[jjk166]

Our L1 defense is actually incredibly good. A human will undergo about 10^16 cell divisions over the course of their lifetime. Around 10^3 to 10^6 of those divisions will result in a mutation that gets past the L1 defenses and need to be eliminated by the T cells. It's not generally easy to make dramatic improvements to something with a 99.9999999% success rate.

The immune system is pretty good too, which means any given improvement to the replication system is, all else being equal, probably going to prevent mutations the T cells would already handle. If you need to do the research to figure out what's getting past the immune system anyways, and improving the immune system is lower hanging fruit, it's the logical place to start.

[top_sigrid]

Thanks for these insights! Do you have any material or sources for a layman to learn more about this and where these numbers come from?

[littlestymaar]

Aren't the elephants and whales orders of magnitude better than us at that though (they have roughly as many cancer as we do, but with respectively x100 and x1000 times as many cells.

Or is it the second layer that works better for them?

[jjk166]

Different species do have different levels of protection, and different lineages tend to employ different methods of protection. For example elephants have numerous duplicates of cancer suppression genes, whereas naked mole rats produce a variant of hyaluronan which prevents tumor formation. When compared to other great apes, Humans seem to be worse at both layers of defense.

It's worth noting though that humans also have much higher levels of exposure to many carcinogens than most animals, and we screen for cancers at a much greater rate for humans, so just because a species has lower cancer rates doesn't necessarily mean their cancer defenses are better.

[vibrio]

also, Elephants have a much higher copy number of a gene called p53/ It codes a protein that acts to force suicide in cells that have damaged DNA (think from UV light, cigarette smoke, age, etc). In cancer this is a common 'early' mutation that allows collection of further mutation and progession towards cancer. In having many more copies of p53, it makes it less likely the p53 function will be eliminated

[cassepipe]

I am not sure how much consensus there is around it but this is so cool I have to repeat it sorry: Whales and elephants do develop cancers but since those cancers also have mutations, well their cancers have cancers and overall the cancers are never able to grow big enough to threaten the whole organism.

Too big to fail basically

[jjk166]

The idea that tumors develop their own tumors, suppressing cancer is known as the Hypertumor Hypothesis and, while it works in computer models, there isn't actually any evidence backing it up.

The hypothesis doesn't really resolve Peto's paradox, the observation that cancer rates don't scale directly with the number of cells in an organism. Not only do large organisms like whales get fewer cancers per cell division, small animals like mice get more cancers per cell division, which can not really be explained by a threshold beyond which hypertumors suppress tumors. The actual evidence suggests organisms just evolve whatever level of cancer resistance they need to have low odds of dying of cancer before something else kills them.

That being said, the main observation underpinning Peto's paradox was actually just due to lack of good data. Over the years much more data has been collected from animal autopsies and it turns out that big animals do get cancer and cancer rates actually do scale with body size, just different species have varying levels of cancer protection, with the levels of protection being similar in closely related species of different sizes.