I will again mention my favorite cancer champions, the bats.
Bats very rarely get cancer (I tried to find the actual # of verified cases of cancers in bats, but came up short), and they have a lot of anti-cancer adaptations in their genome.
They are also really good at taming inflammation and activity of various viruses. That helps them survive infection with rabies - their systems just don't react as aggresively to the infection as ours (and most mammals') do.
This may help them against cancer as well. Not just p53 et al.
>Why hasn't evolution turned the dial up another couple of notches?
Because evolution doesn't care about us beyond reproduction age (after which is when most cancers occur, especially considering that historically that age was between say 16 and 35).
Or even better phrased, because evolution doesn't care or plan at all, it's a blind mechanism.
If a local minimum is ok, we'll stay there for as long as some environmental or other evolutionary pressure gets to move us further.
Cancer wasn't a big issue for most of our existance as species, especially with lower life expectancies, more active lifestyles, zero obesity, zero pollutants, etc.
In evolutionary terms, modern lifestyles are not even a blip, especially post-industrial ones which don't even register.
That's a very late specimen, and in fact one which "led scientists to speculate that he was involved in copper smelting", hardly typical of revolutionary timescales.
In evolutionary timescales, agriculture and permanent houses are a dot in the timeline, there were no longhouse dwellers for 95% of homo sapiens' history, and none at all for hominids before homo sapiens. They were nomadic foragers.
> Because evolution doesn't care about us beyond reproduction age (after which is when most cancers occur, especially considering that historically that age was between say 16 and 35).
This is the lie that needs. to die. Elder people were very important in even the most primitive societies. "lifespan" was low in pre-history, not because no one lived long lives, it was because infant mortality was very high.
Lie implies conscious distortion of the truth, the word you were looking for is "falsehood".
Second, even if "elder people were very important in even the most primitive societies", their role is much much important from evolutionary perspective than the pressures based on reproduction. Which is why most close primates get by with zero roles for post-reproduction grandparents.
Also elder people being "very important in even the most primitive societies" is a cultural and recent in evolutionary timescale phenomenon, first and only secondarily an evolutionary one.
> "lifespan" was low in pre-history, not because no one lived long lives, it was because infant mortality was very high.
They also lived shorter lives to begin with. Even in later historical times (say a couple of millenia or so), people's life expectancy at 15 (meaning, with infant mortality excluded) was much shorter than today.
Nobody said that "no one lived long lives" however. Some did. It's an aggregate limitation, not an absolute one.
Not disagreeing at all that elders are and have been important, but if it’s a benefit after reproductive age where does the selection come in?
I’m open to ideas. The only one I’ve been able to come up with is more second-order: the genetic benefit could come from having your children also pass on your genes, if there was a higher probability of them doing that with their parent alive past reproductive age.
"Bitch" by Lucy Cooke has a chapter dedicated to this if you're interested. It's pop sci but a great read and offers some new perspectives.
Menopause seems to be a biological adaptation to this - most mammals don't have it, they'll keep on having young until they're totally exhausted, and die not long after. Humans seem to be adapted so that women have a wild-type generation's worth (15-20 years) of useful lifespan post fertility.
> Because evolution doesn't care about us beyond reproduction age
I wonder if that's true. There's bound to be some benefits or drawbacks to aggregate fitness when people age. Sure, the contribution is very indirect and so it'll happen yet slower. But imagine if people lived until they were 300 years old. Depending on how frail they are, that could be a drag on reproduction and resources.
>The benefits and drawbacks that appear after reproduction age can’t be passed on.
If we consider grandparents, they could.
E.g. more fit/older grandparents -> more help and experience sharing for raising the kids given to the parents, more infants survive. This would chose for lineages where grantparents are helpful && live more.
What I meant though is that the main evolutionary pressure of us in in reproduction. Sure some past-reproduction-age traits play a role, but hardly as big.
> Because evolution doesn't care about us beyond reproduction age (after which is when most cancers occur, especially considering that historically that age was between say 16 and 35).
True. If we can find a drug or gene therapy that extends the reproductive age of humans, evolution will take care of all diseases in a few million years, give or take.
Could be a cliff fitness function. Heard about this relativ typ schizophrenia here on HN a while back. The idea is that some phenotypes promote survival of the species overall, but due to random mutations are sometimes detrimental to individual members of that species
It could also be indirectly linked to other benefits. Humans have lost the CMAH gene, making us able to run long distances and hunt down large prey animals. But because of this we can no longer process specific sugars that you will still find in mammalian meat. That causes inflammation and arteriosclerosis. But those things only kill you after many decades, so there seems to have been a net positive effect on evolution.
This idea can generally work, but one should be careful of 'just-so' stories in evolutionary biology.
It appears this deletion happens in other animals and may be attributable to pathogen pressure. It's arisen multiple times, which makes it hard to claim that it has a specific role in primates (beyond its presumed antimicrobial benefit, which any animal should enjoy).
Evading pathogen pressure is just another benefit behind the scenes. The point is that I would be careful to attribute any of these things to such weird mechanisms when there are so many much more realistic explanations that we just haven't fully uncovered yet.
> Evading pathogen pressure is just another benefit behind the scenes.
I'm imagining that this relates to a specific pathogen that may no longer exist (like the presumed mechanism of the most common cystic fibrosis mutations and cholera).
I'm not sure how this would relate to humans running, however.
Perhaps, but AFAIK similar things show up in other metabolically "different" animals - sharks, naked mole rats - whereas rodents adapted to a "run hot and fast" kind of a lifeplan seem to be especially prone.
We know that the body has cancer suppressor mechanisms, because when they fail (due to HIV or genetic mutations) people suffer higher rates of the disease. So it's reasonable to guess that evolution has chosen not to dial them up further.
It feels like the immune/inflammatory system is something we understand about as well as the brain, which is to say pretty good at a gross anatomical level, and also at the fine molecular level, but with a heck of a lot of complex system dynamics in between remaining to be mapped out.
From a fast search in Google, life expectancy in bats is 5-15 years. A long life of 70-80 years gives more time to accumulate mutations and get a cancer.
Also, probably only bats in zoos get a cancer diagnosis. Most ills bats just die in the wild and are eaten by other animals.
Many species of bats live longer than that. Like 40. When compared to other mammals, bats live very long lives relative to their tiny size.
Also, short-lived animals get cancer all of the time. Mice, dogs, cats.
The idea of cancer being caused by passive accumulation of mutations over time looks appealing, but does not seem to correspond to actual frequency of cancer mapped by body size (because more cells = more chances of some cell going haywire), nor to maximum age.
Anti-cancer capabilities of a given organism seem to be more important. There are gene variants that are protective against cancer, and the capability of the immune system to kill suspicious cells matters too. (Note that almost all new efficient oncological treatments in the last decade or so involve the immune system of the patient.)
This is also why bats are viral reservoirs and likely sources for mammalian pandemics - their immune system simply doesn't clear infections.
My understanding is it's because they're constantly damaging their own dna from high operating temps (flying mammals). So the immune system must tolerate foreign looking dna at all times, constantly repairing cell damage instead of aggressively attacking foreigners.
It's a common misconception that bats eat mosquitoes.
It comes from a study where bats were trapped in a chamber filled with mosquitoes to see how many they could eat.
A comparable experiment would be putting a human in a cage filled with bread crumbs to see how many the human eats.
In our natural habitat, we eat slices of bread and other food. We don't waste the time and energy of consuming bread crumbs unless given no alternative.
Yes, bats can eat mosquitoes, but why bother when there are much larger, nutritious insects to catch with the same effort?
Bats (extra copies of the p53 gene, immune system, survival adaptations to atmospheric radiation exposure, high telomerase activity), Elephants (extra copies of p53), Mole rats (High molecular mass hyaluronan (HMM-HA) regulating sugar, contact inhibition), Blind mole rats (HMM-HA, protein that causes (apoptotic?) cell death)), Horses, Cows (BLV resistance, general resistance), Bowhead whales (prevention by DNA repair, CIRBP and RPA2, live to 200), Squirrels (hypersensitive cell monitoring, high telomerase activity,), and Tasmanian devils (DFTD resistance adaptation) are all cancer resistant?
If there are natural food sources that treat or inhibit cancer, and humans unwittingly were eating such foods until modern times, could it be that humans have prevented adaptation by supplementation (a support that has collapsed as modern diets have changed)?
> [... list of anti-inflammatory diet foods]
How exposed to CPMV Cowpea Mosaic Virus are humans dietarily in modern and in ancient times? CPMV causes a IFN response?
(CPMV is highly prevalent in cowpeas and black-eyed peas (which are "good luck"))
> Antibody evidence: Studies have tested patient sera for antibodies against CPMV and found that over 50% of tested samples were positive, indicating past exposure. [...] The consistent, low-level dietary exposure to CPMV over human history, and its ability to trigger an IFN response without causing infection, could have provided a form of regular, passive immune stimulation. [...]
> Despite being a plant virus, CPMV is recognized by the mammalian immune system as a "danger signal." This recognition happens through special receptors on immune cells called Toll-like receptors (TLRs), specifically TLR2, TLR4, and TLR7.
> CPMV and IFN-gamma: Studies have shown that exposing human immune cells (peripheral blood mononuclear cells or PBMCs) to CPMV induces the secretion of IFN-gamma, a potent anti-tumor cytokine.
> Encapsulated RNA: The CPMV virus nanoparticle contains encapsulated RNA, which is one of the triggers for the immune response. The RNA activates TLR7/8, which leads to the production of Type I interferons (IFN-α and IFN-β), further boosting the immune system's anti-cancer response.
There are (differently encapsulated) RNA cancer vaccines in development.
CPMV is basically already a general purpose bioengineering platform with significant review IIUC?
How dietarily exposed to EPS3.9 polysaccharide are humans and cancer-resistant animals? Is there a one-two CPMV + EPS3.9 cancer treatment opportunity?
> Spongiibacter nanhainus CSC3.9 is a novel deep-sea bacterium isolated from a [deep ocean] cold seep [with blue light] that produces both a volatile organic compound (VOC) called VOC-3.9 with broad-spectrum antimicrobial activity and a sugar-based compound, exopolysaccharide (EPS3.9), which targets cancer cells by inducing programmed cell death
Could CRISPR or similar produce an alternate bacterium that's easier to brew which also produces EPS3.9 without the cold temperature and high pressure? Are there potentially other natural sources of EPS3.9 besides CSC3.9?
Endocannabinoids and the ECS Endocannabinoid System modulate and regulate immune and inflammatory responses (in non- and pre- insect invertebrates and in all vertebrates). Omega PUFAs are endocannabinoid precursors. There are also (fat-soluble) Omega polyunsaturated fatty acids in algae and in fish.
Bats very rarely get cancer (I tried to find the actual # of verified cases of cancers in bats, but came up short), and they have a lot of anti-cancer adaptations in their genome.
They are also really good at taming inflammation and activity of various viruses. That helps them survive infection with rabies - their systems just don't react as aggresively to the infection as ours (and most mammals') do.
This may help them against cancer as well. Not just p53 et al.