
How Elephants Avoid Cancer (2015) - avenoir
http://www.nature.com/news/how-elephants-avoid-cancer-1.18534
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lordnacho
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?

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ggrothendieck
You don't necesssarily need to know the rates. "If blue whales got 1,000 times
more cancer than humans, they would likely die before they were able to
reproduce and the species would quickly go extinct" yet the species does
exist.
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3060950/](http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3060950/)

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pmiller2
Sure, but such reasoning only puts rather gross bounds on the possible rates
of cancer.

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Retric
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.

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mindviews
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?

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stevenwoo
A mouse lives at most three years in captivity, in the wild they only live one
year due to predation so the effectiveness of the anti cancer mechanism in
mice could be seen as equivalent to those of the elephant! :) Perhaps another
interpretation could be - one animal species doesn't evolve into a larger mass
animal unless accompanied by more effective anticancer measures.

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candiodari
Generally cells get cancer after having processed a certain amount of energy.
That means that some fly species will reach obvious senescence in a matter of
double-digit hours whereas for humans it takes 60 years or so. But cell-for
cell, the cells in those bodies do "about" the same in terms of watts that go
through them (nanowatts in reality, of course).

This is related to age and cell count, but it's not the only factor. For
instance when an animal becomes larger, the size of the animal goes up with
the third power, while energy use only goes up with the second power. So the
bigger an animal, the less individual cells can do.

The way to arrive at this insight is to imagine animals are balls. To about a
factor 2 this is accurate. The energy use is limited by energy exchange with
the outside world, ie, it's limited by the amount of skin they have, which is
the surface of the ball. The amount of cells is related to the volume the
animal occupies.

The net effect of this is that bigger animals live longer. Some details are
different too. For instance, larger animals tend to have larger cells. So the
cell count goes up, but not by as much you'd think (If humans had mouse-sized
cells in their tissues we'd be on average 54cm).

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fiiv
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.”

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lr4444lr
_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?

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ValentineC
This is an article from 2015.

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ajuc
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?

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AnnoyingSwede
They avoid cigarettes and anything else burning like the plague?

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nagVenkat
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).

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headmelted
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.

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forgot-my-pw
Love this part in the Author's Note:

 _In a sense, this is a military history—one in which the adversary is
formless, timeless, and pervasive. Here, too, there are victories and losses,
campaigns upon campaigns, heroes and hubris, survival and resilience—and
inevitably, the wounded, the condemned, the forgotten, the dead. In the end,
cancer truly emerges, as a nineteenth-century surgeon once wrote in a book’s
frontispiece, as “the emperor of all maladies, the king of terrors.”_

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Pica_soO
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.

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folli
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.

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Pica_soO
Large and old are factors on the indivdual. But preyed upon is a factor
impacting on the history of a species (all individuals).

So a (in evolutionary terms recently) huge, old rodent, still carrys the
baggage of the past.

The size matters only in evolutionary time lengths - if a lot of individuals
are to big to be predated.

PS: Was the factor of age reduced cell division as a tumor hiding factor even
removed from the statistics?

Finally what about metabolism rate as amplifier of cancer? Slow metabolisms
with a constant intake (no peaks of production and consumption), no constant
heating costs due to small body size.

My "Speculation" is just there to remind people that taking some individual
factors and correlating them into seemingly meaningful results ignores the
complexity of the situation.

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folli
Please note that the word "animal" in the quote of Peto's paradox and my
comment refers to "species" and not an "individual", as you infer in your
reply.

So yes, the species will include the baggage of the past.

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Pica_soO
Which in itself is interesting.. which animals did we know to continuously
grow for live and only recently hitting upon hard times.

Dinosaurs- but birds do get cancer and are not predated- crocodiles and
Commode-dragons seem to be excluded. Maybe im wrong here.

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folli
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.

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agumonkey
Could you make a curated list of the other factors ?

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nkoren
Mentioned at the end: they don't consume much in the way of junk food and
cigarettes.

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agumonkey
Junk food and cigarettes (and "modern" lifestyle) is not all though.

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another-dave
They rarely eat sausages or other processed meats & were ahead of the game
when "5-a-day" became "10-a-day" for fruit & veg.

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pvaldes
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.

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agumonkey
Plot twist, maybe a minute amount of toxic compounds helps health. After all,
taxol is a yew tree extract.

~~~
autokad
thats certainly true for some substances, but its a very delicate balance.
take selenium, a little but lowers many cancer rates, a little bit over that
and it increases cancer rates.

I am also reminded of steve jobs and his all fruit diet. I recall astin
kutcher got inspired by him and took on the diet and ended up in the hospital
with pancreatic problems. pancreatic cancer killed steve jobs

