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Comment by ccakes | Hacker News Reader

Warning: no background in science, dumb question inc

It seems like the cancer cells are pretty good at evolving to get around our immune system. Is there a reason our immune system doesn’t evolve to outcompete the thing that is killing it?

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I should note this is somewhat outside my normal range, so actual experts may disagree.

There may be a few reasons. First, as another commenter has noted many cancers manifest late in life, after typical reproductive age. This is decent evidence that our immune system is in fact quite effective at killing cancer already. A rough estimate is that a human body experiences 10^16 cell divisions in a lifetime. Each division is a mutation and therefore cancer opportunity; not to mention the constant barrage of DNA damaging chemicals, radiation, and viruses. The numbers for precancerous mutations repaired (or cells destroyed) over a lifetime would be totally staggering.

The flipside of this is that a death from cancer after having kids doesn't reduce the prevalence of your genes in future generations by too much. You already have progeny after all. Humans are social animals and so there's maybe some benefit to having grandma or grandpa around. All that to say that (from an evolutionary perspective) there's not a huge, obvious benefit to having a super good immune system later in life.

There's also probably a balance between having an aggressive immune system and auto-immune disease. An over-eager immune system could attack normal cells as well as cancer cells.

Yes, also the parent generation eventually dying off confers survival advantages to the younger generation: fewer old folks consuming resources and providing little value in return.

Death isn't just a critical part of the individual life -- rather, it seems key to evolution itself, biological or otherwise. clearing the slate/setting a timeout on any given system seems to be a good way to evict the accumulation of fixed points/cycles and other non-global-maxima that accumulate.

I'm completely talking out of my ass here, but I suspect systems will tend towards rent seeking/"cheating"/maintaining a status quo/really, just "overfitting" to the environment by making the ecosystem around them dependent on them.

Death ensures resiliency and progress. If we ever actually achieve some form of (pseudo-)immortality, i'd hope that we introduce an "afterlife" which removes the post-mortal from "living" society/ecosystems after s certain point. at most, living society should be able to inspect & affect the post-living system (afterlife), but the post living system should be airgapped from being able to (at least, directly) affect the living one at all. that said, i'd be wary about indirect affects. to die is to not influence. i'm still influenced by the memory/simulacrum of my grand mother who raised me until middle school. thats some degree of affect on my ecosystem, but it isnt what i would call direct.

i suppose there need not be a singular timeout or ecosystem a system is depolyed to, so long as it converges to zero. Heck, not even monotonically nor with a consistent cohort of systems.

> "afterlife" which removes the post-mortal from "living" society/ecosystems after s certain point. at most, living society should be able to inspect & affect the post-living system (afterlife), but the post living system should be airgapped from being able to (at least, directly) affect the living one at all

Like the Undying Lands in LOTR?

> at most, living society should be able to inspect & affect the post-living system (afterlife), but the post living system should be airgapped from being able to (at least, directly) affect the living one at all.

I feel like this hypothetical scenario is contradictory (and, supposing there was engineering behind both this life and an afterlife, is an argument for keeping the two isolated). Data is code, so data collected from the afterlife is potential for "remote execution from the afterlife" (not that humans are computers, but for example traditionalists who were able to directly study the long-dead would act differently than if they had to piece tradition together from scraps of documents - particularly, it would freeze traditions/memes rather than letting them evolve) and therefore death losing its role as the cessation of influence.

> I'm completely talking out of my ass here, but I suspect systems will tend towards rent seeking/"cheating"/maintaining a status quo/really, just "overfitting" to the environment by making the ecosystem around them dependent on them.

This is also why institutions should have a lifetime. Corporations, government entities, all the things that don't have a natural life length really ought to.

Interesting idea. Like the idea of prohibiting perpetual owership of real property, which I think is a thing in some jurisdictions.

Property/Land tax is similar. Put a carrying cost on things, then people will think about where they want to put their eggs.

The schrodinger's box of future parent cancer death does not impact the reproductive decision at time of conception. Time doesn't work that way.

> fewer old folks consuming resources and providing little value in return.

As a parent living by my in-laws, I can assure you that, far from providing "little value", raising children without support from grandparents would be severely more difficult. Personally, I see generations trying to be independent of one another as a large factor in making modern childrearing increasing difficult.

And this is aside from the knowledge, and labor that would have been so vital in former times. The old woman spinning and knitting is a historical trope, but when you have to hand make all of your textiles, she becomes quite useful indeed.

Sure, but eventually your in-laws will become unable to care for children, maybe even unable to care for themselves. At that point, from a strictly utilitarian standpoint, they become a burden (I'm not making an ethical claim here, because ethics is not part of how nature/natural selection works).

> There's also probably a balance between having an aggressive immune system and auto-immune disease.

This is the key. I’ve had an immunologist explain to me (over a bottle of wine, so my recollection is hazy) that our immune system is actually very very aggressive already and tuned within a few percentage points of being problematic.

And I suppose this aligns with the prevalence of autoimmune diseases?

Some autoimmune diseases appear to be due pathological differences in the intestinal microbiome, typically when its flora diversity is drastically reduced. The latter is more common in first world countries, and especially among highly sanitised environments, such as overuse (unnecessary use) of antimicrobial agents and consumption of too much food which has been processed such that all microbes have been destroyed. Allergies are also a class of immune disorder, more prevalent among those who have little gut flora diversity. Unfortunately, while high diversity reduces the likelihood of developing allergies, increasing intestinal flora diversity does not seem to reduce existing allergies.

Peto's paradox https://en.wikipedia.org/wiki/Peto%27s_paradox is interesting and relevant to your question. To summarize, larger species have evolved better defences against cancer, because they have more cells, so would otherwise experience far more cancer. There's some evidence that these defences reduce fertility, so aren't selected for in smaller species.

Also, the evolution of cancer cells to get around an immune system happens on a completely different timescale to the selective pressures for the human immune system to avoid cancer (days vs decades).

Yes, and there are a few exceptions in the form of small animals which rarely get cancer such as the naked mole rat. This is an area of active research to see if their cancer defenses can be used to develop drugs for humans.

https://doi.org/10.1038%2Fs41568-018-0004-9

There is a tricky balance between an effective immune system and one that's too gungho and you get auto-immune problems.

Frankly it's amazing it works at all - not only does the immune system have to be able to react to stuff it's never seen before - it needs to be able to distinguish between self and non-self - and self is pretty damn complex.

So to make an analogy - cancers like a bunch of terrorists in a busy shopping centre and the immune system is the government response. Only one side has to worry about bystanders.

I think it's probably because most skin cancers manifest after reproductive age.

If you have cancer before reproductive age you're selected out of the gene pool; pretty strong survivor bias.

Probably because acting on a false positive means death (FCVO "death"; some autoimmune diseases are manageable).

You really don't want your immune system to move fast and break things.

It is indeed doing that!

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