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Peto’s Paradox
- cube2222 4y ago> Peto's paradox is an observation that at the species level, the incidence of cancer does not appear to correlate with the number of cells in an organism.[1] For example, the incidence of cancer in humans is much higher than the incidence of cancer in whales,[2] despite whales having more cells than humans. If the probability of carcinogenesis were constant across cells, one would expect whales to have a higher incidence of cancer than humans. Peto's paradox is named after English statistician and epidemiologist Richard Peto, who first observed the connection.
- marginalia_nu 4y agoSeems conceivable that the evolutionary pressure would push cancer rates down to some sort a similar level across species, a sort of cost-benefit equilibrium.
- lordgrenville 4y agoI know about it from this blog post (warning: it's about politics, not biology) https://slatestarcodex.com/2014/06/14/living-by-the-sword/ https://slatestarcodex.com/2014/06/14/living-by-the-sword/
- Sharlin 4y agoThe salient part is that it's hypothetised that whale cancers can't grow big enough to threaten a whale before they themselves get cancer and either stabilize into a benign equilibrium or wither away. Fairly hilarious if true.
- briga 4y agoHow long would whale lifespans be if whales had the same level of medical care as humans? Humans today regular live well beyond our natural lifespans, if we were all dying at 30 cancer probably wouldn’t be much of an issue
- jollyllama 4y ago>Humans today regular live well beyond our natural lifespans Is this really so? My understanding is that humans in antiquity who survived childhood typically lived to what we would now consider retirement age.
- geraldwhen 4y agoYup. Unfortunately “mean age of death” is most commonly known, but in reality many children died at birth, hence lower mean.
- etothepii 4y agoI think traditionally actuarial tables have always been based on given achieving the age of 5 years.
- sonofhans 4y agoYou're correct; GP is wrong. Human normal lifespan is and has been about 70 years, once you account for early demise, especially from infant mortality -- https://www.sapiens.org/biology/human-lifespan-history/ https://www.sapiens.org/biology/human-lifespan-history/
- ravi-delia 4y agoA useful corrective, but perhaps also misleading. Humans didn't peacefully keel over at 60, let alone 30, that's true. And death before 20 was indeed so horrifyingly common that it couldn't help but bias the average hard. But mortality was higher at every age, be it from disease, injury, or childbirth. A person of the past would have understood a death at 40 or 50 to be young, but not all that unusual. Most people would know quite a few who died in that range.
- karencarits 4y agoOur days may come to seventy years, or eighty, if our strength endures; yet the best of them are but trouble and sorrow for they quickly pass, and we fly away Psalm 90:10 (probably from about 1000 BC)
- odabaxok 4y agoKurzgesagt had a video about the topic: https://m.youtube.com/watch?v=1AElONvi9WQ https://m.youtube.com/watch?v=1AElONvi9WQ
- Lucent 4y agoI thought regenerative ability vs cancer incidence was a problem for evolution to optimize per species rather than some statistical certainty per cell.
- jojobas 4y agoI always assumed that's because with people reproductive age precedes cancer age by a long shot, so cancer is not an evolutionary consideration. Blue whales mate till they die, but orcas don't, So I'd expect orcas to have a higher cancer incidence.
- XCSme 4y agoI thought cancer is not about the number of cells, but the number of cells that constantly die and have to be recreated (each time a cell is created, it has a chance to be a cancerous one). Maybe whales don't lose as many cells as humans, probably they sit less in the sun...
- majormajor 4y agoI read this recently - https://www.newyorker.com/science/elements/how-food-powers-your-body-metabolism-calories https://www.newyorker.com/science/elements/how-food-powers-y... Seems potentially related - it discussed this idea in part of it: > Maybe it’s both, but Lane suspects we pay too little attention to the latter possibility. He argues that it might explain the outsized correlation between cancer and aging. From age twenty-four to fifty, your risk of cancer increases ninety-fold, and it continues to grow exponentially from there. A popular hypothesis holds that the root cause of this mounting risk is the accumulation of genetic mutations. But some scientists have argued that the rate of accumulation isn’t nearly fast enough to explain the extraordinary trajectory that cancer risk takes over a lifetime. Nor does the gene’s-eye view explain why some tumors stop growing when moved into a different environment. For Lane, these facts suggest that cancer is best thought of as a derangement of metabolism.
- dinom 4y agoAt this point it's pretty safe to say that behavior has a big influence. I've never seen a whale smoke a cigarette, drink alcohol, or inhale exhaust fumes while sitting in traffic.
- MawKKe 4y agoMaybe you hang out with the most boring of whales
- yellowapple 4y agoWhales tend to be pretty straight-edge. Dolphins, however... well lemme tell ya, those dudes know how to party.
- mcphage 4y agoI dunno, man. I hung out with some dolphins who loved getting high on pufferfish every day, and they’re still living in their parents’ sea floor.
- ceejayoz 4y ago> Peto noted that, on a cell-for-cell basis, humans were much less susceptible to cancer than mice. Probably not explicable by cigarettes or alcohol, and we've dumped quite a bit of pollution into the whales' living environments.
- dylan604 4y agoas much as we've dumped in ours?
- andrewflnr 4y agoI just figured that with enough cells and enough time, any probability of cancer distinguishable from 0 becomes indistinguishable from 1, so large animals either learn to totally prevent cancer or die young.
- ravi-delia 4y agoSame goes for us though, no? Seems like you just need to push the expected time until onset past death by other issues, or at least reproduction
- yellowapple 4y ago> In October 2015, two independent studies showed that elephants have 20 copies of tumor suppressor gene TP53 in their genome, where humans and other mammals have only one.[17] Additional research showed 14 copies of the gene present in the DNA of preserved mammoths, but only one copy of the gene in the DNA of manatees and hyraxes, the elephant's closest living relatives.[18] The results suggest an evolutionary relationship between animal size and tumor suppression, as Peto had theorized. Is it possible that the evolutionary relationship arises from the size relationship? Basically: if elephants' ancestors grew in size and started dying much more quickly and commonly from cancer, nature would select for individuals who just so happened (via their increased risk of mutation) to have more copies of genes like TP53.
- _0ffh 4y ago> The results suggest an evolutionary relationship between animal size and tumor suppression My napkin formula would be p_tumor_body=(V_body/V_cell)*p_tumor_cell, so your statment makes intuitive sense, I'd say. The more cells you have, the more tumor suppression you need to make it a secondary cause of death over your expected life span.
- abstrakraft 4y agoThat expression leads to something that isn't a probability. Try 1-(1-p_tumor_cell)^(V_body/V_cell).
- _0ffh 4y agoI shouldn't comment on HN from bed after an evening out. Of course the rule of proportion is the wrong approach here. Even though the dimensional analysis seems to work out, it's still wrong. Bad case of thoroughly addled brain, this is supremely embarassing, and too late to delete now. I should be able to do this in my sleep, but I clearly wasn't. Seems there's not enough probabilities in my day-to-day, I will make a point of adding a few to fix my intuitions.
- Gatsky 4y agoThis article doesn't quite spell it out, but the current thinking is that the apparent paradox is explained by: 1. Bigger animals have larger cells, so the number of cells does not scale linearly with the mass of the animal. 2. Cells from larger animals are more resistant to cancer development in various ways (eg more copies of TP53, more propensity to die after DNA damage). 3. Large animals have non-linear metabolic scaling. So a cell in an elephant sees fewer metabolic cycles per unit time than a cell in a mouse. Some of this is due to the greater thermal efficiency of large animals. Now that we have more detailed data on animals, I think this paradox is a bit less interesting, albeit generally true. For example, there are some animals that just don't seem to get cancer (eg the blackbuck and the Patagonian mara, from several hundred autopsies each) [1]. Cancer is also very rare in Zebras. This is fundamentally interesting because it shows that being free from cancer is possible in an otherwise normal looking mammal. In theory therefore, we could consider engineering humans to be cancer free. To me, given the high incidence of cancer, the progressively increasing incidence in an ageing population and the incredible amount of misery it causes, this is the most ethically palatable reason to consider widespread genetic modification of humans. I think all anti-ageing efforts will ultimately bump up against cancer as the limiting factor. The technology to safely genetically engineer humans is nowhere near ready for prime time. The association between height and cancer is not thought to be due to 'more cells'. It only applies to some types of cancer and not others. It is believed to be due to growth factor signalling eg growth hormone and insulin-like growth factors. [1] https://www.nature.com/articles/s41586-021-04224-5 https://www.nature.com/articles/s41586-021-04224-5
- mistrial9 4y ago> we could consider engineering humans to be cancer free following until you get to that.. there are multiple mechanisms in the body that can result in "cancer" .. its an end result, not the cause. The jump to "we can engineer this out" is exactly what a reader would expect from an investment-and-profit medical company. There are untold numbers of small poisons and behavioral habits that are known to increase cancer inducement in humans.. all of which could be addressed, but there is little profit in prevention. Overall, I am taking the time to write this because a rush to genetic engineering is something that might behave like cancer itself over time.
- yboris 4y agoSide note that seems relevant: Cancers almost never metastasize to muscle tissue, even though muscle makes up 65 percent of the human body.
- m3kw9 4y agoWhat about shorter and lighter humans vs taller heavier but both have similar good bmi?
- curo 4y agoTaller gets cancer more. See link
- planetsprite 4y agoCancer, mathematically, all things being equal, shouldn't simply scale with number of cells, but rather with number of cell divisions. This differs by species, along with other cell mechanisms that could inhibit cancer that only certain species have evolved.
- nmlt 4y agoSounds like the environment of humans is the explanation. If you were to put a whale in a human city, eating and working there, maybe the whale would have the same rate of cancerous cells
- luhn 4y agoThe effect isn't due to humans being an outlier, it can be seen across a range of species. > A 2015 study, the San Diego Zoo, surveyed results from 36 different mammalian species, ranging in size from the 51-gram striped grass mouse to the 4,800-kilogram elephant, nearly 100,000 times larger. The study found no relationship between body size and cancer incidence, offering empirical support for Peto's initial observation.[8]
- teekert 4y agoStaying Cancer free has a cost, in terms of DNA repair (proteins) and their optimization, immune system and probably more elements. If a species reaches a point at which it can reproduce without incurring too many germ line DNA errors, there is no need to optimize further. I.e., if there was enough evolutionary pressure, our cancer incidence would also still be able to go down. However, the current incidence is not affecting natural selection at a significant magnitude. Same for mice and whales I would guess.
- ClassyJacket 4y agoSide note, but it bothers me when people call a phenomenon a paradox. A paradox isn't just something you wouldn't expect to be true, it's something that causes itself to not be true. For example saying "This statement is false", or time travel shenanigans. This is simply a phenomenon.