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How Elephants Avoid Cancer (2015)

202 points| avenoir | 8 years ago |nature.com | reply

50 comments

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[+] lordnacho|8 years ago|reply
How are animal cancer rates established in the first place? It seems like you'd have to go through the tissues of a large number of creatures to do this. Plus you have the issue that the carcasses you get might be selected unevenly, eg the cancer rate among zoo elephants might be different to the ones in the wild?
[+] Retric|8 years ago|reply
Seems like a mistake to assume drastic differences in the number of cell divisions between say humans and Elephants. Starting from one cell it's an exponential process so it's likely ~50 vs ~54 cell divisions or something.
[+] mindviews|8 years ago|reply
That's not really the right reasoning to use here. The number of cell divisions isn't 50 vs. 54, it's more like 2^50 vs. 2^54.

At some point the animal will exit the growth phase and reach a stable cell count and an elephant that reaches adulthood will just simply have more cells than a mouse. A 5,000kg elephant has a lot more cells that could develop cancer than a 0.02kg field mouse. And if that elephant lives 60 years instead of 1.5 for the mouse (let's just say for the sake of argument that cells divide once per year for replacement), that could be something like a 10,000,000 fold difference in the number of "cell-years" and cell divisions (at once per year) for something to go wrong and cause one of those cells to become cancerous.

"Peto noted that, in general, there is little relationship between cancer rates and the body size or age of animals. That is surprising: the cells of large-bodied or older animals should have divided many more times than those of smaller or younger ones, so should possess more random mutations predisposing them to cancer. Peto speculated that there might be an intrinsic biological mechanism that protects cells from cancer as they age and expand."

So, yeah, it seems like something important has to be going on. If a mouse can die of cancer at 1 year old, how can any elephants survive to 60?

[+] sxv|8 years ago|reply
that's a HUGE difference, no?
[+] fiiv|8 years ago|reply
Good quote from the article:

> Mel Greaves, a cancer biologist at the Institute for Cancer Research in London, agrees that TP53 cannot be the only explanation. “As large animals get bigger, they become more and more sluggish,” he notes, thereby slowing their metabolism and the pace at which their cells divide. And protective mechanisms can only do so much to stop cancer, he adds. “What would happen if elephants smoked and had a bad diet,” he says. “Would they really be protected from cancer? I doubt it.”

[+] lr4444lr|8 years ago|reply
That is surprising: the cells of large-bodied or older animals should have divided many more times than those of smaller or younger ones, so should possess more random mutations predisposing them to cancer.

Can a biologist reading this confirm that? I thought smaller organisms generally have much faster metabolisms to offset their shorter lifespans. Or is it the same at the cellular level?

[+] ajuc|8 years ago|reply
I've read that big mammals (liek whales) can live through cancer without noticing, because cancer often mutates itself to death before it can kill the host.

Maybe that's another reason?

[+] AnnoyingSwede|8 years ago|reply
They avoid cigarettes and anything else burning like the plague?
[+] nagVenkat|8 years ago|reply
Anyone interested in Cancer has to read the Pulitzer prize winning book, The Emperor of All Maladies: A Biography of Cancer by Siddhartha Mukherjee. It's one of the most interesting non-fiction books I had ever read and in one of the latter chapters he mentions about the genes which prevent tumors (as discussed in the posted article).
[+] headmelted|8 years ago|reply
Agreed - utterly gripping history of oncology research for a layman (i.e. me!).

On a side note, I really like his writing style. It's not easy to present scientifically complex concepts in simple terms to someone without a background in the subject matter. This (for me) was right up there with Hawking and Sagan in terms of being easy to follow along with, without being patronizing.

Also, be warned if you're squeamish, the book covers a period in history (before metastasis was understood) when the favoured approach to removing cancer was to just jam the knife in further.

[+] Oras|8 years ago|reply
Thank you for the book recommendation, just bought it. Comments like yours are why I'm keen to HN.
[+] gonehome|8 years ago|reply
I'd recommend his second book too (The Gene) - it's just as good.
[+] agumonkey|8 years ago|reply
Ha, I have this in a list, and unsurprisingly forgot about it.
[+] f4rker|8 years ago|reply
There are like 100+ cancers and likely not all genes affect all cancers.
[+] Pica_soO|8 years ago|reply
There is a corellation between beeing hunted by a predator (external death stimulus) and not beeing hunted by a predator (internal death stimulus). Predators life a dangerous life, for them theire daily activity is a eds. Obviously the benefits of cancer suppressing DNA in a population apply only if you are either to well hidden (naked mole rat, sloth) or to big to be predated (Rhino, Elephant, Whale). Sorry, we as humans are part of a predatable species, so live fast and leave a devourable corpse for your descendants to mourn was our main strategy. If in search for human compatible cancer avoidance, the biggest interest should be on the most well hidden monkey - or the biggest (silverback).

Interesting is also how the re-productive cycle factors into this. If a individual takes a long time to grow up- cancer is a selector tortoises, if the reproduction is fast (mice/birds) cancer is basically not important. If every mice would get cancer after year 2 - the species still would continue.

[+] folli|8 years ago|reply
The following statement from the article is at odds with your speculation:

"Peto noted that, in general, there is little relationship between cancer rates and the body size or age of animals."

According to your speculation, you would expect that large and old animals would have a lower cancer rate.

[+] richmarr|8 years ago|reply
> live fast and leave a devourable corpse

Ah, you know my family motto!

[+] ltwdm|8 years ago|reply
I am curious why "human compatible" patterns would be only found in primates etc.? Aren't these about molecular mechanisms and proteins? Is it hard to translate the results to humans if some promising mechanism is found in more basic molecular level?
[+] folli|8 years ago|reply
Summary:

The gene TP53 is a tumour suppressor, that is activated when cell suffer DNA damage. The encoded protein either repairs or kills the cells, thereby preventing the cell to become cancerous.

Humans and most other mammals have only one copy of this gene, while Elephants (which are known for their very low cancer rates) have twenty copies of this gene.

Compared to other mammals, compromised Elephant cells are killed at a much higher rate, instead of being repaired.

However, this is most likely not the only factor at play.

[+] castratikron|8 years ago|reply
Humans only have one in their genome. You get one from each of your parents. So everyone has two copies of p53. You can afford to lose exactly one of those copies, but once you lose the second...
[+] petard|8 years ago|reply
Curious what the downsides / trade-off is to having twenty copies of this gene.
[+] Aardwolf|8 years ago|reply
How does this tumor suppressor know what is a good cell and what is a bad cell? is there a simple heuristic to decide that?
[+] agumonkey|8 years ago|reply
Could you make a curated list of the other factors ?
[+] another-dave|8 years ago|reply
They rarely eat sausages or other processed meats & were ahead of the game when "5-a-day" became "10-a-day" for fruit & veg.
[+] pvaldes|8 years ago|reply
We should remember that wild fruit and veg is not the same as domesticated fruit and veg. Plants are masters in poison design. Sausages are a much safer diet than being forced to eat Acacia compounds each day

Many times a day here means probably less wattle poison to deal in each meal.