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, This

0:13

Week in Virology, episode

0:15

1095 recorded on March 8th, 2024.

0:22

I'm Vincent Rackeniello, and you're listening to

0:24

the podcast all about viruses. Joining

0:27

me today from Fort Lee, New

0:29

Jersey, Dixon Dapomier. Hello,

0:31

Vincent and everybody else. Well, today

0:35

is a beautiful, beautiful spring day.

0:38

There's only one thing wrong with that statement. It's

0:42

March 8th. It's nowhere

0:44

near spring. Well, it's supposed to

0:47

be spring, but this is very, very

0:49

early. We have a tree that's leafing out across

0:52

the street from me that I can

0:54

see. It's already green. We

0:57

just hope that the polar

0:59

express doesn't hit us again, which

1:02

it could. It could. Here

1:05

in New York, it's 12 C and

1:07

sunny. Yeah. Also

1:10

joining us from Montreal, Canada,

1:12

Angela Mingarelli. Hello,

1:14

everyone. It's actually pretty nice here too. I wrote

1:16

it down, 44 F and 7 C, and

1:21

it's sunny. I closed my blinds because if

1:23

not, there was going to be a lot of glare. Yeah,

1:26

I went for a dog. I went

1:28

for a walk with my dog this morning. It was beautiful.

1:32

It's kind of scary that March 8th

1:34

in Montreal, there's no snow. There's only

1:36

these little patches of dirty, gross

1:39

snow. We're supposed to

1:41

be getting, I think by the end of next week, a

1:43

snowstorm. I know Newfoundland was

1:46

calling for 50 centimeters, so East Coast

1:48

Canada. We're supposed to get tail

1:50

ends of that, but I

1:52

think spring is more or less here,

1:54

which is also kind of scary because normally we'd have

1:56

a month left of winter. Also

2:00

joining us from western Massachusetts, Alan Dove.

2:02

Good to be here. It's 54 Fahrenheit,

2:05

beautiful, as Dixon said,

2:08

spring day, lovely

2:11

day for April. And

2:16

from Austin, Texas, Rich Condit.

2:18

Hi everybody. I think

2:21

I'm in a similar advanced

2:23

spring condition here. We have 84

2:27

degrees, beautiful day. We had a

2:29

thunderstorm roll through this morning, but then it

2:31

cleared up after that. I will say that

2:34

tomorrow's high is supposed to be 63 degrees,

2:37

20 degrees cooler than today. So we're

2:39

swinging back and forth, but I will also

2:41

say that the blue

2:44

bonnets are up. That's a big

2:46

deal in Texas. Okay. They are

2:48

the state flower and

2:51

a wildflower that is just all

2:53

over the place and the harbinger

2:56

of many more other sorts of wildflowers

2:59

to come. So this is a great time of year. I don't

3:02

have quite enough experience to

3:05

be sure of this, but it does seem early.

3:07

I think of blue bonnets as April. Well,

3:11

I'll be heading your way tomorrow. I'm on

3:13

my way to Austin, Texas. Yeah.

3:16

Aren't you guys doing a twos together? We're

3:19

doing several things. We're doing a

3:21

Twivo 100 on Sunday at the

3:24

Science Mill in Johnson City. And

3:27

then we're doing a Twiv

3:29

Monday 11 a.m. at the University

3:32

of Texas with Jason McClellan.

3:35

And then I'm going to be doing

3:37

a session at South by Southwest on

3:39

Tuesday. Cool. Cool. So

3:41

that should be fun. Damn fun.

3:43

The drive to Johnson City is going to

3:45

be fun. You get to see lots of

3:47

blue bonnets and stuff like Road Trip, man.

3:50

We've done this before. Yeah. Vincent,

3:52

you have to get some barbecue and send

3:54

it to us. Barbecue. So I'm

3:57

looking forward to it. to

4:00

that. That'll be fun. It's spring break next week,

4:02

so I don't miss any. Well, that's

4:04

why I'm going because it's spring break and

4:06

I don't have classes. Should be going to

4:08

Padre Island. That's not for

4:10

me. I'm a little too old for that. Well,

4:13

actually, I'm not too old for anything, but I don't want

4:15

to go there now. Often, or

4:17

I think almost always

4:21

since having been to Austin, because it's

4:23

spring break, I've been

4:25

absent for South by Southwest. So

4:29

I will get to see it in

4:32

full bloom this year. That's

4:34

a madhouse, I think, but we'll

4:37

find out. That's

4:39

what I heard. A couple

4:41

of announcements for you. We have

4:45

two meetings that

4:47

tell you about. The first

4:49

one is all about classifying

4:52

viral subspecies. COVID-19 pandemic

4:54

highlighted the importance of collaboration and

4:56

tracing and classifying viral

4:59

subspecies for public health responses

5:02

in preparation for future

5:04

outbreaks. BV, BRC, CDC,

5:06

NCBI, and NIAID, all

5:09

these acronyms will

5:11

host a collaborative workshop on

5:13

viral subspecies classification. It will

5:15

bring together leading experts to

5:18

review existing classification schemes, develop

5:21

best practices, and equip researchers

5:23

and public health professionals with

5:26

knowledge and tools needed to address

5:28

future outbreaks and potential pandemics. The

5:30

workshop is April 8th through

5:32

the 10th this year, 2024. We'll

5:35

put a link for registration in the

5:37

show notes. You can register and go to

5:39

that. And

5:42

then we have another meeting in Australia.

5:44

I've been talking about viruses of microbes,

5:48

which is happening I think in June, right?

5:50

And there's another one in September. Options

5:54

12 for the control

5:56

of influenza. It's like the Super Bowl. They have Roman

5:58

numerals for this year. meeting.

6:00

We're at 12 September

6:03

29th to October 2nd

6:05

in Brisbane. We'll

6:07

put a link to that as well. We're

6:10

going to be doing a twiv. Yes, so

6:12

I'm going to Australia twice, two separate times.

6:14

I'm not staying there for a couple of

6:16

months. You're making two round trips to Australia.

6:18

Okay. I am. I know my carbon footprint

6:20

is... Yes, it's bringing you to springs also.

6:24

Your circadian rhythm is going to be all out of whack. Yes.

6:29

So we're going to do a twiv immune

6:31

because I'm going to be there. Kathy Spindler

6:33

will be there and so will Steph Langel.

6:37

And this is supported by the University of Queensland.

6:39

So we're going to go

6:41

do that. Now, why should you be

6:43

interested in the meeting? It has a

6:45

focus on underserved populations in respiratory virus

6:47

research. You're going to hear

6:49

a discussion with a Nobel Prize winning

6:51

scientist. You can have

6:53

networking events for early career

6:55

researchers. It's going to be

6:57

twiv slash immune. And the most important thing,

7:00

you can cuddle with

7:02

cute Australian marsupials right

7:05

at the meeting site. What do

7:07

you think of that, Angela? So definitely.

7:09

If there's koalas, although koalas

7:11

have certain strains of chlamydia

7:13

that you don't necessarily want

7:15

to. There's koalas too, right?

7:18

There's koalas. You can clap at the koalas,

7:20

yes. Just don't

7:22

pet the plant. They'll pet your back with

7:25

their poison glands. What else

7:27

is a marsupial? Is a kangaroo

7:29

a marsupial? Yeah, kangaroos, possums, everything

7:31

in Australia is a marsupial. Tiny,

7:34

tiny kangaroos, right? Well, everything

7:36

in Australia is a marsupial. The mammals

7:38

in Australia that weren't introduced. That's

7:40

right. That is right accidentally.

7:43

And some of the people of Australia are so...

7:45

All of these are adorable. Please take pictures with

7:47

them, Vincent. They are the one of these. Okay.

7:50

All right. So the day before

7:53

the meeting at the University of

7:55

Queensland, it's Saturday September 28th. They're

7:57

going to have a school for

7:59

influenza. a one-day prep course to

8:01

get you... I think our local elementary school

8:03

does that. Fluent

8:07

in respiratory virus research.

8:11

And early bird registration ends June 13th, so

8:13

go to the website if you want to

8:15

go to this meeting. And

8:17

don't forget to buy a copy of Dixon's book,

8:20

The New City. Learn

8:22

all about what

8:25

Dixon thinks the new city should look like.

8:28

And by the way, Dixon, my daughter, Sophie,

8:32

stuck her head in the office and said, you

8:34

know Dixon Despommier, don't you?

8:39

Yes, he's one of the co-hosts on

8:41

Twitter. I'm just watching a video about

8:43

vertical farms and they're talking about that.

8:45

And apparently this is

8:47

for her AP environmental science class.

8:50

She was learning about vertical farms. Tell her

8:52

to call me, I'll talk with her. So

8:55

that's the thing... You told her to read your book.

8:59

Agriculture has a broader reach than

9:01

viruses, right Dixon? Oh, I'm crazy.

9:04

It's okay. A

9:06

lot of viruses affect agriculture also though.

9:09

And viruses affect non-humans. Well, agriculture

9:11

does too. Yeah. I

9:14

think it's time. All

9:17

right, it's time for In the

9:19

News courtesy of Amy Rosenfeld, our

9:21

first article, Heterosexual Transmission

9:23

of Smallpox. So this is emerging

9:26

infectious diseases. Clade 1 associated with

9:28

M-pox cases associated with sexual contact.

9:31

Democratic Republic of the Congo,

9:33

they're reporting a cluster of clade 1 M-pox

9:35

virus infections linked

9:37

to sexual contact. Case

9:40

investigations were done. PCR

9:43

confirmed infections. And

9:45

this genome sequencing indicates they belong to

9:47

the same transmission

9:49

chain. And

9:53

so the point here is that you're

9:55

thinking, well, I thought it was sexual

9:58

contact already, right? a

10:01

different clade because the one that caused the

10:03

outbreak was clade 2B. So

10:06

now this is, and there are two clades, clade 1 and

10:08

clade 2. And

10:11

clade 2 is further subdivided into two

10:13

sub-clades, 2A and 2B. And

10:15

2B was responsible for the 2022 epidemic. So

10:20

clade 1 can be spread sexually

10:22

as well. Any comments on this,

10:24

Dr. Condit? That does it. You

10:27

know, you got the bottom line there. And

10:30

that it looks kind of like, in

10:33

a way, the sexual transmission of

10:35

the clade 2 viruses. Okay? So.

10:38

That's one of our papers today. In fact, we'll talk about that. We

10:42

have an epidemiological update from

10:44

PAHO, the Pan American Health

10:47

Organization, Oropushe

10:49

in the region of the Americas. That's

10:51

Oropushe virus. We had

10:53

already talked about this previously. And

10:57

now we have positive

10:59

2,104 positive samples in Brazil.

11:07

And now in Peru, 146 cases. So

11:10

the previous time we reported this, it was Brazil.

11:13

Now it's in Peru. So

11:15

it's moving. Probably in other places if it's

11:17

in those two places. Oh,

11:20

sure. Okay. This

11:23

one is for Angela. This is in class

11:25

one. Oterid

11:27

gamma herpesvirus 1 in South American

11:29

first seals and a novel related

11:32

herpesvirus in free ranging South America

11:34

sea lions. Prevalence of and

11:36

effects of age, sex and sample type.

11:40

Yeah, so I think that's just I'm discovering. Yeah,

11:42

it was just like the discovery of a new

11:45

gamma herpesvirus, I believe, like from what I read in

11:48

this population of seals, which

11:51

is cool and sea lions. Well, I mean, cool.

11:54

Not really because it can cause

11:56

carcinomas on these poor animals. But

11:59

urogenital carcinomas. specifically, I think,

12:02

which I've actually seen some of

12:04

these first-hand doing necropses on, not

12:06

in seals per se, but other

12:08

herpes viruses, gamma herpes viruses in

12:10

other cetaceans. In pilot

12:13

whales, I've actually seen them. When I was

12:15

in vet school, we did necropses on beached

12:17

whales that had these urogenital carcinomas as well,

12:21

pretty frequent in marine mammals. Once

12:27

you know, seem to know about sea life,

12:30

Angela, why do humpback whales smack the water

12:32

with their fins? Why?

12:35

Actually, I don't know if

12:38

there's anything, I'm sure somebody, cetacean

12:40

specialist would know this, a whale scientist specifically.

12:42

You know, humpbacks, they breach and it

12:45

looks really cool, right? But then they also

12:47

come up and they stick their one

12:49

fin up and they smack it on the

12:51

water. I've seen some videos of

12:53

it recently. I bet it's

12:55

getting rid of parasites, ectoparasites, right? Or

12:58

it's a signal. Or it's just, yeah, or it's

13:01

just some sort of, because I know that the

13:03

small whales, they'll start, like the calves,

13:05

they'll start breaching excessively just to gain

13:08

strength in their muscles

13:10

to like, like, um, like, they're working

13:12

out and they're younger, literally they're working

13:14

out. But

13:16

when they're older, a lot of it is also

13:18

like when they're happy, or this is what is

13:20

inferred what we think, is that like when they're

13:22

happy or like they start breaching and just like

13:25

with dolphins. If you're happy and you know it,

13:27

clap your fin. Yeah. Exactly.

13:29

But the specifically like the dorsal fin slap,

13:32

I'm not sure if that's anything

13:34

specific. If anyone knows, please email us.

13:37

I doubt I could Google that answer quickly anyway. I

13:40

think it makes sense if they're happy, like you can

13:42

imagine that. Yeah, they're extremely. But you don't think they

13:44

get rid of it? Sorry, go ahead.

13:46

No, I was just going to say that

13:49

they're extremely intelligent. Like these are sentient beings

13:51

that have like when we compare brain mass

13:53

to body size, they're almost some of them

13:56

smarter than us. So they're extremely intelligent and

13:59

they communicate in ways. we don't even

14:01

understand apart from echolocation. So this could

14:03

just be like some sort of demonstration

14:05

of happiness. Ecto-parasites.

14:09

Would you get enough shearing force on just slapping

14:12

a thing down? No, I think the parasites, at

14:14

least that I know that they have, are so

14:16

small that I don't think that would make a

14:18

difference. There's not like large, like some fish will

14:20

have like very large, like

14:23

acrid parasites, but they don't really have those

14:25

as far as I know. We've

14:27

got a lot of barnacles on there.

14:30

Exactly, but those wouldn't really come off.

14:32

They try to rub themselves on boats

14:34

sometimes like to get those off. But

14:36

just hitting the water, I would think

14:38

more it's like happiness. I

14:40

feel now that, since you've told

14:43

me they're intelligent, they're probably

14:45

there, they have these barnacles all

14:47

over them, itching them like hell. They can't

14:49

go to sleep, and they're in water all

14:52

the time. It's

14:54

dark and cold. They must feel really

14:56

depressed. No, but that's how you perceive.

14:59

That's how you perceive the water.

15:01

Yeah. They're at home in

15:03

water. Exactly. They probably, they

15:05

would look at us and say, oh

15:08

my god, they're flopping around on land.

15:10

That's awful. And maybe. Exactly. Exactly. Look

15:12

how giant they look. Angela,

15:14

you remember you're talking about looking at a pig and you look

15:16

in their eyes and you can see intelligence, right?

15:18

I saw a video of a sperm whale's eye.

15:20

And it just rotated and looked at the camera.

15:23

Oh my god, it was so. Did you see

15:25

the Nova? Did you see that Nova special in

15:27

that? No, I didn't. It's called

15:29

Peter and the sperm whale. It's absolutely

15:31

stunning. You should watch it. It's

15:34

surreal almost. A female sperm

15:37

whale actually connected

15:42

with a, not a scuba dive, even.

15:44

He was free diving. But the click

15:46

of his camera and the

15:48

sperm whale's clicks sort

15:50

of started to interact. And

15:53

they recorded all of this. And it

15:55

was phenomenal. He

15:57

intercepted them while an entire pod of

15:59

sperm. worm whales were asleep. And

16:02

he said it was like visiting another planet. They

16:04

were all upright in a

16:06

big giant pod. And then when they woke up, they all

16:08

started to rub each other. All

16:11

of them. They were communicating by rubbing. And he says,

16:13

those whales are trying to teach me something. And

16:15

it might take me my whole life to find

16:17

out what that is. Or maybe I will never

16:19

do that. But I'll end it.

16:22

One time at one point, she left her

16:25

baby, meets this guy,

16:27

and she drove down to get some food, which is

16:29

a lot of mile deep. And

16:32

she came back to the exact same spot, picked

16:35

up her baby, and moved off. It

16:37

was quite remarkable. Dr. John Baxter Left it in

16:39

daycare. The clicks is actually the

16:42

leading theory for the whale ship Essex, which

16:45

was the inspiration for Moby Dick. So

16:48

it was the ship, it was a whaling ship that

16:50

was attacked by a sperm whale. And

16:52

at the time it happened, they were in

16:54

the doldrums. Everything was quiet and flat. And

16:57

the ship's carpenter was working on the ship,

16:59

pounding nails into one of the whale boats. And

17:02

the theory is that that may have

17:05

been interpreted by a male sperm whale

17:07

as a territorial clicking.

17:10

And so it came and rammed the

17:12

ship and sank it. And the whole

17:14

thing has been a huge, huge story

17:17

in Saga. Dr. John Baxter Not only

17:19

that, they've also encountered albino sperm whales.

17:22

Dr. John Baxter Yes. So they have seen white whales.

17:24

Dr. John Baxter White whales, yes. Dr. John Baxter

17:26

So Dixon, these whales, how long can they sleep

17:28

and not have to breathe again? Dr. John Baxter

17:30

About an hour. Dr. John

17:32

Baxter Aw, it's a terrible rest. Dr. John Baxter But sometimes,

17:34

yeah, it depends on the species of the whales. Dr. John

17:36

Baxter They're built for it. Dr. John Baxter

17:39

Penwins get a quarter of a second

17:41

rest. I'm not kidding. They

17:43

have little blinking eyes, and they're taking

17:45

micro sleep little downs. And

17:48

that's what they've determined. Their brain turns on, their brain turns on. Dr.

17:50

John Baxter They don't need eight hours like you live in. Dr.

17:53

John Baxter So they do, maybe not necessarily

17:55

eight hours, but all whales, as

17:58

many people know, they basically can. to

18:00

turn off one hemisphere of their brain

18:02

while the other hemisphere is still in

18:04

a low state of functioning, so they're

18:07

not fully asleep. So if there

18:09

was some sort of prey nearby that they

18:11

could still be awake enough to react. But

18:13

they do have shorter sleeping intervals. Some

18:15

even bob close to the surface

18:18

and can slightly breathe depending on the species.

18:20

But if they are underwater, then it's like,

18:22

yeah, about an hour. But some whales can

18:24

hold their breath for multiple hours for

18:27

diving, like for deep diving. If you're like a

18:29

ciphered species or the sperm whale,

18:31

those are the deepest diving. They

18:34

can hold their breath for a long time.

18:36

Very long time. Welcome to this week in

18:38

Wales. I have for years been

18:40

trying to figure out how to revive the left half

18:43

of my brain. Yeah, right. I'm just going to say

18:45

the important thing is to remember to wake up the

18:47

other half when you're done. I've got a problem with

18:49

all of it, but that's OK. Our

18:53

last paper, our last story news item

18:55

for today is paper in

18:57

PLOS ONE, sex-specific differences in

18:59

physiological parameters related to SARS-CoV-2

19:02

infections among the national cohort.

19:04

So this is looking at sex as a variable.

19:07

And so they looked at

19:09

sex-specific differences in

19:12

four physiological parameters across

19:15

a COVID-19 SARS-CoV-2 infection.

19:17

So they gave people a wearable medical device.

19:21

It measured breathing rate, heart rate,

19:23

heart rate variability, and wrist skin

19:25

temperature, 1,163 participants,

19:29

and roughly half males

19:32

and half females. And then

19:34

they would report daily symptoms and stuff in an

19:36

app. And

19:39

they collected serum also from

19:42

these patients. And they

19:44

looked at sex-specific differences. And

19:46

over 1.5 million hours of

19:48

data were recorded. And

19:51

during the symptomatic period of infection, men

19:53

demonstrated larger increases in skin temperature, breathing

19:55

rate, and heart rate, as

19:57

well as larger decreases in heart rate

19:59

variability. than women and

20:03

that's it. Okay, so differences

20:05

between males and females.

20:08

Not surprising but good to look at. Good

20:11

to confirm. So basically men overreact to

20:13

stress. Is that the idea? Also not

20:15

surprising. I'm joking. And

20:18

the importance of this in the context

20:20

of COVID-19, as people probably remember, is

20:22

that this is

20:24

a virus that tends to do

20:27

a number on men and maybe a little less so on

20:29

women. Yeah, but twofold

20:31

difference in mortality. Okay,

20:34

thank you Amy for that. What

20:37

did you say Angela? I

20:40

don't remember. I'm joking. I'm

20:42

joking because people say, you know, when

20:45

someone has a man cold that sometimes

20:47

when men are ill they

20:49

exaggerate a little bit more than other

20:52

sexes. Got it. I've never

20:54

heard that before but that's cool. We'll see just

20:56

what can I tell you. I'm

20:59

kidding. All right, we have two

21:02

papers for you today. And

21:04

the first one is a cell paper. Under

21:06

detected dispersal and extensive local transmission drove

21:09

the 2022 MPOCS epidemic. And

21:13

this is out of University of

21:15

Washington in Seattle, the Fred Hutch

21:17

Cancer Center in Seattle and

21:20

the Sorbonne in Paris

21:23

and the Riga Institute in Belgium. So

21:26

first author is Miguel Paredes and

21:29

the last author is Trevor Bedford

21:32

who some of you may remember

21:34

he was on Twiv, I

21:36

guess it was last summer. Yeah,

21:39

talking about he pioneered, you know, genomic

21:41

analysis during the COVID pandemic and we

21:44

talked about that. Now he's extended it

21:46

to MPOCS and it's quite interesting. So

21:49

just to remind you before

21:51

2022, most

21:53

cases of MPOCS, we'll

21:56

let Rich give you the MPOCS

21:58

run down in just a moment. But most of

22:01

them occurred in people with a travel

22:03

history to Nigeria or an exposure to

22:05

live animals from endemic

22:08

areas. But in May,

22:10

an individual with

22:12

travel history to Nigeria was diagnosed

22:14

with MPOCs in the UK. And

22:17

then after that, the number of cases

22:19

without a travel history began to increase

22:21

rapidly, epidemic human to human

22:24

spread. And as of July 2023, 88,500

22:26

cases of MPOCs worldwide. And

22:31

this is a virus formerly known as monkeypox. That's

22:34

right. Do you want to tell us a little bit about

22:36

it, Rich? Sure, a little bit. I

22:38

mean, it is a pox virus, an

22:41

orthopox virus, in fact, to get a

22:43

little more precise. In the

22:45

same group, I

22:48

mean, its most notorious cousin is

22:51

smallpox virus or variola. The

22:56

vaccine that was used to eradicate

23:00

smallpox was vaccinia, also a

23:02

closer related virus. I

23:07

think one of the reasons they changed

23:09

it from monkeypox to MPOCs is because

23:11

monkeypox leaves the false impression that it

23:15

actually lives in monkeys. When in

23:17

fact, it probably lives in rodents and

23:21

is endemic in a couple of

23:23

different regions in Africa, as we've

23:25

already said, two clades,

23:27

one and two. One

23:31

is disease wise a

23:34

nastier version than two. It

23:37

probably, as I think I already said,

23:40

is endemic in or it lives the reservoir

23:42

host as some sort of rodent. Hang

23:47

on, I have a... Is that your cat,

23:49

Rich? Yeah, that's my cat. I thought it

23:51

was one of my. I

23:53

thought it was Alan's cat.

23:55

And he's trapped in here.

24:00

here with me because there is an

24:02

individual spraying smelly stuff all over the

24:04

house who has a terrifying vacuum machine.

24:06

Oh, the monster. Oh, cool. Yeah,

24:09

and if he gets out there, he's going to have a bad

24:11

experience, but he doesn't know that yet. Oh

24:13

my gosh. Animals. So

24:16

we'll just put up with him for the time being. Oh,

24:19

he's flopped down again. I

24:21

think he'll be all right. At

24:23

any rate, okay. There are occasional

24:27

zoonoses where there's spillover from the

24:30

rodents into humans. There can be,

24:33

although it's not very efficient, human to human

24:35

transmission. There's

24:37

a certain mortality associated with that, between

24:39

1 and 10%, depending on the clade

24:42

you're talking about. But

24:44

because of the

24:46

low transmission, the

24:48

rodent-specific rodent reservoir,

24:51

et cetera, it hasn't been all that

24:53

much of a big

24:56

deal globally, okay. And

24:58

even in Africa, I don't think it's

25:00

that big a deal relative to lots

25:02

of the other problems that they're dealing

25:04

with. See, Rich, before this outbreak, was

25:06

there human to human spread, or was?

25:10

But not well. My

25:15

understanding was that the human to human

25:17

spread before this outbreak was

25:20

by direct contact

25:24

or respiratory droplets or

25:27

something like that. Typically, within

25:29

families, a kid would be messing with

25:31

a rodent and get sick and bring

25:33

it home, and the other family members

25:35

would get it. However, with

25:38

this that we see now, wouldn't

25:40

surprise me at all, as if you

25:42

could look at the whole thing. Retrospectively,

25:45

you might identify some sexual

25:47

transmission. At any rate, there

25:50

was a case that,

25:52

a travel associated case in

25:55

Western Europe at one point

25:57

and others in the United

25:59

States. UK that

26:03

got into the population

26:05

of individuals, specifically men who have

26:07

sex with men and spread

26:10

within sexually within that community. This was

26:12

I get

26:15

the clients, it's easy to get the clients picked up

26:18

and claim who, okay? And

26:20

as we'll see here in the

26:22

introduction spread globally, totaling

26:25

something like 86,000 cases.

26:27

And so that was a big spill

26:29

out if you like from

26:32

its normal home into the global population.

26:34

And the question is, you know,

26:36

what are the drivers? And this

26:39

addresses some of that. I should

26:41

say one other thing and that is

26:43

that because it's an orthopox virus, the

26:45

same vaccines that are effective against smallpox

26:48

should be effective against monkeypox as well

26:50

and have been shown to be so.

26:53

And we have stocks of those

26:57

vaccines around so that they're

26:59

relatively readily available and distributable.

27:01

There's also a drug called,

27:04

I can't think of

27:06

it other than ST246, but it's... Techavirimat?

27:11

No, Techavirimat is also known as T-pox,

27:13

I think. It's a

27:15

very effective drug that I believe

27:18

should be and I believe is as

27:20

effective against MPOCs as it is against

27:23

smallpox and other orthopox viruses. And

27:26

both of those things were rolled out in response

27:28

to this epidemic.

27:31

And actually another interesting thing here,

27:33

we're talking about a fairly large,

27:35

it used to be the largest,

27:37

now it's a fairly large double-stranded

27:39

DNA-containing virus. These things are

27:41

supposed to be relative to

27:44

RNA viruses, relatively genetically stable.

27:47

However, there's a fair

27:49

number of semi-essential or

27:51

non-essential genes in the virus, so

27:53

there's opportunity for genetic drift and

27:55

you can take advantage of that

27:57

drift to crack the

27:59

virus. as it moves. So,

28:02

Rich, I have a question about the nomenclature then because

28:04

you said that, I'm

28:06

not sure, I don't think you mentioned this

28:09

specifically, but the name monkeypox, if it normally

28:11

circulates within rodents, then it's just like the

28:13

primary reservoir, non-human primates that then spilled over

28:15

into rodents when it was first detected or

28:17

why is the name? No, no, I think

28:19

when it was first detected, it was first

28:21

detected in monkeys. Yeah. Okay.

28:24

Yeah. And I

28:27

think it can spill over from rodents

28:30

into monkeys in Africa

28:32

and wind up, they can be

28:34

an intermediate vector

28:36

basically and it can make

28:39

its way into humans through that vector because

28:42

monkeys get handled

28:44

by humans in Africa, among other things.

28:46

So I think the original... And they

28:48

exaggerate. And they exaggerate. The

28:50

initial associations were with monkeys, that's where

28:52

it got its name, but it

28:54

doesn't, in the real

28:56

scheme of things, it's really

28:59

a peripheral host. Okay.

29:02

The WHO, when they

29:05

renamed it, they cited,

29:07

they said the old name could

29:09

be construed as discriminatory and racist, that's

29:11

why they renamed it. But

29:13

I agree that's probably... But also it's just

29:16

inaccurate because it's not primarily a virus of

29:18

monkeys. I think that's the best reason, I

29:20

guess, I don't know. But M could be,

29:22

I don't know. What should

29:24

it be? It shouldn't be mousepox because that's

29:26

a different virus, right? No. I

29:29

mean, you probably don't want to name

29:31

it after a region. No, gotcha. Okay.

29:34

How about rodent pox? How about rodent

29:36

pox? Rocks. That opens up a can

29:39

of worms. Actually,

29:41

I should know, but I don't

29:43

know whether there is a specific

29:46

rodent reservoir associated with this. My guess is that

29:48

there's more than one, but I'm not sure. I

29:51

think probably the rationale of M pox was just

29:53

take the monkey out of it, but keep the

29:55

M so people know what virus you're talking about.

29:57

Yeah, that works for me. I

30:00

have trouble, I have a little trouble with

30:02

impacts because I've been doing monkey pox for

30:04

40 years. But

30:07

you're right, Alan, that does

30:09

work. All

30:12

right, so this 2022 outbreak, lots

30:15

of human to human spread outside of

30:17

endemic areas. So mainly

30:22

in men who have sex with men, as

30:25

Rich said, it's milder illness than clade

30:27

one. Long incubation period, five

30:29

to 21 days. And

30:32

so they say maybe that

30:34

facilitated undetected spread, which we

30:36

don't know about. And it's one of the

30:38

questions they wanna address in

30:41

this paper. They also wanna address

30:43

whether travel contributed to it and

30:45

whether vaccination campaigns were effective at

30:47

controlling it. And so what they

30:49

do here is use genomic

30:52

epidemiology. They

30:55

combine genome sequencing with

30:57

standard epidemiological information,

31:00

like where was the virus

31:02

isolated, from what person, when,

31:04

and so forth. And

31:06

they can make, they use

31:08

mathematical approaches to answer some of

31:10

these questions. It's quite interesting. I

31:13

wanna, at the outset here, introduce,

31:15

now I'm going off, this

31:18

is me talking, okay? Going off

31:20

the edge here a little bit. I didn't think it was

31:22

Dixon. I wanna introduce a qualification

31:28

or some nuance to the word

31:30

undetected in the bread, okay?

31:33

Because I don't

31:37

think of these viruses as

31:39

having a significant amount of

31:41

asymptomatic transmission. I was

31:43

just about to ask that. Now in this particular case,

31:46

I may be overstating that

31:49

and I'm not entirely sure, but

31:51

certainly with most orthopoxviruses, I know,

31:54

there's very little asymptomatic

31:56

transmission. And so when

31:58

we're talking about undetected, think we're talking

32:00

about undetected at the public health level. You

32:04

know, that includes not only undetected

32:06

but unreported. Okay. So that

32:08

qualification. Okay,

32:13

yeah I agree with that. I think it should be unreported,

32:15

yeah. And that's why smallpox

32:17

was eradicable because it... Absolutely, and that's

32:19

one of the things that makes me

32:21

think about it. Smallpox,

32:24

you only got once, if

32:27

you got it you were scarred so you could

32:29

tell if somebody had it. Okay. You knew when

32:31

you had it. You knew when you had it.

32:33

So this is important because

32:36

some of the take-home messages from this paper

32:39

can be specific to this particular

32:41

virus. Okay. Or viruses that behave

32:43

like this one. Okay, there can

32:45

be viruses with different behaviors that are

32:47

going to have a different dynamic than this. All

32:52

right, so first they describe the outbreak

32:54

here. First detection

32:56

in the UK, May 7th 2022, and then

32:59

in early May cases in

33:02

Western, Southern, Central Europe, peaks

33:04

around mid-July. In mid-May

33:06

cases begin to be reported

33:08

in North America,

33:10

and then after that they start to

33:13

rise in South America as

33:15

well. So they collected

33:18

genomic sequences. They have 1004

33:21

publicly available empox virus

33:23

genome sequences. They have case counts. They

33:25

know where each of these cases are,

33:28

and they try and do

33:31

phylogenetics to see

33:33

where the ancestor is. And

33:35

from that they infer the

33:37

most recent common ancestor of

33:39

the epidemic existed between March

33:42

9th and March 27th. So

33:45

remember the outbreak is

33:47

first detected in May, but apparently

33:49

the ancestor virus is circulating

33:51

back in March, and they

33:53

think this was in Western

33:55

Europe. Phylogeographic

33:59

estimates. put it in Western

34:01

Europe because you know where each of the genome

34:03

sequences came from, right? So you

34:05

can do this sort of calculation. So

34:10

define Western Europe. There was

34:12

a pod in Portugal, right? Without

34:15

starting a war. Portugal

34:18

and Spain. And Spain and Italy a little

34:20

bit, but Portugal and Spain it looks like.

34:23

Sorry, getting back

34:26

to the symptomatic versus asymptomatic.

34:29

It's hard for me to imagine somebody who has

34:31

obvious pox, regardless

34:33

of the cause, not knowing

34:36

that this was transmitted by a

34:38

certain behavior. And

34:41

to continue that behavior would be unethical. Do

34:44

you think that's not a problem here? In

34:49

other words. This gets into a

34:52

sensitive area. I'm trying

34:54

to not... Yeah, because... I'm trying

34:56

to stuff that on.

35:00

Yeah. Almost like

35:02

a red badge of courage. No, not

35:05

a red badge of courage, but we

35:07

may be talking about a situation where

35:09

it's easy to

35:11

ignore stuff like that. Yes.

35:14

Okay. And press on with your

35:16

behavior. Well, another question would be then, you

35:19

said it takes two weeks or three

35:21

weeks. This one has a longer incubation period. What

35:24

is the transmission period? Same

35:27

as the incubation period or different? I

35:31

don't know. You mean how long can it

35:33

be transmitted from an individual to another? Before

35:36

it becomes symptomatic. Oh, before...

35:38

Well, that's just it. I'm not sure there

35:41

is much asymptomatic transmission. Okay.

35:45

Though it could be that there are,

35:47

in this particular case, symptoms that are

35:49

subtle enough so

35:51

that you could wind

35:53

up transmitting it symptomatically

35:55

without really understanding

35:58

what's going on. Okay. The

36:01

presentation of this disease I don't think

36:03

is as in all cases

36:05

as dramatic as some other orthopoxifers diseases.

36:07

I think of, I think

36:10

of pox viruses infections

36:12

as you know, really

36:14

frank, discreet, annoying, painful,

36:18

itchy lesions, okay,

36:20

pustules. But

36:22

in this case, some of the symptoms are described as

36:24

rash, okay. So

36:27

it may be more, I'm not intimately

36:29

familiar with this, but I imagine that

36:31

there can be more subtle symptoms where

36:34

you could be symptomatic, but not

36:37

so frankly symptomatic that you really

36:40

paid a whole lot of attention to it.

36:42

Or you could confuse it with like an

36:44

allergy or something, like contact dermatitis, or you

36:46

know, I'm also not very aware of it.

36:49

But if it's a rash as opposed to

36:51

an itchy pustule, then it could be.

36:54

Now we're going to, spoiler alert, what we're going to

36:56

see from this paper is that when

36:59

the consciousness of this, oh, the

37:01

cat's been released. When

37:05

the consciousness of this elevated,

37:08

it took

37:11

care of it, okay. So

37:13

that's a clue really

37:15

that once

37:18

you understand what's

37:20

going on, you can take appropriate

37:24

action, which implies to me that

37:26

what we're saying is true. There

37:29

wasn't a whole lot of asymptomatic

37:31

transmission. But it's more of

37:33

a thing, uh-oh, I've got these symptoms.

37:36

This could be this, I'd better chill

37:39

out here, okay. Right,

37:41

nobody was thinking of

37:43

MPOCs and they, you

37:45

know, you got a little rash or something,

37:47

whatever. I mean, it gets

37:49

itchy sometimes. Then

37:53

MPOCs was the big story and now all of

37:55

a sudden, oh, my skin's a little itchy. I

37:57

probably ought to get that looked at. That's

38:00

exactly right. Yeah. All right.

38:02

So they also look at these data. They

38:04

find examples where single introductions result in

38:07

big local spread. So

38:09

local spread played quite a role

38:11

in these regional outbreaks. And

38:14

in fact, rapid early spread in

38:16

Western Europe led to introductions in

38:18

other global regions. And then

38:20

for North America, they had repeated

38:22

dissemination into North

38:25

America more than once in other

38:27

words, and then subsequent sustained community

38:29

transmission. So community

38:31

transmission is a word for spread when

38:33

you don't know you're spreading something. You

38:35

don't feel badly enough to suspect that

38:37

you're sick and you're out and about

38:39

and that's community transmission.

38:41

Just spreading the community, yeah.

38:44

They then go on to look at

38:48

within region transmission dynamics. So so far

38:50

we've had a global picture, right? And

38:52

they spend a lot of time talking

38:55

about their methods. But

38:57

it's very interesting. It

38:59

turns out they're computationally intensive, right?

39:03

They use a couple of different methods

39:05

and they say for certain approaches,

39:09

it took 25 and a half days

39:11

of computational demand for one thing

39:13

and 34.3 days for another. And

39:16

they said that's too long. And so we had to make

39:19

efforts to reduce that. Otherwise this paper would

39:22

take forever to get out of it. And

39:24

also CPU time is like billed by the

39:26

second. So yeah. Imagine, oh, my job

39:28

is 34 days. Everybody

39:31

else would kill you. All

39:34

right. Anyway, when they finally do this,

39:36

they see evidence of viral

39:38

circulation before detection in each global

39:40

region. And

39:42

they find the largest outbreak clusters

39:46

arise from introductions before

39:48

detection by public

39:50

health surveillance. Okay.

39:52

And then introductions after

39:54

detection are typically a single

39:57

case and they get extinguished. So as Louise, you're

39:59

just saying. you know, when you're not

40:01

aware that something's going around like a

40:04

rash-inducing virus, that's how

40:06

you spread it. And then once people

40:08

are aware, oh, MPOCS is a thing, then it

40:11

goes down. And they say

40:13

that's really evident in their data. Let's

40:19

see. So then they said, is

40:24

there a difference between our

40:26

data and case counts? And

40:29

they find divergence in the early months

40:31

of the outbreak, which

40:33

they say indicates under detection of cases

40:36

in the earliest months. Now they use

40:38

the word under detection instead of asymptomatic,

40:41

which is really good. So

40:43

that's May, June, et cetera.

40:45

But by August, now

40:48

there's concordance between their data and

40:51

the epidemiological data. So there's no

40:53

more under reporting. And again, that's

40:55

when the word is... Right.

40:57

The awareness goes up. So

41:03

then they look at what happens after

41:06

initial introduction of virus into a

41:08

region. So they analyze

41:10

transmission chains resulting from introductions. They

41:12

see a bimodal pattern where

41:15

most introductions give you a single

41:17

imported case. And a

41:19

very small number of introductions give

41:22

you explosive and widespread

41:25

local transmission. Early

41:28

introductions give you larger and more

41:30

persistent transmission change where, again, those

41:33

introductions that happen after public health

41:35

detection give you smaller outbreaks that

41:37

went out quite

41:39

faster. And they

41:41

find that looking at air passenger

41:44

volumes, there's a good... They're

41:47

a good positive predictor of

41:49

migration between each region.

41:51

So travel does make a big

41:53

difference here and drives it. Well, travel

41:55

drives it partly. It

41:57

drives the initial introduction. It's

42:00

right. It's because it comes from...

42:02

Yeah. But then once you... To get from

42:04

Spain to the US, you got to get on a

42:06

plane. Right. So for it to travel,

42:08

it does have to get on the plane. But then air

42:11

travel, if air travel had been shut

42:13

down after the introduction, that would not

42:16

have shut down the epidemic

42:18

because you've got local community spread.

42:20

So it really argues against travel

42:23

restrictions. Yeah. The same thing

42:25

with COVID, right? In the early months, they said,

42:27

oh, let's shut down travel from China. Horses

42:30

out of the barn. Right. Yeah.

42:33

I wonder... That's

42:35

a really interesting finding. And I wonder

42:37

to what extent that applies to other

42:41

pandemic viruses. Because

42:45

if that is routinely or

42:47

globally applicable, almost regardless of

42:49

what pandemic we're talking about,

42:51

that has a huge impact

42:54

on how we deal with it. I think

42:57

one of the ongoing lessons from the

42:59

COVID pandemic is this, trying

43:01

to understand on a global

43:04

scale, the best way to deal with this. In

43:07

particular, trying to balance public health measures

43:10

with social and economic considerations.

43:12

And air travel is one of those

43:15

things. And it could be that with

43:17

a lot of these things, by the

43:19

time you know what's going on and

43:22

want to restrict spread

43:24

by restricting travel, it's

43:26

too late. I

43:29

am going to predict that that will

43:31

be a general rule. And my reasoning

43:33

is that if

43:35

you have a virus that

43:38

needs multiple introductions in order

43:40

to continue

43:43

spreading, then it's not

43:45

going to be able to be a pandemic

43:47

anyway, because it's not going to be spreading

43:49

enough. Yeah. And what makes

43:51

a virus capable of really spreading around

43:53

the world is that it's

43:55

highly contagious. And once you introduce something

43:58

highly contagious into a popular world, it's going to be a very population,

44:00

you're done. There's

44:03

no point shutting down travel because it's already in. And

44:06

all you have to do, man... Nobody

44:08

could model that, I think. All

44:10

you have to do is boot

44:12

up Flightcracker 24 and look at

44:14

the planes that are buzzing around

44:16

the globe at any given instant,

44:19

and you realize that anything

44:21

that breaks out somewhere is going

44:23

to be global almost instantaneously. It's

44:25

frightening. They

44:29

wanted to know the contribution of

44:31

introduction versus local spread in these

44:33

regional outbreaks, and they see that

44:37

there's usually just one introduction and

44:39

then extensive local spread. You don't

44:41

need multiple introductions to have

44:44

a local epidemic. So following

44:46

the initial seeding, local transmission dominates,

44:49

and introductions play a limited role

44:51

in the later stages of an

44:53

epidemic. I guess that's kind of

44:55

intuitive, but you have to find out. All

44:59

right, then they looked at transmission

45:01

dynamics, and they calculate

45:04

RT. RT,

45:07

right, this is the... What's

45:09

the name of this? Reproductive number, right?

45:12

R, which is some measure of how

45:14

many people an infected

45:16

person on average can infect. And

45:18

RT is the time-varying reproduction number

45:20

as opposed to the R naught,

45:22

which is supposedly a constant but

45:24

really is not. So

45:27

they observe high RT when virus

45:29

first gets established in each region, and

45:31

then it decreases to less than one

45:33

and the epidemic stops because you can

45:35

no longer sustain it if you have

45:38

one person infecting less than one other

45:40

person, right? And

45:45

they remove... When they do their calculation, they can

45:47

remove the introductions, and it has no impact on

45:49

the spread. And that's consistent with

45:51

what they just concluded before. And

45:54

what I found interesting, they say, they... So

45:56

this RT is calculated using a mixture of

45:58

case counts and their... genomic

46:01

data. If they only

46:03

use case counts, which is what most

46:06

epidemiologists do, they vastly

46:09

overestimate the transmissibility of

46:11

MPOCs for each region.

46:15

And all I want to do is remind

46:17

you of with each successive SARS-CoV-2

46:19

variant, the R0 or RT

46:21

kept going up and up

46:24

and I think that's possibly

46:27

why they weren't

46:29

using a combination of the data. Okay,

46:35

U.S. vaccine campaigns, what did they

46:38

do? So,

46:41

North America had most cases throughout

46:43

the epidemic, so they did a

46:45

lot of analysis of that. Introductions

46:47

only account for 5 to

46:50

15 percent of local spread, which is

46:52

consistent with what we've already heard concluded

46:54

here. So preventing introductions,

46:56

as we said, by travel

46:58

restrictions would not

47:01

have made any difference. And

47:03

then they look at the RT

47:06

for North America and it begins to

47:08

decline before we

47:10

start vaccination. Eventually,

47:12

vaccination does have a big role

47:14

in stopping this epidemic, but

47:17

the decline begins already before you start vaccinating and they

47:19

look at the numbers of

47:23

people vaccinated and it's very

47:26

low by the time the RT drops below one.

47:28

So the other measures

47:31

that we've talked about, right, public awareness, that is what

47:33

started to bring it down. I

47:36

would comment that this is a

47:39

situation where public awareness can have a

47:42

huge impact on the

47:51

spread of the infection. There are

47:53

other infections where public awareness

47:55

may be important but

47:58

it can't have as big an impact. SARS-CoV-2.

48:01

I was just going to say. Where

48:03

you're talking about at

48:05

least half of the infections that are spreading

48:08

asymptomatically, okay? And

48:11

so, in those cases, vaccination is going

48:13

to have a bigger impact because, you

48:15

know, you can't snuff it out just

48:18

with awareness and behavior. How

48:20

about when you treat someone who's being very rich? When

48:25

someone is being treated for this, though, how

48:28

long after they start treatment are they

48:30

not infectious? I

48:32

can't tell you specifically. I would

48:34

guess a week or two, okay?

48:37

I think

48:40

of this as being transmissible as long as

48:42

you have active lesions. And

48:45

if you start treatment, it's going to take at least a

48:47

week and possibly more like

48:49

two weeks for those to actually heal up.

48:52

Because saliva and other secretions don't

48:54

have, it's only specifically the pustules

48:56

that are full of viral particles?

48:58

Or is that... In

49:02

the case of, in

49:04

this case, I'm not entirely sure. Certainly the pustules

49:06

are going to have live virus in them. I'm

49:10

not really, I don't, there,

49:13

I think there may

49:15

be some systemic spread which

49:17

would mean that ultimately you

49:20

could potentially get some respiratory

49:22

spread. But I don't think it's a big

49:24

deal in this case. In the case of

49:26

variala, that

49:29

was everything. The primary spread was

49:31

through respiratory droplets. It was the

49:34

primary infection was usually a respiratory

49:36

disease. Then it would spread systemically

49:40

and you would generate pustules.

49:42

And now you've got a big

49:44

problem because it can be spread

49:46

from that individual as

49:49

a respiratory infection from the

49:51

pustules and from things that that

49:54

person contacts, like sheets and blankets and clothing

49:56

and that kind of stuff. They get virus

49:58

on them from the pustules. This

50:01

I think is more confined

50:03

to direct contact from the

50:05

lesions. Okay. All

50:10

right, so the last point I want to make on

50:12

this is that they look, they're looking at the data,

50:14

they notice that a few

50:16

introductions give them a lot of sustained

50:19

local transmission, and

50:21

then those make few

50:23

downstream infections. And that's

50:26

consistent with some people being

50:29

more responsible for transmission than others. And

50:32

this can be measured by a parameter

50:34

called the dispersion parameter,

50:36

or K. It quantifies this heterogeneity

50:38

in transmission. In other words, some

50:41

people transmit a lot

50:43

and others transmit less. And

50:46

so when this, so

50:49

the low values of

50:51

K correspond, you know,

50:53

counterintuitive to a

50:55

higher degree of heterogeneity in transmission.

50:57

And when this transmission heterogeneity is

50:59

high, maybe you

51:02

want to target those individuals that could

51:04

have an impact right on

51:07

the outcome. So they find by looking

51:09

at this for the MPOCS

51:11

outbreak that there's a great deal

51:13

of transmission heterogeneity. There are

51:15

people who seem to transmit to a lot

51:17

of others and then a lot, then others

51:20

who don't. So that's also

51:22

based on behavior, you think, you know,

51:24

because with SARS-CoV-2, obviously it's a respiratory

51:26

pathogen. If you're on a, like, subway,

51:29

you're going to be in a classroom

51:31

or anything. But if you're, obviously

51:34

it's not only via, like, sexual

51:36

contacts, but if you're literally rubbing against people,

51:38

some sort of contact from skin to skin.

51:40

And if you're contacting 50 people as opposed

51:42

to 10, then that would make sense that

51:44

it would be so heterogeneous. Like, some people

51:46

might say about coming contact. And if you've

51:48

read my pick from a few weeks ago,

51:50

Strange Bedfellows by Ina Park, you'll have, will

51:52

have read. Yeah, yeah. So

51:55

she, the term, she applies to,

51:58

you know, there are. people in a

52:00

sexual network who will spread to more people

52:03

than others and she refers to them as

52:05

being affectionate and popular. That's

52:08

right. That's a good thing. And going

52:10

back to Angela's other question about transmission, I think

52:12

if there were in

52:15

this case, if there were significant

52:17

systemic spread in an individual and

52:19

respiratory transmission, it would have had

52:22

a much

52:24

different profile in

52:26

terms of both the epidemiology and the sex

52:29

and what it looks like. It's clearly. And

52:32

not only that, but the symptoms are localized

52:35

primarily to areas associated with

52:37

sexual contact, okay? Okay. So

52:40

this is a direct contact sexually transmitted

52:42

disease. The

52:44

lesions usually show up at

52:46

the same point where the inoculation

52:49

occurred? I believe so. Okay.

52:51

Yeah, I think that's correct, yeah. But

52:55

there is some spread, so that we

52:57

used to talk about that and try and

52:59

figure out. Sometimes you had long distance spread

53:01

and it's not clear what's going on there.

53:03

Right. But, you know, even with SARS-CoV-2,

53:06

if you had someone who's

53:08

asymptomatically infected and goes into a bar with

53:10

a lot of people, that can be a

53:13

super spreader of it. Oh, yeah. Of

53:16

course, yeah. So, I mean, in a sexual network, it's

53:18

sex, but as Angela said,

53:20

in a community transmitted... It's breathing.

53:23

You know, you're in a room with a lot of people, you're

53:25

going to infect them. Okay, I'll

53:27

stop breathing. No, you're

53:29

picking on Dixon again. Always tried, always tried.

53:32

All right, so that's the paper. I just

53:34

want to mention one more thing here. They

53:36

talk about the evolutionary

53:38

rate, the mutation rate of

53:41

these viruses. And

53:43

these clade 2B,

53:45

MPOCs, they say has

53:47

a significantly faster evolutionary rate

53:51

during human-to-human transition driven by

53:54

editing by a deaminase called

53:56

Apobec3, which deaminates bases

53:58

and changes them. in the genome.

54:00

So that's a cellular enzyme to do that. And

54:03

they say, consequently, this mutation rate

54:05

is close to that of an

54:08

RNA virus, which is very interesting.

54:10

Because DNA viruses, typically, we

54:12

think and know sometimes that they have low

54:15

mutation rates, but this one is pretty high.

54:17

So I thought that was interesting. Yeah,

54:19

with comparing it to variola, which was

54:21

one to two substitutions per genome per

54:23

year versus this. Sixteen. And

54:26

then M-POCs is 16.6.

54:28

That's crazy, the difference.

54:33

Throughout this, I found myself

54:35

thinking about our 12 episode

54:38

with Mike Marchelinzky, who

54:41

really is, at least in

54:43

my sphere of influence, the monkey pox

54:45

expert. And his bottom line at the

54:47

end of that episode, when we said,

54:49

okay, so what's going to happen? What

54:51

do we do about this? And he

54:53

just said, behavior. Okay. And

54:56

that turns out to be true. Awareness

54:59

of what's going on and appropriate behavioral

55:01

adjustments and it took care of it.

55:05

And I would also want to point

55:07

out that this may have had a

55:09

lot to do with the specific community

55:11

this affected. So

55:14

men who have sex with men tend

55:17

to be highly aware of viral spread

55:19

and viral dynamics. And because of the

55:21

whole HIV thing, they're

55:24

more likely to be able to grasp this and

55:26

say, oh, all right, got

55:29

to do precautions. So

55:34

the lessons here, public

55:37

health awareness is really important. Vaccination

55:42

didn't start to decline

55:44

here, it was public health awareness. And

55:49

Behavioral modification is really important, education campaigns.

55:51

But They also say, yeah, because we

55:53

didn't detect these early infections, we need

55:56

better detection. we need better surveillance and

55:58

detection. In and

56:00

that that does apply to

56:03

anything everyday. Ah, the

56:05

earlier we can get on top of

56:07

a new. We've been saying this for

56:09

a long time that the earlier within

56:11

get done on time for the better

56:13

off we are. The deal. The delay

56:16

in the ability to test in the

56:18

com and nineteen pandemic was a massive

56:20

problem and you know if you'd had.

56:23

Your tests for as much as I am

56:25

On the other side of that, you you

56:27

can test every patient for everything cause that's

56:29

just a huge waste of resources. But. You.

56:32

Need to have something that's quick and. Off

56:35

and I'm sure that. and I'm sure that in

56:37

the beginning of this. People

56:39

are saw this and didn't understand what they were

56:42

looking at. The height and there's

56:44

going to be other diseases that come

56:46

along where people see us and they

56:48

have no way to think about know.

56:50

Entirely novel were one of what is

56:52

this. And

56:56

if you're into the to read the

56:58

limitations of this study. They. Start

57:01

by saying or or study has

57:03

noteworthy limitations and then they make

57:05

note of them to make nudism

57:07

Yes, and they say mostly, they

57:09

don't matter. Or

57:13

eight onwards. This.

57:16

Is a Nature Communications article

57:18

a humanized mouse model for

57:20

add know associated viral gene

57:22

therapy. Or

57:25

let's see the first daughter is

57:27

there cove first who at his

57:29

I have no idea though yes

57:31

numbers that these authors country we

57:33

did equally. Mercedes, Barzee and Tongue

57:36

ten the first to authors and

57:38

than the last two other is

57:40

Carl Timid too busy this comes

57:42

from Duke University Baylor College of

57:44

Medicine. Texas

57:47

Children's Hospital due to do

57:49

a lot of. Do.

57:52

In Texas is so this is

57:54

about using Add new associated viruses

57:57

as activists, rich foods and Add

57:59

knows. The shield viruses. Kathy's not

58:01

here. Are

58:03

literally gonna say we have to explain With

58:05

this is I added a little video actually

58:07

a three minute youtube video. Move on to

58:10

our see that maybe we can pose for

58:12

the listener and for them size and known

58:14

as good an endless mark was not. Forget

58:16

to come back to the have recovered caviar

58:18

for live video that I did too much

58:20

is because of his paper. Or

58:22

votes so and knows her she

58:25

universe is call and know associated

58:27

bars because it was first detected

58:29

as a virus that showed up

58:31

and cultures of and of ours

58:34

coats. I'm Sandy and Factor: Okay

58:36

so it is a small single

58:38

stranded Dna virus in a native

58:40

caps and and by small I

58:43

mean teeny weeny were talking about.

58:45

I seek it may be as

58:47

much as five kb but not

58:49

the I think it's about five

58:51

kb. Has says to to

58:54

genes rap and cap rap is

58:56

required for ah genome reputation to

58:58

to get it rolling Okay and

59:00

actually actually for Carter. Couple different

59:02

stages in a reputation but mostly

59:05

cellular machinery is used. App is

59:07

the captain Thirty Some of these

59:09

things can run with a by

59:11

themselves. Some of them are so

59:13

lame that they need a helper

59:15

virus like for instance and know

59:18

virus updates to provide functions that

59:20

are that that they are launching.

59:23

A you can you can argue they're clever not

59:25

to has to have a lot of good censoring.

59:27

They're. Dead by

59:29

when. A little help from my friends, right? So

59:33

ah over the years or

59:35

this thing has been engineered

59:37

into a one of the

59:40

prime Ah gene therapy factors

59:42

were what is done is

59:44

to basically got it of

59:47

are all of the are

59:49

functional protein coding genes in

59:51

the virus leaving. it just

59:53

with some depths of dna

59:56

on the hands that are

59:58

important for packaging and replication

1:00:02

of the genome once it

1:00:04

gets into cells and it

1:00:07

becomes, and that way the

1:00:09

engineered virus

1:00:14

becomes just really a delivery

1:00:16

vehicle for these genes into

1:00:18

cells. And

1:00:21

you use various techniques to

1:00:23

get the engineered genome to be replicated

1:00:25

and packaged. You make a stock of

1:00:27

this and then you can introduce it

1:00:29

into a subject and it infects appropriate

1:00:32

cells and the

1:00:35

DNA is maintained,

1:00:39

the dogma is that the DNA

1:00:41

is maintained as an epizome, sometimes

1:00:44

concatomeric, that is an extra chromosomal

1:00:47

molecule and can express

1:00:49

genes over a prolonged period of time.

1:00:54

This is, there are, it's

1:00:56

a parvovirus is the larger realm

1:00:59

of these viruses and

1:01:01

there are human, adeno-associated

1:01:04

type parvoviruses and there

1:01:06

are AAV type viruses

1:01:08

of other creatures as

1:01:10

well. There are many

1:01:12

serotypes in humans, some more

1:01:15

common, some less common. This

1:01:17

becomes important in trying to engineer the

1:01:20

virus because you want to try

1:01:22

and avoid any innate

1:01:25

or I don't know, pre-existing immunity

1:01:28

to whatever vector you're using. So you

1:01:31

try and use a rare serotype. You

1:01:33

can also use the different serotypes

1:01:35

to help you target specific tissues and

1:01:37

etc. The one other,

1:01:39

I may as well introduce the caveat now,

1:01:42

there's one paper that's referenced in here that

1:01:44

I was unaware of that's

1:01:47

where they use a

1:01:49

primate model infected

1:01:52

with or treated with

1:01:54

adeno-associated virus and they

1:01:57

noticed that gene expression

1:01:59

is robust in the

1:02:01

first few months after introduction

1:02:04

and then falls off to

1:02:06

some minimum and their explanation

1:02:09

from that based on their data is

1:02:11

that you get a lot of

1:02:14

expression from the epizomal form of

1:02:16

this thing early on and

1:02:18

then there's some integration in a

1:02:20

small number of cells and you

1:02:22

get a trickle of expression beyond

1:02:24

that. Now that's in a primate

1:02:26

model so we don't know if

1:02:29

that happens in humans but I was

1:02:31

entertained to see your video

1:02:33

Angela because that goes against

1:02:35

the dogma that I've been

1:02:37

taught over

1:02:40

the last several years and if integration

1:02:44

actually happens at any significant

1:02:47

level in humans that's

1:02:49

going to be an issue

1:02:52

for gene therapy. We'll see what happens.

1:02:55

Yeah and so people have been working

1:02:58

on this as a gene therapy vector for

1:03:00

as Rich said a long time and

1:03:03

it has actually been successful in

1:03:06

at least a couple of cases it's

1:03:08

had its ups and downs but there

1:03:11

are now two FDA approved therapies for

1:03:13

two different types of hemophilia, hemogenics

1:03:17

and rocktavian. That

1:03:20

is the middle west. Sorry

1:03:22

I just love that but so

1:03:24

this is actually something that is in

1:03:27

use now clinically and could

1:03:30

potentially be used to treat many

1:03:32

other genetic conditions. And

1:03:34

there haven't been problems that would associate

1:03:36

with integration at this point. The other

1:03:38

one thing that's relevant to this paper

1:03:40

that's worthwhile is a lot of these

1:03:43

therapies can be

1:03:45

implemented by infecting hepatocytes cells

1:03:47

in the liver. And

1:03:50

that is a target of many of

1:03:52

the serotypes. So that's relevant to this

1:03:54

paper. There's

1:03:59

also an AAV. approved, FDA approved

1:04:02

vector for blindness for a certain form of

1:04:04

blindness, Leber's congenital

1:04:08

blindness and it's

1:04:10

called Lux-Turna. I

1:04:12

think it's half a million dollars per

1:04:15

eye. Oh, yeah.

1:04:18

And now you can see. Yeah, you can see. That's

1:04:20

a big deal. How much is it worth to see? How much

1:04:22

does it work? That is, yeah. Yeah.

1:04:25

So the issue in this paper is to try

1:04:27

and make a better animal model, right?

1:04:31

Most people use mice for preclinical studies, right? Before you

1:04:33

put it in humans, you want to put it in

1:04:35

some kind of animal and mice are

1:04:37

typically used. They mentioned, you know,

1:04:39

maybe non-human primates would be better, but this

1:04:42

is expensive and ethically we don't

1:04:45

want to do that. So the problem with

1:04:47

mice is that these

1:04:50

AAVs infect the liver really well.

1:04:53

Mice exaggerate. Mice exaggerate.

1:04:56

They absolutely exaggerate. Now

1:04:59

one of the things that they have done to try and

1:05:01

get around this is they put human

1:05:03

liver, they make human liver chimeric

1:05:06

mice, right? So they add

1:05:08

pieces of human liver to

1:05:10

the mice and they grow and

1:05:12

you get a chimeric animal, like

1:05:14

about 60 percent human, 40 percent

1:05:16

mouse liver and you

1:05:19

can then say, does my vector

1:05:21

infect the human liver cells? But

1:05:25

the viruses still prefer to infect

1:05:29

or preferentially infect the mouse

1:05:31

liver cells. They

1:05:33

say this is like a sink for

1:05:35

your virus. Great use of the word. This

1:05:38

is not good and it

1:05:40

confounds the finding. So what they wanted to

1:05:42

do here is make, get around

1:05:44

that problem. And what they

1:05:47

did was, so I think we

1:05:49

actually did this paper a while

1:05:51

ago on to identification of a

1:05:53

universal adeno-associated virus receptor. All the

1:05:55

serotypes bind this receptor for cell

1:05:57

entry, AAVR. Knock

1:06:00

out the gene in mice. Apparently it's

1:06:02

not needed for anything. We can tell.

1:06:05

And. Madame de Over the Opera. They

1:06:08

don't gardner from Mozart anymore. And.

1:06:11

So they. Combine. This

1:06:14

said knock em us with the humans

1:06:16

chi mirror and so now the none.

1:06:18

No mast cell has a navy receptor

1:06:20

and if you stick human cells. In

1:06:23

the mouse to virus into reproduce in the

1:06:25

human cells, right? So that's the basis for

1:06:27

this paper. And

1:06:30

so the mice. The user. Not your

1:06:32

normal lab mice. They're actually knockouts for

1:06:34

a couple of genes. That.

1:06:36

Are quite. Significant. And

1:06:38

giving you immune responses is a

1:06:40

dizzy i'll tubes com and aids

1:06:42

designer jeans as know de Silva,

1:06:44

measles and these nice race thus

1:06:46

far as a to something to

1:06:48

do is have had a science

1:06:50

was in it was his kidney

1:06:52

and had padded I tend to

1:06:54

look at the gene the as

1:06:56

aids knock out and it was

1:06:58

Nasa said that it was associated

1:07:00

with i am I couldn't figured

1:07:02

I would as those but user

1:07:04

I assume that those are those

1:07:06

not our genes. Or are

1:07:09

there. Are. Not there

1:07:11

are so that. The.

1:07:13

Mouse liver will except for human grass.

1:07:15

Yes, exactly exactly the lymphocytes for sir.

1:07:18

Yeah with her if they were not

1:07:20

lives of the next, the human Grampian

1:07:22

node reject a human cells. Yeah, didn't

1:07:25

have. A Me

1:07:27

I think these these my sir I'm

1:07:29

very is A uses it to be

1:07:31

cells right and nk cells probably to

1:07:34

him and ah trying to believe so

1:07:36

yes for Serbian, T, C and to

1:07:38

So that's where the see take the

1:07:41

human liver so transfer So they take

1:07:43

this knockouts they actually make the knockout

1:07:45

a receptor my Susan crisper and then

1:07:48

and. And put

1:07:50

that on a background of this. I'll

1:07:52

to rags saw etc so

1:07:54

there could tear for my

1:07:56

tiara say here far. As.

1:07:59

Opposed to. Pierce Terse. Maybe should be

1:08:01

thirsty I arrest her sister Teresa.

1:08:05

With or without to receptor. And.

1:08:07

He's my seem to be okay. They.

1:08:09

Have normal liver functions know pathology

1:08:11

they can their okay for mice

1:08:13

was no immune system may rise

1:08:16

in Sydney. Clarify rang to has

1:08:18

actually increased natural killer cells I

1:08:20

just plug says only be attorney

1:08:22

handling to use some answer to

1:08:24

a mechanism as increase and case

1:08:26

of the aisle two receptor gamma

1:08:28

chain is of is another that's

1:08:30

like skid. right? Ah,

1:08:34

Everly so I'll do is

1:08:36

important for t cells specifically

1:08:38

else who. Ah receptor

1:08:40

from the cells actually though

1:08:42

now. A

1:08:45

getting the i'm getting boxing things When I

1:08:47

do I have to our Gamma knockout. So.

1:08:50

Not show. Up.

1:08:53

Mostly T cells as far as I

1:08:55

as long as far as I know.

1:08:58

Ah, I'm. Good

1:09:04

as the dismissal barrier. Not

1:09:06

mature, absence of maturity cells,

1:09:08

and it's it's. basically the

1:09:11

defect in x linked, severe

1:09:13

com and immunodeficiency. Good Seattle.

1:09:16

So you have maturity says degrees nk

1:09:18

cells but you get an increase their

1:09:20

normal number of Be cells but the

1:09:22

Be says at around by do it

1:09:24

poses a serious and if they're also

1:09:26

with i'll to are not out than

1:09:28

they're also decreased nk cells which he

1:09:30

wouldn't have with the rags is I

1:09:32

guess they're compensating for all of us

1:09:34

are immune compartments. Or

1:09:37

really made these mice and now they

1:09:39

bring them to the lab and test

1:09:41

them. They and sex them with a

1:09:43

V Eight. Which.

1:09:46

Is a commonly used sarah type. They

1:09:49

have them. As a reporter

1:09:51

jean and so they can easily track it.

1:09:55

The have the tomato reporters. rate

1:09:58

or juice V8

1:10:02

is a tomato juice. It is. It

1:10:05

is. So

1:10:07

they inject intravenously into both turf

1:10:09

and turf A mice and

1:10:13

minimal transduction in most organs

1:10:16

of the receptor knockout, which is what exactly

1:10:19

you would expect because the receptor is gone.

1:10:21

And transduction, they're looking at, you

1:10:23

know, the red fluorescence signal in

1:10:25

these mice. And

1:10:28

heart and liver seem to

1:10:30

still take up and virus

1:10:32

and produce some fluorescence.

1:10:38

So maybe something else is allowing entry into those

1:10:40

tissues. I don't know. Could

1:10:43

be. And then your turf A

1:10:45

mouse did not, it

1:10:48

had only production of the reporter

1:10:51

in human and not mouse liver.

1:10:54

Very nice sections where you can see the mouse tissues

1:10:56

are dark and the human cells are

1:10:59

red. So

1:11:01

this virus, so you

1:11:03

put human cells in and of course the human

1:11:05

cells have the AAV receptor, right?

1:11:08

It's the mouse that lacks the receptor and

1:11:10

now the virus can infect the human cells.

1:11:12

So you can study whatever you've got in

1:11:15

your AAV, you can now put

1:11:17

it into these animals and study what

1:11:19

it does. Presumably not a tomato gene

1:11:21

for clinical use. You don't want to

1:11:23

put a tomato gene. Well, yeah, exactly

1:11:25

right. So to me,

1:11:27

the really critical image

1:11:30

for my poor brain

1:11:33

in understanding the data

1:11:35

was in figure 1G, the

1:11:38

last two panels where they're doing

1:11:40

immunofluorescence on the mice

1:11:42

and it took me forever to sort

1:11:45

of figure this out. But

1:11:47

the bottom line is if

1:11:49

you have any cell that's infected, so

1:11:53

the human cells are green And

1:11:55

the AAV infected cells are

1:11:58

red. The

1:12:00

human cell infected with a V.

1:12:02

It's gonna be yellow. Night.

1:12:05

I like Iraq the and

1:12:07

so if there are any.

1:12:10

Ah mouse cells. That.

1:12:12

Are infected with Hiv? They're going to

1:12:15

be read: Her. Guy. and

1:12:17

if there's any uninfected human cells,

1:12:19

there's gonna be green. And what

1:12:21

you see is that in the.

1:12:24

Ah, Ah

1:12:26

ah. Parent. If

1:12:28

you like mouse that doesn't have

1:12:30

the receptor knocked out, there's a

1:12:32

whole slog of red cells and

1:12:34

very few yellow cells. Soon as

1:12:37

a whole bunch of mouse cells

1:12:39

getting infected by a V and

1:12:41

very few human cells in the

1:12:43

one where the as a receptor

1:12:45

knocked out all the cells that

1:12:48

are not green or yellow. Okay

1:12:50

so there's none that you can

1:12:52

see that are mouse cells inside

1:12:54

to a navy. So and it's

1:12:57

brilliant just. Brilliant and absolutely clear once

1:12:59

you can wrap your head around it

1:13:01

has since I'm so happy. When she said

1:13:03

this is it since me like ten. Minutes as

1:13:05

well. I'm looking at an island so

1:13:07

confused, irons and stupid, I don't know

1:13:10

what this is. Well, well, we I

1:13:12

get to the next year where they

1:13:14

don't even tell you the result. Yeah,

1:13:16

actually I wound up I was reading

1:13:18

a paper and trying organ of figures.

1:13:21

Okay, now look the figures and I

1:13:23

couldn't understand it and I was running

1:13:25

out of. This

1:13:28

is due to I'll just finish I'll just

1:13:30

finish reading a paper so the understand what

1:13:32

they say or and then of I have

1:13:34

time. I'll go back and see if I

1:13:36

can figure out what is whether the data

1:13:39

supports the conclusions. And that's when I figured

1:13:41

out that little to panel for use in

1:13:43

order to not really nice. Very nice. I

1:13:48

so that's the big signing of this paper that

1:13:50

you can. Limit. The

1:13:52

transaction to the introduced human cells. To

1:13:56

do some other experiments. Of.

1:13:58

us who quickly for example They say,

1:14:01

okay, where's the viral DNA and RNA?

1:14:03

So they can do in situ hybridization

1:14:05

to detect that in the

1:14:07

liver. And they can see lots

1:14:09

of the AV DNA and RNA in

1:14:12

human hepatocytes, right? So you can tell

1:14:14

which ones are human. But

1:14:16

they also found DNA

1:14:19

in murine hepatocytes of

1:14:21

the knockout mice, but

1:14:24

not RNA. So the DNA is somehow

1:14:26

getting into those cells. But

1:14:28

since there's no RNA, I don't think that's a problem

1:14:31

for their model. But I guess there's some kind of

1:14:33

uptake of DNA, right? Or

1:14:35

particles into the non-receptor-bearing

1:14:38

cells. All

1:14:41

right, and now then they say, what

1:14:44

about other human tissues besides liver?

1:14:48

Could we use this model to study that? So

1:14:52

this is very strange. They

1:14:54

do this and then they say it's really not good. They

1:14:58

put a teratoma into

1:15:01

the mice, right? A teratoma is a tumor

1:15:03

that makes tissues from

1:15:05

all three germ layers. Probably Angela knows all

1:15:08

about these. This is actually, so the first

1:15:10

time I saw one in vet school, it

1:15:12

was terrifying. They normally have, well, they're very

1:15:14

heterogeneous, but they'll have hair and teeth. They're

1:15:18

gonna have teeth, yeah. And it's terrifying.

1:15:20

I cut into them at once and

1:15:22

there's pieces of teeth, but they're not

1:15:24

fully formed teeth. They're just like calcified

1:15:27

chunks. And some of the hairs were

1:15:29

like five centimeters long, like chunks of

1:15:31

hair. So yes, teratomas are- So these

1:15:33

happen in animals, non-humans? Also in

1:15:35

both. They can happen in humans. They can happen in animals, yeah.

1:15:37

They do. But you were seeing them in animals, right? I've

1:15:39

seen them in animals, yes. Mine was in a necropsy. But

1:15:42

they're the things of nightmares. That's all they can say. Yeah,

1:15:46

so the important thing for this paper is that they have

1:15:48

all three germ layers. Germ line, yeah.

1:15:51

So you can introduce the teratoma

1:15:53

and it gives you a representation

1:15:55

of how you could potentially get

1:15:57

this to other tissues. Yeah. circumstances

1:16:00

where you may want to target

1:16:02

something other than liver. So

1:16:04

you need a model for that. Yeah.

1:16:07

So they make, they introduce these teratomas

1:16:09

into the mice and they let them

1:16:11

grow for three to four months and

1:16:14

then they put the AAV in them. So these

1:16:16

are the knockout receptor knockout

1:16:18

mice and then they

1:16:20

do sections of the liver and

1:16:23

it's figure four and they

1:16:25

never tell you what the results are.

1:16:27

They stain them with antibodies to different

1:16:29

markers to identify different human tissues, right?

1:16:31

But they never say what's

1:16:34

happening and you have to figure it out yourself, which

1:16:36

is fine, but I think it's weird that they don't

1:16:38

tell you the results, right? Well,

1:16:40

this is a short paper and what

1:16:44

is this, nature? Nature communications. Well, like these

1:16:46

things that you think that they should have

1:16:48

given them enough space to do that. Yeah.

1:16:51

I would think so. They also put

1:16:54

human liver cancer tissue into humanized livers

1:16:56

and they show that the virus will

1:16:58

reproduce in that as well. So you

1:17:01

can introduce a variety of

1:17:03

things into these mice, different cell types and

1:17:05

get infection. But

1:17:07

then they turn around and say, yeah, but

1:17:10

it's not a great model because the teratomas

1:17:12

are not consistent. Yes. Yeah.

1:17:15

They're heterogeneous, right? Yeah. Sometimes

1:17:18

you get teeth, sometimes you don't. Exactly.

1:17:20

That's so weird. Yes. And

1:17:23

it's really good for human liver targeting

1:17:25

AAVs and other tissues remains to be

1:17:27

seen, what you're going to do. And

1:17:31

that's really it for

1:17:33

the story. But I think that, you know, they're very excited.

1:17:35

They say this is a overcoming

1:17:37

significant limitations and

1:17:43

we're looking forward to using it

1:17:45

to study AAV and vectors in

1:17:47

these tissues. So. You

1:17:49

know, it's amazing. These things take

1:17:52

a long time. They take decades

1:17:54

and hundreds, if not

1:17:56

thousands of scientists to

1:17:58

really. And you work

1:18:00

out a few kinks and other kinks pop

1:18:02

up, okay? So this is

1:18:05

really something. Yeah,

1:18:07

and this is something that

1:18:10

would help what the drug

1:18:12

industry calls fail early. So

1:18:14

you, a lot, so many of these

1:18:16

gene therapies over the years, it's been, oh, it

1:18:18

looks great, it looks great, and then it gets

1:18:21

into humans, like it doesn't work. And

1:18:24

this would help really, hopefully, we know

1:18:26

that down and say, oh, you know, it

1:18:28

doesn't work so well in mice. So

1:18:31

Richard, another kink does arise. We

1:18:34

should, throughout the term tomato, introduce the term

1:18:36

Lola. Rotten

1:18:39

tomatoes. Lola. Anyway,

1:18:43

so you could use this for other tissues, right?

1:18:45

You would introduce other human tissues in as well.

1:18:48

So in theory, you could do more than liver. Okay.

1:18:50

And Angela, the video you found really

1:18:52

is good. We could... Yeah,

1:18:55

I thought it was like a little three-minute video that explained it

1:18:57

fairly well. Accessible,

1:18:59

fairly accessible. And like the animation

1:19:01

was very nice. Yeah. So

1:19:04

yeah, we can add that to the show notes. Let's

1:19:07

do a couple of email. And

1:19:10

I put this first so that Angela could read it

1:19:12

because it's to her. Go ahead, Angela.

1:19:14

Okay. Hunter writes,

1:19:17

Dr. Gavincarelli, I am so pleased that a veterinarian

1:19:19

has joined the TWiV team. I

1:19:21

have enjoyed your contributions to the podcast despite

1:19:23

your having to juggle your PhD work at

1:19:25

the same time. I hope

1:19:27

you can access or access this link from the

1:19:29

most recent JAVMA. So

1:19:32

this is the veterinary medical journal. It

1:19:35

is extremely scary and disheartening as now

1:19:37

we are endangering the health and welfare

1:19:39

of our pets in addition to potentially increasing

1:19:41

the risk of rabies in people. And

1:19:44

then there's a link here, which unfortunately

1:19:47

is not open access, but he

1:19:50

continues with, and this is the part that scared

1:19:52

me the most. Results

1:19:55

show that nearly 40% of the responding

1:19:57

dog owners believe canine vaccines are available

1:20:00

are unsafe while more

1:20:03

than 20% consider them to be ineffective and 30%

1:20:05

think that they are

1:20:07

medically unnecessary. Notably, about 37% of

1:20:10

the dog owners surveyed believed that

1:20:13

canine vaccination could cause autism in

1:20:15

their pets despite the lack of

1:20:17

scientific evidence supporting this claim. As

1:20:20

a retired food animal veterinarian, this survey

1:20:22

borders on surreal. Oh,

1:20:24

how far we, in brackets, scientists, have fallen

1:20:26

in the eyes of the general public. Keep

1:20:29

up the great work, but I will continue

1:20:31

to enjoy my pork. Respectfully, Hunter

1:20:34

Lang, Dr. of Vaccinary Medicine. Well,

1:20:38

if you enjoy the pork, I know it's delicious.

1:20:40

I just choose not to eat it. And as

1:20:42

for this publication, so I couldn't

1:20:44

actually access it because I don't

1:20:47

have access to this journal through McGill,

1:20:49

through my university. But the fact that

1:20:51

there are, it's like not surprising that

1:20:54

that many people are also now cautious

1:20:56

of vaccinating their pets because just misinformation

1:20:58

in general among humans not wanting to

1:21:00

vaccinate themselves, they're just extending that to

1:21:03

their pets. It's very unfortunate because

1:21:05

a lot of the things that we vaccinate for

1:21:07

in pets like rabies are

1:21:10

you're just putting your animal's life in

1:21:12

danger. So if you have raccoons and

1:21:14

squirrels exactly in this temper and parvovirus,

1:21:16

there's so many other things that are

1:21:18

in the environment. They are literally surrounded,

1:21:20

your pet is surrounded by them. And

1:21:23

by not vaccinating your pet, you could

1:21:25

potentially be shortening your pet's lifespan by

1:21:27

a decade. So and with rabies, you're

1:21:30

endangering your own life yourself. Exactly. And

1:21:32

that of everybody in your neighborhood. Exactly.

1:21:34

Your own family, your pets, because then

1:21:36

your pet becomes a vector and it's

1:21:40

it's very, yes, disheartening

1:21:42

to say the least, Hunter. Yeah,

1:21:46

please, everyone vaccinate your pets,

1:21:48

vaccinate yourself. Everyone get

1:21:50

vaccinated. All

1:21:54

right, Rich, why don't you take the next one, please?

1:21:56

Sure. Eric writes and I think

1:21:58

I can reveal that this is a. The You for

1:22:00

your friend Eric L. Word. I'm.

1:22:03

See. As you'll see,

1:22:05

the father of. Dark. Matter.

1:22:09

Dear Visit. And. Twelve

1:22:11

Ten Ninety One Rich mentioned

1:22:13

my use of the term

1:22:15

dark matter's to describe still

1:22:17

large fraction of sequences of

1:22:19

unknown origin found in complex

1:22:21

biological samples such as the

1:22:23

gut microbiome or wastewater. Dark

1:22:25

matter is a term I

1:22:28

shamelessly borrowed from the field

1:22:30

of astronomy which describes the

1:22:32

missing mass needed to explain

1:22:34

the structure of the universe.

1:22:37

Typical manage you know make

1:22:39

analyses identify biological. Species true

1:22:42

sequences similarities to already sequenced

1:22:44

reference genome in the pre

1:22:46

prints from the Stanford or

1:22:49

labs we discussed. This is

1:22:51

relevant to that's novel. Computational

1:22:53

tools were developed to identify

1:22:56

short circular are in a

1:22:58

genome capable of folding into

1:23:00

rod like structures. Any coating

1:23:03

previous ah, previously unknown proteins,

1:23:05

a small fraction of other

1:23:07

dark of the dark matter

1:23:10

was therefore. Illuminated without reference

1:23:12

to prior genome and revealed

1:23:14

that were that rather that

1:23:17

written the rather com and

1:23:19

existence of a new type

1:23:22

of vi roid ah like

1:23:24

obelisk elements Of course some

1:23:27

bio informatics base predictions will

1:23:29

have to be tested using

1:23:32

when lab experiments likely using

1:23:34

synthetic genome. So many more

1:23:37

surprises are doubtlessly in store

1:23:39

for young computational. biologists interested

1:23:42

in novel ways of

1:23:44

mining the already immense

1:23:46

and exponentially growing public

1:23:48

sequence databases or as

1:23:50

vincent's included see it

1:23:52

as each case parenthesis

1:23:54

or rather see it

1:23:56

as eat you and

1:23:58

for it and you

1:24:01

shall find, Eric. That's

1:24:03

delightful, Eric. I

1:24:05

really appreciate that DNA, you know, is really

1:24:08

a problem, right, yeah. We

1:24:10

may have to use seek and you shall find for

1:24:12

a title some more. Oh. That

1:24:14

is cute, that's very cute. Very good,

1:24:17

Eric. Yeah, it's, and I like

1:24:20

the plug for bioinformatics for people looking

1:24:22

for something to do with their lives.

1:24:25

Because we're generating, you know,

1:24:28

many, many, many, many, many more times data

1:24:30

that we know what to do with, okay.

1:24:33

And even when we can

1:24:35

see in the dark matter

1:24:37

things that we at least

1:24:39

vaguely recognize, there

1:24:43

are layers of meaning to it that

1:24:45

we don't understand, okay. And bioinformatics is

1:24:47

gonna address all that. Well,

1:24:50

hopefully, maybe. That's

1:24:53

up to the next generation. Bioinformatics

1:24:55

has a chance of addressing that.

1:24:57

Yeah, that's right. Well,

1:24:59

you can tell it that way anyway. Well,

1:25:01

I pitch it to my daughter all the

1:25:03

time. She likes math and bioinformatics. Dixon,

1:25:07

can you take the next one, please? Yes,

1:25:09

sir, okay. Bob writes, read

1:25:12

the dengue snippet article. I

1:25:14

could not read the Nature Medicine article as I do

1:25:17

not have a prescription or a subscription. I

1:25:20

did read the abstract. I wonder if

1:25:23

there was some selection bias in this

1:25:25

study specifically. Folks who are not very

1:25:27

sick did not go to a hospital. Well,

1:25:30

I never saw dengue in my middle American

1:25:32

practice. I think the symptomatic treatment

1:25:34

of mild dengue would be

1:25:36

outpatient acetaminophen or

1:25:38

NSAID, rest and

1:25:40

fluids, just wondering if they only pick

1:25:42

the more ill patients inadvertently. I

1:25:47

have no opinion about this. Well, so this

1:25:49

is the paper where, I think it was from

1:25:51

India, where they found that

1:25:54

the first dengue infections Could

1:25:57

be severe, right? Cause We're always thinking. The

1:26:00

second was it a severe shop and

1:26:02

so. It doesn't matter is actually

1:26:04

if there was selection bias because you're getting

1:26:06

severe cases in a first and section and

1:26:09

that's the point, right? right? Even

1:26:12

if you missed some, Patience is.

1:26:15

The. Are you getting severe dang in? These people. Had

1:26:17

their first and second so. That's. The conclusion

1:26:19

that I think it's okay bob. Sourcing

1:26:22

are so. Or.

1:26:24

I would we have we have. Allen

1:26:26

can dig the next one. Kirk Rights

1:26:28

Hi listening. Now for almost three years

1:26:30

I've donated, but other than that small

1:26:32

gratitude, there are not words in English

1:26:35

to acknowledge what all of you are

1:26:37

providing. So I'll try a little Russian.

1:26:39

Mostly. As possible. Now

1:26:42

an episode Ten Eighty Four, you mentioned

1:26:44

that twenty percent of cancers are caused

1:26:47

by a virus. Is this: Twenty percent

1:26:49

of cases are twenty percent of known

1:26:51

cancers. That can make a colossal difference

1:26:53

and impact For the research said, it's

1:26:55

clear value. For. Flavors

1:26:57

Kurt. I think

1:26:59

that's twenty percent of known campus

1:27:02

as the Way No way I

1:27:04

understand it and I've you know,

1:27:06

I've ah, In

1:27:09

my previous life or Sleep Zero

1:27:11

quoted touted this number along with

1:27:14

a slide that enumerated lots of

1:27:16

different cancers, different types of cancers

1:27:18

and it's unified those which were

1:27:21

caused by versus. Someone.

1:27:24

For example that comes to mind is

1:27:26

easy and I think Gas Shell and

1:27:28

another Sonoma. That

1:27:31

seen by virus and doesn't the number one

1:27:33

that I always think about was a funny

1:27:35

other people think as. He gets

1:27:37

does everyone have one weekend I like

1:27:39

well even in Cervical cancer for the

1:27:41

owner was his own isn't everything accesses

1:27:43

his theory be we do As far

1:27:45

as we have he soon papilloma virus

1:27:47

is right or am I going to

1:27:49

be. My eyes get easier have a

1:27:51

c heavy I eat. Hiv

1:27:54

of course, In

1:27:57

other, there are others that one chances are so.

1:28:00

With Hiv that actually don't know.

1:28:02

Me: The with or not it's not

1:28:04

an Uncle Jean Drapeau in thing right?

1:28:07

but it's from the increased but the

1:28:09

constant proliferation of of various cell types

1:28:11

some and to in the light of

1:28:14

immune. Inflammation right? The Ireland

1:28:16

as he was just a human or.

1:28:18

He had this is human can't

1:28:21

Oh yeah, interoffice and troll if

1:28:23

we're so sorry I'm not imitations

1:28:25

Angelo to your the people with

1:28:27

Hiv than are more susceptible to.

1:28:30

Different. Types of cancers? What you can. I

1:28:32

get this one associated a Saturday so. I

1:28:35

mean an Emmy they will get he

1:28:37

be v cancers to get into busy

1:28:39

cancers and others but also non viral

1:28:41

cancers as well rather than normalcy. Some

1:28:43

farmers are going into a group. I

1:28:46

believe So. society. or yeah

1:28:48

yeah, campuses, sarcoma, herpes, virus

1:28:50

rentals, and animals? that is.

1:28:54

Interesting. All

1:28:56

right, let's do one where you're from, Daniel. Daniel.

1:29:00

As you to have an episode Ten

1:29:02

Ninety One, Skeeter Poo and oboists to

1:29:04

read said that you can't do phylogeny

1:29:06

is just with structures and Allen mentioned

1:29:08

that you could use more foods Yannick

1:29:10

techniques to solve that problem. Pal is

1:29:12

very much correct their in fact scientists

1:29:14

have been using such techniques for a

1:29:16

few years now as as as such

1:29:18

I thought this would be the perfect

1:29:20

moment to talk about the blossoming sealed

1:29:22

of structural Phylogeny. I'm not

1:29:25

a structural file a geneticist, but I'm

1:29:27

doing a phd in structural biology. And.

1:29:30

Attended a meeting on the topic a

1:29:32

few months back, purely out of interests.

1:29:34

Structural Phylogeny has been taking off in

1:29:36

recent years with the advent of more

1:29:38

powerful computational tools and predictors tools like

1:29:40

alpha Fold. A. Range of different

1:29:43

algorithms are available for computing pairwise

1:29:45

differences between structures and these are

1:29:47

used to assemble distant me to

1:29:49

seize for phylogeny construction. Experimental

1:29:52

structures are, of course, savored. However,

1:29:55

deep Mean deep Learning generated structures

1:29:57

can also be used to supplement.

1:30:00

these databases. The

1:30:02

most powerful aspect of structure-based phylogenies

1:30:04

is their ability to probe deeper

1:30:06

in time than sequence-based

1:30:08

phylogeny. Specifically, while

1:30:10

sequence-based homology and distantly related proteins

1:30:13

is lost over time, structural

1:30:15

homology can be detected in proteins that

1:30:18

separated billions of years ago. Genetic

1:30:21

sequences mutate and amino acids are changed, but

1:30:23

the actual base structure of a protein is

1:30:25

usually maintained. This is comparable to

1:30:28

how all vertebrates have the same body plan

1:30:30

which has been modified over time to give

1:30:32

a huge diversity of vertebrate organisms. Similarly,

1:30:35

modifications to a protein fold can give

1:30:37

rise to a large array of different

1:30:39

proteins with diverse functions. I've

1:30:42

seen structure-based phylogenies applied to viruses,

1:30:44

for example, using the delicious-sounding

1:30:46

double-jelly roll fold of the major capsid

1:30:48

protein to develop a model of viral

1:30:50

evolution and give us a link for

1:30:53

that. As you can

1:30:55

probably tell, it's still in its early

1:30:57

stages and there are some limitations, but

1:30:59

structure-based phylogenies can be a very powerful

1:31:02

tool in answering some tricky evolutionary questions.

1:31:05

I'm excited to see where this sort of

1:31:07

thing goes. All the

1:31:09

best, Daniel. P.S., thanks for all you

1:31:11

do at TWIV. I study virus proteins

1:31:13

myself, but my background is more in

1:31:16

structural biology, so this podcast has been

1:31:18

super helpful in expanding my knowledge of

1:31:20

viruses while I study. I've

1:31:22

also discovered a love for viruses, so

1:31:24

I hope to keep studying viral proteins

1:31:27

for a long time. After

1:31:32

that episode, I was thinking back to

1:31:34

that discussion and I realized if you

1:31:36

step back from virology and go back,

1:31:38

you know, several decades, structural phylogeny

1:31:40

was also just called phylogeny. Yeah, it's

1:31:42

true. Oh, good point. Right?

1:31:45

I mean, it's counting the hairs on the

1:31:47

books, but then that's how it's this species

1:31:50

versus that. It's a flying-metavirus.

1:31:52

It's definitely new. Yeah, I have three

1:31:54

things to say. One, I

1:31:56

stand corrected. Two, this is... really

1:32:01

cool and three Daniel you

1:32:03

write well. What a wonderful email. Yeah I

1:32:05

was gonna

1:32:08

say that as well. Yeah so

1:32:10

so hear me out you write

1:32:13

well and that is an extraordinarily

1:32:15

useful talent so don't neglect it.

1:32:19

You can actually make a living on that. I

1:32:23

wonder who he could ask about that. And of

1:32:28

course once you encounter viruses you will

1:32:30

love them and encounter I mean when

1:32:32

you start to study them not to get infected by

1:32:34

them because that's where the

1:32:36

problem arise or can arise. All

1:32:39

right it's time for some picks Dixon what

1:32:41

do you have for us? Well Vincent and

1:32:43

everybody else I am back

1:32:46

with my musical kick and

1:32:48

this I forgot to mention

1:32:51

this guy and he's a remarkable

1:32:53

guitarist. His name is Baden Powell

1:32:55

and as I wrote and

1:32:57

he was named after the Boy Scout the founder of the

1:32:59

Boy Scouts who happened to be I think

1:33:02

English is that right? I think the Boy

1:33:04

Scouts were. He asked me? No well

1:33:06

I thought you're a founder of the Boy Scouts.

1:33:08

I don't really know. I think he might have

1:33:11

been English. I

1:33:14

think Baden-Bell was. At any rate

1:33:16

you should watch this video. He's

1:33:18

playing the theme from the black

1:33:20

movie Black Orpheus and

1:33:23

unfortunately he's got a cigarette

1:33:27

stuck out of his hand and he's

1:33:29

playing and the smoke is going all

1:33:31

over the place right? And

1:33:34

I looked up what he died from. He died from pneumonia. I'm

1:33:36

happy that he didn't die from smoke

1:33:39

related illnesses but at

1:33:42

any rate you should listen to this guy. He's just

1:33:44

absolutely phenomenal and he was Brazil's

1:33:47

greatest musician I think

1:33:50

Barnard and including Antonio Carlos

1:33:54

Jobeem. That's a stiff competition.

1:33:57

He was widely respected as.

1:34:00

the progenitor of all

1:34:02

of the popular

1:34:04

Brazilian music that we now take for

1:34:06

granted. So

1:34:09

that's an uplifting kind of a

1:34:11

musical. If he died of pneumonia,

1:34:13

Dixon, that could very well have been well-con

1:34:15

motivated when you said that. I

1:34:18

was like, hmm. That's not right. You're quite

1:34:20

right. You're quite right. You're quite

1:34:22

right. And yes, it was Great Britain, the

1:34:24

Boy Scouts. I checked this. I checked 1908

1:34:27

Great Britain. And I have to tell you

1:34:29

that my father used to own a cocker

1:34:32

spaniel whose name was Zachariah Baden-Powell

1:34:34

Conde. Oh my God. And was

1:34:37

he a good talker? I

1:34:41

had no idea where his middle names

1:34:43

came from, what my father was thinking

1:34:45

at the time. Dogs with middle

1:34:47

names are hilarious. People that give middle

1:34:49

names to their dogs. Or last names.

1:34:56

Angela, what do you have for us? So

1:34:58

today, I don't have anything specific.

1:35:01

There's no website or anything yet. But

1:35:04

as we actually a few weeks ago on the

1:35:06

last tour that I was on, Rich Vincent and

1:35:08

I went on this little rabbit hole about exercise.

1:35:11

And we actually are planning now

1:35:13

this podcast that we all said that we were

1:35:16

going to do that wasn't really a thing yet.

1:35:18

But when I was on the live stream two

1:35:20

weeks ago, we also talked about exercise

1:35:22

and fitness. And

1:35:26

lots of people had questions regarding

1:35:28

this. So myself and Darren Elcrief,

1:35:30

which is actually a PhD in

1:35:33

exercise physiology. He did his PhD

1:35:35

at McGill. He graduated last year.

1:35:39

We are going to be, well, we are

1:35:41

in the process of creating a

1:35:43

new podcast on the platform of MyGroupTV.

1:35:46

And I'm not going to say his name. I

1:35:49

won't say it yet. But we want to hear

1:35:51

from all of the listeners, please. If

1:35:54

you guys can send us things that you're

1:35:56

interested in regarding exercise or regarding

1:35:59

exercise science. something specific that you

1:36:01

want to learn more about, or nutrition,

1:36:03

or sleep, or all of these

1:36:05

different health and fitness in the realm of

1:36:07

health and fitness, please send it for now.

1:36:10

We will have another email for myself,

1:36:12

but as of right now, it's vincent.microbe.tv,

1:36:15

and he will forward me those emails,

1:36:18

or any of the information. So please

1:36:20

send your ideas, or anything. We'd

1:36:23

love to hear what you guys want to hear

1:36:25

about, and then the first few

1:36:28

episodes, we can build around what

1:36:30

the Microbe TV listeners would like to hear

1:36:32

about. So we're excited about that. Yeah.

1:36:35

You are here to pump them up. Literally,

1:36:38

we can pump, muscle pump them

1:36:40

up. Yeah. Cool.

1:36:43

All right. Looking forward

1:36:45

to the title. Yeah, the

1:36:47

title's really fun. I like it

1:36:49

very much. All right, Rich, what do you have for us? I

1:36:53

have some high

1:36:55

candy. A photo

1:36:57

site called Mark

1:37:00

Smith Photography. I've

1:37:02

stumbled over some of his images,

1:37:05

and videos, and social media, and so

1:37:07

I finally decided to go to the

1:37:09

source, and see what there is. And

1:37:11

this is an incredibly rich

1:37:14

source of nature photography. And

1:37:17

so, you know, you can go, I gave you the

1:37:21

top level directory, but go to Gallery,

1:37:24

and go to Videos, and

1:37:26

just spend some time there. The

1:37:28

videos in particular, it says some

1:37:31

just incredible slow motion photography, of

1:37:33

like ospreys pecking fish out of ponds,

1:37:36

and stuff like that. Or

1:37:38

bald eagles doing the same thing. Amazing stuff.

1:37:40

I will say no more. I love stuff.

1:37:42

I looked through some of them earlier. So

1:37:45

beautiful. So, I love these types of things.

1:37:47

I could sit here for three hours looking

1:37:49

at videos. And he

1:37:51

narrates, I just looked at one of

1:37:53

the videos. I've never seen any of

1:37:55

the stuff done like this. I

1:37:58

just seen clips on social media. He

1:38:00

narrates his own video. He's

1:38:03

got one, you know, like 30 minute

1:38:05

video about ospreys and the guy is

1:38:07

just nuts about ospreys. And

1:38:09

he knows more than just taking

1:38:11

pictures. He knows about how these

1:38:13

birds think. And

1:38:16

how they operate is very cool. And he does

1:38:19

a great job narrating them. It's

1:38:21

just wonderful. Videos of birds of prey

1:38:23

are so beautiful. I find them just

1:38:25

like watching them in slow motion, especially.

1:38:27

I agree. Yeah, they're so beautiful. Cool.

1:38:32

Alan, what do you have for us? I

1:38:34

have also eye candy with

1:38:37

a science bent. So my

1:38:39

pick is two links. There's an article

1:38:41

in Science about it and there's the

1:38:43

actual site. So

1:38:46

this just launched at the

1:38:48

Florida Museum of Natural History.

1:38:52

It's called Open Vertebrate.

1:38:56

And it is a database.

1:38:59

You can, if you're a researcher, you can, you

1:39:02

know, go in and search the database for all

1:39:04

sorts of stuff. If you're just, you

1:39:06

know, like me and you want to look at the

1:39:08

cool pictures, you can click on the

1:39:11

specimen gallery and get a sampling.

1:39:14

They scanned animals.

1:39:18

And these are three dimensional scans

1:39:20

of all kinds of stuff. And

1:39:23

if you go to, they've got lizards, they've got

1:39:25

fish, they've got all these

1:39:28

vertebrates. And

1:39:30

you've got 3D, like

1:39:33

medical imagery in color. It's

1:39:36

just really, really cool. Another

1:39:39

rabbit hole that I could say that was on the

1:39:41

right side. The science article

1:39:43

has says more of the images and

1:39:45

describes what the project is all about.

1:39:47

And this huge effort to get

1:39:50

these specimens and get them scanned and,

1:39:52

you know, they're the challenges of how

1:39:54

do you fit a Galapagos tortoise into

1:39:57

an MRI. you

1:40:00

know, and they used a like

1:40:02

an inner tube and

1:40:04

put it on its back. So it's there on the

1:40:06

inner tube, just like lying there and being fed into

1:40:08

the very cool stuff. I

1:40:11

feel a certain amount of completely unjustified pride here.

1:40:17

Yeah, I'm intimately familiar

1:40:20

with the Florida Museum of Natural History.

1:40:23

It's not a big operation, okay, but

1:40:25

it's extremely well done. And we used

1:40:27

to go there fairly frequently. And in

1:40:30

fact, years ago, there was

1:40:32

another pick from this museum

1:40:34

because they have, what at the time

1:40:36

was the second largest collection of butterflies

1:40:38

in the world, plus

1:40:40

a live butterfly exhibit, the Butterfly

1:40:43

Rainforest. That is, I'll tell you,

1:40:45

it's a destination. So

1:40:48

good on them. Good for you. I

1:40:50

would like them to have the world's largest collection

1:40:52

of Burmese pythons, but I don't think that's going

1:40:54

to happen. Well, the other time. You

1:40:57

see, that's how you fit an MRI into

1:40:59

an animal. The animal actually swallows the MRI

1:41:01

and then you take the picture. This

1:41:05

is so cool, though, Alan. Thanks for

1:41:08

sharing. Yeah. Sure. All

1:41:11

right. My pick is for Angela

1:41:13

and any veterinary nerds who

1:41:16

might be listening. This is veterinary

1:41:19

apparel for veterinary

1:41:21

nerds. And

1:41:23

they have hoodies, sweatshirts,

1:41:26

t-shirts, jackets, accessories. They

1:41:28

have some cool stuff

1:41:30

here. I saw a, what is

1:41:33

it, toxicara, penis thing. Yeah.

1:41:35

Oh, yeah. That's right. All the parasites

1:41:38

things. And then one says, enjoy chewing

1:41:40

your fingernails. And of course, like when

1:41:42

you're in veterinary medicine, I mean, all

1:41:45

the time you shouldn't chew under your fingernails,

1:41:47

but you're always told that obviously like little

1:41:49

tiny parasitic eggs are under your fingernails. So

1:41:52

you shouldn't chew and obviously bacteria as well.

1:41:54

But and

1:41:56

on the homepage, the little guinea pig with

1:41:58

the glasses. It's so funny. Yes.

1:42:01

That's so cute. It's so cute. Thanks

1:42:06

for this Vincent. I love it. And

1:42:08

the little frog, all the ones that's a little frog, it's so

1:42:10

adorable. They got mugs,

1:42:12

they got water bottles, totes. And

1:42:16

the frog says, tired of being a

1:42:18

peritanic host. So funny. Yeah,

1:42:21

that's very funny. We

1:42:24

also have the listener pick from Ann, an

1:42:27

interview with Steve Reed Jobs, son

1:42:31

of Steve Jobs, who started a venture capital

1:42:33

firm to support cancer research. Reed

1:42:36

was studying to be an oncologist during

1:42:38

his father's illness. He talks about why

1:42:40

he didn't complete these studies, but also

1:42:42

why he has returned to fund innovative

1:42:44

research from the description.

1:42:46

Quote, in high school, Reed Jobs was

1:42:49

a summer intern in oncology labs, while

1:42:51

his dad, the late Apples co-founder and

1:42:53

tech icon Steve Jobs, was battling pancreatic

1:42:55

cancer. His biography, Steve, is quoted as

1:42:58

calling in his son's

1:43:00

interest in biotech, the silver lining of

1:43:02

his illness and making

1:43:04

cancer non-lethal has become Reed's life mission.

1:43:07

In 2023, he spun off

1:43:09

the venture capital firm Yosemite

1:43:11

from Emerson Collective, the philanthropy

1:43:14

and family office founded by

1:43:16

his mother, Loreen Powell Jobs,

1:43:18

to focus on cancer research and biotech.

1:43:20

Kara and Reed talk about the research

1:43:23

to start a pipeline, and how he's

1:43:25

been influenced by both of his parents

1:43:27

and whether AI, mRNA, or CRISPR will

1:43:30

be game changers for cancer patients.

1:43:32

Excellent. That's cool, I

1:43:35

didn't know that about Reed Jobs.

1:43:38

And that is 121095, 1095 or 1095, take

1:43:44

your pick at how

1:43:46

to say it. You can find the kind of micro.

1:43:48

1095 sounds better. You like 1095? I

1:43:51

like 1095. For

1:43:53

you, 11... For you, 11...

1:43:56

For you, 1100. Yeah. Yeah,

1:43:58

it is. There's your

1:44:00

notes at twiv at microbe.tv. If you

1:44:03

have questions or comments, twiv at

1:44:05

microbe.tv or a pic, you can

1:44:07

send your pics in, we'd like to get

1:44:09

them. And if you enjoy our work, we'd

1:44:11

love to have your financial support. We are

1:44:13

a nonprofit corporation, so you're in the US,

1:44:16

your donations are federal tax

1:44:18

deductible. Go to microbe.tv

1:44:21

slash contribute. Dixon de

1:44:23

Palmier, trickanella.org, the livingriver.org.

1:44:25

Thank you, Dixon. Oh,

1:44:27

you're so welcome and I love it. I

1:44:30