Peto’s Paradox
en.wikipedia.org
en.wikipedia.org
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.
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.
Can you elaborate on this? To me, it seems perfectly reasonable that a directed and intentional process of man-made engineering could blow the random process of evolution out of the water, both in timescale and in effectiveness. For example, there's not really an evolutionary advantage to eliminating geriatric cancer: kids have been made, genes have been passed, in all likelihood multiple generations down by the time old-age related illnesses develop. Yet, we want to live longer, and live better lives during that time, so we can take the reigns and address what evolution couldn't.
There are plenty of examples of humans rushing to market something they think works one way but upon a much longer study, the results are something much worse than if we had not instead. Heavy use of asbestos, heavy use of lead in fuel, paint, etc.
Genetically modifying anything just sounds like the most obvious of things that should be studied for much much longer than whatever the first company looking to profit is wanting.
After that, we would be left with a conundrum, which is the ethics of modifying the germline of an embryo. I don't know what the solution is there. Maybe it could be justified in families with an elevated risk of cancer, or Mars colonists for whom any sort of cancer will be a death sentence. Another option would be an as yet uninvented way to edit the genome, but provide an 'Undo' function to reverse the edit, say by giving some small molecule.
Less morbid, there are many more substances we "rushed to market" and worked out fine. Should antibiotics still be unavailable, banned even, to complete longitudinal trials? Chemotherapy and radiation "sound like the most obvious of things that should be studied for much longer". Thank God that didn't prevent us from using them to save hundreds of thousands of lives. Hell, asbestos was used for way longer than any of that stuff, didn't make it any safer.
Edit: /s (If that wasn't obvious.)
I don't understand the point you were trying to make here. Why shouldn't we invest effort to research a technology that might mitigate the 2nd leading cause of death in the developed world?
Modifying the source code of humans is like the new hire thinking they can make the code so much faster because they don't know how the section code they are working on is used by the larger system as a whole. All they see is that there's an apparent bug in the section they are viewing now. Never mind the sections of code that have programmed workarounds for that specific bug, and will now break downstream because the buggy returns are no longer present. So how do we know if these kinds of workarounds in the human genome are also not present?
We know for a fact the current code base is full of bugs and convoluted workarounds due to the original coder having no idea what they were doing. While we may not yet know the best way to refactor the code, it undoubtedly needs to be refactored.
All this just means is that progress of science and technology has some qualities similar to natural evolution: namely, there's a bit of trial and error. It's not, however, a condemnation - not unless you can propose a way humanity could do even better.
All the cases you listed is something we've developed, discovered problems with, overcome and mastered in scope of couple generations. Were natural evolution to guide humans through their interactions with lead and asbestos, we'd still be dying in pain from exposure a thousand years from now, because evolution takes time and doesn't care that you're conscious.
> What's the quote, "in their speed to find a solution, they never slowed down to think if they should"?
Sure, but it's neither here or there. If you saw someone running away from a lion, would you throw this line towards them? Perhaps they should slow down and consider if they're not better off being eaten?
The most difficult version of this is modifying the germline. There could be other less extreme versions, for example giving young adults a long lived population of genetically modified immune cells that persist and eliminate pre-neoplastic or neoplastic disease. A more advanced version of this would be introducing a new type of cell lineage that exceeds the limitations of immune cells (for example specific modes of recognition, and restriction to certain anatomical compartments), and delivering it as a therapeutic. But modifying the germline is the only way to really get the incidence approaching zero, I think.
I hope however there is some easier, quicker way... for example if we discover unknown viruses actually cause a lot more cancer than we thought.
You should see the warnings we put on cigarettes.
Bill Hicks: "I found my brand!"
In this case, not sure of the label's use in this conversation.
Screw this disease and screw nature; the misery it causes is just too much. There is a way to get rid of cancer, and the sooner this is achieved, the better. There are protocols to help proceed carefully and ethically.
For example, the ends of chromosomes have telomeres[0]. When chromosomes are copied they can’t copy the full length of the chromosome, so every copy has fewer of these telomeres. When they eventually run out of telomeres, cell division stops happening. (I don’t know whether dog chromosomes have fewer telomeres or if it’s some other mechanism, but telomeres are an example of a cellular mechanism that has a limited lifetime.)
So... we can create pristine new life with biological clock reset at 0, but not do so for our own bodies.
Thats the best mechanism nature have to make sure we are evolving - more precisely mixing genes.
What people forget is that our enemies are constantly evolving and trying to kill us, bacteria, viruses, fungi etc. Passing on you dna and eventually dying frees up resources for your offspring to do the same, creating new combination of genes increasing odds of more optimal defense for current threats.
If lions didn't age. They would compete for same patch of land and given all are at the peak of their development roughly 50% of old genes would win resources. Slowing down gene mixing and genetic diversity.
Actually speaking of big cats. Look up cheetah and what happens when you don't mix genes often enough (for natural or unnatural reason)
"Cheetahs retain only 0.1–4% of overall genetic variation seen in most living species, much lower than other well-known examples of genetic impoverishment including"
Where is this coming from? If I google "do larger animals have larger cells", it says the opposite.
But just consider nerve cells that control limbs. A nerve cell consists of a neuronal body and a long axon. If you have a longer limb, you will need a longer axon, and therefore a larger neuronal body to maintain it.
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.
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.
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.
This differs by species, along with other cell mechanisms that could inhibit cancer that only certain species have evolved.
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.
This is simply a phenomenon.
> 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]
Is this really so? My understanding is that humans in antiquity who survived childhood typically lived to what we would now consider retirement age.
Our 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
And many whales die of what we would consider old age - typically they get weaker and weaker as they grow old until they reach a point where they are unable to consistently swim to the surface for air, and thus drown. Pretty much what you'd expect if you flooded a nursing home.
Dolphins, however... well lemme tell ya, those dudes know how to party.
Probably not explicable by cigarettes or alcohol, and we've dumped quite a bit of pollution into the whales' living environments.