Elephants Rarely Get Cancer, Now We Know Why (2015)
blogs.discovermagazine.com
blogs.discovermagazine.com
My understanding is that cancer is one of those things you die from if you don't die at child birth, get eaten by predators, or get the flu, polio, malaria, the plague, etc.
That is, the reason cancer is such a big deal in modern times is because other causes of death have been controlled.
I don't know much about elephants but I imagine cancer is still low on their list of things to worry about (humans are probably a lot higher up) If they started living a lot longer, it would probably show up more.
People under 40-50 also rarely get cancer. Although I'm sure the human environment has produced some more causes of it that make those rates higher than they used to be.
(source: wife used to be a fancy-rat breeder)
True, it might be easy to claim that there is no way to select for longevity because longevity happens after the birth of the offspring. Having elder generations around to improve the odds of survival for the descendants should make longevity a possible factor in selection.
> Based on Neolithic and Bronze Age data, the total life expectancy at 15 would not exceed 34 years. Based on the data from modern hunter-gatherer populations, it is estimated that at 15, life expectancy was an additional 39 years (total 54), with a 0.60 probability of reaching 15.
https://en.wikipedia.org/wiki/Life_expectancy#Variation_over...
https://www.cancer.org/cancer/cancer-basics/history-of-cance...
Like humans, elephants start their life with one cell, which is then replicated over and over again until the end of their lives. But somehow, elephants manage to reach body sizes 100 times bigger than humans (meaning many more cellular divisions) without having cancerous cells.
I think that's the basic observation that triggers this kind of research.
Disclaimer: I am no expert at all.
Nothing, actually. I'd rephrase the parent comment.
There is in fact a fixed (somewhat small) probability that replication ends up in a mutation. But looking at the continuous replication going on in our cells as a Bernoulli process, you can find a number N such that there is a probability of Q (say 99%) that a mutation happened before the Nth replication.
Also when a cell becomes cancerous it usually has a broken version of many of the checks to avoid uncontrolled division and to ensure that the cell cooperates with the neighbor cells. This will probably cause problems in the formation of the embryo or fetus. Or kill the baby before reproduction age. So cancerous germ cells are self eliminated from the gene pool.
Killing off the misbehaving cells is an obvious solution but this must also shorten the organisms lifespan via organ failure.
You only get so many divisions from the zygote before a cell line must be killed off, put into senescence, or it starts malfunctioning due to accumulated mutations (~60). A good solution produces as many differentiated functional cells as possible while minimizing divisions from the zygote.
Really, this article shows a fundamental misunderstanding of how our bodies work.
Fundamentally we could live a really long time in the far future, which is maybe closer to us today than we are to 0 A.D.
And just because you made it from zygote to birth does not mean your master copy was "pristine".
But yeah, if you could somehow replace your tissue stem cells in situ with ones that are closer to the original state it would generally allow your body to continue functioning for much longer. I mean some of those mutations could be beneficial to your particular environment too, but in general... Yeah.
The idea would be to use some far-future technology to enable a kind of DNA repair that cells themselves can’t do, using non-local information from other cells in the organism.
So I think that could be more difficult than you expect.
"Upregulated p53 activity in humans is implicated in Huntington's disease. Which makes sense, since the symptoms involve early death of brain cells. So this isn't a panacea in itself. But as we learn more of the gene regulatory networks involved, we may be able to develop something much more fine-tuned that has the benefits without the costs." - Suzanne Sadedin
I wonder if they could try putting it in to tasmanian devils, which have suffered enormous cancer rates recently.
Can you back that up somehow? That doesn't sound at all right to me.
Edit: For the upvote, downvote brigade -- with zero reply so far, but this comment has gone to zero and back to one umpteen times already -- I'm genuinely curious. This isn't some kind of gotcha question.
I have a genetic disorder. I have umpteen relatives who have had cancer. I actually have a serious vested interest in better understanding how this stuff works.
I mean, I guess it would depend on how you are introducing the gene. How many cells it is getting into.
But if it causes defective cells to suicide, why would it matter where the defect is coming from? I don't think we really have a good handle on what causes cancer. I suspect more cancer is due to some infectious agent than is generally believed and we know genetic variations have significant impact on the immune system and its ability to function at all.
It's cancer. You're trivializing the ultimate source of the problem. If we could ensure universal targeting of cancer cells, we wouldn't need a technically elaborate method of cellular death, like gene modification.
You might as well suggest solving world hunger by just feeding everyone.
No, I'm not. But it's occurred to me that I'm imagining this as treatment for Tasmanian devils that already have tumors. Maybe other people are envisioning it as a preventative measure.
And maybe that's part of the problem in trying to discuss it.
If the cells knew when they were supposed to die, then it wouldn't be cancer.
If the cure is telling the cells when they're supposed to die, then the cells that don't listen survive, ergo the cancer survives.
Which, in the sense of (non-preventitive) treatment, makes it a problem of universal targeting.
They're less like normal cancers, and more like parasites made of cancerous cells. Moreover, they're not even typical cancer cells -- they're cancer cells which have been dividing (and continuing to mutate) since the disease first came into existence, to the extent that their genetic material has become wildly divergent from that of the host species.
Typical genetic therapies for cancer focus on the hope that enough of the normal apoptotic pathways still exist that the cancer cells can be "convinced" to recognize themselves as cancerous and undergo cell death. In the case of transmissible tumors, though, it's likely that these pathways have been entirely destroyed through selective pressures on the cancer.
I thought I would add that what makes the tasmanian case interesting is that though the body is generally pretty good about detecting and removing foreign cells (including viruses and bacteria), somehow these contagious cancers elude this detection and are allowed to proliferate [1]. It is likely that if the tasmanian devil's immune system were able to detect the intruder cancer cells as coming from another individual, it would eradicate them with ruthless efficiency. Why these cells are able to skirt the host immune system though is a different question.
That’s a great idea.
Also, I advocate to make endangered animals legal to keep as pets.
Look how successful cats and dogs are.
Ya’d need to keep them in an enclosure. They breed in captivity fine.[1]
I wonder if they could be bred to become house pets. Could take a while.
1. http://theconversation.com/tasmanian-devils-reared-in-captiv...
After all, the success of dogs didn't do anything to prevent the near extinction of the wolf.
That's not to say that Tasmanian devils are docile enough to be that kind of pet, though.
Part of what makes the cancer so transmissible with Tasmanian devils is their predisposition for biting each other, especially on the face, well past the point of drawing blood.
I mean, they're not called devils because they're red with horns.
It's been just over 4 years since that article. I wonder what has happened since.
> “When I have a patient in front of me diagnosed with the syndrome, they will almost certainly get cancer,” he said. “But in that moment I’m able to tell them elephants don’t get cancer and we are working with the zoo and the circus to learn from elephants so one day you never have to get cancer.”
This seems a bit unethical to raise hope for a cure that statistically has a very low chance of passing clinical trials
How many cells does a blue whale have?
These genes are also found in humans but the hope is that studying genes from animals like elephants and whales we can find ones that we don't have.
A lot of cancer cells are developed because of constant background radiation, if you get older you just were exposed to more of it.
Elephants have a much higher volume to be affected by it, so just from an evolutionary perspective they had to develop a better resistance. The ones who got cancer early couldn't reproduce as well.
Does that make sense? Or does the article say exactly that?
[0]http://m.cshperspectives.cshlp.org/content/2/2/a001107.full [1]https://www.ncbi.nlm.nih.gov/m/pubmed/18812169/
Increased p53 expression under the endogenous promoter protects “super p53” mice from tumorigenesis without the undesirable effects of premature aging.
https://www.sciencedirect.com/science/article/pii/S153561080...
>Garcia-Cao and collaborators report the generation of novel transgenic mice, called “super p53.” The super p53 mice express wild-type endogenous p53, and also carry one or two extra copies of a normal p53 gene, inserted as transgenes in the form of large genomic fragments of 130 to 175 kilobases. Because the additional p53 gene is expressed from its own promoter, the transgenically expressed p53 seems to be regulated in the same fashion as endogenous p53.
[1] https://nutritionfacts.org/video/how-not-to-die-from-cancer/...
One study from 2014: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3565018/ This compared non-vegetarians with multiple types of vegetarian diets.
> Conclusion: Vegetarian diets seem to confer protection against cancer.
> Impact: Vegan diet seems to confer lower risk for overall and female-specific cancer compared to other dietary patterns. The lacto-ovo-vegetarian diets seem to confer protection from cancers of the gastrointestinal tract.
A more recent perspective on the topic of diet as a cancer risk: https://www.tandfonline.com/doi/full/10.1080/01635581.2017.1...
> Abstract: The role that nutrition plays in cancer development and treatment has received considerable attention in recent decades, but it still engenders considerable controversy. Within the cancer research and especially the clinical community, for example, nutritional factors are considered to play, at best, a secondary role. The role of nutrition in cancer development was noted by authorities as far back as the early 1800s, generally under the theory that cancer is "constitutional" in its origin, implying a complex, multifactorial, multistage etiology. Opponents of this idea insisted, rather vigorously, that cancer is a local unifactorial disease, best treated through surgery, with little attention paid to the etiology and possible prevention of cancer. This "local" theory, developed during the late 1700s and early 1800s, gradually included, in the late 1800s and early 1900s, chemotherapy and radiotherapy as treatment modalities, which now remain, along with surgery, as the basis of present-day cancer treatment. This highly reductionist paradigm left in its wake unfortunate consequences for the present day, which is the subject of this perspective.
(I am citing the second publication only in defense of my original comment, for future reference. In retrospect, when discussing health benefits of diet, I should have used the term whole food plant based diet instead of vegan to avoid the baggage that term carries.)