A thought experiment
on cancer

July 2024, at the end of my first year of employment at the University of Sheffield, I attended for the first time the yearly showcase of the INSIGNEO Institute.

Among several interesting talks was Dr Elena Rainero's, on cancer cell metabolism, its recombinations and adaptations to the local environment.

I got quite struck by the organisational depth tumors were displaying, and ended up starting the following thought experiment: what if all this was not random at all?

I'd like to emphasize here on the fact that, when I do a thought experiment, it is by no means meant to be the truth, but rather a tentative step towards it.

Still, I'll give here an account of which subsequent thoughts I had on the matter.

Consolidation vs. dissemination.

Tumoral cells can either contribute to building the tumor, or disseminate. A first thought of mine was: could it be encoded after cell division, via a "firm" role differenciation? Are there cancer-related cell roles yet to discover?

I then realised that the proportion in which the tumor would create new migratory cells vs. cells building up the local tumor is probably a quite subtle thing to compute. And, sadly, cancer is pretty efficient.

So, would this proportion be already encoded somewhere?

It took me a while to find a simple analogy. Think of a strategy game -- in my teens, this was Age of Empires. You start building a city, and at some point you'll allocate a part of your resources to prepare an expedition to build a new one. Yet finding how much resources you should spend on preparing that expedition, and when to start preparing it, is a challenge that you won't likely get right without a bit of experience -- and lost games.

To sum up here: my feeling is that the efficiency of cancer suggests that it uses some old "code". I found out later on that the atavistic theory of cancer is on that line, but my time is extremely limited at the moment (sadly) and I couldn't dive deep enough into it as of now.

Why?

Why would cancer start? Suppose that this is indeed about running old code -- in other words, expressing old genes, that are typically silent.

My guess would be that the "power on" button to run this old code would correspond to threats from the past (I'm talking about million years and even more).

Before we explore that: my feeling here is that one should consider whether a cell could start this very aggressive survival program (consolidate and disseminate in quite an optimal way) because it feels critically threatened.

I would have a look at "sensor defects" -- in complex systems in general, there often is a lot of safety mechanisms in the core of the system, but sensors are much more fragile.

Could a cell believe that it's under critical threat? Is there a thing such as cell delusion?

Another lead would be: could the local environment of a cell actually be threatening, while most of the individual is doing well? Can there be such a local variability?

Exploring cell evolution.

This is were I have fun with ChatGPT.

I recommend using ChatGPT for widening your thoughts, but then ask it for keywords to search for, and check that enough trusted sources actually back up the point you're interested in.

But since I'm relating a thought experiment, what follows will be drafty -- and should be taken as a base of discussion, not as the absolute truth (this should apply to about everything we say, anyway).

Tumors are estimated to have emerged 800 million years ago. Interestingly enough, this is about when organisms went from monocellular to pluricellular ones -- via an intermediate form akin to communities of cells with some independence, but still with an ability to form structures together. They could notably form colonies, or migrate to establish new ones.

So, what if the signal leading to cancer was a threat from the past? From that age?

I asked ChatGPT for the threats a cell could face 800 million years ago. Sadly after that I had to stop my exploration, I've (yet again) started thinking about other things, and there's job and family to take care of too.

I still remember one puzzling fact -- one of the potential threats was salinity of the surrounding environment.

We do eat too much salt nowadays. Also, I remember reading that lithium lowers cancer risk -- and lithium competes with salt, which is one of the little things we understand about its action mechanism in the brain.

Outcome of the thought experiment.

OK, that's been a bit of a journey.

Let's see what hypothesis we can pack out of it:

"Some cancers could appear as the result of a cell feeling attacked by its environment (due to faulty cell sensors, or to local environmental abnormalities) and would activate silent genes coding the answers that evolution provided to some ancestors to tackle such attacks. Then, the cancer evolution would follow, yet in a very diverse environment, the development strategy in a hostile environment of this ancestor."

One more time, this is a thought experiment, not a belief of mine. Yet I think it sounds worth an exploration.