8:00

at what you want to do. Who's

8:03

this independent committee? Because isn't the idea you

8:05

want people who are trained in the subject?

8:08

You would think so, yes. Who

8:10

are actually doing the work, right? But

8:13

they think you're conflicted. You can't be

8:15

neutral because you just want to do

8:17

your work and get your research funds

8:19

and blah, blah, blah. So no one is accountable,

8:22

apparently. No one can trust anyone else.

8:24

Maybe that's true in the Republican world,

8:26

but you know, scientists, it's

8:28

different. The last

8:30

quote of this paper is good. Nicholas

8:33

Evans, who is a biosecurity effort

8:36

expert at UMass Lowell, thinks

8:39

the guidance we have is fine. Much

8:42

of the concern about Moss's proposed experiment, he says,

8:45

is based on the assumption that a modified clade

8:47

2 virus would be more transmissible than clade 1.

8:49

There's no reason to think that would be the

8:51

case. And that uncertainty means

8:53

that the monkeypox experiment does little

8:56

to inform the discussion over gain of

8:58

function regulation. It's being used as a

9:00

way to prop up a debate about the

9:02

regulation of the life sciences, which I think

9:04

is probably in bad faith. And that's just

9:06

perfect quote, right? Wow. Bad

9:09

faith. Agree. Anyway, the article is written

9:12

by Kai Cooper-Schmidt. I

9:15

saw the headlines even said that Bernie Moss

9:17

made monkeypox in his lab by gain of

9:19

function, you know. Yeah.

9:23

This is the danger of this crap. All

9:27

right. Another news item

9:30

is very interesting. I

9:32

have to let me get to my PDF

9:35

copy. Here

9:38

we go. Wild poliovirus makes

9:40

comeback in

9:42

Afghanistan and Pakistan. So

9:47

as you may know, wild

9:49

polioviruses type 2 and

9:51

3 have

9:53

been declared eradicated because

9:56

there is no more poliomyelitis caused

9:58

by those two. serotypes. Unfortunately,

10:03

most of the polio happening globally

10:05

is caused by the vaccine type

10:07

2 strain, which is another problem

10:09

altogether that we've talked about. But

10:12

type 1 has continued to circulate

10:14

in certain parts of

10:16

Afghanistan and Pakistan.

10:18

And the goal has been to try and

10:21

end all transmission. And

10:25

in 2021-22, they actually

10:28

cleared virus from

10:31

Karachi, which is amazing, is a huge city,

10:33

right? And it also

10:35

disappeared from two other historic reservoirs

10:37

around Keta in the southwest province

10:40

of Balochistan and Peshawar in the

10:42

northern province of Khyber Pakhtunkawa,

10:47

both on the border with Afghanistan.

10:49

But now, wastewater sampling

10:51

reveals that the virus is back in

10:54

Karachi and around Keta

10:57

and Peshawar, likely

11:00

brought in by people from these districts. I would

11:02

argue that probably was never gone. It's just your

11:04

sampling wasn't that good. But

11:07

you know, the idea that you're going to

11:09

stop transmission is defective because OPV does not

11:11

stop transmission. It

11:14

does not stop transmission. So the idea that you can

11:16

stop it by this is wrong. Now,

11:19

the number of polio cases is

11:21

low because many people are immunized,

11:23

right? But they say here plenty

11:25

of virus is circulating, ready to

11:27

strike any unvaccinated kid. So they

11:30

had a goal of stopping all transmission

11:32

of wild type 1. This year, that's

11:34

gone. They have to rethink their

11:36

approach. And you know,

11:39

these are unusual conditions, right? Really high

11:41

population, potentially a lot of movement of

11:43

people, about a million people a day

11:45

move in and out of Karachi every

11:47

day. That's a lot of people. And not

11:50

an easy place to vaccinate. That's

11:52

right. So the

11:54

2024 target of ending all

11:56

transmission will be missed. who

14:00

we talked about before, scientists

14:02

who don't want to give

14:05

money for commerce, I

14:07

guess, to the research. So

14:11

this is of interest to us because most

14:13

of us have received NIH funding for

14:15

our research over the years. It's the

14:18

premier biomedical funding agency in the

14:20

U.S. and, you know,

14:22

you have to make sure that what you

14:24

do is not going to break it,

14:26

right? So the document, which you can

14:28

get, reforming the NIH framework for discussion,

14:31

the time is now to build a

14:33

stronger NIH for the future. Okay.

14:36

What I find interesting, so there's a whole bunch

14:38

of history on the NIH

14:40

and they have a list of the current NIH

14:43

institutes. So maybe not all of you

14:45

know, there are many institutes at NIH

14:47

that do different things like NIAD, National

14:49

Institute for Allergy and Infectious Diseases. There

14:53

are 27 different institutes

14:57

and collectively they get a total of $48 billion in federal

15:01

funding. Things like

15:04

National Cancer Institute, National

15:07

Heart, Lung, and Blood Institute, National

15:09

Eye Institute, National Institute of Aging,

15:12

National Institute for Allergy and Infectious

15:14

Diseases. Okay. So

15:16

they want to reorganize that to 15. They

15:19

want to go from 27 to 15. So

15:25

for example, there will now be, sorry,

15:27

go ahead. Go ahead Vincent. No, I thought it

15:29

was interesting. I was looking through, there's only one, which

15:31

is NIAID. What is

15:34

it, NIAID? NIAID is Allergy

15:36

Infectious Disease. Exactly. And

15:38

it's the only one that's actually going to be

15:40

split into two institutes, into the separately infectious disease

15:42

and then immune system and arthritis. Right.

15:46

Yeah. That was interesting. Because they're like,

15:48

oh, it has too much power, but it's not the biggest

15:50

one. Yeah. No, it's not.

15:52

And only one of them is losing

15:54

funding and losing a very, very

15:56

significant amount of funding. Almost

15:59

a billion. institute.

18:00

All right. There are many causes

18:02

of arthritis. Yeah. Well, the

18:04

National Institute on Body

18:06

Systems Research is

18:09

sort of an interesting one

18:11

in that they're combining heart-long

18:13

blood, arthritis, musculoskeletal

18:16

skin, diabetes, digestive,

18:18

and kidney. I know

18:20

of immunologists who have submitted

18:23

to all of those. And so why

18:25

immunology is different than body systems is

18:28

a little weird. Correct.

18:31

That's kind of odd. And the art,

18:33

I don't know, because technically immunology can

18:35

be implicated in any of these, literally.

18:37

But- I think a

18:39

congressional committee, looking

18:41

at the NIH, is like the blind

18:44

man and the elephant, because

18:46

none of them actually knows what's

18:48

going on underneath those doors.

18:51

They've never been in a

18:53

laboratory. They've never participated

18:55

in any research programs. They're

18:58

just reorganizing for the sake of

19:00

saving money so they don't have to pay an

19:02

institute to do the work

19:05

that they're doing now. I

19:07

think the bottom line is the same. 48

19:10

billion dollars is the budget. 48

19:13

billion, 174. It's the exact

19:15

same. It's just been moved around.

19:17

The budget is next. That's

19:21

next week's article. So

19:23

they gave a little history of NIH. Did you

19:25

know that the NIH- the

19:28

mission is to seek fundamental knowledge about the

19:30

nature and behavior of living systems and

19:33

the application of that knowledge to enhance

19:35

health, lengthen life, and reduce

19:37

illness and disability. So

19:39

there's a little history here, which I won't go into,

19:41

but did you know it started in

19:43

1887 on Staten Island? I didn't

19:45

know that. I did not know

19:47

that. Yeah. Cool.

19:52

Now there's a bunch

19:54

of bullet points, the recommendations

19:57

that I wanted to go through a bit. here.

20:02

Let's get to them. They

20:05

have a graph of NIH funding. Now it's gone

20:07

up over the years.

20:09

It's very nice. We should be investing at

20:11

NIH. It's a good return. Okay.

20:15

So recommendations. Restore

20:18

Congress's role in directing funding.

20:22

So right now, Congress doesn't have

20:24

a say in what gets funded. They

20:27

want to have that back. That is

20:29

exactly right. They want

20:31

to read my grant? Yeah, I was

20:33

going to say how they won't even be able

20:35

to interpret what they're reading necessarily. They will understand

20:37

that. They will say, Breanne is

20:40

in a district with a Democratic representative.

20:42

We're not going to give Breanne her

20:44

money. Crap like that. I

20:47

mean, how would they know? How would they know what

20:50

to do? So

20:52

that I have a lot of problem with. This restore

20:55

Congress's role in directing funding. I mean, historically,

20:57

when I came into the R01

21:00

business, there

21:03

was no congressional involvement whatsoever. And

21:06

then, I don't know if you remember, who was

21:09

the guy Dixon who talked about the Golden

21:11

Fleece Awards? Remember him? Oh, yeah.

21:13

He was from California, I think. He would pick

21:15

out grants and say, why are we funding this?

21:17

Why are we funding a research on a worm

21:20

or a fly?

21:22

What does this have to do with him? He had a

21:24

hair transplant at one point. I know

21:26

a lot about him except his name. So he

21:29

called them the Golden Fleece Award because

21:31

he felt these scientists were fleecing the

21:33

government. And I'll bet if you looked

21:35

at some of the ones he complained

21:37

about, they have all led to

21:39

very important findings. Exactly. I know.

21:41

Why would you study the immune system in

21:44

prokaryotic cells? Yeah, exactly. I couldn't think of

21:46

a reason why that would be useful. No,

21:49

not at all. All

21:52

right. So another bullet point under this part is

21:55

to reexamine indirect costs. So

21:58

for those of you who don't know. So,

22:00

when you get a grant from NIH, you get $100,000 for your research,

22:02

and then your institution

22:07

gets what are called indirect costs. You don't get

22:09

them. They go to your institution to play for

22:11

the lighting and the toilet paper and cleaning the

22:14

floors and so forth, right overhead. And

22:17

the indirect cost rate varies

22:20

according to the institution. Everybody negotiates their

22:22

own rate. Yeah, and not only that,

22:24

it's determined by the Office of Naval

22:26

Research, which I never understood

22:29

that on at all. That's

22:31

right. That's right. So, they

22:33

want to figure out if there's another

22:35

way we could do to

22:38

tie the indirect rate costs to a percentage of the

22:40

grant award instead of making it per

22:43

institution. You know, part of the issue

22:46

is there are universities like, say,

22:48

Columbia that have an

22:51

endowment, right, so they can pay for things. But

22:54

then there are research institutes that don't

22:56

have an endowment, and they need actually

22:58

more. So, in some cases, their indirects

23:00

can be over 100%. Right. So,

23:03

every dollar you get, the university is getting maybe a

23:05

buck and a half. So,

23:07

you know, Congress doesn't like that, and they want

23:09

to fix that. But the

23:11

universities, the institutes are going to be

23:13

very stubborn

23:16

about changing that because that's what

23:18

makes them support

23:21

their infrastructure, right? Yeah.

23:24

Understandably so. Okay. Now,

23:28

the next one, grant

23:31

reform. NIH

23:33

grant research must protect against national

23:35

security risks and threats and

23:37

be independent, innovative, responsive, and

23:40

transparent. And this is

23:42

where gain of function research comes

23:44

in. And

23:46

they write here, there's

23:48

been increased concern about NIH approval management

23:50

and oversight of gain of function research

23:52

and dual use research, particularly

23:55

that involves pathogens with enhanced pandemic

23:57

potential, gain of function research. is

24:00

used as a broad term to

24:02

encompass scientific inquiries where an organism

24:04

gains a new property or

24:07

an existing property is altered.

24:09

That's a good definition, right?

24:12

I can take that. This

24:14

includes both naturally occurring and

24:16

experimentally induced changes in organism

24:19

to better understand transmission, infection,

24:21

and pathogenesis. A subset, sometimes

24:23

called gain-of-function research of concern,

24:27

go frock, go

24:30

frock. Okay. It's

24:32

often, involves experiments that

24:34

enhance a pathogen's transmissibility

24:36

or virulence or disrupt pre-existing

24:39

immunity. So, for example, if you make a

24:42

virus resistant to a monoclonal antibody and that

24:44

virus is a human pathogen

24:46

that could be construed as gain-of-function

24:49

of concern, right? And

24:52

so, this all

24:55

started with the

24:57

H5N1 transmission studies back in 2015,

24:59

which we covered extensively

25:02

on Twitter, that

25:04

two laboratories made H5N1

25:07

transmissible above mammals, which it hadn't been

25:09

ferrets in specific. And people were like,

25:11

whoa, why would you do that? And

25:15

neglected to point out that when

25:17

it gained transmissibility in ferrets, it's

25:19

lost all its virulence, right? That

25:22

was just not even mentioned in

25:24

the dialogue. So, that started this

25:26

whole thing that we need more

25:28

oversight of gain-of-function research. Now,

25:30

they do point out, there

25:33

is a scientific community that says we need

25:35

to understand viruses, right? We need to do

25:37

these kinds of experiments. So, you can't not

25:39

do them. And then there

25:41

are other people who say we should never do them and

25:44

just forget it, which, you know, some, there

25:47

has to be some in between, right? Because

25:49

you can't just not do experiments on H5N1.

25:51

And they

25:53

bring up the monkeypox virus experiments

25:55

that we've talked about here. They

25:57

bring up the EcoHealth Alliance NIH

26:00

grant that was used to support coronavirus

26:03

research in Wuhan. They

26:06

say it was mismanaged, and technically

26:09

it was. Apparently, they didn't

26:11

file some reports that they were supposed

26:13

to file, but experimentally, there

26:16

was no mismanagement. Experiments

26:19

were done properly. So

26:22

it's all a technicality essential. So

26:24

basically, their idea is that NIH,

26:26

in particular, NIAID, doesn't have a

26:28

good process in place to weigh

26:30

the risks and benefits of

26:33

such experiments. And

26:36

so they propose that

26:39

we have a committee that

26:42

does this, and they have some

26:44

recommendations which I find really interesting here. First

26:46

of all, grant recipients must remain dynamic. Provide

26:50

grants and award only to primary investigators

26:52

that do not have more than three

26:55

ongoing concurrent NIH engagements.

26:58

That's going to piss a lot of people off, because there are a

27:00

lot of people that have more than three NIH grants. Big

27:03

labs. And so

27:06

I don't know what the point is

27:08

when we're having a discussion here about gain

27:10

of function, research, and safety. What

27:12

is having more than one grant

27:15

to do with that? I

27:17

think they don't want people to have a particular

27:20

amount of power. If

27:23

you have many NIH grants,

27:25

then you're directing a lot

27:27

of what's going on in research. Another

27:33

one, continue prohibition of risky gain

27:35

of function research. Prohibit

27:39

NIH from conducting or supporting certain risky

27:41

gain of function occurring in countries that

27:43

have been designated as foreign adversaries, and

27:46

pause any such gain of function research of

27:49

concern until a thorough comprehensive policy

27:51

with appropriate guardrails to monitor research

27:54

that has the potential to pose risks to public

27:56

health and national security is enacted. You

27:59

know, all of this is... started

28:01

from the avian h5 transmission experiments

28:03

and of course more recently SARS-CoV-2

28:06

origins right is that

28:08

the vast majority of Congress thinks this virus came

28:11

from a lab and they're just wrong as we

28:13

pointed out on our episode a couple of weeks

28:15

ago but it's

28:17

made into a political issue

28:20

because it's convenient to do so right but

28:23

now they say oh this is dangerous risky research

28:25

we have to regulate this gain of function you

28:28

can see that this virus may

28:30

have come from a lab this is not

28:32

good it's just it's

28:34

wrong it's all wrong wild when you think about

28:36

it where they pull all of the grants and all of

28:39

the funding for for viral

28:41

discovery so to actually try to

28:43

to see what's out there in the

28:45

wild sampling animals sampling wildlife and then

28:48

also the viruses that we do know

28:50

exists we can't even like learn from

28:52

them now so either way it sounds like

28:55

it just seems wild that we can't

28:57

we don't know what is out there and then what we

28:59

know is out there we can't even understand at this point

29:01

because we can't get funding for invest

29:03

like for doing experiments on these viruses yes

29:06

there's obviously levels of different ways

29:08

you can manipulate or viruses but

29:10

I mean just saying that everything is

29:12

gain of function and like stopping all

29:14

gain of function research within like funding

29:16

from the NIH seems crazy I

29:19

mean well there might be some maybe

29:22

some undertones of religiosity

29:25

associated with this too because if

29:28

you look back in history to the

29:30

great scientists of the past particularly the 16th

29:32

and 17th century even Isaac Newton was

29:39

criticized for doing

29:42

experiments rather than allowing God to have

29:44

its way with whatever and the

29:48

mathematic mathematicians were also

29:50

criticized for their

29:52

role in revealing something

29:55

that God had kept secret for

29:57

so long I think in this case

29:59

it's more a Republicans,

34:00

perhaps. But this

34:02

article by Leslie. Jocelyn

34:06

Kaiser. It's, okay. The

34:12

lawmakers also want to pause so-called

34:14

gain of function research at NIA.

34:17

Studies that manipulate viruses in ways that make

34:19

them a pandemic threat until stronger oversight policies

34:22

are in place. Some Republicans

34:24

worry that gain of function research in

34:26

Wuhan created SARS-CoV-2. Why

34:29

don't they listen to Twiv? If

34:32

they're so smart, then they follow the science. And if they

34:34

understood the science, they'd know that it didn't come from a

34:37

lab. But more

34:39

importantly, why is it that the Republicans feel

34:41

that way and the Democrats do not? That

34:43

makes zero sense, right? Well, it

34:45

does if you look at it as a political football

34:47

and nothing else. Anyway.

34:55

So much of it, I think, is fine, but there are these

34:57

few points that I think are really

35:01

ill-advised. I

35:04

don't have a problem with streamlining, but starting

35:06

to meddle in funding decisions and

35:09

reviewing proposals. We're

35:12

not talking about a lot of proposals here. I

35:14

think somewhere I read maybe 100

35:16

proposals a year would need this extra

35:19

review. So this panel,

35:21

whoever it may be, I think I'm going

35:23

to nominate you for it, Dixon. Thanks. I'd

35:26

be glad to serve on it if I'm

35:28

still alive. Why

35:31

wouldn't you be? It's only a few months away. One

35:35

never knows, do one. One

35:37

never knows, that's right. Reorganization

35:40

sounds fine, but maybe ask some

35:42

people at the NIH and some

35:45

scientists what makes sense. That

35:47

would be advisable, I

35:50

would think. At that point, they might get

35:52

good advice. What would they do with

35:54

that? Hmm. Well,

35:58

you have transformed a scientific process. To

50:00

hear. Ever

50:02

since I saw that I thought of you

50:04

talking about fitness during the pandemic. Some

50:07

people have listened right. Just

50:10

think of changes in a viral

50:12

genome as affecting fitness without you

50:14

knowing exactly what that means.

50:16

So they said let's assess fitness of

50:18

these swine viruses for cells

50:20

of the human respiratory tract. They

50:23

make cultures human or oncular epithelial

50:25

cultures at an air liquid

50:27

interface of the cells differentiate into the

50:30

proper air liquid epithelium

50:32

that you have in your respiratory tract.

50:35

And they in fact with these different

50:37

viruses. So they include

50:39

the two thousand nine pandemic and then

50:41

the gamma and the alpha virus so

50:44

the gamma replicated half

50:46

as well as the two thousand

50:48

and nine. And

50:51

the alpha replicated

50:53

about seventy to eighty percent as

50:55

well so. They

50:58

say that's good that's comparable enough to fight despite

51:00

all the amino acid changes in the human gluten

51:02

and. These

51:05

viruses reproduce well in human cells

51:07

and that moves it along the

51:10

pandemic risk decision tree. Yeah

51:13

so at this point we found that

51:15

these viruses the the alpha virus. Is

51:19

something that we don't already have immunity

51:21

to. Is

51:23

something that seems to be able

51:25

to interact with human cells based

51:28

on multiple measures right and

51:31

so just in vivo

51:33

types of things this virus

51:35

looks bad. Or

51:38

potentially potentially. And

51:40

certainly not good. Potentially concerning.

51:43

Yeah. All

51:46

right so. Again

51:49

no matter. Excuse me no

51:51

matter what the amino acid differences. They

51:54

replicate pretty well in human bronchial epithelial cells which

51:56

is where the viruses are going to be reproducing

51:58

in humans so that's a concern. for

54:00

these viruses in human cells. The

54:05

other important part of this

54:07

is the neuraminidase, the other spike

54:09

protein on the surface of the virus. You need to

54:11

have a balance between HA

54:13

and NA. The NA allows the viruses

54:16

to move away from the cells and

54:18

be transmitted. So they measured neuraminidase activity

54:20

of these swine viruses, and they found

54:22

the alpha swine H1 has

54:24

similar neuraminidase activity as the 2009 pandemic

54:26

virus, which

54:29

they say is a feature consistent

54:31

with a virus capable of

54:33

airborne transmission. And they always

54:35

say, and requires further characterization. They say that all

54:37

the time. We need more money

54:40

to study this. Okay,

54:42

now we go into ferret

54:45

models to study transmission.

54:48

So in the ferret, human

54:50

seasonal influenza virus

54:54

transmit between ferrets two days

54:56

after exposure of your first ferret.

54:58

So if you infect a ferret, two days later, the

55:01

human influenza viruses will transmit within two days. So

55:05

they infect ferrets, which we call

55:07

donors, and

55:10

then they put them in a cage with recipients, with

55:12

a divider in between, so

55:14

that any transmission will be by respiratory

55:17

droplets, not

55:19

by ferrets, but by the human. So

55:23

it's touching each other, which they like to do. And

55:29

how you know that transmission occurs is

55:31

you have virus in

55:34

the nasal secretions of the recipient

55:38

ferret or seroconversion. The

55:40

ferret makes antibodies to

55:42

the virus. All

55:44

right, when you do this, four

55:46

of four recipients without prior immunity

55:49

shed alpha swine H1N1 two

55:52

days post exposure. So that's

55:54

consistent with human

55:58

transmission. So,

56:01

alpha swine H1 efficiently transmutes to

56:03

animals without prior immunity within

56:05

two days. Remember, these

56:08

animals are sort of negative.

56:10

But then they ask, what's

56:12

the effect of immunology on

56:15

these transmission? Immunology,

56:18

which is going to be taken out of the NIAID. Yeah,

56:24

yeah. And then they put with arthritis, which

56:27

is also immuniated sometimes. So

56:31

they have four recipient

56:34

ferrets. They're infected with H3N2

56:37

or H1N1. Then

56:41

four months later, once the

56:43

antibody response, well, they say the immune response

56:47

has waned, then

56:49

they expose them to infected

56:52

donors for two days. And in particular, the

56:55

alpha swine H1. So

56:57

they wait because if

57:00

you do the

57:02

experiment two weeks after

57:04

immunizing them, you're going to have very high antibody

57:06

and T cell levels and not going to be a

57:08

good reflection of what's going on, right? Right.

57:12

So they take these

57:16

infected ferrets and they expose them

57:18

to alpha swine H1 donors for

57:20

two days. And

57:22

one experiment, four of four

57:25

H3N2 recipients shed alpha

57:28

swine H1 at four days and two

57:30

of four shed in their second

57:33

replicate. So H3N2

57:36

would be a caterologous

57:38

virus. That shouldn't give any

57:40

cross-reactivity. Maybe

57:43

one of four recipients

57:46

of the H1N1 pandemic, 2009

57:49

virus shed detectable levels

57:51

of alpha swine

57:53

H1N2. And

57:57

all these animals were infected, which suggests

57:59

that. the Alpha Swine

58:01

H1 can transmit to

58:03

animals with prior immunity, which

58:06

puts them in a higher risk, higher

58:08

pandemic risk category. Although

58:11

we don't know yet if they could spread them, we just know

58:13

that they're shedding them. We're going to do that in

58:16

the next experiment. Okay,

58:19

it's a little bit complicated. Hopefully

58:21

you're following. Okay,

58:24

next. Transmission,

58:28

of course, is a part

58:30

of the pandemic risk assessment. So

58:33

they asked whether ferrets who

58:37

received the virus

58:39

could then transmit it onward

58:41

to naive recipients. So they

58:44

have two different change where they

58:46

have four Alpha

58:49

Swine H1 infected donors. They're

58:53

exposed to H1N1 2009 recipients in the adjacent

58:55

cage for two days. And

58:57

then those are transferred to another cage to

58:59

see if they can infect another

59:02

recipient, right? So you want to establish

59:04

a chain of transmission. So in the

59:06

first replicate, two of the four ferrets shed

59:08

swine Alpha Swine H1 and 2, whereas in

59:11

the second, all four had Alpha Swine H1

59:13

and 2 in their nasal secretions. Most

59:16

of this shedding was on day three. But

59:18

only 50% of the infected donors

59:20

transmitted onward to another ferret. So

59:23

even though they're shedding, it's probably not

59:25

enough to transmit to another

59:28

ferret. So

59:31

that's good at least that some

59:33

pre-existing immunity may block

59:35

transmission potential. That's right.

59:38

That's the conclusion. Onward transmission

59:40

of swine Alpha Swine H1 is possible even

59:42

in the context of pre-existing immunity. So

59:45

it's got a higher risk potential. Then

59:49

they looked at the pathogenesis of

59:51

infection with this virus.

59:54

So no difference in

59:56

Alpha Swine, tied or was observed between H3N2

59:59

and H1. infected ferrets and those

1:00:01

with no prior immunity. However, the

1:00:03

H3N2 immune ferrets cleared

1:00:05

the virus by five days. So

1:00:08

there's apparently some cross-reactivity. Ferrets

1:00:12

with pre-existing H1N1 2009 immunity

1:00:15

shed less virus on days one

1:00:17

and two and three

1:00:19

compared to ferrets with no immunity. They

1:00:22

found robust

1:00:25

replication of the virus in the lungs in ferrets

1:00:27

that were not immune. The

1:00:29

lungs trachea soft palate, nasal

1:00:31

turbidus, whereas the H3N2 immunized ferrets

1:00:33

had only detectable virus in the

1:00:35

soft palate. That's alpha swine H1N2.

1:00:38

And these ferrets immunized

1:00:40

with H1N1 2009

1:00:43

had completely cleared the

1:00:45

virus from their respiratory tract

1:00:48

on day five. Next,

1:00:52

H1N1 immune and non-immune

1:00:54

ferrets were infected with alpha swine

1:00:56

H1N2 and sacrificed on day three.

1:01:00

They could find detectable virus

1:01:02

in the respiratory tract, although

1:01:04

the titers were less than in

1:01:07

animals without prior immunity.

1:01:09

So to summarize all this, prior

1:01:11

H1N1 2009 immunity can

1:01:14

reduce the viral load in the

1:01:17

respiratory tract and decrease the time to

1:01:19

transmission to clearance of alpha swine

1:01:21

H1N2. Remember 2009 H1N1, the pandemic virus,

1:01:28

came from pigs. So this is not surprising

1:01:31

that there's some cross-reactivity. And

1:01:35

then they do some pathology to compare pathology

1:01:38

of these viruses. They

1:01:42

basically find that pre-existing immunity can reduce

1:01:44

the pathology, pre-existing immunity to 2009 H1N1,

1:01:47

can reduce the pathology caused by alpha swine H2N2

1:01:49

infection. And

1:01:56

finally, clinical outcomes. So

1:01:58

intranasal, the alpha-swine

1:02:01

H1-infected ferrets with no

1:02:03

prior immunity or with

1:02:06

H3N2 immunity had similar symptoms,

1:02:10

weight loss and other signs and so

1:02:12

forth, while

1:02:14

the intranasally-infected ferrets

1:02:18

that had been immunized with 2009

1:02:20

H1N1 had no symptoms whatsoever. So

1:02:25

the summary is that although alpha-swine

1:02:27

H1N2 can transmit between

1:02:29

immune animals, its

1:02:32

replication and severity is limited

1:02:34

by prior immunity. So

1:02:37

that's the decision tree that

1:02:40

you do here. A couple

1:02:42

of points I want to

1:02:44

make. First of all, they

1:02:47

mentioned that protection against influenza

1:02:50

virus in hosts without antibodies can

1:02:52

be conferred by CD8-positive T cells,

1:02:55

which recognize conserved influenza

1:02:58

virus proteins, right? So many

1:03:00

of these viruses likely have conserved proteins

1:03:02

other than the HA and the NA.

1:03:05

It may not prevent infection, as they

1:03:07

say, but it will more

1:03:09

efficiently allow clearance of virus and

1:03:11

faster recovery from illness. And

1:03:14

in fact, that's what they saw in their

1:03:16

experiments. They immunized with H1N1

1:03:18

2009 and challenged with

1:03:20

alpha-swine H1 to get faster decrease

1:03:23

of shedding and fewer diseases. So

1:03:26

it's very cool. So

1:03:29

swine H1, alpha-swine

1:03:31

H1 has a higher pandemic risk than

1:03:33

gamma, and they say we should

1:03:35

keep doing surveillance to capture

1:03:38

zoonotic events, which means let's

1:03:40

see if this spills over into people, right?

1:03:44

And maybe we should consider

1:03:46

vaccinating pigs against this particular

1:03:48

virus, right? That

1:03:50

would be very expensive. Probably

1:03:55

you won't convince the farmers to do that,

1:03:57

right? Yeah. it's

1:04:00

to protect people. It has

1:04:02

nothing to do with the

1:04:04

pigs, right? Yeah, it's unfortunate.

1:04:08

And it will probably raise the price of pork

1:04:10

also. Yeah.

1:04:15

But it would be the right thing

1:04:17

to do to try and decrease the

1:04:20

virus circulating in pigs, right? You bet.

1:04:22

Anyway, if you wanted to know how you do

1:04:24

risk assessments, those are the experiments for

1:04:26

this particular swine influenza

1:04:28

virus, though it was pretty interesting. Let's

1:04:34

do a couple of email. Dixon,

1:04:39

can you take that first one? Sure. John

1:04:43

writes, Vincent et al.

1:04:45

I had heard about the

1:04:47

honeybee disease foul brood that kills

1:04:49

off the entire hive, but didn't

1:04:51

realize it was a bacteria. Pain,

1:04:55

the basil is species

1:04:58

infection. But the rule

1:05:00

that is, if there's a bacterium, there's

1:05:03

a phage for replies.

1:05:05

And while phage therapy aimed

1:05:08

at human diseases is

1:05:10

nothing new, there seems to

1:05:12

be complications with its development

1:05:14

deployment. But

1:05:16

honeybee hives appear to offer

1:05:18

a much simpler system than humans

1:05:20

for introduction of phage into. And

1:05:23

my old departments, Heather

1:05:26

Hendrickson, now in New Zealand, and

1:05:28

mentioned in an earlier letter as

1:05:31

co-organizers of the VOM

1:05:33

meeting, is behind such an

1:05:35

effort there. And phage

1:05:38

to the pentabacillus

1:05:40

to the bee's sugar water. In other

1:05:44

words, you add the phage to the bacillus,

1:05:48

and then you add the bacillus to the sugar

1:05:50

water that the bees feed on, and they will

1:05:52

wind up incorporating it into the hive. Apparently,

1:05:55

this is not a novel idea, but in

1:05:57

New Zealand, they had to develop their own

1:05:59

phages. because of import

1:06:01

restrictions and because of a

1:06:03

prayer collection that had been

1:06:06

destroyed. So the second link

1:06:08

contains details on phage hunting

1:06:10

there, and that involved beekeepers from all

1:06:13

over New Zealand, and validation of

1:06:15

the positive isolates sounds like a lot of work.

1:06:18

Here is the version of popular consumption. Apparently

1:06:20

it was a news item

1:06:23

published in New Zealand. And

1:06:26

here's the publication behind it, and he

1:06:28

lists that. Meanwhile, a

1:06:30

lovely afternoon yesterday when I started

1:06:32

this, in the lower 20 seas,

1:06:36

in greater Braddock, after drying

1:06:38

out from the rain that came Friday

1:06:40

during and after a warming, a

1:06:42

warning of tornadoes that largely didn't materialize.

1:06:45

Where is John from, anyway? Is John? He's

1:06:48

not from New Zealand, is he? No, no.

1:06:50

No. Braddock. Braddock.

1:06:53

Greater Braddock. Where

1:06:56

is Braddock? Let's see. This

1:06:59

has come up before

1:07:01

Pennsylvania. Pennsylvania, Pennsylvania,

1:07:03

okay. So

1:07:05

just to clarify, the

1:07:08

penny bacillus is causing infection

1:07:10

in the honeybees. Yeah, by the way. So they add

1:07:13

the phage to the drinking water of the

1:07:15

honeybees, and that takes care of the infection.

1:07:18

Right. That's very cool. Yeah. Phage

1:07:21

therapy for bees. I

1:07:23

love it. So you skip

1:07:26

the first one, but I'll read it. Yeah, I

1:07:28

saw that. Again, Dixon there was a

1:07:30

one-liner, a two-liner. Sterling writes,

1:07:33

you have credit lines for everyone

1:07:35

participating in Twiv, including timestamps and

1:07:37

music. Who's responsible for

1:07:39

the puns, the titles? Credit

1:07:42

and blame must be given, where blame

1:07:44

and credit are due. All

1:07:47

right, so I don't understand the rest. Oh,

1:07:49

part of it is great. Alan

1:07:54

A.D. says, Shirley, you must be

1:07:56

joking. That's from a

1:07:58

movie called Airplane. I believe.

1:08:00

Really? Yeah. The

1:08:03

person's name who wrote it is Shirley. And

1:08:05

he was telling jokes and so he said, Shirley, you

1:08:07

must be joking. And I

1:08:09

wrote the second one, arg times two, because I couldn't get

1:08:11

a, to

1:08:15

the two, to the second power over arg.

1:08:17

I don't have those instructions up here above

1:08:20

me on my editorial

1:08:23

list. So

1:08:27

the titles are mostly

1:08:29

Alan, but not

1:08:31

always. Sometimes

1:08:34

others make titles too, like other

1:08:36

people, right? Yes. We

1:08:39

discuss at the end of

1:08:41

every episode. Yeah, after recording,

1:08:44

we discuss titles and we

1:08:48

come up with things. I

1:08:50

always want the straightforward titles so that people

1:08:52

know. There's a lot of people writing this.

1:08:54

I don't know what the episode is about

1:08:56

if you make these clever titles. So

1:08:59

there's a, there's an argument

1:09:01

for that, right? There

1:09:04

is. But we still have some

1:09:06

clever titles. All right. Brianne,

1:09:09

can you take the next one? Sure. Patrick

1:09:12

writes, dear Twivers, I

1:09:14

cannot overstate the influence you and your

1:09:16

podcast have had on me. Like

1:09:19

many of your followers, I

1:09:21

joined the viral bandwagon during the early

1:09:23

days of the COVID pandemic. I

1:09:26

was working as a chief resident of

1:09:28

the UC San Diego pediatrics residency program,

1:09:30

where I completed half of

1:09:33

my med-peds residency. And Victor

1:09:35

Nizet, Nizay, recommended

1:09:38

Twiv on a well attended university-wide

1:09:40

town hall. I

1:09:42

have been a devoted follower since, at

1:09:45

least when my work schedule allows. And

1:09:47

when I moved to the southern tier of

1:09:49

New York state to work as a hospitalist,

1:09:51

Daniel's weekly clinical updates helped me stay up

1:09:54

to date on COVID as our hospital was

1:09:56

inundated with sick patients in successive waves over

1:09:58

the next few years. Last

1:10:01

year, when I learned of a vacant

1:10:03

infectious diseases fellowship position at University of

1:10:06

Rochester Medical Center, my regional

1:10:08

hospital's quaternary referral center, I

1:10:10

applied and was offered the position. Officially

1:10:13

entering the field is the fulfillment of

1:10:15

an aspiration born more than two decades

1:10:18

ago when I began reading about disease

1:10:20

hunters who traveled the world to study

1:10:22

and control emerging pathogens. One

1:10:25

of the many perks of joining the fellowship

1:10:27

here was having the opportunity to work with

1:10:29

doctors Anne Falsy and Ed Walsh, two

1:10:32

of the world's top RSV researchers who

1:10:34

have spent my entire lifetime and most

1:10:36

of theirs studying the virus and helping

1:10:39

to make the RSV vaccines a reality.

1:10:42

In addition to wanting to express my gratitude for

1:10:44

the work you do, I wanted

1:10:46

to facilitate an introduction and gauge your

1:10:48

interest in having Anne and Ed as

1:10:50

guests on TWIV to discuss their work

1:10:52

and what they see for the future

1:10:54

RSV vaccines and therapeutics. They're

1:10:56

as kind and witty as they are

1:10:58

brilliant and I assure you they would

1:11:01

be dynamic, entertaining and insightful guests. Thanks

1:11:04

again for enriching my professional and personal

1:11:06

life through your expert knowledge, cheerful

1:11:08

chatter and devotion to the pursuit of truth.

1:11:11

All the best, Patrick. Sure,

1:11:14

we can look into having them on. That would

1:11:16

be great. Sounds good. Angela,

1:11:20

you're next. Do you

1:11:23

want me to do the one line by David

1:11:25

and then Alison? Because David writes that he thought

1:11:27

this would be of interest to us that there

1:11:29

was a measles

1:11:31

death unfortunately of a child under five

1:11:34

in Toronto here in Canada, which is

1:11:36

very tragic. Also

1:11:39

the one about vaccinating

1:11:42

cattle. Oh, sorry, the David above that. Sorry, I

1:11:44

missed that one. There's two Davids. David,

1:11:47

Dave writes, just

1:11:49

listen to a discussion with Richard Webby

1:11:52

regarding influenza and cows. TWIV

1:11:54

1013. Unless

1:11:56

I miss something, I heard nothing said about

1:11:58

vaccines. As

1:14:00

such, we generate our own lentivirus and cell

1:14:02

libraries. This takes large amounts

1:14:04

of work and time and incubator space,

1:14:07

and is sort of the bread and butter of Jan's

1:14:09

lab. In addition to the exciting

1:14:11

science, we pull out using

1:14:13

these generated libraries. We

1:14:16

do purchase plasmid libraries, but from there,

1:14:18

we generate our lentivirus and build libraries

1:14:20

to have very specific gene coverage. This

1:14:22

takes a lot of work, but allows

1:14:24

us to feel confident in our screening

1:14:26

results. I know you all

1:14:28

have so much science to comb through in order to share

1:14:30

with the public, but felt this

1:14:32

was worth mentioning, especially when others plan

1:14:35

or design crisper screens for their own

1:14:37

projects. Thanks

1:14:39

so much for taking the time to read this email, and thank you

1:14:41

for all that it is that you do. I truly

1:14:43

look forward to each episode. Best Allie. P.S.

1:14:47

Kathy Spinler was one of my committee members

1:14:49

for my graduate training, as well as an

1:14:51

instructor during my graduate courses. I love hearing

1:14:53

her take on new science. She

1:14:56

makes me feel I'm back in a committee

1:14:58

meeting. Alison Dubczyk, she's

1:15:00

a PhD at, or postdoctoral

1:15:02

fellow, I should say, Stanford.

1:15:04

To have

1:15:06

1111, we talked about using crisper

1:15:09

to disrupt necropetosis, and that

1:15:11

improves survival after influenza infection.

1:15:14

I had said, yeah,

1:15:16

they probably bought the libraries, but this

1:15:18

tells us that they make their own.

1:15:20

Thank you very much for that. All

1:15:23

right. We only have one more

1:15:25

here. Walt writes, I'm always

1:15:27

a fan, but specifically wanted to thank your team

1:15:30

for the well-organized and thoughtful

1:15:32

episode 11, 21,

1:15:35

and the Five Key Points excerpt. You

1:15:38

often state the importance of basic, who

1:15:40

knows where this will go research. While

1:15:44

this is true also for science

1:15:46

communications, it draws a

1:15:48

wide range of people to love

1:15:50

open-mindedness and inquiry. There's also a

1:15:52

burning need to recognize what's most

1:15:54

salient to changing the course of

1:15:56

the world today and to

1:15:58

defend against those who hate open

1:16:01

inquiry. I don't think

1:16:03

Twiv would be well served by morphing into

1:16:05

a broader discussion of the role of politics

1:16:07

in science, but even as you did a

1:16:09

superb job of sticking to the facts, not

1:16:12

insinuations or conjectures in rebutting

1:16:14

Dr. Chan and Mr. Ridley, it's

1:16:17

important to understand what helps push

1:16:19

their ideas to the public.

1:16:23

No better example at hand than

1:16:25

this recent Washington Post story how

1:16:28

politicians shut down a group that

1:16:31

attempted to counter malevolent COVID

1:16:33

disinformation among other topics and gives

1:16:35

a list a link for that.

1:16:38

Thank you again and Godspeed. That's

1:16:42

bad. I think

1:16:44

they're getting not only their

1:16:46

spewing nonsense but they're preventing

1:16:48

people from trying to correct them. What

1:16:53

are we heading for in this country? Oblivion.

1:16:58

Come to Canada. I don't know if

1:17:00

we're doing much better. I

1:17:03

think you have some issues in Canada too. Nobody's

1:17:06

perfect. But

1:17:09

maybe less, I don't know,

1:17:11

maybe better. That's

1:17:14

smaller, that's for sure. Sure. No, it's

1:17:16

more scenic also. True.

1:17:18

Well, I don't know. You guys have some beautiful... No,

1:17:21

no, no. You've got all

1:17:23

of Jasper and Banff.

1:17:26

Those are great places. Also Angela

1:17:28

can go outside today. Yeah,

1:17:30

that's right. True. I was sitting

1:17:33

outside reading the papers earlier. This is my balcony. I

1:17:35

was sitting on my couch. Sounds

1:17:37

good. All right, let's wrap

1:17:39

up with some picks of

1:17:41

the week. Angela, what do you have for us? Okay,

1:17:45

so this is maybe spoiler alert but we

1:17:47

all chose like space things except for Vincent.

1:17:49

It works that way. This

1:17:52

was in

1:17:55

nature actually. So it's by Alexandra

1:17:57

Witts and it is called Staring at the

1:17:59

Sun. close-up images from space rewrite

1:18:01

solar science. So I just thought

1:18:04

the coolest part of this was this so

1:18:06

basically when you click on this link you'll

1:18:08

see this solar snake so they call it

1:18:10

a solar snake it's basically a what do

1:18:13

they call it a plasma a

1:18:16

solar snake of plasma appeared across the Sun

1:18:18

and you act there's actually

1:18:20

like this little video where you can see it

1:18:22

looks like literally a snake is like like

1:18:25

I don't know slithering across the Sun I thought

1:18:27

it was so cool and then they also have

1:18:29

another beautiful image of one of the

1:18:31

giant solar eruptions on February 15th it was in

1:18:34

2022 but it's just like a beautiful

1:18:36

image about the Sun and they have

1:18:39

more information about like research going on

1:18:41

solar researchers but basically

1:18:43

I wanted to share it mostly because of the solar snake I

1:18:45

thought it was so cool. Yeah.

1:18:51

Rian what do you have for us? So elsewhere

1:18:53

in the solar system I

1:18:56

read this article recently I thought it was

1:18:58

really cool that there were some scientists who

1:19:00

were looking at images of

1:19:03

different parts of Mars and suddenly realized

1:19:05

that they actually were seeing frost on

1:19:09

some calderas of some volcanoes.

1:19:12

What? This

1:19:14

was particularly exciting because these volcanoes

1:19:16

are actually in the equatorial region

1:19:18

which is a hotter area of

1:19:20

Mars and so if they're seeing

1:19:22

frost there then that tells

1:19:25

you a lot about potential for water

1:19:27

elsewhere. They saw this

1:19:31

it is only one

1:19:34

hundredth of a millimeter thick layer

1:19:38

of frost and it's only there for

1:19:40

a very small number

1:19:42

of hours per day sort of

1:19:45

in the first time in the morning

1:19:47

and so they really had to look

1:19:49

out to happen to look at images

1:19:51

at the right time in the right

1:19:53

place. That wasn't what they were originally

1:19:55

looking for but they originally

1:19:57

saw it so they show for example

1:20:00

an image here where you can see a little bit

1:20:02

of frost in a caldera at 7.20 a.m. solar time

1:20:07

in one location. And

1:20:09

this was, again, a big

1:20:12

surprise and also

1:20:14

leads to some interesting questions about what might

1:20:16

be going on with a water cycle in

1:20:18

terms of where water has or has not

1:20:20

been found, what the hours are

1:20:23

of where the water is present and

1:20:26

where it's going in other times. Right.

1:20:29

What does it mean, Brianne? It

1:20:33

means it's cool that we can start to

1:20:35

see other places with water. And it's

1:20:38

also something that, you know, if ever we

1:20:40

were to go to other

1:20:43

planets or other places, we'd need to have water and

1:20:45

we'd need to figure out whether there's some there or

1:20:47

whether we need to bring it or make it. So

1:20:50

knowing that, I think they said that if

1:20:52

you could collect all of this frost because

1:20:54

these volcanoes are huge, they said that one

1:20:56

of the volcanoes was not only

1:20:58

bigger than a volcano in

1:21:00

Hawaii, but it could fit all of Hawaii in

1:21:02

the volcano. So they said

1:21:04

that if you could actually get all of

1:21:07

that one hundredth of a millimeter thick frost

1:21:10

together, it would be 150,000 metric tons

1:21:12

of water ice or the equivalent of 60

1:21:14

Olympic swimming

1:21:18

pools. That's a lot

1:21:20

of ice. Yeah. That's so

1:21:23

I did the resolution of their cameras to see

1:21:25

a hundredth of a millimeter. That's amazing. I

1:21:27

know. Yeah, but Albedo is incredible.

1:21:30

Yeah. Albedo is everything. But

1:21:32

this means there could be life there as

1:21:34

well, right? Either

1:21:36

now or in past. Yeah. Cool.

1:21:40

The other thing they worry about is they

1:21:43

know there were oceans on Mars at one

1:21:45

point because of the

1:21:48

geology and the residues. The

1:21:50

hematite represents a mineral

1:21:53

that's only deposited in aquatic environments.

1:21:55

At any rate, they think the

1:21:57

water is still on Mars. where

1:22:00

would it go right and it's

1:22:02

underground so there are

1:22:04

oceans of water waiting to

1:22:06

be tapped. So

1:22:10

let's all go. Well I don't particularly want to.

1:22:12

It's much cooler on Mars right now than it

1:22:14

is. It's a ride. You guys can go. Cheap

1:22:17

ride. What

1:22:19

is it eight days to get there or

1:22:21

more right? Well they've got

1:22:23

a new propulsion system so it might only

1:22:25

take three months. Nope not happening to me.

1:22:29

Only three months. Nope. Cool.

1:22:33

Can I bring a comfy couch and my candle? I

1:22:35

don't think so. You can't bring your cat. Bring

1:22:40

a deck of cards. I can't bring my

1:22:42

dog. There's no am going. It's a lot of solitary

1:22:44

I tell you. Dixon, what do you have for

1:22:46

us? Well another

1:22:48

space first. This

1:22:51

one involves the Crab Nebula. The

1:22:54

James Webb Space Telescope has just

1:22:57

published. The most

1:22:59

resolved picture,

1:23:01

a single picture of the

1:23:03

Crab Nebula which represents the

1:23:07

remnants of a very large sun

1:23:10

which meant supernova. And

1:23:13

the explosion is evident by

1:23:15

looking at the trajectory

1:23:17

of all of the debris that

1:23:19

has come out of that event.

1:23:23

When the star exploded, it

1:23:26

did so by imploding and

1:23:28

the result was a neutron star

1:23:31

which has the diameter of

1:23:35

like one fifth of the Earth. But

1:23:38

the mass, if you

1:23:40

took a spoonful it would go

1:23:43

all the way from here to China so to speak. It's

1:23:46

extremely, extremely dense. In fact,

1:23:48

there are no spaces between

1:23:51

the neutrons. They're

1:23:53

all stuck together and

1:23:55

the explosion caused an angular

1:23:58

rotation which was... not

1:26:00

hours, not minutes,

1:26:03

not seconds, but milliseconds. It

1:26:07

rotates once every 33 milliseconds.

1:26:10

Can you imagine how fast that

1:26:12

actually is? And they can

1:26:15

time the pulse and

1:26:17

it's better than an atomic clock. So

1:26:20

they use it for all kinds of measurements

1:26:22

and various other things. It's

1:26:24

a remarkable, it's

1:26:26

a, you see the old Star Trek's and

1:26:29

even the new Star Trek's, they avoid all

1:26:31

this stuff. They

1:26:33

didn't know about it. They don't even know, they didn't

1:26:35

know about it, but they don't want to know about

1:26:37

it. This

1:26:40

is really beautiful in

1:26:42

nature though. It's actually, the symmetry

1:26:44

of these things are just incredible.

1:26:47

And there's another picture of

1:26:49

the Crabbed Ambulance, by the way, for those who are

1:26:51

interested in where our elements come from. It's

1:26:54

been colorized according to the elements

1:26:57

that were ejected from this gigantic star

1:26:59

that went into a neutron

1:27:02

star. And the amount of,

1:27:05

you know, you talk about how much ice

1:27:07

you can collect in a volcano on Mars,

1:27:10

and it's 100 million, 150,000 gallons of water, something

1:27:14

ridiculous like this. The amount

1:27:16

of nickel created by

1:27:18

the explosion of this star

1:27:21

is enough to make a

1:27:23

pauper rich in a second and a half. It's

1:27:28

such a beautiful picture, the one that's linked.

1:27:30

It's quite gorgeous. They're beautiful,

1:27:32

beautiful objects, but powerful.

1:27:35

And you wouldn't like to stand next to one.

1:27:38

I have to add that since the last

1:27:40

episode I was on Rich, told me about

1:27:42

the astronomy photo of the day from NASA,

1:27:45

and now I have it on my Google

1:27:47

Chrome. Yes, Kathy

1:27:49

told me about that, and it is my homepage.

1:27:51

So whenever I open a browser window, that's what

1:27:53

I get. And I feel like there are some

1:27:55

days where I just think of random reasons I

1:27:57

need a browser window because the picture is so

1:27:59

beautiful. We just leave it

1:28:01

open and at the lab I have like the second screen people

1:28:03

will come and they're like, Oh, what

1:28:05

is that? It's like, yeah, I'm not

1:28:07

mistaken. The Crab Nebula was actually the

1:28:10

explosion when the star went to supernova

1:28:12

was actually, it occurred during

1:28:14

humanity's occupation of earth and it

1:28:16

was recorded by a bunch of

1:28:19

cultures. And so we, we,

1:28:21

it was quite an event because you could,

1:28:23

they claim that you could see it during

1:28:25

date daylight. Cool. Well,

1:28:28

I don't know. You guys love space. I know that,

1:28:30

but we do. I am more grounded here.

1:28:35

Rarely pick a space thing. I don't know why,

1:28:37

but the article today is in science-based

1:28:40

medicine by Clay Jones.

1:28:42

And the title is will your tattoo

1:28:44

give you cancer? Probably not. But

1:28:47

maybe. Hopefully not. So,

1:28:49

but maybe I have like

1:28:51

five, hopefully not. You have a tattoo? I

1:28:54

have like five. Do you guys have,

1:28:56

you got, brand, you don't have any

1:28:58

tattoos? I do not. I've definitely thought

1:29:00

about it. I used to play baseball

1:29:02

and one day we got tattooed, but that was about

1:29:05

it. Since

1:29:08

you get 12. So why are

1:29:10

they, so this is based on

1:29:12

a study out of Sweden in

1:29:14

e-clinical medicine. Okay. Which

1:29:16

showed that the risk of tattoos

1:29:19

increase your risk of malignant lymph by 21%. And

1:29:21

I think this is a good example

1:29:24

of how you do an observational study

1:29:27

and it's just fraught with problems. So

1:29:29

why did they do this in

1:29:32

the first place? It turned out, turns out that tattoo

1:29:34

inks have lots of

1:29:36

stuff in them. Some of which

1:29:38

are actually carcinogens. Right? So

1:29:42

they scoop

1:29:44

in Sweden. They

1:29:46

took 12,000 subjects.

1:29:50

A little over half of them had lymphoma. And

1:29:53

21 of the subjects with lymphoma had tattoo

1:29:56

exposure compared with 18% with no. tattoo

1:30:00

exposure, okay? That's

1:30:03

where the 21% relative risk increase

1:30:06

comes from and they point out that it's

1:30:08

not much at all. Versus 18? So

1:30:12

malignant lymphoma is not very common. The

1:30:15

risk is 0.72% in men and 0.35% in women worldwide

1:30:20

compared to 4% with

1:30:22

colon cancer, for example. There

1:30:25

are many other risk factors for

1:30:27

lymphoma, including viruses and autoimmune disorders

1:30:29

and certain other things. But

1:30:32

he says that a study like this is

1:30:37

like an observational study which probably has

1:30:39

all kinds of other problems

1:30:42

that you didn't pick up, right?

1:30:46

Right. He makes

1:30:48

the point here, which is really very good.

1:30:50

He says where

1:30:54

is that? I

1:30:57

have to read this for you. Where

1:31:01

is it? Where is it? There's this

1:31:03

great statement. Hang on. Okay,

1:31:12

the confidence interval of

1:31:15

the results 0.99

1:31:18

to 1.48 and

1:31:20

the author says that a confidence

1:31:22

interval that includes one does not

1:31:24

inspire any confidence in a

1:31:26

study like that. Correct. They

1:31:31

said there's some other things that we

1:31:33

should note. Risk of lymphoma was higher

1:31:35

when tattoo exposure occurred less than two

1:31:37

years before a cancer diagnosis, which strikes

1:31:39

me as odd, but also when a

1:31:41

first tattoo was at least 11 years

1:31:44

old, which makes more sense. Cumulative

1:31:46

and higher exposure to

1:31:49

immunogens should increase risk, but there was

1:31:51

not any apparent increase in risk from

1:31:53

having a larger total tattooed body surface

1:31:55

area. Finally, some lymphomas appeared

1:32:00

me to be more common than others in subjects

1:32:02

with tattoos compared to those without. I

1:32:05

can't help but worry that this is

1:32:08

all just an example of the

1:32:10

Texas sharpshooter fallacy, the

1:32:12

most famous example of which to me being

1:32:15

the uproar over power lines causing

1:32:17

leukemia in Swedish children. To

1:32:19

be fair, the authors of the study are aware

1:32:21

of the many limitations. Many of these

1:32:23

assumptions are a stretch. Ultimately,

1:32:25

I think we could all agree that it's

1:32:27

impossible to put too much stock on an

1:32:30

observational and retrospective study like this

1:32:32

one, and we need to have better

1:32:36

studies, essentially. So this

1:32:38

has got a lot of press, but if you read this

1:32:40

article, you will understand that

1:32:42

it's probably not likely that

1:32:44

a tattoo is going to cause cancer. If

1:32:47

someone is super excited about tattoo

1:32:50

biology, I'm reminded of a paper

1:32:52

that Cindy told us about on

1:32:54

Immune about how tattoo ink persists

1:32:56

because of macrophage turnover at the

1:32:58

site, and the macrophage being unable

1:33:00

to digest the ink and turn

1:33:02

over. It's a really, really cool

1:33:04

paper. Oh, that's cool. They

1:33:07

pass it on to other macrophages when they die. Yeah, it's very

1:33:09

cool. Wait, what? Yeah.

1:33:11

The macrophages take up the die, and then

1:33:14

when they die, they turn

1:33:16

over the die to the new cell. Yeah.

1:33:19

Yeah. That's so cruel. They turn into

1:33:21

melanocytes. But they do eventually fade. I guess that's

1:33:23

more like UV exposure that they fade then, no?

1:33:25

Or are they fading because there is a slow

1:33:27

digestion? It just takes a long time. I

1:33:30

wonder. I have to read this paper. That's

1:33:34

cool. It's in the chat. Thank you.

1:33:36

We have a listener pick

1:33:38

from Jessica. Thank you for years of

1:33:40

fun, interesting, and essential

1:33:42

education. I thought this little listener pick

1:33:45

about an old epidemic might interest you

1:33:47

even though it wasn't viral, but bacterial

1:33:49

in origin because of it being

1:33:51

one of the first times PPE were used to

1:33:53

try and control the spread of an infection. Pictures

1:33:56

are interesting too. That's

1:33:58

from Jessica, who's an RN and... in MA.

1:34:00

And this is an article on

1:34:03

Wikipedia, the Manchurian plague, a pneumonic

1:34:05

plague that occurred in 1910 to

1:34:07

11 in Manchuria killed

1:34:09

60,000 people, stimulating

1:34:12

a multinational medical response and

1:34:14

the wearing of the first

1:34:17

PPE. Wow. It's

1:34:19

thought to have originated with a Tarbagan

1:34:21

marmot infected with bacterial pneumonia.

1:34:24

They were hunted for their fur in

1:34:26

Manchuria. It's an airborne disease, incredibly deadly,

1:34:28

100% mortality rate. Very cool. Wow. Thank

1:34:33

you for that, Jessica. And

1:34:36

that will do it for TWIV 1125. You can find the show

1:34:40

notes at microbe.tv slash

1:34:42

TWIV. You can send your questions and

1:34:44

comments to TWIV at

1:34:46

microbe.tv. And if you enjoy

1:34:48

our work, we would love to have your

1:34:50

financial support to keep this going. Go

1:34:53

to microbe.tv slash

1:34:55

contribute. Dixon

1:34:57

de Pommier, trichinella.org, thelivingriver.org.

1:35:00

Thank you, Dixon. Thank you, Vincent.

1:35:03

Welcome back. And don't

1:35:05

try to miss another one, okay? I won't. I'm

1:35:07

here. Otherwise,

1:35:10

I won't learn a goddamn thing. No, you can

1:35:12

learn. You'll learn. It's fine. Brianne

1:35:16

Barker's at Drew University, bioprof

1:35:18

Barker on Blue Sky. Thanks,

1:35:20

Brianne. Thanks. Thanks. It

1:35:22

was great to be a part of that. We learned a lot. Angela

1:35:25

Mingherelli is at McGill University, immune vet

1:35:28

on X. Thank you, Angela. Thank

1:35:31

you. I had a great time. I'm Vincent

1:35:33

Draconello. You can find me at microbe.tv.

1:35:35

I'd like to thank the American Society

1:35:38

for Virology and the American

1:35:40

Society for Microbiology for their support

1:35:42

of TWIV. Ronald Jenkies for the

1:35:44

music, Angeline for the

1:35:47

timestamps. You've been listening to

1:35:49

This Week in Virology. Thanks for joining

1:35:51

us. We'll be back next week. Another

1:35:54

TWIV is viral.