36:37.340
Hydroxychloroquine, of course, is used for malaria.
link |
02:36:41.260
And what it does, when your cell takes up things
link |
02:36:46.260
from the plasma membrane, including viruses,
link |
02:36:49.620
it goes through a pathway called the endocytic pathway,
link |
02:36:52.140
which involves a vesicle moving through the cell.
link |
02:36:54.100
And as it moves through the cell, its pH drops.
link |
02:36:57.580
And that lets a lot of viruses out actually.
link |
02:37:00.180
And hydroxychloroquine blocks that.
link |
02:37:01.820
So it blocks infection with a lot of viruses.
link |
02:37:06.340
So the problem with those early studies that were published
link |
02:37:10.140
is that they were done in kidney cells and culture,
link |
02:37:14.100
where the only way the virus can get in
link |
02:37:16.280
is through the endosome.
link |
02:37:18.820
And hydroxychloroquine inhibits that,
link |
02:37:20.940
and that's why it inhibits in kidney cells and culture.
link |
02:37:24.420
But lung cells and respiratory cells of humans
link |
02:37:28.060
where the virus reproduces can get in two different ways.
link |
02:37:31.540
It can get in from this endocytic pathway,
link |
02:37:34.680
which is inhibited by hydroxychloroquine,
link |
02:37:37.860
or it can get in at the cell surface,
link |
02:37:40.340
which is not inhibited by hydroxychloroquine.
link |
02:37:43.140
So when you treat patients, it has no effect in the lung
link |
02:37:46.500
because the virus can just bypass it.
link |
02:37:50.160
And all the usage initially were based on
link |
02:37:54.580
the studies done in kidney cells and culture.
link |
02:37:57.220
So that was just wrong, scientifically incorrect,
link |
02:38:00.580
yet it drove a lot of, and today many people
link |
02:38:02.980
still think they should be taking it, but.
link |
02:38:04.980
So that not panning out kind of resulted
link |
02:38:09.220
in a loss of optimism about other similar things panning out.
link |
02:38:14.060
Well, that and many other repurposed drugs were tried,
link |
02:38:17.860
and a lot of HIV antivirals were tried.
link |
02:38:20.180
I think the problem with hydroxychloroquine
link |
02:38:23.460
influenced the ivermectin narrative.
link |
02:38:26.060
People thought that the data was being hidden
link |
02:38:29.340
about hydroxychloroquine, so they said,
link |
02:38:30.940
well, they must be doing the same thing with ivermectin,
link |
02:38:33.100
but with hydroxychloroquine, it just scientifically
link |
02:38:36.020
could not work as an antiviral.
link |
02:38:39.860
The other problem that is more broad
link |
02:38:42.080
that is important to point out is that
link |
02:38:45.820
when you have COVID and you need an antiviral,
link |
02:38:49.580
it's usually because you can't breathe
link |
02:38:50.900
and you go in a hospital.
link |
02:38:52.920
Because if you're mildly ill,
link |
02:38:53.940
you're never gonna go to your doctor
link |
02:38:55.340
and ask for an antiviral.
link |
02:38:56.820
And the problem is when you can't breathe,
link |
02:38:58.380
it's no longer a viral issue.
link |
02:39:00.380
It is now an inflammatory issue,
link |
02:39:02.260
and no antiviral in the world is gonna help you.
link |
02:39:05.300
So that's why remdesivir doesn't work very well,
link |
02:39:08.980
because it's mainly given intravenously
link |
02:39:10.540
to people who go in a hospital.
link |
02:39:13.100
If you get ivermectin in the hospital,
link |
02:39:16.740
it's not gonna do anything for reducing virus,
link |
02:39:18.980
because by that time, you have very little virus
link |
02:39:20.860
to begin with.
link |
02:39:21.780
You have an inflammatory problem
link |
02:39:23.140
that you need to treat in other ways.
link |
02:39:24.860
So this is why a lot of the antivirals failed,
link |
02:39:28.900
because they're used too late.
link |
02:39:30.860
What you need is a pill you take
link |
02:39:32.980
on that first positive test,
link |
02:39:34.460
when you have a scratchy throat.
link |
02:39:36.780
You get a PCR in 15 minutes, I'm positive,
link |
02:39:39.620
take a pill, boom, that's gonna inhibit it.
link |
02:39:42.740
If you wait till you can't breathe,
link |
02:39:44.900
and that's why the monoclonals even don't work
link |
02:39:47.580
if you're in hospital that well,
link |
02:39:49.140
because it's too late.
link |
02:39:50.140
And the approach now is if you're in a high risk group,
link |
02:39:54.360
if you're over 65, if you are obese or have diabetes
link |
02:39:58.900
or any other comorbidities,
link |
02:40:00.700
your first sign of a scratchy throat positive,
link |
02:40:03.780
you get monoclonals, then they might help you.
link |
02:40:07.300
But if you wait till you go in a hospital, it's too late,
link |
02:40:09.820
because the viral curve drops.
link |
02:40:12.060
After that first symptom, within three days,
link |
02:40:15.540
you're no longer shedding enough virus to transmit.
link |
02:40:19.580
Drops really quickly.
link |
02:40:20.700
So that's the reason a lot of these antivirals failed,
link |
02:40:23.180
because they were tested in hospitalized patients.
link |
02:40:25.860
And we have nothing but remdesivir now, unfortunately.
link |
02:40:29.500
So it was the wrong approach.
link |
02:40:30.940
We should have been giving it to people
link |
02:40:33.780
who just tested positive from the start.
link |
02:40:35.900
Or just even for preventative and see.
link |
02:40:38.140
You could do that too.
link |
02:40:39.660
But I have to say, the other issue is,
link |
02:40:42.040
this molnupiravir is a drug in phase three now,
link |
02:40:45.020
it's an oral antiviral, it looks good.
link |
02:40:48.420
If we go ahead with just one,
link |
02:40:51.140
we're gonna get resistance within a few months,
link |
02:40:53.320
and it will be useless.
link |
02:40:54.360
We need to have at least two or three drugs
link |
02:40:56.860
that we can give in combinations.
link |
02:40:58.820
And we know that, because that's what took care of HIV,
link |
02:41:01.700
that's what took care of HCV, hepatitis C virus.
link |
02:41:05.260
It really reduces the emergence of resistance.
link |
02:41:08.980
Joe Rogan got quite a bit of heat recently
link |
02:41:11.600
about mentioning a paper and a broader idea,
link |
02:41:16.620
which I don't think is that controversial,
link |
02:41:19.920
but maybe we can expand on it.
link |
02:41:22.820
And the idea is that vaccines
link |
02:41:26.180
create selective pressure for a virus to mutate
link |
02:41:32.420
and for variants to form.
link |
02:41:37.380
First of all, from a biological perspective,
link |
02:41:40.380
can you explain this process?
link |
02:41:42.100
And from a societal perspective,
link |
02:41:45.680
what are we supposed to do about that?
link |
02:41:47.620
So let's get the terminology right.
link |
02:41:49.580
So as we talked about earlier,
link |
02:41:51.860
viruses are always mutating.
link |
02:41:54.060
So no vaccine or no drug makes a virus mutate.
link |
02:41:57.660
Right, that's the wrong perspective
link |
02:41:59.460
in which to look at it, got it.
link |
02:42:01.180
What the immune response is putting pressure,
link |
02:42:04.940
selection pressure on the virus.
link |
02:42:07.020
And if there's one particle with the right mutation
link |
02:42:11.500
that can escape the antibody, that will emerge, right?
link |
02:42:15.260
So that's what happens with influenza virus, right?
link |
02:42:17.700
We vaccinate every year,
link |
02:42:20.220
and there are not a lot of people that get infected,
link |
02:42:22.160
so they get natural immunity.
link |
02:42:24.780
And then the virus is incredibly varied.
link |
02:42:28.900
It mutates like crazy.
link |
02:42:30.260
And in some person somewhere,
link |
02:42:32.120
there's one variant that escapes the antibody,
link |
02:42:34.380
which has been induced either by infection or vaccination.
link |
02:42:37.100
It can be both.
link |
02:42:38.860
And that drives the emergence of the new variants,
link |
02:42:41.260
so the next year we need to change the vaccine.
link |
02:42:43.860
So I would say both natural infection and vaccination,
link |
02:42:48.960
sure, select for variants.
link |
02:42:51.440
Absolutely, there's no question,
link |
02:42:53.500
because they're inducing immunity.
link |
02:42:55.420
Now, what happened last year was at the beginning of 2020,
link |
02:43:00.060
very few people in the world were immune
link |
02:43:02.340
as the virus first started spreading.
link |
02:43:05.960
But you can see in the sequences of those isolates
link |
02:43:09.140
from the beginning of 2020,
link |
02:43:11.040
you can see all of the changes that are now present
link |
02:43:14.660
in the variants of concern at very, very low frequencies.
link |
02:43:17.700
They were already there,
link |
02:43:18.700
but there was no selection for them to emerge.
link |
02:43:21.940
Until November, when we now had many millions of people
link |
02:43:25.340
who had mostly been infected, but also some vaccinated,
link |
02:43:29.780
then we saw the alpha variant emerge in England,
link |
02:43:33.060
probably because of immune selection.
link |
02:43:35.360
Now, the virus that had the change
link |
02:43:38.300
that evaded the antibody had an advantage,
link |
02:43:41.980
and that virus drove through the population.
link |
02:43:44.060
So that's what we're seeing.
link |
02:43:45.300
All these variants are simply antigenic selection.
link |
02:43:47.980
So the variants, the mutations
link |
02:43:50.780
that are at the core of these, quote unquote, variants,
link |
02:43:55.500
they were always there all along the vaccine,
link |
02:43:58.380
or the infections did not create them.
link |
02:44:00.440
No, the infections don't create them, they're selected.
link |
02:44:02.660
It's like the vaccine wipe out a lot of the variants,
link |
02:44:09.020
and then by making your body immune to them,
link |
02:44:13.740
but some of them survive.
link |
02:44:15.540
Yeah, exactly.
link |
02:44:16.820
And then there's another tree that's built,
link |
02:44:19.500
and it's unclear what that tree leads to.
link |
02:44:23.880
I mean, it could make things much worse or much better,
link |
02:44:26.980
and we don't know.
link |
02:44:28.340
Well, with flu, we see year after year the virus changes,
link |
02:44:31.220
we change the vaccine, we deal with it,
link |
02:44:33.580
we change it again, there's an unending series.
link |
02:44:35.540
But see, that's a very different story.
link |
02:44:37.260
If, do you think COVID will be with some likelihood,
link |
02:44:42.260
like the flu, where it's basically variants,
link |
02:44:47.860
we'll never be able to eradicate it?
link |
02:44:52.780
It will never eradicate it in any case, ever.
link |
02:44:57.380
Well, come up with a vaccine
link |
02:44:59.820
that makes you immune to enough variants
link |
02:45:03.140
where there's not enough evolutionary room.
link |
02:45:07.240
Well, if you cut down the number of infections,
link |
02:45:09.100
then you reduce the diversity, sure, right?
link |
02:45:12.180
The problem is if, let's say you're a cynic
link |
02:45:15.140
and you say, well, vaccination is just selecting
link |
02:45:18.100
for variants, so let's stop it.
link |
02:45:20.020
But then you're gonna have infection,
link |
02:45:21.460
and that's gonna select for variants.
link |
02:45:23.280
And there, you're more likely to get very sick
link |
02:45:26.260
because we know the vaccines are really good
link |
02:45:28.620
at preventing you from dying.
link |
02:45:30.060
So that's why it still makes sense to use vaccines
link |
02:45:34.060
because they prevent you from dying.
link |
02:45:36.900
That's the bottom line.
link |
02:45:38.180
But can we ever make a vaccine that deals with all variants?
link |
02:45:44.560
Absolutely.
link |
02:45:45.580
And the reason I say that is because people
link |
02:45:49.240
who get naturally infected with SARS COVID,
link |
02:45:53.420
they develop COVID, they recover.
link |
02:45:56.860
If you give them one vaccine dose,
link |
02:45:59.580
they make an immune response
link |
02:46:01.460
that handles all the variants that are around right now.
link |
02:46:05.740
All of them.
link |
02:46:06.580
Much better than people who've gotten two doses of vaccine.
link |
02:46:10.380
For some reason, their immune response is suddenly broadened
link |
02:46:14.340
after the infection vaccination,
link |
02:46:16.860
and they can handle all the variants that we know of so far.
link |
02:46:19.340
So that tells me we can devise a strategy
link |
02:46:22.780
to do the same thing with a vaccine
link |
02:46:24.540
that makes a really broad vaccine
link |
02:46:26.620
that'll handle all the variants.
link |
02:46:27.940
Well, you actually, on the virology blog,
link |
02:46:30.660
I don't know if you're the author of that, but.
link |
02:46:32.340
I am, I am, yes.
link |
02:46:33.900
Oh, the blog, yes, but there's a particular post
link |
02:46:36.820
that's talking about reporting on a paper
link |
02:46:39.400
that a mix and match strategy.
link |
02:46:40.860
Oh, yes, that's one of my co writers, Trudy Ray, yeah.
link |
02:46:44.180
Yeah, it's an interesting idea
link |
02:46:46.620
that there's some early evidence now
link |
02:46:49.380
that mixing and matching vaccines,
link |
02:46:52.380
like one shot of Pfizer and one of like Moderna or something,
link |
02:46:56.500
that creates a much better immunity
link |
02:47:00.460
than does two shots of Pfizer.
link |
02:47:02.820
I think that's worth exploring, absolutely.
link |
02:47:05.420
And this is relevant, what we're doing with influenza,
link |
02:47:09.100
you know, instead of having to vaccinate people every year,
link |
02:47:11.240
why can't we devise a vaccine
link |
02:47:12.860
which you'd get once in your lifetime
link |
02:47:14.780
or maybe once every 10 years, okay?
link |
02:47:17.420
So the spike of influenza, it's a long protein,
link |
02:47:22.440
kind of like the spike of SARS CoV2,
link |
02:47:24.740
it's stuck in the virus membrane,
link |
02:47:26.340
and the very tip, that's the part that changes every year.
link |
02:47:31.340
This is where the antibodies bind.
link |
02:47:33.740
But the stem doesn't change.
link |
02:47:37.540
And if you make antibodies to the stem,
link |
02:47:39.860
they can also prevent infection.
link |
02:47:41.660
It's just that when people are infected
link |
02:47:44.020
or with the current vaccines,
link |
02:47:45.940
they don't make many antibodies to that stem part,
link |
02:47:48.820
but we're trying to figure out how to make those
link |
02:47:51.380
and we think they would be broadly protective
link |
02:47:53.620
and you'd never be able to,
link |
02:47:55.400
or more rarely be able to have a variant emerge
link |
02:47:59.020
that escaped it.
link |
02:48:00.820
And I think we can do the same thing
link |
02:48:02.460
with coronavirus too, for sure.
link |
02:48:06.660
Can I ask you about testing?
link |
02:48:08.380
Sure, sure.
link |
02:48:10.220
You mentioned PCR, what kind of tests are there?
link |
02:48:13.300
The antigen test, what are your thoughts on each?
link |
02:48:18.160
Maybe this is a good place to also mention like viral load
link |
02:48:22.460
and the history of the virus as it passes through your body
link |
02:48:27.460
in terms of what's being tested for
link |
02:48:31.260
and all those kinds of things.
link |
02:48:33.380
So the first tests that were developed were PCR,
link |
02:48:39.100
polymerase chain reaction.
link |
02:48:40.260
They're basically nucleic acid amplification tests.
link |
02:48:43.780
And they were very first ones.
link |
02:48:44.820
They stuck the swab all the way up into your brain almost.
link |
02:48:49.260
I had that done a couple of weeks ago.
link |
02:48:50.860
Oh my gosh, it's really nasty.
link |
02:48:53.420
But now they do an anterior Nares swab.
link |
02:48:56.280
They get a little, they get a bunch of cells
link |
02:48:58.940
and some mucus which has virus and parts of virus,
link |
02:49:02.660
stick it in a test tube and then they run a reaction
link |
02:49:05.980
which by the way involves reverse transcriptase
link |
02:49:09.020
because it converts the viral RNA to DNA
link |
02:49:11.980
and then you amplify it.
link |
02:49:14.240
And you can specify what part of the viral RNA
link |
02:49:18.940
you wanna amplify and then a machine will detect it
link |
02:49:22.540
and it can be done in 15 minutes.
link |
02:49:25.100
But you're detecting pieces of RNA, not infectious virus.
link |
02:49:29.100
So we're measuring viral RNA loads, right?
link |
02:49:32.420
And a common mistake that many people
link |
02:49:36.060
who should know better, physicians and scientists
link |
02:49:38.700
of all kinds, they think that indicates
link |
02:49:41.180
how much virus you have.
link |
02:49:43.620
It doesn't.
link |
02:49:45.580
It's a diagnostic of whether you have bits of RNA in you
link |
02:49:48.620
and it probably means you're infected.
link |
02:49:51.320
But you can't use it to shed light on what's going on
link |
02:49:55.300
and I'll tell you why in a bit.
link |
02:49:56.880
But first we have to explain some other things.
link |
02:50:01.940
So until you get to about a million copies of RNA,
link |
02:50:06.380
so you can measure the copy number in this test,
link |
02:50:08.540
this PCR test.
link |
02:50:10.660
It's a number called CT or cycle threshold.
link |
02:50:13.860
The test, the way the machine works, it goes through cycles
link |
02:50:16.420
and every cycle it amplifies what you put in
link |
02:50:19.980
and the more cycles you need to see something,
link |
02:50:23.900
that means there's not a lot of RNA there.
link |
02:50:26.660
So if you do a test and you have a cycle threshold of 35,
link |
02:50:31.100
you have very little RNA in you.
link |
02:50:33.660
Contrary, if you have a cycle threshold of 10,
link |
02:50:36.160
you have a ton of RNA and it only took 10 cycles
link |
02:50:38.700
to detect it.
link |
02:50:40.700
And you can extrapolate from that number,
link |
02:50:42.780
the number of copies you have per sample, say per swab.
link |
02:50:46.100
And if you don't have a million, you're not infectious.
link |
02:50:49.120
You're not gonna infect anyone.
link |
02:50:50.740
So in the early days, no matter what CT,
link |
02:50:53.300
what PCR result you had, they would quarantine you.
link |
02:50:56.020
And that was wrong because you're not shedding.
link |
02:50:58.340
You don't need to be quarantined,
link |
02:51:00.020
but wasn't thought through properly, right?
link |
02:51:02.740
And that's where you had like 14 days
link |
02:51:04.540
or something like that.
link |
02:51:05.380
14 days, which is now we know is too long
link |
02:51:07.900
because you don't shed for that long in a normal infection.
link |
02:51:11.580
Now it's 10 days should be fine.
link |
02:51:14.120
So what happens is you get infected,
link |
02:51:16.140
you don't know it of course.
link |
02:51:17.820
The virus starts to grow very quickly.
link |
02:51:19.780
And within four or five days,
link |
02:51:21.900
you reach a peak of shedding.
link |
02:51:24.660
You're making a lot of RNA and you may be asymptomatic.
link |
02:51:28.220
You're shedding, you can infect others.
link |
02:51:30.040
And then you may or may not have your symptom onset.
link |
02:51:33.940
So you shed for a couple of days before symptom onset.
link |
02:51:36.240
And then within three days, four days,
link |
02:51:38.620
the viral RNA crashes and you're no longer shedding,
link |
02:51:41.460
you're no longer transmitting.
link |
02:51:42.940
So that's the one kind of test we have.
link |
02:51:44.540
It can tell you if you're infected at the moment,
link |
02:51:47.640
but it won't tell you
link |
02:51:49.020
if you're gonna be infected tomorrow, right?
link |
02:51:51.460
Cause if you're negative today,
link |
02:51:52.660
you could be positive tomorrow.
link |
02:51:54.020
You just might be in a different part
link |
02:51:56.140
of the incubation period, right?
link |
02:51:58.300
So that's one test been used the most.
link |
02:52:01.060
You can now get 15 minute versions of them
link |
02:52:05.020
in a walk in or whatever fine.
link |
02:52:06.860
Then there are antigen tests,
link |
02:52:08.040
which look for the proteins that the virus is making.
link |
02:52:11.620
So as it's reproducing in your nose,
link |
02:52:13.440
it's not only making genomes, it's making proteins.
link |
02:52:16.140
And so these you can buy in the drug store.
link |
02:52:18.340
And these would have been great if they had,
link |
02:52:22.140
Michael Minna last year had the idea
link |
02:52:24.300
that if we could make a little stick,
link |
02:52:26.460
a little piece of paper that you would suck on
link |
02:52:28.580
and it would tell you if you're infected or not,
link |
02:52:30.340
if this could cost less than a buck,
link |
02:52:32.540
everybody could test themselves.
link |
02:52:33.980
Which they can cost less than a buck, by the way.
link |
02:52:37.020
Yeah, but they were never made, right?
link |
02:52:38.820
Right, they're never mass manufactured.
link |
02:52:42.300
So his idea is to do like daily tests.
link |
02:52:44.740
Yeah, daily and then the kid's going to school,
link |
02:52:47.340
he's positive or she's positive.
link |
02:52:49.860
Well, if it's cheap enough, you just take another test
link |
02:52:51.820
because they have a certain error frequency.
link |
02:52:53.540
If it's positive twice, you stay home
link |
02:52:55.300
and the next day you try again.
link |
02:52:57.180
And I think this would have revolutionized
link |
02:52:59.860
because the PCR tests are more expensive at the time
link |
02:53:02.460
and they take longer to do and so forth.
link |
02:53:05.320
But that never happened.
link |
02:53:07.060
But now we do have $20 Binax now
link |
02:53:09.500
and others that you can buy and people buy them.
link |
02:53:12.420
But that can still happen, right?
link |
02:53:13.980
And this is the very frustrating thing to me
link |
02:53:16.020
because I'm worried about variants,
link |
02:53:18.980
but I'm also worried about future,
link |
02:53:20.660
much more deadly pandemics.
link |
02:53:23.600
Like I know we kind of said, yes, COVID, lots of deaths,
link |
02:53:28.460
but like it could be a lot worse too.
link |
02:53:31.380
And so I'm thinking what is going to be the right response
link |
02:53:35.780
for the future pandemic of its kind?
link |
02:53:38.580
And what's the right response
link |
02:53:39.900
for continued number of variants
link |
02:53:41.640
and some of the variants might be deadlier
link |
02:53:44.620
or more transmissible?
link |
02:53:45.940
Well, we can, the antigen tests
link |
02:53:49.980
will pick up the variants.
link |
02:53:51.860
That's not a question.
link |
02:53:52.700
The PCR may be influenced by changes,
link |
02:53:55.100
but you can quickly adapt the primers that you use.
link |
02:53:58.500
So that's what I mean.
link |
02:53:59.340
Like to me, all of these discussions
link |
02:54:00.980
about vaccines and so on.
link |
02:54:03.300
Vaccines, we got very lucky that they took so little time.
link |
02:54:08.060
And you have to be aware no matter what
link |
02:54:10.540
that there's hesitancy with the vaccines
link |
02:54:12.340
in this country before.
link |
02:54:13.780
I mean, yeah, that's a reality.
link |
02:54:15.700
You can't just be like magically saying
link |
02:54:17.580
that you're going to overcome that.
link |
02:54:20.420
And I don't think there's any hesitancy
link |
02:54:22.200
and cheap tests at home.
link |
02:54:24.040
I agree.
link |
02:54:24.880
I think if someone, so the question is
link |
02:54:27.020
if someone tested positive, would they stay home?
link |
02:54:29.220
That's the question.
link |
02:54:30.060
What if their job depends on them going in?
link |
02:54:32.380
I mean, that's.
link |
02:54:33.580
Well, you have to look at sort of aggregate,
link |
02:54:36.660
how many people would decide.
link |
02:54:38.180
And I think, again, a lot of that is in leadership,
link |
02:54:43.060
but I think a lot of them,
link |
02:54:45.060
I would say most people would stay home.
link |
02:54:47.140
I think that Mina had the idea
link |
02:54:49.460
and it would have changed the whole situation for sure.
link |
02:54:53.180
If it could have been made when we talked to him last spring,
link |
02:54:56.220
I think, or summer, we would have gotten around
link |
02:54:59.900
a lot of the issues that we're in today
link |
02:55:01.540
because I think people would have stayed home
link |
02:55:03.060
and not transmitted.
link |
02:55:04.000
And I think it's still valuable to this day.
link |
02:55:06.060
In the fall, if we don't have vaccine uptake,
link |
02:55:09.820
we could just test kids every day
link |
02:55:12.380
and keep them home when they're infected.
link |
02:55:14.240
It cuts, and we don't have it.
link |
02:55:17.580
But I think, and I'm not privy to what was going on,
link |
02:55:20.620
but I don't think a lot of emphasis
link |
02:55:22.980
was put on testing early on.
link |
02:55:25.100
The CDC developed the first one, it was flawed.
link |
02:55:27.940
They had to recall the kits.
link |
02:55:29.380
I mean, that's a fiasco.
link |
02:55:30.380
They should have had 100 companies
link |
02:55:32.200
making the tests initially, right?
link |
02:55:34.700
So for the future, I think what we have learned
link |
02:55:37.960
is we need to have a rapid antigen test right off the bat.
link |
02:55:42.280
It's doable.
link |
02:55:43.700
You can't do it in a day like you can for PCR
link |
02:55:46.220
because you need to make antibodies
link |
02:55:49.700
to the protein that you're looking for
link |
02:55:51.180
and you need to do those in animals.
link |
02:55:52.920
But you can do it in weeks and we should be ready for that.
link |
02:55:57.660
Yeah, because I mean, to me, that's obvious.
link |
02:56:00.680
That's obviously the best solution.
link |
02:56:02.820
Second to that, if we understood how well masks work.
link |
02:56:08.500
Like, maybe let me ask you this question.
link |
02:56:11.300
Let's put masks aside.
link |
02:56:14.040
How well do we understand how COVID is transmitted?
link |
02:56:18.100
There's droplets of different sizes,
link |
02:56:22.140
aerosols, tiny, tiny droplets.
link |
02:56:26.500
It seems like that's a very difficult thing
link |
02:56:28.480
to understand thoroughly.
link |
02:56:29.840
So it seems like it's transmitted both ways.
link |
02:56:33.320
It's unclear how exactly.
link |
02:56:35.640
So how much do we understand
link |
02:56:38.480
and why is it so difficult to understand fully?
link |
02:56:40.680
Well, I think it's clear that it's transmitted
link |
02:56:43.080
through the air mostly.
link |
02:56:44.760
It's not touching.
link |
02:56:46.240
We thought initially it would be a lot of touch,
link |
02:56:47.920
but very little of that.
link |
02:56:50.040
It's through the air and when you talk,
link |
02:56:53.120
mainly when you talk, you expel a lot of droplets, right?
link |
02:56:56.640
Even the plosives that your foam thing here
link |
02:56:59.240
are meant to pee, right?
link |
02:57:01.560
That you send out little sprays
link |
02:57:03.040
and those have viruses in them.
link |
02:57:05.520
And the big drops fall to the ground
link |
02:57:08.200
and the little ones can go 100 feet or more, right?
link |
02:57:11.280
But the little ones also have less virus in them.
link |
02:57:15.720
So I'm not sure, well, we certainly do not know
link |
02:57:18.720
how much virus you need to be infected.
link |
02:57:21.360
But it's probably at least several thousand particles,
link |
02:57:24.920
if not more.
link |
02:57:26.160
And it could be that for most people,
link |
02:57:30.320
the tiny droplets don't have enough virus
link |
02:57:32.720
to infect someone else.
link |
02:57:34.200
But there's one observation about this virus
link |
02:57:37.080
that's really interesting.
link |
02:57:38.640
And that is that 80% of transmissions
link |
02:57:42.080
are done by 20% of the people, of the infected people.
link |
02:57:46.360
Not every infected person transmits.
link |
02:57:49.840
That's been borne out in multiple studies.
link |
02:57:51.920
And in fact, there's a study at University of Colorado
link |
02:57:55.520
where they quantified the viral RNA loads
link |
02:57:58.720
in all the swabs that had been done of students
link |
02:58:01.320
for like a six month period.
link |
02:58:03.760
And most of the infectious virus,
link |
02:58:07.880
most of the RNA copies were found
link |
02:58:10.680
in 15 to 20% of the people.
link |
02:58:14.600
The rest had really low
link |
02:58:15.760
and that's probably why they don't transmit.
link |
02:58:18.320
So those are the ones that might get enough virus
link |
02:58:22.320
in the tiny droplets to be able to infect
link |
02:58:24.840
someone at a distance.
link |
02:58:26.520
And I think that's entirely possible.
link |
02:58:28.840
Why is it hard to study?
link |
02:58:31.040
You can't do it in real life
link |
02:58:32.800
because you don't know who's infected.
link |
02:58:35.360
And if you do, there's not a controlled environment
link |
02:58:37.800
to measure droplets and so forth.
link |
02:58:39.240
You'd have to do it in a laboratory situation.
link |
02:58:42.280
If you use an animal, you just don't know
link |
02:58:44.160
what the relevance of that is to people.
link |
02:58:46.520
You'd have to use human and do challenge experiments.
link |
02:58:50.000
And we don't do that at this point,
link |
02:58:51.880
at least not for this virus.
link |
02:58:53.320
So that's why it's hard to know what's going on.
link |
02:58:55.920
So we have to make inferences
link |
02:58:58.240
from epidemiological associations
link |
02:59:01.240
where you're studying, say transmission in a household
link |
02:59:03.840
where people are stuck in the same rooms together
link |
02:59:06.080
and you can get an idea of what kind of droplets
link |
02:59:09.160
were involved.
link |
02:59:10.000
So that makes it much harder too.
link |
02:59:11.320
If you're leaning on epidemiological stuff
link |
02:59:14.160
as opposed to like biophysics
link |
02:59:15.680
or something like the mechanic.
link |
02:59:17.280
Very hard.
link |
02:59:18.320
So that makes it really hard to then develop solutions
link |
02:59:23.120
like masks, to ask the question, how well do masks work?
link |
02:59:26.600
Because then to answer that question,
link |
02:59:28.800
you can lean on epidemiological stuff again,
link |
02:59:32.280
like looking at populations that wear masks
link |
02:59:34.520
versus don't wear masks.
link |
02:59:36.560
As opposed to actually saying,
link |
02:59:40.320
like from an engineering perspective,
link |
02:59:41.840
like what kind of material and what kind of tightness
link |
02:59:46.600
by which amount decreases the viral load
link |
02:59:50.440
that's received on the other end.
link |
02:59:52.480
But some experiments have been done with masks
link |
02:59:55.800
and just droplets with no virus in them, right?
link |
02:59:58.680
And you can measure the efficiency
link |
03:00:01.360
of different mask materials at keeping those in.
link |
03:00:04.400
So if I say that this mask stops 70%
link |
03:00:09.880
of this or larger size droplet,
link |
03:00:13.760
that leads to this percent decreased transmission.
link |
03:00:18.000
And also on both the generation
link |
03:00:23.040
and the receiving end and the giving end.
link |
03:00:27.520
Sure.
link |
03:00:28.360
So how well do masks protect you from others?
link |
03:00:30.560
How well do you do mask protect others from you?
link |
03:00:34.200
Like all of those things seem like
link |
03:00:36.920
they could be more rigorously studied.
link |
03:00:40.120
There's no doubt about it.
link |
03:00:41.560
And now is the time because once this is over,
link |
03:00:46.120
nobody's gonna do it.
link |
03:00:47.200
Nobody's gonna care.
link |
03:00:48.360
No. Right.
link |
03:00:49.200
But it seems like to me, so tests is one thing,
link |
03:00:52.880
but masks, like the good mask,
link |
03:00:57.480
whatever the good means, whatever that means,
link |
03:00:59.960
like some level of quality of material on your face,
link |
03:01:04.200
if it's shown to actually like thoroughly shown to work well,
link |
03:01:08.960
that seems like an obvious solution
link |
03:01:12.120
to reopen society with.
link |
03:01:14.840
If you have a good understanding of how well they work.
link |
03:01:17.920
Because if you don't have a good understanding,
link |
03:01:20.040
if there's a lot of uncertainty,
link |
03:01:21.800
that's when you get,
link |
03:01:23.000
and you have people speaking from authority,
link |
03:01:24.960
that's when you start getting the politicization
link |
03:01:27.960
of the solution.
link |
03:01:28.800
Of course, of course.
link |
03:01:29.640
No, the data, there are some data,
link |
03:01:33.200
most, they're mostly epidemiological
link |
03:01:36.320
and they show some effect in some countries, right?
link |
03:01:39.120
But they could be way better.
link |
03:01:40.800
Yeah.
link |
03:01:41.640
And, but the fact that they're not perfect,
link |
03:01:44.920
then people take advantage of and say,
link |
03:01:46.800
well, look, they don't work that well,
link |
03:01:48.120
so I'm not gonna wear it.
link |
03:01:49.120
I think, as you said, people can use it as an excuse.
link |
03:01:53.040
But even if it works, so Daniel always says,
link |
03:01:56.200
a mask will cut down transmission by 50 to 60%,
link |
03:02:00.680
and then distance will do another 30%.
link |
03:02:03.480
Yeah, those numbers are made up though.
link |
03:02:05.800
I mean, they're not made up, but they're estimates.
link |
03:02:08.360
Absolutely.
link |
03:02:09.200
And many of them are made based on models, right?
link |
03:02:12.720
Yeah.
link |
03:02:13.560
We make this model,
link |
03:02:14.400
and let's say the mask cuts down this much,
link |
03:02:16.480
what will be the effect on it?
link |
03:02:17.920
I mean, yeah, they're models,
link |
03:02:19.000
and it's for the same reason.
link |
03:02:20.760
I don't believe the transmission of the variants
link |
03:02:25.000
because it's all based on statistical models as well,
link |
03:02:27.280
not biological experiments done in a lab.
link |
03:02:29.520
So in that sense, vaccine data is much better
link |
03:02:32.000
than mask data.
link |
03:02:33.200
For sure, for sure.
link |
03:02:34.480
So my problem with the mask data,
link |
03:02:37.160
which I always thought was fascinating,
link |
03:02:38.440
I stopped talking about it.
link |
03:02:39.600
I was in a paper about masks.
link |
03:02:41.400
I stopped talking about it
link |
03:02:42.400
because what started happening
link |
03:02:45.080
is masks created assholes on both sides.
link |
03:02:48.000
The people that were like in Silicon Valley,
link |
03:02:50.400
the friends of mine that were wearing masks,
link |
03:02:52.520
the way they look at others who don't is like...
link |
03:02:56.160
Well, that's a whole nother issue, right?
link |
03:02:58.240
Yeah, I understand.
link |
03:02:59.880
That happens when you don't have solid science.
link |
03:03:02.560
Understood.
link |
03:03:03.400
They now start judging you like you're a lesser human being.
link |
03:03:07.240
You're not only dumb, but you're almost like evil.
link |
03:03:11.520
You're doing bad for society by not wearing a mask.
link |
03:03:14.280
And then the people looking in the other way
link |
03:03:17.120
are seeing you for the asshole that you're being
link |
03:03:19.800
for judging them unrightly.
link |
03:03:22.040
So they almost wanna say F you by not wearing the mask.
link |
03:03:24.480
And there's this division that's created
link |
03:03:26.640
that was heartbreaking to me because masks like testing
link |
03:03:30.400
is a solution that was available early on.
link |
03:03:33.400
And if understood well, it could be deployed
link |
03:03:35.920
in a mass scale, and it seems like there's
link |
03:03:37.880
some historical evidence for other viruses
link |
03:03:40.120
where it does very well.
link |
03:03:41.760
That's correct.
link |
03:03:42.600
And so like the fact that this was politicized,
link |
03:03:47.200
yeah, it was a little bit heartbreaking.
link |
03:03:48.760
You can find in the literature studies,
link |
03:03:51.800
mostly of healthcare workers and influenza,
link |
03:03:54.560
where you can actually,
link |
03:03:56.240
because you see the people every day that can sample them,
link |
03:03:58.440
you can actually see what masking does.
link |
03:04:00.520
And some of them show an effect and others do not,
link |
03:04:04.040
then that's the problem.
link |
03:04:05.600
Like any trial, sometimes if it's not big enough
link |
03:04:08.280
and then people latch onto that, see,
link |
03:04:10.360
it doesn't really work.
link |
03:04:11.600
But I think the main issue is that in January,
link |
03:04:15.000
both CDC and WHO said masks don't work, don't use them.
link |
03:04:20.000
That was the kiss of death for masks
link |
03:04:22.240
because when they then changed their mind,
link |
03:04:25.920
they didn't say we screwed up.
link |
03:04:28.040
They just said wear masks.
link |
03:04:29.240
If they had said we made a mistake, we were wrong,
link |
03:04:33.000
I think more people would have worn masks.
link |
03:04:35.400
But they didn't.
link |
03:04:36.600
And like you said, admitting you're wrong
link |
03:04:39.080
is like a real big part of it.
link |
03:04:41.440
And I also think almost the better way
link |
03:04:43.200
is not just saying you're wrong,
link |
03:04:46.560
but in January saying,
link |
03:04:49.760
like revealing the uncertainty under which we operate.
link |
03:04:52.360
Like actually, like reveal what was done
link |
03:04:56.440
with the Spanish flu at the beginning
link |
03:04:58.360
of the previous century,
link |
03:05:01.080
because there's a lot of mass controversy then too.
link |
03:05:03.240
It went back and forth.
link |
03:05:04.120
And that was actually the source of a lot of distrust
link |
03:05:05.960
there too.
link |
03:05:06.920
So, and then look at influenza,
link |
03:05:09.280
like how is it effective with that?
link |
03:05:11.080
And just reveal this, we don't know,
link |
03:05:13.880
but like with some probability,
link |
03:05:17.680
this is the best option we got currently.
link |
03:05:20.120
And then in a month or two, adjust it,
link |
03:05:23.600
saying that, you know what,
link |
03:05:25.280
our like uncertainty decreased a little bit.
link |
03:05:27.840
We have a better idea.
link |
03:05:29.440
Like that was an incorrect estimate,
link |
03:05:32.320
but reveal that you're struggling.
link |
03:05:34.840
It's not like this weird binary clock
link |
03:05:36.840
that goes one direction or the other.
link |
03:05:38.440
You're struggling with uncertainty.
link |
03:05:41.200
And like trusting,
link |
03:05:43.240
people maybe criticize me sometimes for this,
link |
03:05:45.040
but I think most people are actually intelligent.
link |
03:05:48.960
Like trusting the public to be intelligent
link |
03:05:51.760
with if you give them, if you have transparent
link |
03:05:54.040
and give them information in a real authentic way,
link |
03:05:57.680
like don't look like you're hiding something.
link |
03:05:59.560
I think they're intelligent enough to use that data
link |
03:06:01.920
to make decisions.
link |
03:06:03.120
It's the same thing as with the testing,
link |
03:06:05.080
is if you put that power in the people's hands
link |
03:06:07.600
to know if they're sick or not,
link |
03:06:08.640
they're gonna make unmasked the right decision, I think.
link |
03:06:14.240
The masks and the testing has been a bit heartbreaking.
link |
03:06:18.000
I think that's a good point though,
link |
03:06:19.440
that most people don't seem to have an objection
link |
03:06:21.640
to testing.
link |
03:06:23.040
It's a good point.
link |
03:06:23.880
Yes. Yeah.
link |
03:06:24.720
And then obviously Macamina makes that point brilliantly.
link |
03:06:27.960
And still there's very little excitement around that.
link |
03:06:33.320
But he said he was going to do it.
link |
03:06:35.000
I don't understand.
link |
03:06:35.840
I mean, I haven't spoken to him since then.
link |
03:06:37.600
So I don't know why.
link |
03:06:38.720
He's pushing it.
link |
03:06:39.560
Well, I mean, but he can't do it alone.
link |
03:06:41.640
He has to get, so one of the resistances,
link |
03:06:44.680
FDA doesn't like cheap things.
link |
03:06:48.160
Yeah.
link |
03:06:49.120
They don't wanna approve it.
link |
03:06:50.240
So they makes the mass manufacture
link |
03:06:52.960
like with the emergency exceptions,
link |
03:06:55.120
all those kinds of things very difficult.
link |
03:06:57.440
And then there's not much money to be made on it
link |
03:06:59.560
without that.
link |
03:07:00.760
I don't know.
link |
03:07:01.600
I think there's just economic pressures against it.
link |
03:07:04.840
And because so much investment was placed on the vaccines
link |
03:07:10.920
and obviously there's an incentive mechanism there
link |
03:07:13.360
where the companies, lobbyists and all those,
link |
03:07:17.200
there's this machine that says arguing for tests
link |
03:07:21.440
is difficult because the thing that's worked
link |
03:07:23.240
for most severe viruses in the past is vaccines.
link |
03:07:27.160
Now we have vaccines.
link |
03:07:28.320
Why the hell would you need tests?
link |
03:07:30.360
At that time, like why the hell do you need tests
link |
03:07:34.440
when we can be working on vaccines?
link |
03:07:36.080
It seems like the obvious thing to be working
link |
03:07:37.720
is the vaccines from their perspective,
link |
03:07:40.680
but it's not obvious at all to me.
link |
03:07:43.160
I think you should have both.
link |
03:07:44.440
I think have vaccines and good testing
link |
03:07:46.600
and that covers you really well
link |
03:07:48.920
because you're always gonna have people
link |
03:07:50.080
who don't get vaccinated.
link |
03:07:52.080
I don't know if you've been paying attention to this.
link |
03:07:54.200
There's a guy named Brett Weinstein.
link |
03:07:55.720
There's a guy named Sam Harris.
link |
03:07:57.760
They have good representation.
link |
03:08:00.760
I would say of two sides of a perspective on the vaccine.
link |
03:08:06.240
So from Sam Harris's perspective,
link |
03:08:09.680
it's obvious that everybody should get vaccinated
link |
03:08:13.240
and it's irresponsible to not get vaccinated.
link |
03:08:18.560
I think he represents a lot of people's belief in that.
link |
03:08:22.360
And then Brett talks a lot about ivermectin,
link |
03:08:28.520
but also talks about hesitancy towards the vaccine
link |
03:08:32.720
for people who are healthy,
link |
03:08:35.040
for people who are younger, that kind of thing,
link |
03:08:38.480
and saying we should consider longterm effects
link |
03:08:40.840
of the vaccine in making this calculation.
link |
03:08:45.200
What do you make about this conversation?
link |
03:08:47.520
Some of it happens on Twitter.
link |
03:08:49.400
Some of it happens in the space of podcasts.
link |
03:08:54.000
Do you pay attention to this kind of thing?
link |
03:08:56.240
What's your role in this?
link |
03:08:58.240
What do you hope is the way to resolve this conversation?
link |
03:09:02.080
Do you think it's healthy?
link |
03:09:04.040
Well, a conversation is always healthy,
link |
03:09:05.760
but to make definitive statements is not
link |
03:09:09.280
because it suggests you have information that you don't have.
link |
03:09:12.200
So we talked about longterm effects.
link |
03:09:16.880
I think you need to balance those versus longterm effects
link |
03:09:20.360
of the disease and you can make your decision.
link |
03:09:22.520
I don't think you need to tell everybody to get vaccinated.
link |
03:09:26.560
I think you need to present the case.
link |
03:09:28.760
You say, here, we made good vaccines.
link |
03:09:30.400
Here are the safety profile.
link |
03:09:32.240
Here's the risk benefit balance.
link |
03:09:34.400
And you should decide.
link |
03:09:35.280
You're a smart person.
link |
03:09:36.160
You should decide.
link |
03:09:37.880
Now, companies are gonna do differently, right?
link |
03:09:41.240
Companies may say you have to be vaccinated to work here.
link |
03:09:43.320
My employer, Columbia, said we have to be vaccinated
link |
03:09:46.720
to work in the fall.
link |
03:09:47.560
And if you wanna be a student, you have to be vaccinated.
link |
03:09:49.440
So you decide whether you wanna go or not.
link |
03:09:52.240
But the idea that you should make a decision
link |
03:09:58.000
based on longterm effects, there is no evidence, right?
link |
03:10:02.480
So how can you make a decision
link |
03:10:03.760
when we don't have evidence,
link |
03:10:05.200
whereas we do have evidence
link |
03:10:06.280
that there are longterm effects of getting COVID?
link |
03:10:08.440
So I don't think that's a fair argument
link |
03:10:10.200
and it just makes people scared to say that.
link |
03:10:13.640
But on the other hand, for someone to say
link |
03:10:15.000
it's a no brainer and to denigrate people
link |
03:10:18.280
for not being vaccinated, that's not the approach either
link |
03:10:20.400
because they're gonna dig in and say,
link |
03:10:23.320
I'm not doing this because you tell me to, right?
link |
03:10:25.680
I think the middle ground is to say,
link |
03:10:28.600
take a bit of both and say, here are the potential issues
link |
03:10:33.600
and here are the benefits and this is what I would do.
link |
03:10:37.280
And you have to just decide on your own.
link |
03:10:38.680
I'd leave it to them.
link |
03:10:39.520
I say, you decide.
link |
03:10:40.360
And if you don't want to, it's up to you.
link |
03:10:42.280
You don't have to get vaccinated.
link |
03:10:44.480
And you'll probably get infected at some point
link |
03:10:46.360
and maybe you'll be okay.
link |
03:10:50.040
But here's the best available data
link |
03:10:51.640
and it looks like the vaccines are pretty damn smart solution.
link |
03:10:56.760
They seem to work.
link |
03:10:57.600
I think you tell people what you did
link |
03:11:00.000
and present both sides calmly.
link |
03:11:01.880
And I think digging in, like in a debate,
link |
03:11:04.720
I don't think that's terribly useful.
link |
03:11:06.920
So that's my view.
link |
03:11:08.920
I mean, people come to me all the time and ask me,
link |
03:11:11.440
I'm worried, what should I do?
link |
03:11:14.680
And I say, what are you worried about?
link |
03:11:16.120
Let's talk about it and go through it calmly.
link |
03:11:18.960
And if they want to still take ivermectin,
link |
03:11:20.720
I say, it's fine, it's your choice.
link |
03:11:22.640
And I have a problem with that.
link |
03:11:23.480
I love that.
link |
03:11:24.960
I love that's the way you think.
link |
03:11:26.680
People should definitely listen to This Week in Virology
link |
03:11:32.040
and follow your work, it's brilliant.
link |
03:11:33.920
I've been really enjoying it lately.
link |
03:11:35.760
It's like, it's my favorite way to stay in touch
link |
03:11:38.320
with the happenings of COVID.
link |
03:11:42.160
Obviously you put in a lot of other stuff in there, but.
link |
03:11:45.520
We used to do other viruses before COVID.
link |
03:11:47.760
It was quite interesting.
link |
03:11:50.040
And I'm trying to slip other viruses in
link |
03:11:52.520
because I think they're informative in many ways.
link |
03:11:56.120
And we're gonna do more and more of that.
link |
03:11:57.280
But I have to say I canceled,
link |
03:11:58.600
usually I record on Tuesday and Friday
link |
03:12:00.840
and I canceled today so I could be with you.
link |
03:12:02.960
It's a huge honor, I appreciate that.
link |
03:12:05.040
No, no, it's fine.
link |
03:12:06.680
I think a couple of other people were gonna be away anyway.
link |
03:12:10.240
So I do a lot of different pods.
link |
03:12:12.040
They're all on YouTube, but I also do a live stream
link |
03:12:15.680
on Wednesday nights on YouTube, which you can find.
link |
03:12:18.480
And that's where people can come and ask questions.
link |
03:12:21.360
We don't have an agenda.
link |
03:12:22.440
We just start and by 30 minutes in,
link |
03:12:25.280
there's 700 people with questions
link |
03:12:27.440
that I can't even get through
link |
03:12:28.600
because there's so many of them.
link |
03:12:29.600
And I'm actually astounded
link |
03:12:31.720
that so many people have really good questions.
link |
03:12:35.640
Most of them are reasonable and they come back every week.
link |
03:12:38.960
So it's turning into a great forum
link |
03:12:41.880
to have a nice discussion.
link |
03:12:44.120
And the YouTube channel is called what?
link |
03:12:46.920
So you could search for my name,
link |
03:12:48.960
which is Vincent Racaniello, it'll turn up.
link |
03:12:51.280
Or my handle on YouTube is ProfVRR, P R O F V R R.
link |
03:13:00.000
Have you read The Plague by Camus by any chance?
link |
03:13:03.040
Years ago, years ago.
link |
03:13:05.800
I have to read it again.
link |
03:13:07.160
That's really relevant.
link |
03:13:08.720
Let me sort of ask you a question about it.
link |
03:13:10.840
It describes a town that's overtaken by a plague
link |
03:13:14.000
and it's blocked off from the rest of the world.
link |
03:13:16.480
And it kind of reveals the best, the worst of human nature.
link |
03:13:19.480
That's like how people respond to that.
link |
03:13:21.240
Sort of the encroaching, their own mortality,
link |
03:13:25.120
their own death on the horizon.
link |
03:13:27.240
I think one of the messages in the book
link |
03:13:28.960
that ultimately like love for others.
link |
03:13:34.160
So like a lot of people want to become isolated
link |
03:13:36.800
and they hide from each other,
link |
03:13:38.440
but ultimately the thing that saves you is love,
link |
03:13:42.040
which is one of the things of just watching this pandemic,
link |
03:13:46.680
with the distance, with the masks, that's all fine.
link |
03:13:50.560
But there's a distancing from people of that tension,
link |
03:13:55.560
the breaking of the common humanity between people.
link |
03:13:59.240
That's one of the reasons when I came to Austin
link |
03:14:02.280
earlier this year just to visit,
link |
03:14:05.200
I fell in love with the city
link |
03:14:06.440
because even with the masks and the distance,
link |
03:14:09.040
there was still a camaraderie, like, I don't know,
link |
03:14:14.600
just a love for each other,
link |
03:14:15.800
just a kindness towards each other.
link |
03:14:18.040
And that's why I took away from The Plague.
link |
03:14:20.840
Mostly it's told to the story of the doctor
link |
03:14:23.400
who basically gives in
link |
03:14:27.000
and just gives himself as a service to others.
link |
03:14:30.480
And that love is the thing that liberates him
link |
03:14:33.000
from his own conception of mortality,
link |
03:14:34.680
the fact that he's here, he's going to die.
link |
03:14:37.920
What do you think about the effect of the virus?
link |
03:14:41.760
We talked a lot about biology,
link |
03:14:43.080
but the effect of the virus
link |
03:14:45.280
on the fabric of the common humanity that connects us.
link |
03:14:50.280
Well, that's what a pandemic does.
link |
03:14:54.200
It really cuts that, right?
link |
03:14:56.280
Because small outbreaks, they're local,
link |
03:14:58.440
they don't have global effects.
link |
03:15:00.880
But when you have something this big
link |
03:15:03.080
where pretty much nobody escapes,
link |
03:15:07.440
and not just making people sick,
link |
03:15:10.200
it changes your life, right?
link |
03:15:12.480
People lose jobs, they change jobs,
link |
03:15:14.600
they move somewhere else.
link |
03:15:17.240
They have all kinds of disruptions.
link |
03:15:20.000
You know, kids can't go to school.
link |
03:15:22.080
It really shows you.
link |
03:15:23.560
I mean, I always like to say,
link |
03:15:25.520
a tiny virus can bring Earth to its knees.
link |
03:15:30.240
A tiny virus that you can't even see them,
link |
03:15:31.920
that most people don't even think about most of the time.
link |
03:15:35.240
And the real effect is not just sickness,
link |
03:15:37.720
it's what it does to people.
link |
03:15:39.240
Because in the end, we are animals,
link |
03:15:42.800
and most animals like each other, and they interact,
link |
03:15:46.040
they have great social structures,
link |
03:15:47.600
and that makes them do well.
link |
03:15:49.960
And I guess the exception is people in AI, right?
link |
03:15:53.320
They could be on their own.
link |
03:15:56.600
Well, that's why you build robots,
link |
03:15:57.840
that you fall in love with.
link |
03:15:58.960
That's right.
link |
03:15:59.800
And so I think when a,
link |
03:16:02.000
the real story is what it does to society, for sure.
link |
03:16:06.040
Which has ramifications way beyond
link |
03:16:08.640
the number of people dying,
link |
03:16:10.520
and the vaccines, and the tests, and all of that.
link |
03:16:12.720
And this one has really made a big rupture.
link |
03:16:15.640
And you could tell, not now so much,
link |
03:16:17.360
I think being out and about now,
link |
03:16:18.680
things look pretty normal,
link |
03:16:21.080
except for some people wearing masks.
link |
03:16:23.760
You would never know.
link |
03:16:25.000
I mean, the airport this morning was completely jammed.
link |
03:16:28.200
People going, and they're all on vacation,
link |
03:16:29.680
they're all wearing shorts, right?
link |
03:16:31.480
So they're back to normal.
link |
03:16:32.960
It's August.
link |
03:16:34.320
But last year is really different.
link |
03:16:36.800
In New York, where you're used
link |
03:16:38.880
to lots of people on the street, it was eerie.
link |
03:16:41.160
It was just quiet.
link |
03:16:43.040
But under it all, people are still,
link |
03:16:46.000
most people help each other when they have to, right?
link |
03:16:50.120
Most people are willing to,
link |
03:16:52.320
if something happens to someone,
link |
03:16:53.640
to reach out and help them.
link |
03:16:56.360
There are always exceptions where people are mean,
link |
03:16:58.840
and that's just the way animals are.
link |
03:17:01.880
We're not the only ones that can be mean to our own species.
link |
03:17:05.280
But I think most of the motivation
link |
03:17:08.680
for everything that was done is to help other people.
link |
03:17:12.200
I mean, I do think that the vaccine manufacturers,
link |
03:17:15.600
maybe not the leaders, but the people working in the labs
link |
03:17:18.120
really wanted to get this out quickly
link |
03:17:20.480
and help people, right?
link |
03:17:22.720
I think at every level, people who are contributing
link |
03:17:26.320
really wanted to help other people
link |
03:17:27.920
and feel proud that they're able to do that.
link |
03:17:30.160
So I view it as we're never gonna be 100% good
link |
03:17:35.640
because animals are not.
link |
03:17:37.640
Evolution made us, I mean, we're lucky.
link |
03:17:40.440
We somehow rose above by having incredible brain
link |
03:17:43.480
and so forth, but a lot of our base instincts
link |
03:17:45.520
are animals, and they chase each other
link |
03:17:47.920
and have alpha males and all that stuff,
link |
03:17:51.200
and we always have a little bit of that in us.
link |
03:17:53.440
But we do have some humanity
link |
03:17:56.800
that this really ripped up, it really did.
link |
03:18:00.960
And I think for me, someone who studied viruses
link |
03:18:05.160
for over 40 years, it's just amazing
link |
03:18:07.760
that an invisible thing can do that, right?
link |
03:18:11.240
It goes back to the thing you found fascinating,
link |
03:18:13.320
which is a virus affecting human behavior.
link |
03:18:15.200
Yes.
link |
03:18:16.040
Or behavior of the organism.
link |
03:18:18.680
Yes, so humans can make weapons and do harm
link |
03:18:22.920
and you can see that, but this you can't even see.
link |
03:18:25.280
Yeah.
link |
03:18:26.240
You can't, and look what it has done.
link |
03:18:27.640
And it'll do it again, there'll be more.
link |
03:18:29.720
I just, I wish we would be more prepared
link |
03:18:32.800
because we know what to do.
link |
03:18:34.800
We know we should be making antivirals vaccines,
link |
03:18:38.120
masks, testing masks, making test modalities
link |
03:18:42.080
that we can really quickly redesign.
link |
03:18:46.120
But after SARS one, all that went out the door.
link |
03:18:49.080
People didn't do anything,
link |
03:18:50.160
and that's why we're in this situation.
link |
03:18:51.880
So people ask me this all the time,
link |
03:18:54.840
are we gonna be ready for the next one?
link |
03:18:57.800
And I always say, we should be.
link |
03:18:59.520
We have all the information we need to know what to do.
link |
03:19:03.000
But somehow I think people forget.
link |
03:19:05.840
That said, sometimes we really step up
link |
03:19:12.760
when the tragedies run in front of us.
link |
03:19:14.840
We do.
link |
03:19:15.680
When the catastrophe.
link |
03:19:16.520
So I don't know, somehow humans have still survived.
link |
03:19:18.720
The fact that we had nuclear weapons for so many decades
link |
03:19:21.080
and we still have not blown each other up,
link |
03:19:23.120
whether by terrorists or by nation is quite surprising.
link |
03:19:27.520
That's always, after reading the Pentagon Papers,
link |
03:19:30.640
it's even more amazing, right?
link |
03:19:32.920
So I don't know how we do it.
link |
03:19:34.400
I tend to believe there's that at the surface,
link |
03:19:40.280
you notice the greed, the corruption, the evil,
link |
03:19:43.480
but the core of human nature, the human spirit
link |
03:19:46.560
is one in the scientific realm is curiosity,
link |
03:19:50.840
and more deeply is kindness, compassion,
link |
03:19:54.280
and wanting to do good for the world.
link |
03:19:56.800
I believe that desire to do good outpowers
link |
03:20:00.160
all the other stuff by a large amount.
link |
03:20:03.000
And that's why we have not yet destroyed ourselves.
link |
03:20:06.960
There's a lot of bickering.
link |
03:20:08.320
There's a lot of wars on the surface,
link |
03:20:10.360
but underneath it all,
link |
03:20:11.520
there's this ocean of love for each other.
link |
03:20:16.240
I mean, I think there's an evolutionary advantage to that.
link |
03:20:21.280
And it would be a good explanation
link |
03:20:23.640
why we still haven't destroyed ourselves.
link |
03:20:25.440
God, we had so many opportunities.
link |
03:20:27.440
If you look at all the wars in history, so many.
link |
03:20:29.840
I was just, my son was telling me
link |
03:20:33.360
about the Ottoman Empire, right?
link |
03:20:35.880
I mean, it's just war after war,
link |
03:20:39.520
and then other countries splitting up countries
link |
03:20:42.120
with no regard to who's living where, right?
link |
03:20:46.560
It's just, how can these people do this?
link |
03:20:49.440
Yeah, it's fascinating.
link |
03:20:50.840
Human history is fascinating,
link |
03:20:52.040
and we're still young as a species.
link |
03:20:54.600
We have a lot more time to go,
link |
03:20:57.360
and a lot more ways to destroy ourselves.
link |
03:21:00.520
Do you have advice?
link |
03:21:01.660
Like you said, you have many decades of research
link |
03:21:03.880
and an incredible career and life.
link |
03:21:06.400
Do you have advice for young people about career,
link |
03:21:09.880
about life, people in high school, people in college,
link |
03:21:13.360
of how to live a life they can be proud of?
link |
03:21:17.460
So what I like to do is tell people,
link |
03:21:20.000
don't plan it, because I didn't plan anything.
link |
03:21:22.360
Everything I did was one step at a time.
link |
03:21:25.000
You don't have to plan.
link |
03:21:26.660
I just found things that were interesting to me.
link |
03:21:30.800
And so my father was a doctor,
link |
03:21:33.440
and he wanted me to be a doctor,
link |
03:21:35.780
but I was not interested in taking care of people.
link |
03:21:39.040
I learned that, but I couldn't say no to him.
link |
03:21:43.160
So I was a biology major in college,
link |
03:21:46.320
and I graduated, and I didn't have anything to do.
link |
03:21:51.660
So I liked science, so I got a job in a lab.
link |
03:21:54.800
And it was very exciting,
link |
03:21:57.720
and that led to everything else
link |
03:22:00.680
that I've done one step at a time.
link |
03:22:02.880
And I think the most important thing you can do,
link |
03:22:05.800
well, there are two important things.
link |
03:22:06.960
You can be really curious all the time.
link |
03:22:08.640
You mentioned curiosity.
link |
03:22:10.040
I think curiosity is essential.
link |
03:22:12.980
You have to be curious about everything.
link |
03:22:15.580
And if you are, you're never gonna be bored.
link |
03:22:19.240
And so people who say they're bored,
link |
03:22:20.920
I say, you are not curious.
link |
03:22:22.520
You should just think about things
link |
03:22:24.200
and say, look at something and say, how does that work?
link |
03:22:27.440
Or what is it doing, and how do they get there?
link |
03:22:29.320
And you'll never be bored.
link |
03:22:30.480
And the other thing is when you find something,
link |
03:22:32.840
which may take time, it's fine.
link |
03:22:36.960
You have to be passionate about it.
link |
03:22:38.540
You have to put everything into it.
link |
03:22:40.860
And that's what I did with viruses.
link |
03:22:42.920
So I think they're amazing.
link |
03:22:46.240
And I tell my classes, I love viruses.
link |
03:22:51.160
They're amazing, and people think I'm morbid
link |
03:22:53.120
because obviously they kill people,
link |
03:22:55.320
and I shouldn't love something.
link |
03:22:56.560
But that's not the point.
link |
03:22:57.480
That's not what I mean.
link |
03:22:58.320
I love them in the way they have emerged
link |
03:23:00.520
and how they work and so forth
link |
03:23:03.080
and all that we don't know about them.
link |
03:23:04.240
So you need to be curious and passionate,
link |
03:23:06.240
and don't plan too much.
link |
03:23:07.720
And just find something that you don't call a job.
link |
03:23:12.240
As someone said on the livestream last week,
link |
03:23:14.520
I wish I had a job I liked as much as you.
link |
03:23:17.360
I said, it's not a job.
link |
03:23:18.440
I never looked at it as a job.
link |
03:23:20.400
It's my vocation, it's my passion.
link |
03:23:23.720
If it's a job, then you're not gonna like it.
link |
03:23:25.880
Yeah, something that doesn't feel like a job.
link |
03:23:28.400
So you said viruses are kind of passive,
link |
03:23:33.880
nonliving, you could say, or even cells are passive.
link |
03:23:38.520
And humans are kind of active.
link |
03:23:39.840
We seem to be making our own decisions.
link |
03:23:42.320
So let me ask you the why question.
link |
03:23:44.720
What do you think is the meaning of this life of ours?
link |
03:23:47.620
Oh, there's no meaning.
link |
03:23:49.780
It just happened.
link |
03:23:51.340
It's an accident.
link |
03:23:53.500
I think there's no life elsewhere
link |
03:23:55.020
because this is just a rare accident
link |
03:23:56.740
that happened in the right conditions.
link |
03:23:58.660
I mean, people all think I'm wrong
link |
03:24:00.300
because there are billions and billions
link |
03:24:01.700
of stars out there, right?
link |
03:24:02.860
So there's a lot of opportunity.
link |
03:24:05.140
There's no meaning.
link |
03:24:06.260
It's just, what do they call it?
link |
03:24:10.500
A perfect storm of events
link |
03:24:12.660
that led to molecules being formed.
link |
03:24:14.900
And eventually, I mean, it took a long time
link |
03:24:17.260
for life to evolve, right?
link |
03:24:19.900
But it's just driven by conditions.
link |
03:24:23.980
If something emerged that worked,
link |
03:24:25.500
it would then go on to the next step.
link |
03:24:26.980
There's no meaning other than that.
link |
03:24:29.140
The only difference is that we,
link |
03:24:32.180
and I think many other animals can probably,
link |
03:24:34.060
we have the ability, we're sentient, right?
link |
03:24:36.020
We can influence what happens to us.
link |
03:24:39.160
We can take medicines, right?
link |
03:24:41.420
We can alter what would normally happen to us.
link |
03:24:44.420
So we can remove some of the selection pressure.
link |
03:24:48.740
But I think everything else on the planet
link |
03:24:50.840
just goes, looks for food and give a lot of offspring
link |
03:24:55.180
so you can perpetuate.
link |
03:24:56.220
It's just a natural biological function.
link |
03:24:58.740
Yeah, they're much more directly concerned with survival.
link |
03:25:01.980
I think humans are able to contemplate their mortality.
link |
03:25:04.620
We can see that even if we're okay today,
link |
03:25:08.500
we're eventually going to die
link |
03:25:10.300
and we really don't like that.
link |
03:25:13.020
So we try to come up with ways to push that deadline
link |
03:25:16.140
farther and farther away.
link |
03:25:17.060
Well, we have really, I mean,
link |
03:25:18.740
we used to die in our 30s, right?
link |
03:25:20.460
Now it's 70s, 80s.
link |
03:25:22.020
Well, most of us used to die in the first few weeks.
link |
03:25:26.140
That's true.
link |
03:25:27.260
Yeah, infant death.
link |
03:25:29.140
I always tell people the only thing that's 100% is death.
link |
03:25:34.260
It's the only thing in the world that's 100%.
link |
03:25:36.300
Do you think about your own mortality?
link |
03:25:37.700
No, I never think about it.
link |
03:25:39.020
I'm just enjoying day to day and I don't think about it.
link |
03:25:42.220
Really?
link |
03:25:43.060
You work on viruses.
link |
03:25:44.140
You don't contemplate your own mortality
link |
03:25:47.580
given the deadliness of the viruses around us?
link |
03:25:51.660
I never thought COVID would kill me.
link |
03:25:53.580
No, I never was afraid of that.
link |
03:25:55.460
Not at all.
link |
03:25:56.460
I mostly feared for other people getting sick,
link |
03:26:00.380
especially people who could die of it.
link |
03:26:02.380
I didn't want that to happen to them.
link |
03:26:03.600
But I always thought that it's obviously
link |
03:26:06.860
not a realistic viewpoint not to be worried
link |
03:26:10.740
because many people are.
link |
03:26:13.820
But I've been relatively healthy.
link |
03:26:17.100
They should sequence my genome because it works really well
link |
03:26:19.740
and I have a good immune system.
link |
03:26:21.260
Maybe you'd be the first immortal person.
link |
03:26:24.100
There's gotta be a first.
link |
03:26:25.820
I don't think so.
link |
03:26:27.100
I think that biologically you just can't,
link |
03:26:31.180
the ends of our chromosomes keep getting
link |
03:26:32.940
shorter and shorter and that's eventually what kills us.
link |
03:26:37.200
So you just can't keep going on.
link |
03:26:39.580
But that's fine, I don't need to.
link |
03:26:42.220
I understand from the vampires
link |
03:26:43.700
that it's not good to live forever.
link |
03:26:47.340
I guess make the most of the time you got.
link |
03:26:50.380
That's the, bacteria live a much shorter time
link |
03:26:53.200
so we got that on bacteria.
link |
03:26:55.180
Bacteria are just little bags of chemicals that split.
link |
03:27:00.100
So they have no stake in the matter at all.
link |
03:27:05.260
It doesn't bother.
link |
03:27:06.540
I think that you have to go a long ways
link |
03:27:08.180
before you get into some kind of consciousness.
link |
03:27:12.960
Yeah, it's weird that this bag of chemicals
link |
03:27:15.420
has a stake in the matter.
link |
03:27:17.040
Like our human body, consciousness is a weird thing.
link |
03:27:21.380
Not just in us, but they make half of the oxygen
link |
03:27:23.540
on the planet.
link |
03:27:24.380
20% of the oxygen comes from bacteria.
link |
03:27:27.920
And they made, in the beginning of Earth,
link |
03:27:29.900
they made enough oxygen to start oxygenation going,
link |
03:27:34.060
life going.
link |
03:27:34.900
I mean, they have an incredible role.
link |
03:27:36.500
It's all an accident, just happened.
link |
03:27:40.500
Well, Vincent, like I told you, I'm a huge fan.
link |
03:27:44.660
It's a big honor that you would talk to me today.
link |
03:27:47.060
Thank you so much for coming down.
link |
03:27:48.420
Thank you for spending so much time with me.
link |
03:27:51.660
And thank you for everything you do
link |
03:27:53.020
in terms of educating about viruses,
link |
03:27:54.900
about biology, microbiology, and everything else.
link |
03:27:57.300
I can't wait.
link |
03:27:58.160
Everybody should check out Vincent's YouTube,
link |
03:28:00.540
watch his lectures, listen to the podcast.
link |
03:28:03.020
It's truly incredible.
link |
03:28:05.060
Thank you so much for talking to me, Vincent.
link |
03:28:06.780
My pleasure.
link |
03:28:08.220
Thanks for listening to this conversation
link |
03:28:10.220
with Vincent Racaniello.
link |
03:28:12.260
To support this podcast,
link |
03:28:13.380
please check out our sponsors in the description.
link |
03:28:16.540
And now, let me leave you with some words
link |
03:28:18.740
from Isaac Asimov.
link |
03:28:20.980
The saddest aspect of life right now
link |
03:28:23.140
is that science gathers knowledge
link |
03:28:25.380
faster than society gathers wisdom.
link |
03:28:27.720
Thank you for listening and hope to see you next time.