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  • Cancer is a creepy and mysterious thing.

  • 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.

  • [Kurzgesagt Theme]

  • 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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  • [End Credits]

Cancer is a creepy and mysterious thing.

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B1 cancer paradox tumor immune tumour large

Why Blue Whales Don't Get Cancer - Peto's Paradox

Video vocabulary