One of the big points of contention with SENS has been that of nuclear DNA repair. Aubrey de Grey has proposed WILT for dealing with the problem of nuclear DNA mutations. Simply put, Aubrey's position is that cancer is such an overwhelming problem with regards to nDNA mutations that the rest of the DNA essentially gets a free ride. Appealing to mathematics, the level of DNA repair necessary to maintain genetic fidelity for 70 years on average before even one cell out of trillions becomes cancerous, is a level that seems stupdenously efficient.
As animals have grown larger, lifespans have increased. DNA repair has presumably been part of this increase: a human couldn't live 85 years with DNA repair rates only sufficient to stave off cancer for a few months in flies or years in mice. In fact, as animals have increased in size by several orders of magnitude, one would expect the DNA repair rates to be nearly flawless.
As I was writing a reply to noam in another thread regarding the following quote, I began to wonder about whether this is as true as it seems on the surface.
link to entire quote
if we: 1. Remove extrinsic death factors for a vertebrate, and 2. Remove its ability to die of cancer, then the amount of time (after its old extrisic life expectancy period) that will take him to lose that certain amount of cells which will make it dysfunctional, will be relatively very long.
The gist of it is, an organism can lose a large fraction, say 1%, of its cells, and still survive. In a human body of 100 trillion cells, this could mean a trillion defective cells. Yet if the DNA repair rates are good enough to prevent even one metastatic cancer cell for 70 years, then certainly it must be good enough to prevent a trillion defective cells for several lifetimes' worth.
I started approaching this idea from the top side: what's good enough for 70 years isn't adequate for 90 years, let alone 140. It's a basic tenet of aging in higher organisms, that for the most part, age-related diseases (and by association, the underlying damage) increase near-exponentially. Reliability theory adds a subtle kink: the damage might accrue linearly (or faster, or perhaps even slower), but the overall effect is a roughly polynomial increase in the incidence of disease, essentially exponential over the period of interest.
So, while non-cancer-related genes might be in very good shape for 70 years, we might still expect a pathological level of mutations in less than 140 years.
But, as I was approaching this from the top, I started wondering about the approach from the bottom. Depending on the cancer, about 4-8 genes need to mutate for cancer to metastatize. I'm fuzzy on the number, but that's what I seem to recall.
Well, for simplicity, let's just call it 6. Six genes need to mutate in a single cell and a few years later (a small fraction of its lifespan, and hence a selective pressure), the organism is dead.
Well, we need a further qualification. It appears that not all cells are equally liable to develop into cancers. Stem cells and other mitotic cells seem to be the main culprits, which makes sense. They may already have telomerase active, which reduces by one the number of mutations needed. Additionally, they replicate their DNA, which exposes their DNA to more potential mutations.
So let's say that in some small fraction of the body's cells, five mutations are needed. I'll just pick a number, say a billion, or 10**9. Well, as it turns out, the mutation rate (of unrepaired, undetected mutations) that can be tolerated is the fifth root of a billion, since five genes need to mutate. Why? Because you multiply that mutation rate by itself for each gene that must mutate within a single cell.
And 1/10**1.8 turns out to be about 1.6%. That's right, for stem and other mitotic cells, it's a 1.6% mutation rate for each cancer-related gene, in a (roughly) 70-year period. Using 10 billion or 100 billion cells as our starting point hardly changes things, reducing this rate to 1% or 0.6%, respectively. Using the full 100 trillion cells and six genes (e.g. adding telomerase back in), we get (10**12)**(1/6), or 1%, so it's not much better for the rest of the body.
Assuming that all genes get this same "free ride", then we should expect that in a 70-year-old, nearly 1% of all genes in all cells should be mutated in some way.
This is staggering. Note that I didn't say 1% of all cells would have mutations (which in and of itself would be worrying). No, 1% of each of the 25,000 genes, or about 250 genes per cell, with only a small standard deviation. The overwhelming majority of cells in the body would have at least several dozen mutated genes. This certainly doesn't seem like the "free ride" we were promised. What happened? Using this math, the vast majority of cells in a 25-year-old's body would already contain a dozen or more mutations, and a significant percentage would already contain scores.
Certainly these numbers seem too high, and I'd say this is because DNA repair is better than it needs to be to fight off cancer. Cancer's a walk in the park compared to having 250 mutated genes in almost every cell in the body.
But the principle can't be ignored: mathematically speaking, cancer doesn't buy our genes a free ride. The rate of undetected, unrepaired mutations that can be tolerated before cancer becomes pathological is on the order of 1% of every gene in each and every cell. That's a horrible repair rate. Cancer might seem like it's done us a favor, but I don't buy it. Evolution needed better ammunition to fight cancer than just DNA repair, and it found it in the elaborate system of checks and balances, tumor suppressors, etc., that require a single cell to develop multiple specific mutations, and probably in a fairly strict if not absolute order.
On top of this, evolutionary theory would seem to dictate that pathological systems are only made at best slightly less pathological than other systems. Because of the (near) exponential rise in pathology, a disease with a 1% incidence at one age might have a 90% incidence just a fraction of a lifespan later. Non-cancer pathology arising from nuclear DNA damage is probably at best a couple decades behind cancer, and we should not assume that fixing cancer will end all our worries about DNA damage.
With that said, I think that Aubrey has still taken a prudent course of action, because, thanks to the principle of escape velocity, WILT doesn't need to buy us more than probably two or three decades. In fact, WILT, if ever used in human treatments, will probably only be a stopgap measure for those who already are at very high risk of imminent cancer or already have cancer. For those with low risk (less than 5% or 10%), I seriously doubt it would be worth the risks. But it's a nice idea that, if nothing else, is good for putting to rest the arguments that cancer can't be stopped.
Edit: Updated "I seriously it would be worth the risks", adding "doubt"