Cancer and Evolution with Kat Arney

In this episode of Stuff to Blow Your Mind, Joe chats with Kat Arney about her upcoming book "Rebel Cell: Cancer, Evolution, and the New Science of Life's Oldest Betrayal."

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Episode Transcript

Speaker 1 (00:03):
Welcome to Stuff to Blow Your Mind production of My
Heart Radio. Hey are you welcome to Stuff to Blow
Your Mind? My name is Robert Lamb and I'm Joe McCormick.
And today we're bringing you another interview that I conducted
last week while Robert was taking a break from work.

(00:24):
That's right. Once a year, I like to bury myself
in some sacred imported soil and allow my my body
to break down and then reconstitute itself so that I
can rise once more and be up to the challenges
of podcasting in this day and age. Today we are
going to be sharing the conversation that I had with

(00:44):
the British geneticist and science communicator cat Arnie talking about
her upcoming book, Rebel Cell Cancer Evolution in the New
Science of Life's Oldest Betrayal. So a little bit of
biographical information. Cat Arnie hosts the Genetta Unzipped podcast and
she holds a PhD in developmental genetics from Cambridge University.

(01:06):
She was a key part of the science communications team
at Cancer Research UK from two thousand four to co
founding the charity's award winning science blog and acting as
a principal media spokesperson She's also the author of Hurting
Hemmingway's Cats, Understanding How Our Genes Work and How to
Code a Human and she's written for Wired, The Daily Mail, Nature, Mosaic,

(01:31):
News Scientist and more, and has presented many BBC radio programs.
You can find Cat Arnie on Twitter at at cat
Underscore Arnie A r in E Y and UH. I
should note that the book is coming out at different
times in the UK in the US, so Rebel Cell
can be found in the UK starting on August six,

(01:52):
and then in the US I believe it's coming out
on September twenty nine, but you can go ahead and
preorder it online. All right, Well, I'm I'm in a
rare position here because I am just like the listeners
out there. I have not heard this interview yet myself,
so I am excited, uh to to to listen in
as she sheds light on this, uh, this fascinating topic.

(02:15):
Cat Arnie, thanks so much for joining us today on
the podcast. Thank you for having me. It's an absolute pleasure.
It's a pleasure to have someone on the show who
has not only written a great book, but you're actually
a podcaster yourself, so you're so you're used to this
whole game talking into the mic with alone by yourself
in a room. Yeah, I've been making the Genetic sun
Zipped podcast. I did have to say that through this

(02:36):
time we've we've deliberately made it a COVID free zone,
so it is currently a COVID free genetics podcast. So
that's been that's been a nice thing to do during
during this time. I gotta say I was listening to
one of your episodes of the Genetics sun Zip podcast,
the one about mount Sly and Pauline Gross, which I
thought was fantastic. Of course it connects to the book

(02:56):
that we're gonna be talking about today. So, uh, personal
endorsement from me of your podcast. Don't really like it,
thank you. Yeah, it's really fun. We we alternate. We
do sort of interviews with scientists who are working now
in genetics. But I also really like to go back
through those stories and and dig out, particularly the untold
women who were often they're doing the work, doing lots
and lots of stuff, incredibly detailed observations and breeding experiments,

(03:20):
and then basically didn't really get the credit for it
because until the middle of the twentieth century or later,
women weren't really respected as a scientist, so it's it's
just a wonderful exploration you come up with all these
incredible people, although, of course, in the early twentieth century
lots of them do turn out to be eugenicists, but
that's different. Podcast. Yeah, so I think maybe a good

(03:40):
place to start when talking about cancer. Of course, your
book is about cancer, and specifically a lot about the
genetics of cancer. I wanted to maybe start off by
talking about this strange kind of gut feeling or almost
superstition that somehow, unlike other diseases, cancer is a modern synthetic,

(04:02):
some kind of perversion in some way against nature, and
that it sometimes comes with this odd edge of moralism,
that cancer is not just unfortunate, but it's somehow decadent
in an indicator of something wrong with our age. Parts
of your book indicate to me that you've come up
against this kind of thinking a lot as well. What

(04:23):
do you think this sort of thinking signifies. I think
it's absolutely fascinating. Cancer is not a new disease, and
that really became abundantly clear to me. So, just as
a little bit of background, I spent twelve years working
at Cancer Research UK, the UK's biggest cancer charity, answering
lots of questions from the public, and all the time

(04:43):
this question comes up. It's like, why me, isn't it
just a modern disease? Oh, it's all this stuff in
the air, Oh it's stress. What what is it? And
you start to look into what cancer really is, and
it's it's ancient. It's hardwired into our biology because it's
just cells doing what they're going to do. Cells multiplying,

(05:04):
cells jostling for space, cells competing with the cells around them,
obeying the processes of evolution. And so when you really
start to look, it's not surprising that you find cancer
going all the way back through human history, all the
way back through the history of of animal life on
this planet. But at the same time, when people start

(05:24):
to become aware of cancer as a disease, they start
to ask questions about, well, where did this come from?
Why has it affected me? You start to get the
Greek doctors, people like Hippocrates, who were writing about cancers
in their patients and saying, well, what what has caused it?
It must be the gods, it must be the humors.
Something is out of whack in here, and then you

(05:45):
start to get the slightly more religious thing of well
it is it's sins visited on us, it is something
to do with immorality, modern living. And then you bring
up to today this we don't necessarily have such a
strong religious view of it, but certainly the idea of
almost wellness as a religion. You've done something toxic to
yourself and that's why you you now have cancer, and

(06:07):
you look back at the history of cancer as a
biological phenomenon, and that's simply not true. You know. It's
it's basically like the dark side of life rather than
anything that we have particularly brought on ourselves in our
modern life. Yeah, that's one of the things I really
loved about your book was the way you how you
show cancer to be so fundamentally integrated with with with

(06:30):
life itself or I guess, multi cellular life. Um. And
so so maybe we should focus on on a couple
of these ideas in particular, one of them, I guess,
is the idea of modernity, right, the idea that that
cancer is something that was very rare until recently. You
make an argument against and people have argued this, but

(06:51):
you make an argument against this in the book, and
you cite some both some reasoning about why a lot
of cancers wouldn't necessarily show up in the kinds of
remains we can examine, and then pointing out examples that
we do find in fact, in the human record and
physical remains of human society and prehistory. Yeah, it's the
classic thing in biology that you find what you're looking for,

(07:14):
and people have not been looking for signs of cancer
in ancient remains. And the thing about cancer is that
that when you're thinking about ancient remains that we find,
mostly you're talking about bones, and particularly when you get
very ancient, you're talking about fossilized bones. And not every
cancer leaves its trace in the bones. So when you're

(07:35):
thinking about cancers that affect the soft tissue, you may
never see the traces of a cancer that killed someone. Also,
you know, ancient remains don't turn up in beautifully age
matched structured populations, so you can say, oh, this is
exactly the population that was alive at the time, this
is exactly the number of cancers in this population. I
think some people have argued that the fact that cancers

(07:58):
are rare in ancient humans is an argument that cancer
was very very rare. But I slightly feel the other
way around. I feel like the fact that the more
people start looking for cancers in human and animal remains
from from way way back, the more cancers they start
to find suggest that it was more common. We will

(08:21):
never know how how common it was, because you can't
do you know, a lovely epidemiological study on the sort
of stuff that you can get out of the ground.
You get what you get and you get on with it, basically.
But I do think that cancer is not an exclusively
modern disease. I will say, certainly it is more common
as we live longer. So another of the things I

(08:42):
go into later in the book is the idea that
there's almost a sort of a shooting up point. After
you have got to a certain age, your risk of
cancer does significantly go up. So if you think about
ancient populations when there were many, many, many more things
that we're going to kill you, your chances of getting
to an age where you could dive cancer before something

(09:02):
else got you worse smaller. So it's not surprising we
find fewer ancient remains with cancer. But when you think
about some children have been found with types of cancer
that are very very rare in populations, and the fact
that we have found them at all suggests that this
is a disease that has always been with us, and

(09:23):
it's not exclusively a confection of modernity. It's it's basically,
you know, it is with us and always has been.
And what about the part of the misconception that views
cancer is something that is uniquely kind of human and
maybe associated with uh, with the synthetic products of human
industry and all that. Like, this ties into the idea

(09:45):
that sharks don't get cancer, right, that there's a widespread
belief that that, for some reason, animals that don't engage,
you know, don't live in cities and drive cars and
eat processed food and stuff won't get cancer. But they do. Yeah,
And this really my mind. I can see over on
my bookshelf. I'm so tempted to go and grab it.
But there's a book where someone has gone through all

(10:07):
the different species that have been known to have cancer
in In some cases it's many examples, in some it's
just a few. But it's pages and pages and pages.
It's everything from like odd wolves to zebras, and almost
every branch of the animal kingdom develops cancer. There are
a couple of really weird exceptions. So one is comb jellies.

(10:29):
Comb jellyfish don't seem to get cancer, never been detected.
And also sponges really weirdly resistant to sponges. There's this
guy in in Arizona, guy called Carlo Malei, who is
zapping sponges with enormous amounts of radiation like that would
kill a human, and they're just fine. They just shrug
it off. So there are some species that are cancer resistant,

(10:52):
but pretty much everything else to a greater or lesser
extent is and humans aren't even the most susceptible species.
There are some that are much more susceptible to cancer
than humans are. So this idea that it's it's just
a modern disease, it's just a human disease, it just
doesn't stack up. You know. Yes, there are things that
we do in our modern lives that increase the risk

(11:14):
of cancer, and our lovely living to a nice old
age is a major risk factor. You know, Thank god
we don't all die in childbirth and of infectious diseases
before our tenth birthday. But you know, we are we
are not, you know, unique and wonderful when it comes
to cancer again, it's it is just part of life.
There are some other interesting observations you mentioned in your

(11:37):
book about what might create a specific propensity for cancer
in certain species versus others. Are One that I recall
is that you mentioned that it's cancer seems to be
more prevalent in species that have been through a genetic
bottleneck at some point in the relatively recent past. So like,
if their breeding population was reduced to a pretty small

(11:58):
number at some point, they tend to be more susceptible
to cancer. Is that correct? Yes, So that does seem
to be the case, which suggests that there are genetic
factors at work. Because if you shrink a population down
to a very small what's called an effective breeding size,
you've got quite a small population that's all breeding with
each other. You do start to get a pile up

(12:18):
of mutations being passed from generation to generation, which might
be increasing the risk of cancer. One of my favorite
species in this case is the Syrian hamster, which all
the Syrian hamsters pretty much that are in pets and
labs all over the world are descended from one litter
of hamsters, and they are incredibly cancer prone because they're

(12:38):
just massively in bread um. But yeah, every every species,
some more than others and some much less than others.
So elephants very surprisingly, you'd think when you think about
it logically, animals that are very very big, they have
lots of cells that they live for a very very

(12:58):
long time. You think that elephants should be riddled with
cancer by the time they die, but they are not.
They are amazingly resistant and really long lived animals like
bowhead whales, even some of the really long lived bats,
brand bats that live for forty years, very resistant to cancer.
So they have evolved mechanisms that enable them to live

(13:21):
these very long, luxury lifestyles and be resistant to cancer.
Whereas you have very small rodents, things that live fast
and die young. Why bother. You know, you're going to
be around for a couple of breeding seasons and then
you're out. And humans are kind of in the middle.
You know, we live for many decades, we reach our
child bearing years in between our sort of twenties to forties,

(13:44):
hang around for a bit after, and then the risk
of cancer does start to go up. So you know,
this is when you put humans in the context of
all of life, you start to understand how our evolution
as a species is in trance tied to our as
a species risk of cancer. But you do have to
separate that from personal risk of cancer as well, and

(14:07):
that's a that's kind of a bit hard to get
your head around. So we're talking about evolutionary risks versus
personal risks. So one of the most interesting ideas in
your book that that you keep returning to is a
framework for thinking about multicellular life through the analogy of
a society, that a multicellular organism is a society of cells.

(14:31):
Could you explain this way of thinking in some of
the implications that extend from it. Yeah, this really really
blew my mind when I started to understand this. So,
this idea of cells as a society, it goes about
quite a few decades. A lot of the things I
discovered while I was researching the book are quite old

(14:51):
ideas that have got, you know it, subsumed or left
behind in this this rush to just understand cancer as
a purely genetic disease. But the idea is that that
cells and organisms and individuals in a species, they live
in societies, and there are rules of societies at every
single level. You know things like do the job you're

(15:12):
meant to do, don't take more than you need, clean
up after yourself, all these kinds of things. There are
rules to societies that make societies work productively. And you
start to look around at groups of cells that are
in tissues and in organs in your body. You look
at societies like ants and bees. You look at colonies,

(15:34):
you look at troops of chimps and herds of deer,
and you look at human societies and they all work
in the same way. And this particularly an idea that
I was influenced by. There's a researcher in Arizona called
Athena Actipis, and she works a lot on social cooperation
and cheating and the idea that cancer cells basically cheat

(15:59):
in society. They are cheaters. They take more than they need,
they produce waste, they proliferate out of control, they don't
die when they're meant to. They are not good cells. Now,
if every cell in your society was doing that, it
would just be, you know, mad max style dystopia. Nothing
would work, your body would not function. But you can

(16:20):
get away with being a cancer cell and cheating and
keeping going and keeping going because to a certain extent,
cheaters do prosper, and it's the same in many animal societies.
So one of the lovely examples that I found was
these cape honey bees. So this just wonderful example. So

(16:42):
cape honeybees, they have a classic honeybee population structure. You
have the queen, and you have all the workers, the
female workers, but the queen is the only one who
gets to reproduce, and so all the workers are busy
doing all the work in the hive, and the queen's
just cleaning around basically like a um and you know,
popping off to reproduce when she feels like it. But

(17:02):
there is a genetic change, single genetic change that means
that these worker bees can become queens and they start
to just sit around, you know, queening it up, and
eventually the hive starts to collapse under the weight of
all these cheaters. And it's just a single genetic change

(17:23):
that enables them to do this. And actually some of
these queens will go off to other hives and start
to infect them and turn them into cheaters as well.
And it's almost like a bee cancer, I suppose, because
ultimately it leads to the destruction of the hive, and
you say, well, why would the bees have this, Why
would it be so fragile that one genetic change can

(17:46):
disrupt it like this? And it turns out that where
the bees live it's very, very windy. So there's a
risk that if you just have one queen and that's
all you get, your queen could get blown off course
and you might lose her totally, and then your hive
would collapse anyway. So the ability to flip into queen
mode it's really useful for the bees for their evolutionary survival,

(18:09):
but it comes with a risk. And it's the same
with cells. So we need to be able to make
new cells. You need to regenerate millions of cells in
your body every day, millions of cells in your skin,
your blood, your bowel. You need to be able to
heal yourself if you're wounded. You need to be able
to grow from one cell into an adult human. Cells

(18:33):
need to reproduce, they need to do stuff. Flip side
of that is that they can sometimes go out of
control because it's the same mechanisms that make cells grow
and multiply in the right way that they kind of
harness and hijack when they decide to cheat and grow
out of control in the wrong way. So that's interesting.
You're sort of showing how cancer is one side of

(18:56):
an evolutionary balance where on one hand, you've got you know,
as your ability to do something good goes up, the
risks associated with those same genes that code for that
also go up. So we know on one side what
the downside is. We can see tumors in cancer, and
you're saying that the the the goods that make those

(19:16):
risks worthwhile are basically being able to proliferate quickly in
cell growth. And this would have to do not just
with growth in youth, but in healing and things like that. Yeah, exactly,
And you see this. This starts to explain the differences
across species because if you if you cut a mouse,
mice heal amazingly fast. Their cells just basically knit themselves

(19:38):
back together. It's it's absolutely incredible. Um. One of the
stories that I discovered when I was talking to a
researcher in Santa Barbara who's trying to work with the
animals in the zoo to understand their cancer risks. She's
she went to the zoo and said, can I get
a little bit of skin from your giant tortoise, and
they were like, hell, no, cut a tortoise. It takes
a year to heal, and tortoises live for a very

(20:02):
long time. They are incredibly cancer resistance, but they the
flip side of that is that they don't heal very easily.
So humans again somewhere in the middle. We don't heal
as fast as mice. We live much longer than mice.
So there's there's all of this stuff is a trade
off about the evolutionary journey that your species has taken.

(20:22):
And one of the things that I sort of took
this to its logical conclusion, and I was like, if
there's aliens, aliens would get cancer, that there's very unlikely
that they would not if they obey the general rules
of evolution, and this idea that like cells, organisms living
in a society behave according to the rules of that

(20:45):
we know make a good society. I don't think there's
any reason why aliens wouldn't get cancer. She's like, that's
a bit of a that was a bit of a
sort of late night thought. I think, because all that's
necessary is that they exist by cell division, right, I mean,
that's pretty much it. Yeah, yeah, exactly, if you have

(21:06):
cells and your cells are doing cell division, and also
if you have evolution by natural selection, which is basically
the engine that drives cells to to proliferate and be
selected for and to keep going, and species to keep
proliferating and keeping going, then yeah, you probably could get cancer.
And that's what we generally see across the entire animal kingdom. Well,

(21:29):
thinking about aliens getting cancer makes me think of another
interesting part of your book, which was about difficulties in
classifying what appears to be some form of uncontrolled cell
growth in animals or even not animals, other organisms that
are very different from us. So can you look at
what's going on in a clam and say that it
has cancer? Yeah? Probably, But what about a mushroom or

(21:52):
in an algae or something? Yeah, this was this was interesting.
So you know, what is cancer and n is cancer?
Is an interesting question. And when you get to more
organized animals and particularly mammals, we define invasive cancers as
cancers that kind of break through the sort of molecular
I guess you'd call it like saran wrap that's around

(22:14):
your organs and your tissues. They break through this membrane,
and that's what we call invasive cancer. But really, you know,
the phenomenon of cells growing out of control is all
over the place. You can see it in plants when
they get ghouls, you can see it in in fungi.
You can see it in all sorts of things. And
what are the interesting questions is you know something like endometriosis,

(22:36):
which is a condition where you get rogue tissue within
the body and it's sort of it grows and its
spreads and it bleeds and it's very very painful. It's like,
but that's not cancer, it's not invasive. But actually, when
you look at that kind of tissue, it has lots
and lots of the kind of mutations and changes we'd
expect to find in cancer. But that's not cancer, and

(22:58):
that's in humans. So this this idea that mutations it's
not just what makes cancer. Uncontrolled cell growth is not
just what makes cancer. It's it's sort of this this invasive, aggressive,
evolving characteristic that really is what we can classify as

(23:19):
as cancer. All Right, we're gonna take a quick break,
but we'll be right back, and we're back. So maybe
we should shift to talking about the history of our
understanding of the proximate causes or maybe better to say,
the risk factors for cancer where it comes from, whether
that's there's a hereditary component and an environmental component. There's

(23:42):
a part in the book where you mentioned this thing
that was called the Daily Mail Oncology Ontology blog, which
I've really appreciated because so the idea was this was
an attempted list of all the things that either cause
or cure cancer, according to the Daily Mail, And that
made me say, I've got to it's something I read
a lot of science and medical news from my work,

(24:03):
and I have all but completely turned off my recognition
system for articles about, you know, new supposed causes or
cures for cancer, because this was already like a cliche
to the point of being a hack joke for comedians
in the nineteen nineties. Is there something we should learn
from this, like the way that we get this conditioned
kind of num reaction to these types of news stories. Yeah,

(24:27):
that's we used to get a lot of that when
I was at Cancer Research k. You know, I think
that the stupidest one was that water gives you cancer,
and also that turning on turning on the light at
night to go to the bathroom, gives you cancer. So
you know, this is this is really really frustrating. So
there's kind of a couple of there's a couple of

(24:49):
things to dissect because it's also comes down to like
what what is actually the nature of cancer? And the
way that cancer has been thought about for a very
long time is according to what scientists like to call
the somatic mutation theory of cancer. So this is this
idea that cells pick up changes in their DNA in
their genome that the instructions that they use to do

(25:11):
what they do, they pick up these changes, these mutations,
and that enables them to do more bad things. And
then they pick up more and they do more bad things.
So it's this gradual accumulation of nasty mutations terms nice
well behaved cells into aggressive cancer cells. And we can
start to see some of the characteristic fingerprints that different

(25:34):
agents leave in the genome. So we can see, for example,
cigarette smoke or ultra violet light from the sun, we
can see those characteristic fingerprints of damage in the genome.
What that doesn't necessarily tell us because when you start
looking closely at a cancer or even in fact at
normal tissue, you start to see these changes and mutations everywhere.

(25:58):
So this kind of simplistic model that it's a hit
in this gena hit in this gena hit in this street,
and a hit in the street in a bang there,
you've got a cancer cell is nonsense. Because loads of
healthy cells such a peppered with mutations and loads of
things do damage our DNA. And that's kind of like
it's mostly fine. So it's a bit more of a

(26:21):
sophisticated understanding of yes, there are things that damage DNA.
A lot of them we know about, some of them
we don't know about yet. Researchers are trying to figure out,
you know, how do we match up these signatures of
damage to things that are in the environment alas Mostly
the most single, most damaging thing you can do for
your DNA is a breathe oxygen. Literally, just being alive.

(26:46):
The processes of life in your cells damage your DNA unfortunately.
But then if all your cells are to some extent,
you know, more or less messed up. Everyone's got a
few mutations here and there, some more than others. What
is it then that tips the cell into becoming a
cancer cell? If everyone's a bit weird, what makes that

(27:09):
cheating cell kind of slip the bonds of good society
and really start going for it. And that really is
is an evolutionary question that cell has involved the capacity
to do that, and so I think it's it's far
too simplistic to say, oh, well, you know your cancer

(27:30):
was absolutely caused by smoking, that was it. It's like, well,
that was a risk factor and it certainly didn't help,
but there were many other things. And also many people
who do smoke don't get cancer. So it's like we've
got to be more sophisticated in understanding what makes normal
cells become damaged and what makes kind of sad cells

(27:50):
become really bad cells. Yeah, this is an important point
about thinking about risk factors instead of causes. And I
know that that's it's in fure creating to people especially.
I think if you don't have a lot of like
training in a statistics oriented field, that it just doesn't
feel very comfortable to think about, especially something that's a

(28:11):
really important life and death issue like cancer in terms
of probabilities. You want to know like what it was
or what what did it? Yeah, exactly. I think the
best analogy that I really came up with is and
this is spoilers now if anyone's seen Agatha Christie's murder
on the Orient Express where and I am this is
a massive spoiler, but come on, the books like really

(28:32):
old you should have read about now see the movie
with Albert Finning too. It's great, but it's a murder,
but all the people involved they all have a stab,
so you never know who actually was the murderer. So
it's it's kind of like this. So you know, we
have lots and lots of genes that we know are

(28:52):
implicated in cancer. There are lots of things that can
damage our DNA. There are lots of things that can
like impre of the environment of our tissues or not.
We know that things like you know, keeping keeping well
and healthy and doing all the boring healthy living stuff
that helps to keep your your body healthy makes yourselves
more likely to fall into line. But saying exactly like

(29:16):
it was that thing, you know it was, it was
that sunny holiday in Marbea in that damage that skin
cell that gave you cancer. As I know that's that's
simply not possible. So trying to say oh it's this,
oh it's that, do this, don't do that, I think
is not terribly helpful, because at some point we've just
got to get on and live and try and negotiate

(29:38):
the risks that we're happy with taking. Right though, at
the same time, you do point out how there are
certain factors that increase your likelihood so far above the
baseline that maybe at that point it even though you
still can't quite say it's a cause, it's something closer
to a cause. What I think one common example given
would be tobacco. Remember you mentioned another example in the

(29:58):
book about just chronic exposure dermal exposure to soot in
chimney sweeps. I believe it was. Yeah, this was the
first example of someone actually showing that something, a substance
in the environment could increase the risk of cancer. And
this is an English surgeon called Percival Pot who had

(30:21):
a purely professional interest in the scrotums of young boys,
purely professional because he was interested in chimney sweeps in London.
Now this was in the seventeen hundreds and chimney sweeps
were basically sent naked up the chimneys by gangmasters to
clean the chimneys. So they were exposed to a lot
of soot and they noticed that they started to get

(30:43):
these cancers in their genitals and they were called soot warps,
and these were very very very nasty cancers, really horrible
kind of stuff. And Pot realized that it was the
soot that these boys were being exposed to that was
causing these cancers. And he said, right, you know, we
gotta get nice in Germany that all the chimney sweeps
had these nice kind of tight fitting uniforms so they

(31:06):
weren't being directly exposed on their skin. And he was like, right,
we've got to get those in. I got to protect
these boys, stop sending them naked up your chimneys. Um Alas,
it took over a hundred years for people to actually
change in Britain because the gang masters were like, no,
those those uniforms are too expensive. They'll make our sweeps
too expensive. You know, they're they're cheap. We don't really care.

(31:27):
So that was really tragic that they managed to link
this cause to these very horrible cancers. And there was
something that everyone knew could be done that was helping
in other countries. And nope, nope, it didn't happen for
a very long time. Um but yes, that Percival part
is kind of the father of this idea of external

(31:49):
sources of of carcinogenic chemicals, I think, but I think
it has stuck in the imagination that like it's all external,
it's all from from something you've done, or something you've got,
or something you've touched or eaten or being exposed to. Well,
to go to the other side. So there's a part
of your book where you explored I think we actually
mentioned this earlier about your podcast episode about Maud Sly

(32:11):
and Pauline gross and in the role for example of
the research of maud Sly in establishing that there is
a hereditary component to cancer that I think at the
time you say that, you know, the primary argument was
about two different major theories of external causes, whether cancer
was caused primarily by inflammation or by infectious agents and parasites.

(32:35):
Is that correct? Yea. So at the beginning of the
twentieth century, the early twentieth century, there was this idea
that cancer was either all caused by external things like
certain things in the environment, or it was viruses. Mostly.
There were a couple of good examples in animals where
you could take viruses, exposed the animals to them and

(32:56):
they would develop certain types of cancer. So the first
one were as a guy called Peyton Rouse who discovered
a virus that caused cancer and chickens. So by the
sixties everyone was just obsessed with the idea that it
was viruses. And now, you know, we really understand that
there are families that are affected by multiple cases of cancer,

(33:16):
that cancer can be to some extent influenced by the
genes we inherit. But really this was almost a completely separate,
parallel strand running up through the first half of the
twentieth century, and it was work in mice in families.
In the podcast, we talk about the story of Maud
Sly who bred all these mice together to show cancer

(33:37):
could be inherited. And then the story of Pauline Gross,
who was a seamstress who meant a scientist and she said,
you know, I'm going to die young, and he mapped
out all her family because so many members of her
family were affected by the same types of cancer. And
it took, you know, decades until they pinned down the
particular gene fault that was responsible. But yeah, they're all

(34:01):
these lines were like running a completely separate to each
other until it all started to coalesce together in this
understanding that you know, there are things that damage our genes.
There are genes in our cells that make ourselves replicate
that that stop ourselves from dying. This is good normally,
but they can go wrong. They can be mutated, they

(34:22):
can be changed, We can inherit versions that affect their function.
And it all sort of started to coalesce into this
very sensible idea of of how cancer starts. But I
think it just became very very focused on the genes
and the cells, just yes, single genes, shopping lists of
genes and changes, and forgot to look at this broader

(34:44):
picture of the environment in which cells are, the society
in which they're living, how they can interact with each
other cheap, overcome expand push against each other. This more.
I hate to use the word holistic because it sounds
really kind of hippie dip it, but you know, it's
it's part of our bodies. It's not an external alien thing.

(35:06):
These cells obey the rules of our bodies to to
a certain extent, they cheat the rules to another extent,
but it's all kind of part of one piece. And
we've just focused on on genes and molecules for the
past couple of decades, I think far, far too much.
All Right, we're going to take a quick break. We'll
be right back with more than than all right, we're back.

(35:30):
So you mentioned in the book that you believe that
the future of our resistance against cancer and medical treatments
of cancer are going to rely on quote shifting towards
a new way of evolutionary and ecological thinking about cancer.
So I assume there you're connecting to the ideas you
were just articulating. But could you expand on what you
mean by that. Yeah, So, as all the sort of

(35:53):
strands of cancer research over the past that one years
started to coalesce on this eye dear that that cancer
starts when cells pick up certain genetic mutations and they
go out of control. And then we started to get
to this idea that then, well, the way you treat
them is you find the molecules the genes that are
making them go out of control, and you target them

(36:15):
with drugs. And that's going to be the way we're
going to cure cancer. And there's been so much, so
much effort, money, research, time, patients, lives in clinical trials
have gone into testing these very molecularly targeted drugs, and
you know, some in some cases there have been incredible

(36:36):
success stories. So, for example, a drug called gliveck for
treating a certain type of leukemia is incredibly successful. It
targets a very specific genetic fault in the cancer cells,
and it is it was game changing, and it continues
to be game changing. But lots and lots of the
other drugs that have been developed along these lines, they

(36:59):
have not transformed survival in the way that we would
hope they've They've eked out, you know, in some cases months,
in some cases, you know, a few years. In one case,
I saw a paper that said nine days increase in
survival with this particular incredibly expensive targeted drug. And you're like,

(37:20):
these are not cures. The these are these are the
magic bullets that we were promised, and they are not cures.
And in virtually all these cases, the cancer comes back.
And why does it come back? Because of Charles Flipping Darwin.
You know, it's it's evolution. You hit something, you get
rid of most of the cells that are sensitive, and

(37:41):
you've still got a core of resistance because you've got
so much genetic diversity in that population. Of cancer cells,
and so they start growing again, and this time they're
resistant to the drug. So maybe you try another drug,
same thing happens. You get rid of the sensitive cells,
you've still got a core war of resistance, and they

(38:01):
grow back, and eventually you run out of options, and
there's time now to think about cancer in a much
more evolutionary and ecological way, as you say, thinking about, well,
if we know that this process of evolution is at work,
that if you get rid of the sensitive cells, the
resistant ones come back, Like, well, why don't we try

(38:23):
and approach this in a different way. Why don't we
try not to knock them all out? Why don't we
try and balance these populations, keep them suppressed, keep them
under control, much in the way that say a farmer
would try and control the pests in his crop, rather
than completely trying to nuke them all from orbit or
eradicate every single last grasshopper. You know, and understanding the

(38:46):
ecology the tissue biology, so you know, are you actually
causing more damage two tissues by treating with drugs or
radiotherapy or surgery. How can we minimize that so that
it doesn't encourage cells to to cheat even more In
a damaged environment. So it's this this idea is starting
to come through, But I think I think it does

(39:09):
take a bit of a subtle and sophisticated understanding of
cancer as an evolutionary process within the tissue environment of
the body, rather than just like, these are some rogue
cells that have gone wrong and they're growing out of control,
and we just need to hit them with enough magic
bullets and they'll go away. You know, the classic cure

(39:29):
for cancer that that we've almost been sold. It's I
don't think it's it should look like that, um because
we've tried that and it's not really working. So I
think we need to try a different approach. This way
of talking about tumors is reminding me of something you
mentioned earlier in the book actually, which I thought was

(39:49):
really interesting image that stuck with me. The idea of
a hypothetical hyper tumor. I'd never considered this before, but
the idea that a tumor can get a tumor. Yeah.
So again, it's the thing that really jumped out at
me researching this book is that cancer is a microcosm

(40:09):
of evolution. It's it's a crucible of evolution, a dumpster
fire of evolution is probably the best way of putting it.
Cancer is a dumpster fire of evolution. Then you go, um,
but yeah, everything every innovation of life that you see
on Earth, cancer can evolve because you have a very large,

(40:31):
genetically diverse population of cells that have got lots of
opportunity to try stuff out. So you know, it's not
surprising that even within a horrible cheating atmosphere of a
cancer you might get some really really badass cells that
will start proliferating even more and actually suppress the original

(40:52):
tumor by just out competing them in a Darwinian sense.
And then there's some really wild things, um that I discovered.
So the most crazy innovation is that a guy is
a guy called Kenneth Pienta in Baltimore has discovered that
cancer cells have invented how to have sex. This this

(41:15):
really blew my mind because the implications are massive. Here.
We have this idea that cancer cells they just they
reproduce basically by splitting into that's fine. You know, you
have one cancer cell, it becomes two, it becomes for
all of that kind of thing. There's no transfer of
information between cells and after that. But he's discovered with

(41:36):
these prostate cancer cells that they fuse together and become
resistant to treatments, and then they start kind of budding
off little cells that are resistant to treatment. And you're like,
what you know that looks like sex, I mean, for
a very poor value of sex, but that you know,

(41:56):
that's the biological process of Sex's two cells fusing to
other and and creating more. And you're like, whoa, because
that's a way of genetically combining forces. And again, it's
an evolutionary innovation. Sex has evolved on this planet multiple times.
You know, it's not unheard of. And if you have

(42:19):
enough rolls of that dice, as might happen in in
a cancer you know, weird, weird, weird, our stuff is
going to happen in there. Um. It's just it really
is mind blowing every innovation of life. Cancer cells, you know,
at some point somewhere might have a go at. And

(42:39):
so when I realized this, when I realized that, you know,
cells can have sex, cells can do all these kind
of crazy evolutionary things. They can smash their chromosomes out,
they can glue themselves back together. It's all kind of crazy.
And then I started learning about the thing that was
just really incredible. So, right, imagine there's a disaster movie happening. Right,

(43:03):
you know what happens in a disaster movie. Everything's going wrong.
You've got the guy and you've got the girl, and
what do you do when your world's ending, right, you
have sex basically, So that's like a last ditch attempt
for cancer cells to try and come up with some
kind of evolutionary innovations that are going to get them
out of trouble. But then there's one more thing that

(43:24):
happens at the end of a disaster movie, right, you
leave the planet. Sure, yeah, and like and cancer cells
do this, and this is absolutely incredible. So so so
this is where we get to infectious cancer, the idea
that it could actually be contagious. Yeah, so this is

(43:45):
this is kind of spooky and scary because it's a
very medieval idea that cancer is contagious, that you catch
it from someone. And I will say that in certainly
in humans, there's no contagious cancers that we know of.
But the first example was the Tasmanian Devils. So this
was back in the nineties nineties. The Tasmanian Devils, they're

(44:06):
all in Tasmania. Southern Australia. They're very cute animals, but
like they're evil. They they're very you know, they're they're
placid more or less around humans, but they absolutely hate
each other. So when you get two Tasmanian devils together,
they're just like, really, go for it now, biting each
other's faces. And researchers started to notice that these animals

(44:30):
were getting big tumors in their faces and in some
cases it was killing them, and that they're already endangered
as it is, and this cancer started sweeping through the
populations and I was like, oh no, what we're going
to do. And a woman in Australia, she was working
for the for the government in a hospital. She she
was looking at cancer samples from humans and looking at

(44:53):
the chromosomes. It was a way back then of identifying
the kind of cancer you might have. And so she
started looking at these Tasmania devil cancer samples. Now, the
thing about human cancers is every human cancer is a
one off. It's a unique evolutionary event. It starts in you,
it grows in new it evolves in you, and it
it dies in you one way or the other. When

(45:16):
she was looking at these devil cancers, like they're all
the same from every animal. The chromosomes were absolutely the same,
and it's like that does not happen. That is that
she was like, this is a contagious cancer and U

(45:37):
and eventually they kind of pinned it down and it said, yes,
it was cancer cells transmitting from one devil to another
through that mechanism of biting and fighting and scratching. So
it's a you need with a contagious cancer. You need
to have a mechanism of transfer to get the cells
from one organism to the other. So with the devils,
it was it was biting and fighting. Um. And then

(46:00):
there was another cancer, contagious cancer. Which are we allowed
to talk about dog genitals? Oh? Yeah, I just I
just did. Um. Yeah. So there's a dog genital cancer
called canine venereal tumor as CTBT and so yeah, it's
again when when dogs have sex, it's not pretty, but

(46:22):
they get kind of tied together in the the gentleman
and lady department and that can cause some injury. So
again you have a mechanism for cancer cells to transfer
from one dog to the other. And this cancer it
transmits through populations. And there's a woman called Elizabeth Murchison
who's in Cambridge University. She started studying the devils and

(46:45):
then she started studying these dogs and they discovered that
these cancer cells in the dogs have been around for
thousands of years. The first dog with that cancer lived
and died thousands of years ago, and it's gone all
over the world. And that's like, it's like the oldest
I don't know, it's like the oldest mammal. I suppose.

(47:07):
It's just incredible. Um this they've worked out what kind
of dog it was. It was, you know, a little
kind of dog with like pointiers and a sandy coat,
and it's amazing. So when you're saying it's the oldest mammal,
in a way, you're saying that the tumor is, in
a sense a part of that original dog. It is
that dog. It is that dog's body exactly. The tumor

(47:30):
arose in the dog. It's got the genome of the
original dog. Like seriously messed up, I mean, and these
cancers are now evolving independently in different dog populations all
over the world. But yeah, it's it's an incredibly long
lived organism. I suppose. So that that was one devil
cancer which was relatively recent a dog cancer, and then

(47:51):
they found a new second devil tumor that had arisen
even more recently. So that's very unlucky for the devil's
and they think it's because again they're an inbred population.
So with this this fight e bity mechanism of transfer,
so you've got quite a high probability that this might happen.
And then there's all these weird shellfish that have cancer

(48:14):
and seem to transfer it between each other by shedding
cancer cells into the sea, which is just disgusting. Um
has made me rethink my idea of swimming. But there's
some really incredible examples of transmissible cancers in nature. And
again I think the more we look, the more we're

(48:34):
going to find. You know, each one of these papers
just gets published and less and less impressive turn or
is more and more more and more turn up. But
there are some examples in humans, and I talk about
a couple in the book. So there's one which is
they're absolutely horrendous. Is a guy called Chester Southam who

(48:55):
was in New York, I think in the fifties, and
he was doing experiments on prisoners, mostly black prisoners in
the US people in care homes can existing cancer patients.
People are very desperate and not consenting to these experiments properly.
And he was putting cancer cells into them and in
some cases they did developed humors. Mostly they didn't, which

(49:18):
shows the human immune system will fight these cells off,
but some of them did. And also there's a very
sad story of a woman who developed melanoma. And at
the time, this is around about this the sixties. I
think it was an idea that you could transplant some
cancer cells into someone to get an immune reaction going uh,

(49:41):
and then give that kind of blood back to the
patient and it would help to treat their cancer. It's
sort of an early idea immunotherapy, so basically getting someone's
donor immune system to generate some antibodies to neutralize the
cancer when you donated them. And so this woman's mother said,
all right, I'll do this. You transplant me with a
bit of my daughter's cancer. I'll generate the antibodies, and

(50:05):
then you can take my blood and give it to her.
And unfortunately, the daughter actually passed away very quickly, and
a few weeks later it was discovered that the mother
actually did have the cancer growing in her, and and
then shortly after that the mother passed away from the
cancer that had killed her daughter. And you're like, it's

(50:26):
rare and probably because they were related. You overcome the
problems of immune rejection, but you're like, ohhs, well, it
could happen. Ah. And then there's the most absolutely disgusting one,
which is this is really sad and awful but also gross. Um. So,

(50:52):
there was a man who walks into an HIV clinic
in Colombia complaining of feeling very unwell and so HIV
for a long time, so his immune system was very suppressed.
He hadn't been taking his medication, and he was feeling
very unwell. And they looked in his body and they
found all these little nodules in his body and and

(51:15):
they were like, well, these don't look like human cells.
This is very weird. And they were well, maybe it's
a parasite or something. And they gave him some some treatment,
and he went away and and he came back in
his life, it's still no better, and there's more and
more of these weird things. And they looked more closely,
they got them analyzed, and it was he'd been infected

(51:36):
by tapeworm. But the tape worm had a cancer and
the cancer had infected the man, and you're like, whoa,
that is a just the stuff of nightmares. Um, be
highlights how powerful the human immune system is at the
best of times. And see is like, oh my god.

(51:59):
You know, also tape worms can get cancer, so it
sort of highlights a lot of the principles at work here.
And very sad for that man, but unfortunately he couldn't
be treated in the time. Um but it's like, this
is an incredible biological phenomenon really, that we were only

(52:19):
just starting to understand. Yeah, I mean, these are all
just unbelievable examples and and go in the column of
you know, the case you make that we should shift
towards that thinking of cancer in an evolutionary and ecological
way instead of a purely molecular way. So if that's
the dark side, what about thinking about cancer in an

(52:40):
evolutionary and ecological way gives you hope? Do you see
lines of research extending from that framework that give you
hope for the future and of cancer treatment and and
the fight against cancer? Yeah, so you know, you can
get very sort of nihilistic about this, and I oh yeah,
resistance always emerges. Evolution is so powerful. But then I

(53:02):
look at the kind of researchers that are really getting
to grips with evolutionary therapy, and it's a growing bunch.
It's all started, particularly, I think, from the Mopic Cancer
Center in Tampa and Florida and a man called Bob
Gattenby and his team there, and they are just really
incredible people. So, I mean, I'm a biologist, I am biased,

(53:24):
I will say against mathematicians and physicists. But it turns
out the secret the secret weapon in the war on
cancer is maths. So there you go. So he's brought
together all these mathematicians and biologists and they're actually doing
evolutionary modeling on cancer populations, trying to understand the rise

(53:46):
of the fall of resistant and sensitive cells, trying to go, Okay,
if if resistance is going to emerge when you treat,
can we predict how that's going to happen? How do
we kind of let cell populations balance them cells out
and stay in control rather than just you know, nuke

(54:06):
it from orbit, which is kind of the conventional idea
about cancer therapy. And so they've they've done a most
successful clinical trial so far is in prostate cancer. And
it's it's an absolutely fascinating trial of an approach that
they call adaptive therapy. And the way it works is
you assume that within any cancer at any size, there

(54:28):
are going to be sensitive cells to the drug and
there's going to be resistant cells to the drug. And
it's a drug called abbiratarone that they use, and so
what you do is you you also have to have
a marker that will tell you how much tumor is
in anyone's body at any given time. And for prostate cancer,

(54:48):
we have quite a good marker. It's called p s A.
So you can look at someone's p s A level
in their bloodstream and say, okay, that's a proxy for
how much cancer is in their body. And so they
start eating this these men with prostate cancer advanced prostate cancer,
so they're there. Probably their their life expectancy is about
eighteen months on this drug before it starts to get

(55:10):
really gnarly for them. And and they treat them with
this drug and it starts to work and their tumors
start to shrink, and then the difficult bit is you
wait till it's shrunk to half the size it was
and then you stop treating and you wait. So the

(55:31):
idea is you've knocked down all the sensitive cells, or
as many of them as you. You feel the urge too,
and there's still some sensitive cells there which are keeping
the resistant cells in check. And then you wait and
you wait for them to grow back. But because being
resistant to the drug is kind of it's it's it's
not very good for you, these cells are less fit,
they struggled to grow as much. So it's the sensitive

(55:52):
cells that grow back as so you treat them again.
And so you ride this kind of roller coaster of
start the drug, let the tumor shrink, stop the drug,
let the tumor grow. Start the drug, let the tumor shrink.
And they have men who have been on this regime
for four years. I mean gradually in the end the
tumor does, the cancer does start to evolve because that

(56:16):
population of resistance cells does start to get bigger, very
slightly every time. But this is you know, if this
was a drug and you were saying, I've gone from
average eighteen months through to four years, you know, if
this was a drug, the industry would just be throwing
itself at trying to to get this you know, get
this to the clinic, get this to work, get this

(56:37):
to everyone. So that was that was a really powerful
demonstration of an evolutionary therapy of understanding and accepting you've
got these cell populations in there and they're kind of
how to balance them. There are other sort of adaptive strategies,
evolutionary strategies. There's one called the Suckers gambit, which is
where you treat cancer cells with a drug that you

(56:59):
want them to develop evolved resistance too. But you know
that for them to have evolved resistance, they have to
have activated certain molecular pathways, they have to have gone
down an evolutionary route in one direction, and then you
hit them with another drug that they can't get out of,
so you're sort of you you get them into a
blind evolutionary end. It's like a double punch, yeah, exactly.

(57:23):
You know, there's there's lots of ideas out there about
using the drugs we have, maybe even using drugs that
are less you know, less good. I suppose less potent, less,
less toxic, because you don't want to just nuke everything.
You want to start thinking about how to balance cells,
how to control cell populations. But this comes to the

(57:46):
really difficult thing, which is the psychological element of this,
because this is not the cure for cancer that we
were promised. This is not the magic bullet. This is
not eradicated from your body. There may be some approaches
where we actually can and you know, the earlier you
can diagnose cancer if you can treat it with surgery. Um,

(58:07):
some cancers can be treated really effectively and cured at
an early stage. But for cancers, once that evolutionary process
is really kicked off, you have to approach them with
an evolutionary mindset, and that may mean driving them to
extinction with the right combination of sort of extinction events

(58:28):
at the right time. Um. But it's a it's not
going to be this kind of perfect cure that I
think people want that we've been led to expect, and
it certainly won't be one magic bullet drug that like, Yep,
that's it, that's that's the cure. That's it. We can
now sell this and give it to everyone because as

(58:49):
I said, you know, every every individual cancer is a
is a one off, it's a special snowflake. It's an
individual evolutionary event. So we need to understand that where
is it going what's it doing, what are what are
the contingencies in there? And how can we either drive
this cancer to extinction or drive it to a place

(59:11):
where we can control it for the rest of someone's
natural lifespan. And you know, that's not a cure for cancer,
but to me, that's you know, I think that's getting there. Yeah,
I really like that thinking of the body, not like
as a malfunctioning car with a part that needs to
be replaced or fixed, but as an environment with natural

(59:32):
populations within it that in the relationships between them need
to be managed. Yeah, sort of tending the garden is
the idea, but you can take the ecological thing further.
There are different sorts of cancers. You know. Some are lush,
exotic rainforests that are really going for its summer arid deserts.
Some are more like, you know, kind of neatly tendered gardens.

(59:53):
But we've got to understand what each person's cancer is
really like and how it's behaving, not just a shopping
list of mutations that you can try and fire magic
bullets at, but a much more holistic understanding and accepting
that evolution is going to happen, always has done. That's
why we're here, that's why the diversity of life is here.

(01:00:16):
But if we can harness it and work with it,
then I really think we can start to make some
progress in in some of these most difficult advanced cancers. Alright,
I guess we will wrap it up there. But again,
the book is Rebel Cell. It's a fantastic reed. We
we really think you'll like it. And also you can
check out cats podcast, the Genetics Unzipped podcast. Is there

(01:00:38):
anywhere else they should look for your work right now,
Cat um, my first book, Herding Hemmingway's Cats, is available.
I've got another book called How to Code a Human
and you can find me at on Twitter. I'm Cat
underscore Arnie. Pretty much yeah, every everything is pretty much there.

(01:00:59):
All right, Well, that does it. Thanks again to Cat
Arnie for joining us for this discussion. Again, if you're
trying to look her up, you can find her on
Twitter at at k A T Underscore A R N.
E Y. And if you're looking for her book, Rebel
Cell Cancer Evolution and the New Science of Life's Oldest Betrayal. Uh.
The UK version is coming out on August six. The

(01:01:20):
US version is coming out on September twenty nine. You
can pre order now, I believe, If not, keep an
eye out for it, and you can also look it
up on her website at Rebel cell book dot com
or check out her work on the Genetics on Zipped
podcast at Genetics n zipped dot com. It's just such
a great book title. I just keep coming back to

(01:01:41):
how much I love that book title. It really is
great and uh and it has some resonance throughout the
book with some other themes and metaphors she discusses in there,
such as the Society of Cells. So, Robert, I really
do recommend you read it if you get a chance.
I I really enjoyed this one, all right. I'll have
to look for in September. In the meantime, Yeah, everyone
out there would like to listen to additional episodes of

(01:02:02):
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(01:02:23):
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