In the process of trying to understand it, to get better at killing

it, we discovered a biological paradox

that remains unsolved to this day.

Large animals seem to be immune to cancer.

Which doesn't make any sense. The bigger a being,

the more cancer it should have.

To understand why, we first need to take a look at

the nature of cancer itself.

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Our cells are protein robots made out

of hundreds of millions of parts.

Guided only by chemical reactions, they create

and dismantle structures, sustain a

metabolism to gain energy, or make almost

perfect copies of themselves.

We call these complex chemical reactions pathways.

They are biochemical networks

upon networks, intertwined and stacked

on top of each other.

Most of them can barely be comprehended by a

single human mind, and yet they function perfectly.

Until... they don't.

With billions

of trillions of reactions, happening in thousands of networks

over many years, the question is not if

something will go wrong, but when.

Tiny mistakes add up, until the grandiose

machinery gets corrupted. To prevent this from

getting out of hand, our cells have kill-switches that

make them commit suicide.

But these kill-switches are not infallible.

If they fail, a cell can turn into a cancer cell.

Most of them are slain by the immune system very quickly.

But this is a numbers game. Given enough time, a cell will

accrue enough mistakes, slip by unnoticed, and

begin making more of itself. All

animals have to deal with this problem.

In general, the cells of different animals

are the same size. The cells of a mouse

aren't smaller than yours. It just has fewer cells in total

and a shorter lifespan.

Fewer cells and a short life means a

lower chance of things going wrong, or cells

mutating. Or, at least, it should mean that.

Humans live about fifty times longer, and have one

thousand times more cells than mice. Yet the rate of

cancer is basically the same in humans and

in mice. Even weirder, blue whales,

with about three thousand times more cells than humans

don't seem to get cancer at all, really.

This is Peto's Paradox- the baffling

realisation that large animals have much, much

less cancer than they should.

Scientists think there are two main ways of explaining

the paradox: evolution, and hypertumours.

Solution one: evolve, or become a blob

of cancer.

As multicellular beings developed six hundred million

years ago, animals became bigger, and bigger.

Which added more and more cells, and hence, more

and more chances that cells could be corrupted.

So, the collective had to invest in better and better

cancer defenses. The ones that did not died

out. But cancer doesn't just happen- it's a

process that involves many individual mistakes

and mutations in several specific genes

within the same cell.

These genes are called proto-oncogenes, and when they mutate, it's bad news.

For example, with the right mutation, a cell

would lose its ability to kill itself.

Another mutation, and it will develop the ability to hide.

Another, and it will send out calls for resources.

Another one, and it will multiply quickly.

These oncogenes have an antagonist, though.

Tumour suppressor genes.

They prevent these critical mutations from happening

or order the cell to kill itself

if they decide it's beyond repair.

It turns out that large animals have an increased number of them.

Because of this, elephant cells require more mutations

than mice cells to develop a tumour. They are not immune-

but more resilient. This adaption

probably comes with a cost in some form, but researchers

still aren't sure what it is.

Maybe tumour suppressors make elephants age quicker

later in life, or slow down how quickly injuries heal.

We don't know yet.

But the solution to the paradox may actually be

something different: hypertumours.

Solution two:

Hypertumours. Yes, really.

Hypertumours are named after hyperparasites: the

parasites of parasites. Hypertumours

are the tumours of tumours.

Cancer can be thought of as a breakdown in cooperation.

Normally, cells work together to form structures like

organs, tissue, or elements of the immune system.

But cancer cells are selfish, and only work for

their own short-term benefit. If they're successful,

they form tumours- huge cancer collectives that

can be very hard to kill.

Making a tumour is hard work, though.

Millions or billions of cancer cells multiply rapidly,

which requires a lot of resources and energy.

The amount of nutrients they can steal from the body

becomes the limiting factor for growth.

So the tumour cells trick the body to build new blood

vessels directly to the tumour, to feed

the thing killing it.

And here, the nature of cancer cells may become

their own undoing.

Cancer cells are inherently unstable, and so

they can continue to mutate- some of them faster

than their buddies. If they do this for a while,

at some point, one of the copies of the copies of the original cancer cell

might suddenly think of itself as an individual again, and

stop cooperating. Which means, just like the body,

the original tumour suddenly becomes an enemy,

fighting for the same scarce nutrients and resources.

So, the newly mutated cells can create a hypertumour.

Instead of helping, they cut off the blood supply to

their former buddies, which will starve and

kill the original cancer cells.

Cancer is killing cancer.

This process can repeat over and over,

and this may prevent cancer from becoming a problem

for a large organism. It is possible

that large have more of these hypertumours than we

realise. They might just not become big enough to notice.

Which makes sense. A two-gram tumour

is 10% of a mouse's body weight, while it's less than

0.002% of a human.

And 0.000002%

of a blue whale.

All three tumours require the same number of cell divisions,

and have the same number of cells. So an old blue whale

might be filled with tiny cancers, and just not care.

There are other proposed solutions to Peto's Paradox,

such as different metabolic rates, or different cellular

architecture. But right now, we just don't know.

Scientists are working on the problem.

Figuring out how large animals are so resilient

to one of the most deadly diseases we know could open the path

to new therapies and treatments.

Cancer has always been a challenge. Today,

we are finally beginning to understand it,

and by doing so, one day, we might finally

overcome it.

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