How Elephants Avoid Cancer (2015)
nature.com
nature.com
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?
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).
Cancer is not a single mutation. So, generally the first cancer cell is a descendent of the first cell that had a dangerous mutation. Further, some cells are being constantly produced over a lifetime (skin, GI tract etc), so you can mostly ignore mussel fiber or fact cells when calculating cancer risks.
In that context there are divisions related to growth and divisions related to homeostasis. Tacking on 4 extra related to growth is relatively less important vs lifespan and other factors especially when you look at human cancer risks pre 44.
> 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.”
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?
Maybe that's another reason?
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.
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.”
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.
"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.
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.
So yes, the species will include the baggage of the past.
Dinosaurs- but birds do get cancer and are not predated- crocodiles and Commode-dragons seem to be excluded. Maybe im wrong here.
Ah, you know my family motto!
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.
I wonder if this means resistance against mutation and lower rates of adaptability to environment?
Furthermore, there's an additional protein (HDM2) that binds to TP53 in healthy cells and deactivates TP53.
But in short, no, there's not a simple heuristic. As most often the case in the cell, it's a finely tuned balance of several pathways, which tips in one direction or the other depending on the environment and all the other pathways in the cell.
Many times a day here means probably less wattle poison to deal in each meal.
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