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?
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/
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.
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?
Prostate cancer is not a huge risk because the Prostate is a massive number of cells. So, cell type matters and elephants for example don't have the same number of skin cells relative to body mass as humans.
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.
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.
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).
> 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.”
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?
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.
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).
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.
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.”
I really enjoyed his style of going back and forth between present time and history. His style of connecting all the dots in evolution of cancer diagnosis and research is mesmerzing. Can't wait to read his other book, The Gene.
Seconded, I just finished this book and it is an introduction to the basic science and history of genetics that reads like a masterfully written narrative. If you have any interest in genetics I think The Gene would be well worth your time.
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.
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.
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.
As weight and lifespan increase, unchanging cancer rates per capita actually mean substantially increasing cancer
resistance per cell/year, as discussed here: https://news.ycombinator.com/item?id=14699628
Of significant note is the naked mole rat (a 30g 8cm rodent so about the size and weight of the average house mouse) which for a long time was though immune to cancer (they're not, but they are ridiculously resistant to it).
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?
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.
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...
20 copies seems ridiculously redundant evolutionarily speaking. There must be other uses for this gene that having any fewer would mean a lower survival rate.
I wonder if this means resistance against mutation and lower rates of adaptability to environment?
TP53 is activated by phosphorylation (i.e. the addition of a phosphoryl group to the enzyme). The enzymes which phosphorylate TP53 in turn respond to several types of stresses (e.g oxidation, membrane damage, heat) and a cascade of checkpoints that respond to different kinds of DNA damages.
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.
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.
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
