0:00

I'm Dr Karl coming to you from

0:02

the lands of the Gadigal people of

0:04

the Eora nation. I acknowledge Aboriginal and

0:06

Torres Strait Islander peoples as the first

0:09

Australians and traditional custodians of the lands

0:11

where we live, learn and work. G'day

0:15

Dr Karl, Shuttleers of Science, University

0:17

of Sydney here with an insight

0:20

about life. Oh my god and where

0:22

it came from and how we discovered

0:24

it. So let me introduce the microphone

0:26

associate professor Gregory J Morgan. Hello I

0:29

am at Stevens Institute of Technology

0:31

which is in Hoboken, New Jersey

0:34

just over the Hudson River from Manhattan. It's an

0:36

engineering school and I teach in the history and

0:38

philosophy of science. This is the weird insight and

0:41

I'm just going to give it to everybody right

0:43

now and then we'll try and understand it. So

0:46

you're a philosopher person working in

0:48

a school full of engineers and

0:50

you've written a book called Cancer

0:53

Virus Hunters. To

0:55

my surprise the way we've discovered this thing

0:57

called life you know DNA and the ladder

0:59

of life and all that sort of stuff

1:03

it's been driven by viruses that

1:05

cause cancer. By looking at viruses

1:07

that cause cancer we've made a

1:09

huge number of our discoveries. It's

1:11

pushed us along the pathway of

1:13

working out how this complicated thing

1:15

called DNA works. Is that a

1:17

correct summary? I think that's a nice summary. We were

1:20

sort of lucky in picking the viruses that

1:22

we studied and because viruses were nice and

1:24

simple they were like a little package of

1:26

life and had a limited number of

1:28

genes in them. We focused on

1:31

genes that were really important to the

1:33

cell cycle and to how cells reproduce

1:35

themselves. A significant number

1:37

of discoveries in the last

1:39

half century have come from looking

1:41

at these viruses. In the early

1:43

days of molecular biology so DNA is

1:46

discovered in 1953 it's

1:48

a big long-wieldy molecule but

1:51

viruses are a small piece of it so they're like

1:53

a sort of a small package of life with

1:55

a limited number of genes. The

1:57

cancer viruses they can take over a cell

2:00

and make it reproduce uncontrollably so they interact

2:02

with the cell in a certain way. And

2:05

so looking at the interaction we made all these

2:07

discoveries. The

2:09

virus is simple and then

2:11

we turn to cell cancerous and we apologise

2:13

for the poor patient who suffers from or

2:16

animal or whatever that suffers from it. It

2:18

causes a specific pathway that we

2:20

can then look at and it reproduces and we

2:22

can look at it really carefully and think, oh

2:24

we've just discovered something new about the DNA. Is

2:26

that what you're saying? Yes

2:29

exactly. At one point there are

2:31

genes in the virus itself which

2:33

help make a cancer cell cancerous that

2:36

turn a normal cell into a cancer

2:38

cell and then there's also the interactions

2:40

between whatever the virus is doing with

2:42

the cellular machinery itself. And

2:45

today we know these things, we'd

2:47

call them oncogenes and tumour suppressor

2:49

genes. And even our DNA.

2:52

They are in every cell in your

2:54

body and they regulate how cells reproduce

2:56

themselves and when they stop reproducing. Cancer

3:00

is effectively uncontrolled reproduction of the

3:02

cell. What the virus does

3:04

is it disables all that machinery and allows

3:06

for the cell to keep reproducing uncontrollably. Well

3:09

that was a big surprise for me because

3:11

I always thought before I did medicine that

3:13

cancer was some sort of external disease that

3:15

came upon you. It can be caused by

3:17

these viruses, I'll get back to them in

3:19

a second, but basically cancer is your own

3:21

cells not following the rules to grow

3:23

so far and then stop. And

3:25

so instead of growing so far and

3:27

stopping they just keep on growing uncontrollably,

3:29

I guess the advantage for the virus

3:31

is that it's got multiple copies of

3:33

itself and nothing personal like they say in

3:35

the mafia, it's just business, it just wants

3:37

to make more copies of itself. Now

3:40

I only know of three viruses that

3:43

cause cancer. This is before I read

3:45

your book. There's hepatitis B and

3:48

then there's Epstein-Barr virus or

3:50

glandular fever and then HBV

3:53

cervical cancer. And can

3:55

you just name a few more? It seems like there's

3:57

a short load of them. causes

4:01

tumors in chickens and

4:03

it was a very important virus. Another one SV40 can

4:06

cause tumors in newborn mice and other

4:09

things so they were more important for

4:11

the research. In terms of actually

4:13

human cancer I think you've named the big

4:15

ones there that there's multiple strains of HPV

4:17

which cause various types of cancer not just

4:20

cervical cancer but cancers of the throat and

4:22

the anus and other places and

4:24

I thought that maybe as many as 20%

4:27

of all cancers are caused by viruses. Are

4:30

we talking humans or animals or

4:32

both? 20% of human cancers are

4:34

thought to be caused by viruses.

4:36

Wow I mean viruses can

4:38

cause cancers maybe a couple but

4:41

from your work you're you because you've done

4:43

this really exhaustively you've interviewed so many of

4:45

the people it really fits in with the

4:47

whole history and philosophy of science. You're saying

4:49

20%? Yes 20% it's maybe slightly

4:53

higher in the underdeveloped world and

4:55

slightly lower in the developed countries

4:57

like Australia but it's still a

4:59

significant percentage. It turns

5:02

out that the only reason we

5:04

have such profusion of chickens today

5:06

is that we came up with

5:08

a vaccine against the coronavirus. We

5:11

started attacking chickens like

5:13

crazy in the early 1900s and kill

5:15

100% of a flock within 24 hours. There's

5:18

a long period when a chicken was

5:21

a really special meal that you

5:23

would offer to somebody own leaves. They were

5:25

really wonderful and that was because the only

5:27

way we could deal with this incredibly infective

5:29

coronavirus that was killing chickens around the world

5:32

was by having a little chicken

5:34

farm here and another one over

5:36

there and using isolation which

5:38

meant that we had small numbers of chickens which

5:40

meant that chickens were special and now chickens are

5:42

almost compulsory everywhere and it turns out that the

5:45

weight of chickens is more than the weight of

5:47

all the other birds on the planet. So this

5:49

chicken virus would be very

5:51

important and the one sv40 was

5:53

that vaguely related to AIDS research?

5:57

sv40 is a very well studied virus and pieces

5:59

of it are used in various tools

6:01

for molecular biologists. So you might have

6:04

heard of the promoter out of the

6:06

genome that's been used in other things

6:08

including some vaccines. It was a very

6:10

controversial virus actually because during the manufacture

6:13

of the polio vaccine, it turns out

6:15

that it was injected into millions of

6:17

people that got the polio vaccine. But

6:20

luckily, it's only cancerous if you don't

6:22

have a well-developed immune system. So it

6:24

causes cancer in mice if you inject

6:27

them before their immune systems boot up.

6:30

It's safer on adult animals and

6:32

adult humans. I'm guessing

6:34

there would have been a few adult humans and

6:37

children humans who had compromised immune

6:39

systems who end up getting cancers

6:41

as a result of this unwitting

6:43

contaminant. I don't know if

6:45

we know that for sure actually. At the

6:48

time, they had to make a judgement call

6:50

about what was more important trying to wipe

6:52

out polio or this very small risk that

6:54

you're creating more cancers in humans. Majority

6:57

of biologists think it didn't have any effect,

6:59

but you can find people out there that think it

7:02

did. When

7:04

I was a kid in school, every class

7:06

had a kid with polio and it

7:08

just got wiped out. The risk-benefit ratio

7:10

would be huge there. So how did

7:13

we actually discover viruses in the early

7:15

days? Well, the first viruses

7:17

were just things that reproduced or had some

7:19

sort of effect that you could filter with

7:22

very, very fine filters. So it would

7:24

be a filter that would filter out all the

7:26

cells and anything smaller than a cell, if it

7:29

got through, had a certain effect, we

7:31

called a lot of those things viruses.

7:33

Virus sort of meant something like poison

7:35

in the 19th century and in the

7:37

1890s we found some plant viruses that

7:39

would cause mottled features of leaves on

7:42

tobacco plants and that was one

7:44

of the first perhaps tobacco mosaic virus. So

7:46

I could tell the invention of electron microscopy

7:49

before we could actually see anything. We couldn't

7:51

see the viruses that are too small for

7:53

light microscopes. It's not really until the 30s

7:55

and 40s that we start actually thinking of

7:57

them in these little spheres or cemilos. But

8:01

we knew that they were there because they

8:03

could pass through an incredibly fine ceramic

8:05

filter like unglazed porcelain

8:07

for example and there were cells, bacteria would

8:09

stay on one side but the liquid would

8:12

go through and blow me

8:14

down. There was something there that could cause disease

8:16

so there was some sort of living thing in

8:18

it. Yes, 1908 and Rouse

8:20

did that exact experiment with the first

8:22

cancer virus. He took a chicken

8:25

tumour and he ground it up and

8:27

minced it up and then filtered it through a fine

8:29

filter and found that whatever went through the filter if

8:31

you inject it into a chicken it would cause cancer

8:34

in that next chicken and you can do this again

8:36

and again and again. And you mentioned

8:38

in your book there were a few tricks there

8:40

as well that it had to be a chicken

8:42

of a certain age or something. Initially it had

8:44

to be a closely related chicken but it turns

8:46

out that if you do this long enough the

8:48

virus is able to jump to

8:50

other chickens and actually eventually to other species

8:53

as well like rodents,

8:55

other birds and things. So the

8:57

virus gets better at jumping species

8:59

boundaries. You mentioned

9:02

there's something about cat leukemia. Cats

9:04

can get a leukemia which is a cancer type

9:06

thing from a virus. It's contagious

9:08

actually. It's a virus that causes leukemia

9:10

in cats which is a blood cancer.

9:13

It was discovered in the 1960s in

9:15

Scotland by a veterinarian called Jared

9:18

and he was even to show that cat

9:20

ladies that had large collections of cats if

9:22

they had one cat with leukemia it would

9:24

eventually transmit to the other cats and eventually

9:27

they would all get it. This

9:29

led to a lot of money being poured

9:31

into this area because we wondered if there

9:33

were human leukemia viruses too. And

9:36

so the US government spent millions and millions

9:38

of dollars looking for it and funded a

9:40

lot of the early tumor virology but they

9:42

didn't find one in humans, nothing like the

9:44

cat version. And you've got a wonderful chapter

9:46

there, Insights from the Field with I see

9:48

the names Epstein and Burkert.

9:50

It turns out that the same

9:53

virus called the Epson bar virus

9:55

causes lymphoma in African type people,

9:58

glandular fever in western. type

10:00

people and in my

10:02

medical studies I was taught that it

10:04

gave nato-faryngeal cancers of people

10:06

in Hong Kong. You say here is

10:09

the first human tumor virus can you

10:11

tell us about that? Birkett caught himself

10:13

a bush surgeon in Africa and he

10:15

noticed that he was getting these young African

10:17

children that would have these cancers of the

10:19

jaw effectively that have these big growths on

10:21

their jaws and it was

10:24

often fatal and what was

10:26

really curious about it was that it only

10:28

occurred in certain geographical areas and

10:30

it turns out it really only happens where

10:32

there is climate that's conducive to mosquitoes. So

10:35

it looked like it could be transmitted by

10:37

mosquitoes and Epstein back in England thought well

10:39

it must be a virus so he said

10:41

about trying to find the virus and he

10:44

spent a long time looking and he

10:46

eventually with Yvonne Barr, a great Australian by

10:48

the way, was able to find this

10:50

virus which was sort of a herpes-like virus. Epstein

10:53

Barr virus is associated with many

10:56

different diseases including more recently multiple

10:58

sclerosis perhaps. That was interesting

11:00

with the United States military being

11:03

able to look at blood samples that have

11:05

been kept in storage for the better part

11:07

of a century. Is my memory right on

11:09

that? Yeah they did. They went back and

11:11

looked at samples that have been stored to

11:13

see who had been infected and they spent

11:15

a lot of time actually in Africa trying

11:17

to show that the virus was a causative

11:19

feature of this type of cancer but took

11:21

thousands and thousands of samples. Along

11:24

the way as we look at

11:26

each virus and the cancers that are

11:28

caused we discover yet another little thing

11:30

about the DNA. You mentioned here

11:32

hepatitis B virus. I remember being among

11:35

the first people as a medical doctor

11:37

to get the hepatitis B vaccine.

11:39

The interesting thing about hepatitis B virus

11:41

is that when it reproduces it makes

11:44

a fully functional virus and

11:46

occasionally it also makes just

11:48

the protein shell that's empty.

11:51

The hepatitis B virus, one of the

11:53

first human viruses that caused liver cancer,

11:56

it causes hepatitis mostly but occasionally that

11:58

leads to liver cancer. It turns

12:00

out you can make a vaccine by just taking

12:02

the protein coat of the virus

12:04

and not using any genetic material

12:07

and injecting that into people. It's a

12:09

cancer vaccine effectively. We don't talk about it like

12:12

that but if you've got a

12:14

hepatitis B vaccine you're less likely

12:16

to get liver cancer. I had no idea

12:18

that that was the trick that you got this

12:20

hollow shell which will get into a human

12:22

cell then you just chuck what you want inside

12:24

it and I do remember at the time

12:26

when I got the vaccine I said proudly to

12:29

my family and so forth, hey I've had

12:31

an anti-cancer vaccine. Yeah I mean

12:33

a number of virus have that

12:35

feature actually where they reproduce themselves

12:37

so fast that occasionally they make

12:39

just a shell without the deadly

12:41

genetic material inside it. It's an

12:43

effective way of making a vaccine.

12:46

We can use it for HPV as well

12:48

and a similar strategy to hepatitis B virus.

12:51

Now you mentioned and I do remember

12:53

learning about this but I've now forgotten

12:55

reverse transcriptase.

12:58

Assume that our audience is a 10 year

13:00

old who has a good sense of curiosity.

13:02

Can you explain it to them and me

13:04

of course accidentally? Right. Turns out

13:07

there's two different sorts of tumiviruses. There's

13:09

some that are called DNA tumiviruses and

13:12

some that are called RNA tumiviruses

13:14

and they've got different genetic material. The

13:17

RNA ones evolve faster. There's one reason

13:19

that SARS-CoV-2 is such a problem right?

13:21

It evolves very quickly because it's an

13:23

RNA virus. The

13:26

RNA virus has sort of presented a

13:28

puzzle to biologists. How do they reproduce

13:30

themselves? Because the central dogma of molecular

13:33

biology said that you start with DNA,

13:36

the DNA makes RNA and the RNA

13:38

makes protein. For a long

13:40

time we slowly painfully built up this

13:42

knowledge. You've got this ladder of life

13:45

that's got two side rails and it's

13:47

got all these rungs and there's about

13:49

three billion rungs and we call that

13:52

DNA. DNA then makes RNA

13:55

which then makes protein. The painfully one

13:57

knowledge was that that's the part of

13:59

it. halfway it goes and now

14:01

you're telling me something with the word

14:04

reversed in it? So the question was

14:06

how do these RNA viruses reproduce themselves?

14:08

Because we think reproduction requires DNA and

14:11

there would need to be an enzyme

14:13

that took you from RNA back to

14:15

DNA and most biologists in the 1960s

14:18

thought that was just impossible. Luckily we

14:20

had a very tenacious researcher called Howard

14:22

Terman who searched this for a long

14:24

time and he concurrently with David Baltimore

14:26

they found an enzyme that would take

14:29

RNA and make DNA and they

14:31

called that virus reverse transcriptase. The

14:33

transcription was the process where you

14:36

went from DNA to RNA and

14:38

reverse transcription goes from RNA back to

14:40

DNA and takes the information from RNA

14:42

and puts it into DNA. This

14:45

is an example of where looking

14:47

at viruses that can cause cancer

14:50

in various creatures gives us

14:52

more knowledge? Yeah it modified what was

14:54

called the central dogma of molecular biology

14:56

but perhaps even more importantly it gave

14:58

us a tool because now

15:00

we could move the information from RNA and put

15:02

it in DNA and that's incredibly

15:05

important for the HIV

15:07

pandemic because it allows us a

15:09

tool to detect if you have

15:11

a virus or not. If

15:13

you can find any instances where

15:15

this RNA being transcribed into DNA

15:18

with that enzyme that it's come from a

15:20

virus because we humans don't have that enzyme

15:22

only the viruses have it. Reverse

15:25

transcriptase, ASE, the ending ASE means

15:27

it's an enzyme. Yeah so it's

15:29

a really important tool that molecular

15:31

biologists now use all the time

15:33

partly because RNA is super unstable

15:36

and it breaks down very quickly and DNA is

15:39

quite stable it lasts for a long time. Actually

15:41

I remember when I was working in a lab that

15:44

they kind of made fun of people work on RNA

15:46

because it's so difficult to work on if you accidentally

15:48

heat it up it would degrade. One thing you

15:50

talk about are oncogenes and this has

15:52

always bothered me is an oncogenes something

15:54

in our DNA that can cause cancer

15:56

is that right? Yeah

15:58

I mean what we have in our genes are

16:01

sometimes called proto-oncogenes. So

16:03

it's a gene that has a normal function.

16:06

It's part of this machinery that

16:08

tells the cell when to stop reproducing.

16:12

If it gets mutated in the right way,

16:14

it turns from a proto-oncogene to an oncogene,

16:16

and then it can cause cancer. And

16:19

the reason that's important in my story is

16:21

that it turns out that Roush sarcoma virus

16:25

not only has viral genes in the genome, it

16:27

also carries with it some genes from the host.

16:30

And it happened to pick up a

16:32

proto-oncogene that then mutated into an oncogene.

16:34

And so now when you have this

16:36

gene that when it gets inserted into

16:38

your cells, it will cause cancer. Why

16:42

do we have part

16:44

of our DNA having the

16:46

potential to cause cancer? What's

16:49

that all about? Isn't that a bit of a design

16:51

fault? Can we take it back to the manufacturer and

16:53

get a new one under warranty or something? Yeah, well,

16:56

it's a bit like why do you have an accelerator in

16:58

your car if it gets stuck down

17:00

and it can cause accidents? But

17:02

you need the accelerator for normal use of

17:04

your car. And just like that,

17:06

you need these proto-oncogenes for your cells to

17:09

work properly. It's just when they get broken

17:11

and mutated, that causes the problems. That

17:14

can be caused by a virus or it

17:16

can be caused by other things like smoking

17:18

tobacco or spending too much time in UV

17:20

light when you're sunbathing. That

17:22

can also cause the same mutations in those same

17:25

genes and it will cause cancer in those cells

17:27

too. That's a fantastic

17:29

explanation. I now realise that the problem is

17:31

not with the oncogene, but the name, if

17:34

you jump across to a car, instead of calling

17:36

it an accelerator, if you call it the, it

17:39

will kill you if you hold a down pedal

17:41

or the pedal of death as part of a

17:43

balance. So can you

17:45

tell me about the other side of the

17:47

coin then, the anti-cancer gene? Yeah,

17:50

there's a very famous one that was discovered

17:52

by a tumovirologist called P53. And

17:55

it's called P53 because it's about 53 kilodaltons

17:58

in size. and

18:00

adultin? Adultin is a measure of mass

18:02

that we use to measure proteins and

18:04

how big they are. And so a

18:06

hydrogen atom is one and carbon

18:08

is 12 and oxygen

18:10

is 16. So this one's 53,000. To use the current

18:14

allergy the p53 is a bit like the

18:17

brake in your car. Even

18:19

if the accelerator is stuck on you could

18:21

still maybe stop if you've got a working brake.

18:23

If the brake is broken too then you've

18:26

got a real problem and that's what happens

18:28

in many tumors. You have oncogenes that are

18:30

activated and tumour suppressor genes that are

18:32

broken and when you get those two things happen then

18:35

you've got a bad case of cancer unfortunately. And this

18:37

p53 is possibly implicated in the pitot

18:42

paradox, pitot paradox which is how come elephants

18:44

which have got many hundreds of times our

18:46

weight they do not have 100 times cancer.

18:48

In fact they have less. It may be

18:50

part of it. I don't think it's the

18:52

whole story with that paradox because it's all

18:54

about how much DNA repair genes

18:57

and things you have going on. So

18:59

can you recover from mutations? But some

19:01

animals will have more copies of

19:03

p53 than others and

19:06

you might think it's all of benefit but there

19:08

can be some costs too if you have too

19:10

much of it. It's like drinking water. A little

19:12

bit is good but too much. People have found

19:14

this in a marathon. Drinking too

19:16

much can kill you. So with the

19:18

elephant it's 100

19:20

times our weight. It's got 100 times more

19:22

cells and if you assume

19:24

cancer happens in cells that divide and

19:27

do it wrongly, why does it live

19:29

for our lifetime instead of only

19:31

seven years? Well it's got 100 times more

19:33

cells. Surely we'd be getting 100 times more

19:35

cancer. And apparently some of their

19:37

cells can have up to 22 copies of

19:40

the p53 gene and I've idly

19:42

kind of thought what would

19:44

happen if we could modify humans so

19:46

that instead of having just one copy

19:48

or so we've got a

19:51

couple. There's many people that

19:53

kind of think we can hack the genome so

19:55

to speak right and do things to make us

19:57

live longer and in theory it sounds

19:59

good. They can practice what you find

20:01

this when you start putting extra chains and

20:03

the chain imo have some unforeseen effects that

20:06

won't be good as well. so it's not

20:08

quite as easy as that sounds. I would

20:10

guess. Celebrate with hundred coming to the into

20:12

their time here and we didn't get a

20:15

chance to talk that a seal the and

20:17

Hiv spit odors when people read your book

20:19

is silly academically. Yeah, what I tried to

20:21

do was include a lot of. Biographical.

20:24

Material of the people that did all the research.

20:27

And science And they're trying to sort

20:29

of square the circle and having a

20:31

book as popular and readable. That.

20:33

Doesn't dumbed down the science too much.

20:35

is exhaustive and deep and also a

20:38

good dude. Best in lieu buys the

20:40

but now to buy now seats loses

20:42

Think about it's about time ago to

20:44

the and I'm seeking says this is

20:47

how that happened in the audience. This

20:49

so many viruses that is a can

20:51

cause cancer and divorces simple system and

20:54

and also because it interacts with the

20:56

potent cellular machinery. As gotta

20:58

do thanks to the south are already

21:00

interacts with really important proteins and the

21:02

cell pay Fifty three was discovered because

21:04

it was interacting with something that the

21:06

virus was making so video want to

21:08

understand molecular biology? It's and as essential

21:10

as really pick up how we got

21:12

the it's This is the book. So

21:15

tense a virus hunters I'm guessing Amazon

21:17

good books of the you live separately

21:19

says how they get hold of it.

21:21

Johns Hopkins University Press has a website

21:23

to better yet Amazon I think is

21:25

probably the easiest way. Thousand people who

21:27

follow. You and you'll find

21:29

work, Twitter and Threads and

21:32

just recently Blue Sky at

21:34

Doctor Gregory. Morgan. trying

21:36

to think about which my rabbit some

21:39

other my keep up periods and they

21:41

are some of them sign a hot

21:43

spot as i that doctor gregory morgan

21:45

with or without periods and between the

21:47

doctor and and the gregory on threads

21:49

blue sky and twitter or x i

21:51

guess you so much professor grigory to

21:53

take me through this and for it's

21:56

blowing my mind it so much of

21:58

the knowledge that we have game about

22:00

molecular biology and life itself has come

22:02

from looking at viruses that can cause

22:05

cancers in various creatures. I had no

22:07

idea. Yeah, I think it's a victory

22:09

for what you might call reductionism in

22:11

biology. Looking at simple systems first to

22:13

see what you can learn. Thank you very

22:16

much. Thank you for having me. Shirtloads

22:18

of science is washed, spun and aired

22:20

by the University of Sydney.