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 intro music) Kurzgesagt in a Nutshell 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 functioned 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 slained by
the immune system very quickly. But this is a numbers game. Given enough time a cell would accrue enough mistakes, slipped 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 50 times longer and
have 3!,000 times more cells than mice, yet the rate of cancer is basically
the same in humans and in mice. Even waiter, blue whales with about 3,000 times more cells than humans don't seem to get cancer at all really. This is PETO'S PARADOX: The baffling realization that large animals
have much much less cancer than they should. Scientists think there are two main ways of
explaining the paradox; evolution and hyper tumors. Solution one: evolve or become a blob of cancer. As multicellular beings
developed a 600 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 will 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; tumor 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 tumor. 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 tumor 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. "Hypertumors" Solution 2: Hypertumors Solution 2: Hypertumors
(Yes) Solution 2: Hypertumors
(Yes, really.) Hypertumors are named after
hyperparasites: the parasites of parasites. Hypertumors are the tumors of tumors. 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 tumors;
huge cancer collectives that can be very hard to kill. Making a tumor 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 tumor cells trick the body to build new blood vessels directly to the tumor, 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 tumor suddenly becomes an enemy, fighting for the same scarce nutrients and resources. So the newly mutated cells can create a hypertumor. 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 animals have
more of these hyper tumors than we realize, they might just not become big enough to notice Which makes sense a two gram tumor
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 tumors 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. This video was sponsored by... YOU! Bird: WHAT? If you want to help us make more,
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Ooh, I'm a biologist who specifically investigates Peto's paradox, attempting to uncover the cancer suppressive mechanisms in large mammals.
Alas, Kurzgesagts' second suggestion - that hypertumours may play a key role in cancer resistance - is little more than a pretty batshit hypothesis. There is no evidence whatsoever that hypertumours exist; the hypothesis presented is basically the outcome of a couple of models a few scientists came up with back in the mid-2000s. Indeed, more recent computational and experimental models looking at competing lines of cancer cells in the tumour microenvironment tentatively suggest that this sort of competition promotes tumour expansion, rather than suppressing it.
One of the actual key reasons why large mammals have lower incidence of cancer compared to relatively smaller mammals is, in fact, due to their lower metabolic rates (per unit mass). A typical blue whale epithelial cell cycle may take something like an entire week before division, compared to ~24 hours in a human, or even shorter in a mouse.
Given that the sorts of mutations required for cancer progression take place largely during cellular division, if the timing and duration of these divisions is more spread out, then it turns out the rate at which, say, a whale is accumulating mutations as a function of lifespan is actually pretty low (i.e. a human cell might accumulate many several mutations in the time it takes a whale to get just one).
And so, it simply takes much longer for whales and other large mammals to accumulate the mutations needed for cancer to form into tumours that are genetically well-equipped to spread. Hence why their rates of cancer are super low.
TL;DR: There is no evidence hypertumours exist or play a part in cancer suppression in large mammals. Kurz' throwaway comment about metabolism however is actually currently thought to be the main variable that determines why large mammals have much lower rates of cancer than expected.
I'm really really skeptical about this "hypertumor" business. On the face of it, it just sounds far fetched. But looking it up, I find very little evidence for it. There's a bunch of news articles, but they all stem back to a single 2007 paper.
And reading the paper, it's really not very convincing. They basically wrote a couple of computer programs to simulate the concept of hypertumors, and hey, their simulation found hypertumors. If you can even call it a simulation - seems like it's just a differential equation that "models" hypertumors. Most importantly, no one has ever actually observed a hypertumor, as far as I can tell. Besides mentioning it in a couple survey papers, it doesn't seem like any scientists found it fruitful enough to search for them.
The people who didn't ignore it were science media, which thought the idea of a tumor getting a tumor is really compelling storytelling. I guess kurzgesagt agrees - really good storytelling.
They don’t get cancer because they can’t keep their cigarettes lit
That cancer getting stabbed in the head at the end was so satisfying!
Haha