How the pandemic began in Nature, in 5 key points

How the pandemic began in Nature, in 5 key points

Released Monday, 10th June 2024
 1 person rated this episode
How the pandemic began in Nature, in 5 key points

How the pandemic began in Nature, in 5 key points

How the pandemic began in Nature, in 5 key points

How the pandemic began in Nature, in 5 key points

Monday, 10th June 2024
 1 person rated this episode
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0:00

This week in virology, the

0:02

podcast about viruses, the kind

0:05

that make you sick. From

0:11

microbe TV, this is Twiv

0:13

this week in virology, episode

0:16

11 21 recorded on June 7, 2024. I'm

0:23

Vincent Draconiello and you're listening to

0:25

the podcast all about viruses. Many

0:28

of you know, because you've written to us

0:30

that an opinion piece was published

0:33

in the New York times, uh,

0:35

in the past week by Alina Chan. And

0:38

the title is why the pandemic probably

0:40

started in a lab and five key

0:42

points. We've received

0:44

many email requests to discuss

0:46

this. And so that

0:49

is what we are going to do

0:51

because the title

0:53

isn't correct. And we're

0:56

going to go through each of the five key points and

0:58

tell you why. But I

1:01

think before we launch into that discussion specifically,

1:03

Jolene, do you want to run down the,

1:05

um, uh, this is not the first time this

1:07

has come up on the show. Yeah.

1:09

So, uh, we're going to

1:11

go through and discuss some of the

1:14

article, but we have done this in

1:16

much greater depth, actually discussing the papers

1:18

that address these points as well as

1:20

talking to some of the scientists and,

1:23

and just to remind people of where

1:25

they can hear about this, uh, discussed

1:27

in greater depth and kind of listen

1:30

to the evidence that has been presented.

1:33

I wanted to run through a few

1:35

of the episodes that we have. We'll

1:37

put a list in the show notes

1:39

that where these things have been discussed.

1:41

So twiv 10 19 Eddie Holmes on

1:43

SARS-CoV-2 origins, twiv nine

1:45

40 also Eddie Holmes in

1:47

on viral origins. We

1:50

have a twiv 861 rough draft

1:52

of Omicron origins, twiv 762 SARS-CoV-2

1:54

origins with Robert

1:59

Gary. where we did

2:01

talk about things like the receptor binding

2:03

domain in the furin cleavage site and

2:06

the two lineages circulating in the

2:08

Wuhan wildlife markets. Twiv

2:10

760, SARS-CoV-2 origins with

2:12

Peter Daschak, Thea Colson, Fischer

2:15

and Marion Koopmans. And

2:18

Twiv 777, SARS-CoV-2 fitness

2:20

with Ron Foucher, fitness and

2:23

the ability of

2:25

SARS-CoV-2 to replicate

2:27

and spread in other organisms.

2:31

There is a long list. I'm not

2:33

going to read all of them but

2:35

look in the show notes for many

2:37

more instances of Twiv episodes where we

2:39

discussed with guests and just discussing papers.

2:41

A lot of these points are about

2:44

to go through. And if

2:46

you're on YouTube that'll be down right below

2:48

this video. So there are five

2:50

points in this opinion but there is

2:52

an introduction. And let me read

2:54

from the introduction. Quote,

2:57

a growing volume of evidence gleaned from

2:59

public records released under the Freedom of

3:01

Information Act, digital sleuthing through online databases,

3:04

scientific papers analyzing the virus and its

3:06

spread and leaks from within the US

3:08

government suggest that the pandemic most

3:11

likely occurred because a virus escaped

3:13

from a research lab in Wuhan,

3:15

China. End quote. Ooh,

3:17

secret, newly revealed knowledge. Whoo!

3:21

In fact, most evidence

3:23

that has been published in journals, which

3:25

we have covered in many of those

3:27

episodes that Jolene talked about, supports a

3:29

natural origin, not a lab origin. And

3:32

Dr. Chan is ignoring most

3:34

of those data because

3:36

they don't fit with her

3:38

narrative. We understand now

3:41

and we've talked about this

3:43

a lot. The pandemic began when

3:46

a virus jumped multiple times from

3:48

animals on sale in the Huanan

3:50

seafood market in Wuhan to humans.

3:53

There are several papers on

3:55

this and they basically

3:57

are devastating to the level.

4:00

origin hypothesis. They show that the

4:02

market was the early epicenter, that

4:05

two lineages were circulating there, that

4:07

susceptible mammals like raccoon dogs and

4:09

civic cats were sold in the

4:12

southwest corner of the market and

4:14

we have environmental samples from

4:16

there that showed the presence of both animal

4:19

DNA and viral RNA

4:21

from SARS-CoV-2. So this statement,

4:23

the growing volume of evidence

4:25

suggests it occurred because the

4:28

virus escaped the lab is

4:30

simply wrong. If

4:33

people are particularly interested in things

4:36

that Vincent mentioned,

4:38

I particularly found

4:40

the discussions in episodes

4:42

876 and 995 to really

4:47

be particularly enlightening and the data that

4:50

we saw in those two really like

4:53

was very clarifying to me and made it

4:55

very obvious to me. Yes, so

4:58

yeah and I just want to harp a little

5:01

bit on this two lineages thing because

5:03

when I saw that, I mean

5:06

when those data came out, that's

5:09

it's a subtle but really damning

5:12

point if you want to say

5:14

that this came from a lab

5:17

that there were two genetically distinct

5:19

lineages of this virus at

5:21

the very very earliest days of the

5:24

outbreak in Wuhan and there

5:26

is simply no way to get to

5:29

that from a leak

5:31

from a lab on a virus somebody

5:33

was working on. Yep. Alright,

5:37

point number one. Quote,

5:39

the SARS-like virus that caused the pandemic

5:41

emerged in Wuhan, the city where the

5:44

world's foremost research lab for SARS-like viruses

5:47

is located. Bats in

5:49

other parts of China have not been

5:51

found to carry viruses that are as

5:53

closely related to SARS-CoV-2.

5:57

Alright, so we have to talk

5:59

a little bit about what is

6:01

closely related to SARS-CoV-2. The

6:03

closest relative at the

6:06

onset of the pandemic is

6:08

a virus is a genome sequence called

6:11

RATG13 which was

6:14

taken from a bat in a cave called

6:16

Tonguan Cave in southern Yunnan which is about

6:19

1800 kilometers from Wuhan. RATG13

6:21

is 1,200 bases different from SARS-CoV-2

6:26

that's 96.2% similarity. So RATG13 could not have been

6:28

the progenitor

6:35

of SARS-CoV-2. And

6:37

96.2% genome identity

6:39

we're talking a little bit about this before the show

6:41

you know if you get 96.2% on a test you

6:45

aced it but if your genome is

6:47

96.2% identical to something

6:49

else that's what what is

6:51

that humans and sooty manga base or something I

6:53

mean that's yeah something like that

6:55

and this is particularly

6:58

important because coronaviruses for

7:01

RNA viruses are quite large so

7:03

the you know

7:06

the genome size of the virus is 30,000 base

7:09

pairs and so

7:11

1% difference

7:15

would be 300 base pairs

7:19

and so you somehow have to

7:21

account for if it was 1% difference

7:24

and of course this is you know 4% difference

7:27

1,200 unexpected

7:30

changes between these viruses

7:32

1,200 and scattered ones

7:34

not ones that are all next

7:36

to each other and so I think that I

7:39

often find that thinking about that number it's

7:41

one thing to be like oh so that

7:44

means four base pairs happen to change no

7:46

we're not talking about it's not

7:48

a hundred base pairs and the only four changed you

7:51

have to be able to account for how some

7:53

there are random mutations at 1,200 sites

7:57

compared to these other viruses that are known

7:59

and to your point of 1200 sites, this

8:01

is not one segment of the genome that's

8:03

been changed. This is all over the place.

8:07

Yeah, exactly. So basically, and

8:10

we're going to hammer on this more, no

8:14

one had something close enough to source COVID-2

8:18

to be able to engineer it to become

8:20

a pandemic virus. This

8:23

RATG13 is too distant. Its

8:25

1200 bases, by the way, it would take 20

8:28

to 30 years at minimum for

8:31

a virus circulating in nature

8:34

to accumulate those number of mutations given

8:36

the mutation rate of the virus. And

8:39

if you were going to engineer something in the lab

8:41

to study it, for example, you

8:44

would not change 1200 bases

8:46

scattered throughout the genome. That's

8:48

just nobody would even embark on

8:50

such a project. Who would even know

8:53

what to change? Exactly. That

8:55

changes that would not have any effect

8:57

on proteins, and therefore you would not

8:59

choose to make that kind of a

9:02

decision as a scientist who's designing something

9:05

because you don't know. You would

9:07

imagine that the majority of them would have impacts that

9:09

you couldn't predict. Right.

9:12

And I think that people

9:14

have tried to argue at some point, oh, well,

9:16

those changes came because of, you got the

9:19

virus and passaged it in the lab for

9:21

a while after you did all that engineering.

9:23

But how do you get 1200 changes

9:26

around the virus but none in

9:28

the spots that you engineered? Right.

9:31

It just doesn't make any sense. All

9:34

right. One more quote from point one. Quote,

9:37

bad coronavirus spillover into humans

9:39

is rare. End quote. I

9:42

would say that pandemics are rare, but

9:44

spillovers are not. All right. Before

9:47

SARS-CoV-2 emerged, four coronaviruses

9:49

made the jump. And

9:52

these are the common cold coronaviruses

9:54

that continue to cause seasonal respiratory

9:57

disease to this day. One

10:00

in 2002 was a spillover, MERS-CoV

10:02

in 2012. And

10:05

during SARS-CoV-2 pandemic, we

10:07

talked about on Twiv spillovers

10:09

of pig and canine coronaviruses

10:11

into people. Research

10:15

from wildlife markets in Southeast Asia

10:17

has been done to quantify zoonotic

10:19

risk in these kinds of settings

10:21

where you have animals being

10:23

sowed. And one

10:26

study found that in a sampling of

10:28

lotion markets, civets, which

10:31

are one of the animals sold in these

10:33

markets, averaged seven human contacts per hour so

10:36

that a single infected civet might get over

10:38

50 opportunities to infect the person in an

10:40

eight-hour day. And furthermore,

10:42

studies in rural China have shown

10:44

that about 3% of the population

10:46

of antibodies to SARS-related coronaviruses, bats

10:48

indicating that spillovers are not rare

10:51

at all. So this is not

10:53

a correct statement. Absolutely.

10:56

Yeah. I

10:59

think that we

11:01

can also think about just general

11:04

how frequently are virus

11:06

spillovers from animals into humans

11:09

happening. Is the

11:11

general idea of spillover rare? And

11:13

it is very much not. It's

11:16

sort of the way we think this

11:18

happens in almost every other situation. So

11:20

again, the idea

11:22

that this doesn't happen is weird. It

11:26

happens with so many viruses in so

11:28

many ways. This is a relatively

11:30

recent change in our

11:33

perception of how often spillovers occur

11:35

because previously we didn't have the

11:37

tools to detect these unless they

11:39

became pandemics. So we

11:41

said, oh, well, coronaviruses have only spilled

11:43

over four times, five times, because that's

11:47

the only evidence we

11:49

had now in

11:51

part due to not just the

11:54

advanced molecular biology, but all the

11:56

attention on SARS-CoV-2 now

11:58

that we're looking. that we can look, we

12:01

see, oh, in fact, this

12:03

is a day to day

12:05

occurrence for all kinds of viruses, coronaviruses

12:07

and several others. How would we know?

12:09

If you want some, if you

12:11

want, I'm sorry, Jolene. That I was

12:13

going to say, how would we know that

12:16

there was SARS-CoV-2 in spreading in deer if

12:18

we didn't have the tools we use today?

12:20

And we've been talking about H5N1 in cows

12:23

and we talk about

12:25

previous influenza spillovers and mixing

12:28

that happens in pigs. And these

12:30

are maybe things that we

12:33

don't see them in our

12:35

everyday life, but at the

12:37

population level, they happen more than we

12:39

used to think. And

12:41

since we've found out how

12:44

easily SARS-CoV-2 hops species, this

12:46

is an incredibly promiscuous virus.

12:49

Um, you know, the spill back

12:51

to deer, the spill back to cats,

12:54

the spill back to pretty much everything

12:56

with fur. I mean, it's the, we've

12:58

talked about this on our later episodes. This

13:00

is a, this is a virus that can

13:02

go anywhere. So it's prone to this

13:04

kind of thing. For

13:07

anybody interested in a layman's read

13:09

of this larger topic, I would

13:12

refer them to David Klaman's book, Spillover.

13:14

Yes. It's a great read. Yeah. It's

13:16

got lots of different examples. I think it came

13:18

out in 2013. So,

13:21

um, it's not, you know, not as if

13:23

this idea was new and just

13:25

something's going to be a true dog

13:27

in this fight. That's right. It's actually,

13:29

actually subtitled animal infections and the next

13:31

human pandemic. This

13:34

was inspired among other things, uh, by the

13:36

Ebola outbreak, the big one

13:39

in Africa. Yeah. And

13:41

I think there's one other piece that's sort of related

13:43

to something we've been saying

13:45

here about this point one that Dr.

13:48

Chan makes. Um, because when I

13:51

read this point one, I, I

13:53

feel like at least lay people are saying,

13:56

well, that can't be a coincidence that

13:58

this pandemic emerged in the. same

14:01

city as

14:03

the Virology Institute. We've

14:06

mentioned some details about

14:08

how we don't always detect

14:12

all virus spillovers. We in the

14:15

past have largely detected the ones

14:17

that have become pandemics. We

14:21

have some pretty good evidence that we detected

14:23

very early cases, but we should note that

14:26

we are talking about the first cases that

14:28

were detected here. One

14:30

of the things that is important in detection is

14:32

a good medical care

14:34

infrastructure, a place where

14:38

you could do that. In

14:40

fact, you needed to have

14:42

physicians who could say, hey, we

14:44

have these patients who have pneumonia

14:46

that is atypical, and we are

14:48

going to actually do sequencing and

14:50

find out what they have and not just say,

14:52

huh, you got weird pneumonia. That sucks

14:54

for you. If

14:57

we think about a bunch of other infectious

15:00

diseases we know about, we

15:02

can think about what we know about their

15:04

origins, but in many cases, the

15:07

first ever case that was

15:10

seen and published was

15:13

seen in a place that had

15:15

particularly good hospitals and medical care

15:19

to diagnose those patients and

15:21

probably was not the first

15:23

situation of an infection. I

15:26

often use the first published

15:29

account of HIV is a

15:31

morbidity and mortality weekly report

15:33

article talking about five patients

15:35

in Los Angeles. That

15:38

does not mean that Los Angeles is

15:40

where HIV emerged. It is the first

15:42

place it was detected because of some

15:44

good work that was done by

15:47

physicians. It should

15:49

be noted that Wuhan is a

15:52

city where there are these types

15:54

of facilities to be able to

15:56

detect these patients and diagnose them

15:58

with a weird coronavirus instead

16:00

of saying, wow, that's sad

16:03

that you have weird pneumonia. And

16:05

so I think that some people

16:08

look at this and say, well, this is no coincidence.

16:10

But in fact, the

16:12

reason that it is a city that

16:14

has good ability to do this detection

16:16

and good ability to do this care

16:18

is a reason why

16:20

it could be an early place

16:23

where we would detect the emergence. And

16:25

also, in selecting Wuhan for

16:27

this center, part

16:30

of the rationale was it's a major

16:32

city where we've got this kind of

16:34

infrastructure and it's in

16:37

a region where we've got a lot of people moving

16:40

in and out. All

16:44

right. Point number two, the

16:47

year before the outbreak, the Wuhan Institute

16:50

working with US partners had proposed creating

16:52

viruses with SARS-CoV-2's defining feature. We're going

16:54

to get back to that. All

16:57

right. And it continues. Dr. Shee's group took

16:59

samples from bats and other animals as well

17:02

as from sick people living near animals carrying

17:04

these viruses or associated with

17:06

the wildlife trade. The lab pursued

17:08

risky research that resulted in

17:11

viruses becoming more infectious. Coronaviruses were

17:13

grown from samples from infected animals

17:15

genetically reconstructed and recombined to create

17:18

new viruses unknown in nature. These

17:21

viruses were passed through cells from bats,

17:23

pigs, primates, and humans and were used

17:25

to infect civets and humanized mice. In

17:27

essence, this process forced these viruses to

17:29

adapt to new host species and the

17:31

viruses with mutations that allowed them to

17:34

thrive emerged as victors. This

17:37

is science fiction. This

17:40

description completely overstates and

17:42

misrepresents what was actually being

17:44

done at the institute. We

17:47

need to go into that so you understand that. Yang

17:50

Li Shee's laboratory was sampling

17:52

SARS-related coronavirus from bats. This

17:55

is SARS-1, not SARS-CoV-2.

18:00

And the research described was

18:03

based on a bat SARS-related

18:06

coronavirus called WIV1 and

18:09

then another version of WIV1

18:12

where its spike gene was

18:14

replaced with spikes from bat

18:16

coronaviruses called SCH14, WIV16, and

18:19

RS4231. All

18:24

four of these viruses are

18:26

in the SARS-CoV-1 branch of

18:29

the SARS-related virus family and

18:31

they're very distinct from SARS-CoV-2.

18:33

Nowhere in this report is

18:37

there evidence of research on SARS-CoV-2

18:40

related viruses. And so really these

18:42

experiments are relevant to the origin

18:44

of SARS-CoV-2. The idea was to

18:46

see if the spike proteins

18:49

from these bat-related SARS-related coronaviruses could

18:51

let the viruses reproduce in human

18:53

cells and if they caused a

18:55

different disease in ACE2

18:58

transgenic mice. There was no

19:00

forced adaptation to new species,

19:02

right? Now one

19:05

of the points made in this piece

19:07

is that they

19:09

made more dangerous viruses, right?

19:11

So one chimeric virus had

19:14

enhanced viral replication relative to WIV1

19:16

in the lungs of ACE2 transgenic

19:18

mice that caused greater weight loss,

19:20

which is a common proxy for

19:22

disease severity in mouse

19:24

models. The other two chimeric viruses

19:26

had similarly enhanced virus

19:28

replication in mice, but one caused

19:30

the same weight loss as the

19:32

parental WIV1 and the other WIV16

19:35

caused no weight loss at

19:37

all. So there's no consistent

19:40

correlation between virus replication in

19:42

the lungs and disease severity

19:44

as defined by weight loss

19:46

in this transgenic model. And

19:48

in fact, this transgenic mouse

19:50

model has no defined correlation

19:52

with disease severity in humans.

19:55

So all of that writing is

19:58

really misrepresented. going on

20:00

there. And this is very

20:02

typical of this entire editorial and I would

20:04

assume the entire book that this

20:06

writer is flogging on the world for

20:09

the past couple of years, which is

20:11

basically the same argument in book form

20:13

as I understand. There's

20:16

another point in number

20:18

two, which is, quote, it

20:20

remains unclear whether the Wuhan is to

20:22

possess the precursor of the pandemic virus.

20:24

And I want to tell you why

20:26

that is simply a wrong

20:30

statement. It's very clear that

20:32

they did not have a

20:34

precursor. There's no evidence that the Institute-

20:36

It's very clear that we don't have any

20:38

evidence of a precursor, we should say. Yes.

20:41

We can't say something's not there. We have no

20:43

evidence of a precursor. We have evidence that they

20:45

worked with SARS-CoV-1. RITG

20:48

13, remember, was reported in 2016 and 2020. In 2022,

20:51

a large number of sequences appeared in

20:57

a database GenBank related

20:59

to a manuscript from the WIV. And

21:02

it basically provides a view into

21:05

the viral sequence collection at the

21:07

WIV in the run-up to the

21:09

pandemic. The only viruses related to

21:11

SARS-CoV-2 are RITG 13 and eight

21:13

others, which are collectively called RITG

21:15

15. And remember, RITG 13 is

21:17

1,200 bases different. This

21:20

was an unpublished manuscript in 2018, which includes

21:23

phylogenetic trees confirming that no

21:25

other viral sequences related to

21:27

SARS-CoV-2 were being studied. Therefore,

21:30

it is not unclear whether

21:32

the WIV possessed a

21:34

precursor to SARS-CoV-2. And furthermore,

21:37

we have two

21:39

US intelligence reports that

21:42

conferred this. They released two declassified documents on

21:44

the origin of SARS-CoV-2, one in 2020, one

21:46

in 2023, and both addressed this question whether

21:52

the WIV held either

21:55

SARS-CoV-2 or a direct progenitor prior

21:57

to December 2019. So

22:01

the 2021 report, it's called the

22:03

updated assessment on COVID origin states.

22:07

Early in the pandemic, the WIV identified that

22:09

a new virus was responsible for the outbreak

22:11

in Wuhan. It is

22:13

therefore assessed that WIV researchers

22:15

pivoted to COVID-19 related work

22:17

to address the outbreak and

22:20

characterize the virus. These activities

22:22

suggest that WIV personnel were

22:24

unaware of the existence of

22:26

SARS-CoV-2 until the outbreak was

22:28

underway. And the other

22:30

report, the 2023 report on

22:33

potential links between the WIV and

22:35

the origin of COVID-19, reports

22:39

that the lab was

22:41

working on a number of coronaviruses,

22:43

no known viruses that could plausibly

22:45

be a progenitor of

22:47

SARS-CoV-2. Information

22:49

available to the intelligence community

22:51

indicates that the WIV first

22:54

possessed SARS-CoV-2 in late December 2019,

22:58

when it was identified from

23:01

patients. And the IC, the intelligence

23:03

community, assesses that this work

23:05

was intended for public health needs and

23:08

that the coronaviruses known to be used were too

23:10

distantly related to have led to the creation of

23:12

SARS-CoV-2. IC has

23:14

no information indicating that any WIV genetic

23:17

engineering work involves SARS-CoV-2, a close progenitor,

23:19

or a backbone that is closely enough

23:21

to have been the source of the

23:24

pandemic. So these are two U.S.

23:27

intelligence reports, which

23:29

conclude they didn't have anything closely related. And

23:31

when they refer to the intelligence community, they're

23:34

talking about the CIA, Department of Defense, you

23:37

know, people who sit in

23:39

rooms perceiving China as a threat and

23:42

trying to figure out what's going on there.

23:44

They do other things. But that's a major

23:47

focus, is starting with the assumption

23:49

that what China is doing is

23:51

going to be harmful to the U.S. in

23:53

a lot of cases. And so these are not touchy-feely

23:56

agencies who are trying to, you know,

23:59

make everybody happy. in the world. These

24:01

are hard-nosed realists who perceive the entire world

24:03

as a threat. Right. And

24:05

again, when I've talked to people who tried

24:08

to convince me about this, and they

24:10

will think that we'll have the conversation

24:13

about this point, and

24:15

we'll say from

24:18

our evidence does not suggest that they had

24:20

this virus, that they had any viruses very

24:22

close to this beforehand. What are

24:25

you talking about? It starts to

24:27

become this conversation of,

24:30

well, they had other ones they were getting from nature,

24:32

so they just must have had some that they weren't

24:34

telling us about. And it's

24:36

kind of like, no, they actually have done a

24:39

very good job of publishing

24:41

the work that they have

24:43

done throughout their careers. And

24:46

so that would be a departure from everything

24:48

else that they had done. They

24:50

have been publishing these sequences for a

24:53

long time, and there's no good reason

24:55

why they would want to not tell

24:57

us about things that they had in

24:59

2018 or something like that.

25:03

Because for them, science works

25:06

in the same way that it works for the rest of

25:08

us, in that we want

25:10

to publish our work and move

25:13

forward in the scientific community and show our

25:15

evidence. So I point

25:18

this out because in a few places

25:21

where we're going with some

25:23

of these arguments,

25:27

you start to have to say, well,

25:29

they lied, well, they faked it. Well,

25:31

there's this conspiracy about this. And if

25:34

you really sort of add them up, we

25:37

will end up with, well, they

25:39

lied about like 20 things. You

25:42

have to sort of infer

25:45

or you have to invoke all

25:48

these lies versus the way

25:51

other viruses have

25:53

come into the human population. And

25:56

so as you're looking at these two

25:58

sort of different options,

26:01

realize that in some way, when

26:04

you really start to poke at it, you

26:06

almost have to invoke, but everybody lied all

26:08

the time to make

26:10

this work, including to say, oh, well, it

26:12

remains unclear, but I bet they just did

26:15

and they lied. It's

26:17

definitely a very conspiratorial

26:20

attitude to take towards

26:22

it, to take

26:24

towards the people who are doing the work.

26:28

It's one thing to think that

26:30

about a government. It's another to

26:32

think that about individual scientists who

26:34

are really caring and clearly

26:36

over time demonstrating that they take

26:39

care in how they do their

26:41

experiments and how they report their

26:43

experiments and data to the rest

26:45

of the world. Exactly.

26:49

All right, another point from this, we're still on

26:52

number two. In

26:56

2021, the Intercept, which is

26:58

a publication, published

27:00

a leaked 2018 grant proposal for

27:02

a research project named Defuse. This

27:05

was a collaboration between Equal Health

27:08

Alliance, the Wuhan Institute, and Ralph

27:10

Barak at University of North Carolina.

27:12

And Chan writes, the proposal described

27:15

plans to create viruses strikingly similar

27:17

to SARS-CoV-2. End quote.

27:20

This statement is disingenuous. Strikingly

27:23

similar, refers only to the

27:25

presence of the furin cleavage

27:27

site. Now, the furin cleavage

27:29

site is a short amino acid sequence

27:31

in the spike protein that allows

27:33

it to be cleaved or

27:36

caught by proteases that

27:38

are present in cells. And

27:41

one of the core arguments

27:43

of the lab leak hypothesis is

27:47

that we don't

27:49

find SARS-like viruses with a

27:51

furin cleavage site, and therefore it must

27:54

have been added by

27:56

humans, which is a crazy alternative,

27:58

right? find it, you don't

28:01

automatically say that people put it in.

28:04

So, Diffuse was going to look

28:07

at sequence data for SARS-related

28:09

coronaviruses from bats, see if they

28:11

have furin cleavage sites, and then

28:13

if they did, they were going

28:15

to introduce them into these laboratory

28:18

viruses like WIV1 that

28:20

we mentioned before. However,

28:23

bat-SARS-related coronaviruses do not have

28:26

furin cleavage sites. And

28:28

so, they wouldn't have found one

28:30

and hence, they wouldn't have introduced. This

28:32

work was not funded, it's not clear that any

28:35

of it was done. And

28:37

so, the whole idea that they were trying

28:39

to create something, as she

28:41

says, strikingly similar, it's just a furin cleavage

28:43

site out of 30,000 bases

28:46

is simply wrong. And the closest,

28:48

as we've said, the closest sequence

28:50

is 1,200 bases. So, you could

28:52

not take that viral genome and

28:54

put in a furin cleavage site

28:56

and get SARS-CoV-2. One

29:01

more point from number two. This is

29:03

very important. And here is her writing.

29:05

One alarming detail leaked to the Wall

29:07

Street Journal and confirmed by current and

29:09

former US government officials is

29:11

that scientists on Dr. Xi's team fell

29:14

ill with COVID-like symptoms in the fall of 2019.

29:17

One of the scientists had been named in

29:19

a Diffuse proposal as the person in

29:22

charge of virus discovery work

29:24

the scientists denied having been

29:26

sick. And quote, well,

29:28

it turns out that US

29:30

government intelligence reports that we

29:33

were citing before consistently assert

29:37

that these illnesses that took place in the fall of

29:39

2019 at WIV were consistent with a variety

29:43

of conditions and not diagnostic

29:45

of COVID. Some

29:47

were actually inconsistent with COVID-19.

29:49

Now, Dr. Xi has stated

29:51

publicly that none of her

29:53

researchers tested positive for SARS-CoV-2

29:56

in 2023. Intelligence assessments states

30:00

there's no evidence that the

30:02

WIV had SARS-CoV-2. And

30:05

Marion Koopmans of the WHO committee

30:07

investigating the origin stated there's no

30:09

evidence that any of these workers

30:12

had COVID. So there's zero evidence

30:14

that they were sick with COVID,

30:16

yet Dr. Chan says

30:19

that they had COVID. And reminder,

30:21

fall of 2019. Yes,

30:24

I was sick in fall of 2019. Yeah,

30:27

some people in the lab came down

30:29

with a respiratory virus. Gosh, what a

30:31

shock. It's flu

30:33

season. It's flu season. It's, yeah.

30:36

OK. Point number three. Chan

30:40

writes, the Wuhan lab pursued this type

30:42

of work under low biosafety conditions that

30:45

could not have contained an airborne virus

30:47

as infectious as SARS-CoV-2. OK.

30:50

End quote. Research on SARS-related

30:53

coronaviruses at the WIV was

30:55

routinely carried out at BSL2. In

30:58

the other lab that did similar work, the

31:00

Barrick lab used BSL3. And

31:02

the differences involved personal protective

31:05

equipment and different engineering differences

31:07

to increase containment. But

31:11

the issue is not whether a

31:14

lab-acquired infection could result

31:17

in a pandemic, whether it didn't. There's

31:19

no evidence linking the WIV or any

31:21

lab to the pandemic. And given there's

31:24

no evidence that WIV

31:26

had SARS-CoV-2 or a

31:28

plausible progenitor, they could

31:30

have worked without any biosafety controls at

31:33

all and not sparked the pandemic caused

31:35

by SARS-CoV-2. So Chan is saying that

31:38

their containment would not have contained

31:40

SARS-CoV-2, but they didn't have SARS-CoV-2.

31:42

So all of it is moot.

31:44

And finally, just note that WHO

31:47

recently allows people now to work with

31:49

SARS-CoV-2 under BSL2 conditions.

31:53

And I was just looking it up. Someone can

31:55

correct me if you know otherwise. But measles, which

31:57

is considered to be one of the most contagious

32:00

viruses that can spread between

32:03

people and is similar,

32:06

not a similar infection, but it

32:08

is also worked with under BSL2 conditions.

32:10

It is. It's correct, yeah. Another

32:14

quote from that point number three, if the

32:16

virus had escaped from a BSL2 lab in

32:18

2019, the leak most likely would have gone

32:20

undetected until too late, end quote. Why?

32:23

I don't even

32:25

understand the point. Yeah. Because

32:27

it would have, if it leaked from the WIV,

32:29

that would have been the early epicenter. Yeah. And

32:32

it's not. The Juanon market is

32:34

the early epicenter. And

32:38

you would have one lineage. Sorry, but I've

32:40

got to keep coming back to that. Yes, of course.

32:42

No. You wouldn't get those amazing plots

32:46

or maps from the Werobe paper

32:49

that showed the epicenter so clearly as

32:52

the market and even pointed out where

32:54

the lab was, that was not the

32:57

epicenter. One

32:59

more point from number three, quote, in

33:03

one experiment, Dr. Shih's group genetically

33:05

engineered an unexpectedly deadly SARS-like virus,

33:07

and she writes not closely related

33:10

to SARS-CoV-2, that exhibited

33:12

a 10,000-fold increase in the quantity of virus

33:14

in the lungs and brains of humanized mice.

33:17

WIV scientists handled these live viruses

33:19

at low biosafety levels, including BSL2,

33:21

end quote. Already discussed

33:24

this above, I just

33:26

want to point out that the

33:29

levels of virus were determined

33:31

by PCR, which does not

33:34

correlate with infectivity, so 10,000-fold

33:36

is not indicative of

33:38

a higher virus titer. And this information is actually

33:40

in year five, progress

33:42

report of an NIH grant

33:45

between Ralph Barak and EcoHealth

33:47

Alliance. Also,

33:52

some of these points have been about what

33:55

happens with these different viruses in mice. Yes.

34:00

COVID-2 doesn't

34:02

kill mice. Notoriously doesn't

34:04

kill mice. It's actually kind of

34:06

a thing for researching it. The

34:09

original SARS-CoV-2 did not

34:11

infect mice. They made ACE-2

34:13

transgenic mice, and

34:15

the ones that are driven by a

34:18

keratin promoter, they get

34:20

neurological disease, which that's what kills them.

34:22

So it's a completely wrong model. Yeah.

34:25

So even if they –

34:27

so, okay, let's imagine that I take –

34:30

they made this unexpectedly deadly virus

34:32

in mice. Right.

34:35

So this was a pandemic that wasn't

34:37

with an unexpectedly deadly virus

34:39

in mice. These things do not seem

34:41

related. Yeah, they're not. This is

34:43

– and this is typical of

34:47

this writer and of pretty much everybody

34:49

in the lab leak camp. Take

34:53

a bunch of circumstantial,

34:55

kind of maybe

34:58

sketchy sounding things and whip

35:01

them up together. And

35:04

they start to sound persuasive when

35:06

you group them and number your

35:08

arguments. All

35:11

right. Number four. Point number four.

35:13

Quote, the hypothesis that COVID-19 came from an

35:15

animal at the Huanan Seafood Market in Wuhan

35:17

is not supported by strong evidence. End quote.

35:20

It wouldn't be more false. There

35:23

is so much evidence for this. Multiple

35:26

independent analyses. The Warby paper

35:28

is frankly devastating to the

35:30

lab leak hypothesis. And that's

35:32

why Dr. Chan doesn't like

35:34

it. You cannot like

35:36

data. That's your prerogative. But

35:40

she's wrong about this. Okay.

35:42

So one point she makes is, quote, the

35:44

bias in the search for early cases meant

35:46

that cases unlinked to or located far from

35:48

the market would be missed. So the idea

35:50

here is, end quote. Early

35:54

on, the cases were at the market. And so

35:56

they're saying then people just looked around the market.

35:58

And so there was an aspect. ascertainment bias.

36:00

But the paper went through several

36:03

advanced statistical testing to check that

36:05

the results held there is no

36:07

ascertainment bias. So that's very clear.

36:11

All right, another quote from this point number four.

36:14

A pair of papers published in Science made

36:16

the best case for SARS-CoV-2 having emerged naturally

36:18

from human animal contact at the market by

36:20

focusing on a map of the early cases

36:22

and asserting that the virus had jumped from

36:25

animals into humans twice. More

36:27

recently, the two papers have been counted

36:29

by other virologists who convincingly demonstrate that

36:31

the available market evidence do not distinguish

36:34

between a human super spreader and a

36:36

natural spillover event. This end

36:38

quote, this is also wrong. There

36:41

were two lineages of

36:43

SARS-CoV-2 A and B circulating

36:45

in December at the market. There

36:47

would have had to been two human

36:50

super spreader events to produce this

36:52

pattern. In other words, someone got

36:54

infected elsewhere, they went to the

36:56

market and infected a lot of

36:58

people. That would have had

37:00

to happen twice with two independent lineages,

37:03

which is highly unlikely. They would

37:05

have had to both get infected

37:07

somewhere else, and then both

37:09

go to the market, and

37:11

both be really transmitting at the

37:13

market, and neither

37:16

be really transmitting somewhere else. And

37:18

they both had to have acquired

37:20

different strains, different lineages of the

37:22

virus that are genetically distinct, which

37:24

if you were working with it

37:27

in the lab is

37:29

preposterous. And they went to the same part

37:31

of the market. Yes, they went to the same,

37:33

right. And super

37:36

spreaders are like 10% to 20%

37:38

of all infections. So it's relatively

37:40

rare, so it further makes it

37:43

highly unlikely that that happened. But

37:45

you don't even have to posit

37:47

that. This paper that we've been talking about, it's

37:49

Warby et al. 2022, the

37:52

Huanan Seafood market, wholesale market in

37:54

Wuhan was the early epicenter of

37:57

the COVID-19 pandemic. They consider early

37:59

cases. and look at their locations.

38:01

And one of the

38:03

best results in that paper, they

38:06

test whether so they have

38:08

cases clearly linked to the market. In other

38:10

words, I worked in the market and I

38:12

got sick. I went shopping in the market

38:14

that day and I got sick. Those are

38:16

linked cases. There are other cases

38:18

unlinked to the market but near it

38:21

and they wanted to know what

38:24

was the difference. They

38:26

asked whether the market unlinked cases

38:28

are geographically associated with the market

38:30

because that will tell you if

38:32

community spread is happening anywhere

38:35

other than the community around the market.

38:38

They calculate the distance from

38:40

the market and where the cases

38:43

were and they show unambiguously

38:45

that the market unlinked cases

38:47

were significantly closer to the market

38:49

than market linked. In other

38:51

words, the market linked cases, people

38:53

could have lived anywhere. The

38:57

market linked are people in

38:59

the neighborhood engaging in community

39:01

activities. Maybe they went to a cafe and

39:04

there was a worker from the market there

39:06

and that's how they got infected. That didn't

39:08

happen anywhere else. These

39:11

market unlinked

39:13

cases are

39:15

in the immediate vicinity and it's the only place

39:17

in Wuhan where this is happening. As I said,

39:20

if the spillover occurred at the WIV, you would

39:22

have seen this pattern there. I

39:25

want to point out again, following up

39:27

on Jolene's earlier comments, that we interviewed

39:30

the author of this paper, Michael

39:32

Warby, in 2876

39:35

so you can get the

39:38

story from the horse's mouth in that

39:40

episode. That was following on this

39:42

publication. Chan

39:46

also in number four writes, Furthermore,

39:50

the existing genetic and early case data

39:52

show that all known COVID-19 cases probably

39:55

stem from a single introduction of

39:58

SARS-CoV-2 into people and the outbreak the

40:00

Wuhan market probably happened after the

40:02

virus had already been circulating in

40:04

humans. This is 180 degrees wrong. This

40:07

is completely wrong. She sows

40:09

a phylogenetic tree in

40:11

the piece, which is just a

40:13

crappy phylogenetic tree. As we

40:16

have said, there were two lineages

40:18

circulating, at least two separate

40:20

introductions. They're called A and

40:22

B. They were both found

40:25

in the market in December. And

40:28

we know this from this environmental

40:31

surveillance that the Chinese

40:33

authority did. There's

40:36

no question that there were more than

40:38

one. In fact, another

40:40

paper in this collection estimates

40:44

that there were probably at least

40:46

eight separate spillovers from eight infected

40:48

animals to people, and only

40:50

two of them seem to have proceeded. Vincent,

40:54

one of the things that she

40:56

talks about that you've quoted is

40:59

a couple of papers that are supposedly

41:08

question, at least question, the statistical analysis

41:10

in the Warby paper that caught my

41:12

attention. Could you address that, please? Yeah.

41:16

So one of the issues that was claimed

41:18

was that there was an ascertainment bias. In

41:20

other words, we were looking at the market

41:23

because we knew it was an early epicenter.

41:25

And they used really advanced statistical methods to

41:27

show that there is no ascertainment bias. And

41:30

in fact, many of the early physicians

41:32

were picking up the cases before they

41:34

knew anything about the market. They were

41:36

really good at saying, oh, this is

41:38

an unusual respiratory disease. So that was one point.

41:41

The other point, there was a mistake in the

41:44

computer program that was used to calculate the

41:46

probability that there was more than one spillover.

41:48

So they corrected it. Someone wrote and said,

41:50

you have this mistake. They corrected it. The

41:53

error gave them 99% probability

41:55

that there was more than one spillover. And

41:58

after the correction, it was 99%. 97%

42:01

probable. So it made no material effect

42:03

on the conclusions of the paper. All

42:07

right, another point from number four, quote,

42:09

not a single infected animal has ever

42:11

been confirmed at the market or in

42:13

its supply chain without good evidence that

42:15

the pandemic started at the seafood market.

42:17

The fact that the virus emerged in

42:19

Wuhan points squarely at its unique SARS-like

42:21

virus laboratory. End quote. Oh

42:24

my God, no one tested animals

42:26

in the market. They were all

42:28

taken away on January 1st and

42:31

moved into the countryside or slaughtered.

42:33

This is a completely dishonest statement.

42:35

They shut down the market. They killed

42:37

everything. They disinfected the place. So I

42:39

want to make a statement that's sort of parallel

42:42

that might help people if they're not on top of

42:44

this. So the statement

42:46

that Vincent quoted is not a single

42:48

infected animal has ever been confirmed at

42:50

the market or in its supply chain.

42:53

And I just wanted to let you know

42:55

that also it has never

42:58

been confirmed that

43:00

my right hand was

43:02

not radioactive for one

43:04

day during the year where I was

43:06

17 years old. And

43:09

the reason, and I say that, and the

43:12

reason is because we never looked. Maybe

43:15

it was randomly. And so

43:17

it's important to say it

43:21

has never been confirmed because

43:23

you didn't look, but also

43:25

note that this is something that

43:27

we can't go back and check.

43:29

We don't have the samples from

43:31

those animals. I

43:33

don't have samples from my hand when I

43:35

was 17 years old. And so yes,

43:38

we are going to be able to say we

43:40

have not, no, there's no evidence to confirm this

43:42

because we didn't check at the time and you

43:44

can't go back in time and do it. And

43:48

the reason the market was shut down and

43:50

everything cleared out was not some kind of

43:52

cover up. It was because there was evidence

43:54

early on that the virus had emerged in the

43:56

market. And so they shut down the market out

43:58

of a public health concern. It made perfect

44:00

sense at the time and now of course we would

44:02

really love it if they had maybe

44:04

frozen some of those animals. And

44:07

there have been numerous historic examples

44:09

of situations like

44:11

this, SARS-CoV-1 for

44:13

example, arising in markets

44:15

under these situations. So

44:20

if I were them, I would want to put a

44:22

lid on this as quickly as possible. Yeah.

44:25

And in that situation, they left the market

44:27

open for a while. And

44:30

so those animals were still available for

44:32

testing and they did in fact find

44:34

the infected animals and get

44:37

that great piece

44:40

of evidence there. But we can't

44:42

do that here. Which was in

44:45

the case of SARS-1, great for

44:47

virology but not so great for

44:49

public health because the market

44:51

remained open with the animals

44:54

that were carrying the virus. Yes.

44:56

Yes. For seven months because they didn't

44:59

want to tell anyone. There was an outbreak. All

45:01

right, finally we're at point five. Quote,

45:04

key evidence that would be expected if

45:06

the virus had emerged from the wildlife trade

45:08

is still missing. Despite the intense search

45:11

trained on the animal trade and people

45:13

linked to the market, investigators have not

45:15

reported finding any animals infected with SARS-CoV-2

45:17

that had not been infected by humans.

45:20

Yet infected animal sources and other connective pieces

45:22

of evidence were found for the earlier SARS

45:24

and MERS outbreaks as quickly as within a

45:27

few days despite the less

45:29

advanced viral forensic technologies of two days

45:31

ago. End quote. There

45:34

has not been an intense search. The

45:37

Chinese authorities are not doing it. In

45:39

SARS-1, the markets were not

45:41

closed. Animals were

45:43

found to be infected seven months

45:45

later, not days within days as

45:47

Dr. Chan states. MERS

45:50

was identified in 2012, found in

45:52

camels in 2013, so the

45:55

claim of days is fabrication. And

45:57

as we have already discussed, war be it out.

48:00

And finally, let me get to Wei

48:02

Guishan, who was a shrimp vendor. She got

48:05

sick, one of the first known cases of

48:07

COVID in Wuhan. She got sick on December

48:09

10th, and she ended up

48:12

in the hospital. She was interviewed by

48:14

the Wall Street Journal in 2020 about

48:17

how she thought she got infected. And

48:20

looking back, there's a quote from the article. Ms.

48:23

Wei thinks she may have been

48:25

infected via the toilet she shared

48:27

with the wild meat sellers and

48:30

others on the market's west side. She

48:32

said the vendors next to her on both sides got

48:35

sick, and the man kitty-corder from her almost died. One

48:37

of her daughters, a niece, and the niece's husband caught the virus

48:39

too. So she

48:42

got sick in the

48:44

market from meat sellers, who in turn

48:46

got sick from their animals that they

48:49

were selling. It's

48:51

really an interesting story. All right,

48:53

we're almost done here. A couple more points. Quote,

48:58

even though Wuhan is the home base

49:00

of virus hunters with worldly leading

49:02

expertise in tracking novel SARS-like viruses,

49:06

investigators have either failed to collect or

49:08

report key evidence that would be expected

49:10

if COVID emerged from the wildlife trade.

49:13

For example, they have not determined that

49:15

the earliest known cases had exposure to

49:17

intermediate host animals before falling ill. No

49:19

antibody evidence shows that animal

49:21

traders in Wuhan are regularly exposed to

49:23

SARS-like viruses as would be expected. End

49:27

quote. None of these studies

49:29

have been done. She writes it as if they've

49:31

been done and we didn't find anything. They've

49:34

not been done. So

49:36

the statement is dishonest. And

49:38

the opportunity to do a lot of these

49:40

studies, as Brianne mentioned, passed

49:45

and was lost amid very appropriate

49:47

public health measures at the time.

49:50

Gee, why didn't you go out and sample a

49:52

bunch of wildlife in early 2020? Well,

49:55

because the entire country of China was locked

49:57

down and nobody could go anywhere. So,

50:00

yeah. Why don't we go? Here,

50:03

I have a great experiment for you. Let's

50:07

find all of the animal traders

50:09

in Wuhan today who, or

50:12

we'll find all of the people today who

50:14

were at that time working in Wuhan. And

50:16

let's look and see if they have any

50:18

antibodies to SARS-CoV-2. All right. It's

50:20

a great experiment. The experiment doesn't make so much

50:22

sense now, does it? No,

50:24

because they have had plenty of opportunity

50:27

to be infected or to have been

50:29

vaccinated. So, we need

50:31

to know before most people

50:33

in the world had those antibodies. Did

50:35

they have that? So, Wuhan is the home

50:38

base of virus hunters with world-leading expertise. Yeah,

50:40

that's true. But they

50:42

can't do these experiments because the opportunity

50:44

to do them passed. And so, that's

50:46

why we don't have any of this

50:49

evidence. It's gone. All

50:51

right. One more

50:53

paragraph. Quote,

50:56

with today's technology, scientists can detect how

50:58

respiratory viruses, including SARS, MERS, and flu,

51:00

circulate in animals while making repeated attempts

51:03

to jump across species, which

51:05

is viruses don't make

51:07

repeated attempts. Okay. But,

51:09

okay. Thankfully, these variants usually fail

51:11

to transmit well after crossing over to a

51:14

new species, tend to die off after a

51:16

small number of infections. In contrast, virologists

51:19

and other scientists agree that SARS-CoV-2 required

51:21

little to no adaptation to spread rapidly

51:23

in humans and other animals. The virus

51:25

appears to have succeeded in causing a

51:28

pandemic upon its only detected

51:30

jump into humans. End

51:32

quote. Except for the other lineage. Yeah.

51:35

Exactly. I mean, this is gibberish.

51:37

It's only two detected jumps into humans.

51:40

SARS was not detected until it first

51:42

jumped into people. The first detection of

51:44

MERS was in a human with pneumonia.

51:47

I mean, that's how we find them

51:49

when they jump into people. So there's nothing special.

51:52

And we don't know what happened before that. We

51:54

have no idea. This could have been going on

51:56

for years. Right. You know,

51:58

that one guy with a weird. just

54:00

look at the data. We don't do any conspiracy stuff.

54:02

We don't lie about it. We do

54:04

the science and it tells us that

54:06

it originated in an animal. There's no

54:09

question about it. Anything

54:14

else? No, it's just all

54:16

too bad. Yeah, it is all too bad.

54:18

But the truth floats.

54:21

Unfortunately, it takes a long time to

54:23

get to the surface. I'm thinking

54:25

about climate change and all the

54:28

acquaintances I have who have been climate

54:30

deniers for so long. It's

54:35

so blatantly obvious. I

54:37

like that statement. The truth floats. I really like

54:39

that. I'm

54:42

Vincent Raconiello. You can find me

54:44

at microbe.tv. I'd like to thank

54:47

the American Society for Virology and

54:49

the American Society for Microbiology for

54:51

their support of Twiv, Ronald

54:54

Jenkes for the music and Jolene

54:56

for the timestamps. You've

54:58

been listening to this week in virology.

55:01

Thanks for joining us. We'll be back

55:03

next week. Another Twiv is

55:06

viral.

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