Lots of treatments work very well in mice but fail to show benefits in human trials. They’re false positives, and they get lots of people excited over treatments that never end up working in humans.

(Why do they work so well in mice, I wonder? Is it because so much of our research uses them? I wonder, if we were willing to completely throw morals out the window, could we get those sorts of results in humans by experimenting on them directly? Not that I’m advocating this.)

I just realized something blindingly obvious: there are false negatives too. But how are these handled? Treatments that don’t work in mice never make it to human trials, even though they may work in humans. Without doing human trials on treatments that failed to work in mice, we can’t evaluate a false negative rate, but it could potentially be high. Certainly it’s nonzero in any case.

This is another example of snap judgments shooting down ideas, but this is far less clear-cut than most criticism because failing to analyze the treatment prior to human trials can endanger people’s health.

I think that what we need are better computer models.

Unless the specificity of an anticancer drug approaches 100%, anything that kills off cancer cells is going to kill off some normal ones as well. This means side effects, often quite nasty.

But what if, instead of killing off cancerous cells, we just shut down their invasive potential?

I’ve been reading up on what differentiates noninvasive cancer cells – carcinoma in situ – against invasive cells. The literature on this has been surprisingly sparse, so either I’m not looking for the right things (quite possible), or this is a very understudied approach. The papers I’ve read have identified a few gene loci and a protein called Twist, but that is as far as I can take my search, lacking the resources to experimentally pursue such lines of study.

My point is this: carcinoma in situ is harmless except in its ability to become invasive cancer. Most of the proteins that seem to cause aberrant behavior in cancer cells seem those that are present during embryonic development (which makes sense in a way, since embryonic development is high-rate controlled, regulated division, whereas carcinogenesis is high-rate uncontrolled, unregulated division), but these proteins are all but absent in adults.

So rather than attempting to kill off the cancer cells, why not attempt to remove their ability to invade (and thus metastasize, destroy tissue, and cause other problems)? Even if the treatment were nonspecific, side effects should be far milder than the “killer” drugs, since normal cells are not known to depend on the function of the identified proteins. And unlike drugs that kill cells, there is little selective pressure against the treatment.

I see so many solutions to this problem. How I wish I could take part…

Not being a biologist, I had assumed that telomerase was “hard-coded” with the telomere DNA sequence it writes at the end of a chromosome. This is actually not quite the case; the coding for a telomere is encoded in a sequence of RNA that the telomerase wraps around (making it a ribonucleoprotein) called TERC.

I, probably like many others, had once thought that inactivation of telomerase would result in a cure for many different cancers. However, for some reason, probably due to activation of other immortality pathways, this is not the case (although drugs that rely on this principle appear to be among the more successful treatment modalities in trials). This also appears to be one of those ideas that everyone is aware of but no one is acting on – I blame the way that science currently works for this (as I’ve mentioned before, how you express your values tangibly affects the impact you will have on reality; if you prefer to publish a lot and have a stable job, then you will not have the time to embark on the sorts of long-range high-risk research projects that actually make a difference).

Anyway, mere inactivation is unlikely to work. However, because TERC actually provides a template for what telomerase writes on the end of the cell’s chromosomes, inactivation is not necessary.

Here’s the fun part where I get to speculate wildly about the current state of the art because I can’t get the training that actually matters to actualize these sorts of ideas (you want your “committee of experts” and I’m the computer scientist. Fine, but the whole team suffers for the lack of synergy and vision):

Modification would do as well. If we could change what telomerase writes out to the end of the cell, we can write anything we want to it – and it would be specific to telomerase-immortalized cells (few normal cells carry this immortality, but it is very common in cancer cells), which means a treatment based on this idea would have few to no side effects.

What could we code for? I’m really not qualified to answer this, but some choices that seem obvious to me are the tumor suppressors that the cancers are inactivating in the first place, such as p53. Reactivate the suppressors, stop the tumors, and they won’t harm normal cells that produce telomerase but are making tumor-suppressors already. Again, minimal to no side effects.

And that’s the idea! It’s another interdisciplinary fusion:

This is what, in computer science, we would call a “buffer overflow with arbitrary code execution”. The code in this case is DNA. The “program counter” is the position of the ribosome. The end of the buffer is the telomere. Telomerase writes code out to the end of this buffer. You can take advantage of software this way by executing whatever code you want; you should be able to do the same to cells.