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Comment by ricardo81 | Hacker News Reader

It would be interesting to hear of the evolutionary benefit of this, considering the stage of life it is at.

I would guess it's just like a very complex dam bursting. Nothing intended, just side effects of very complex systems no longer functioning properly.

This is correct. For obvious reasons, selection pressures on terminal physiological processes are non-existent (or at least very small). Also, the press release makes it sound as this "wave of death" is something these people discovered or even characterized. It is a well known phenomenon that anybody doing any sort invasive brain imaging observes at some point. As they state in the abstract of the paper:

> While the molecular signature of anoxic depolarization (AD) is well documented, ...

The molecular mechanism is also pretty straightforward: dying cells rupture and release ATP. ATP is not only the ultimate energy source but also a potent messenger molecule. In the brain, it excites other neurons, resulting in activation and hence depolarisation of other neurons. Furthermore, in large concentrations, it also induces apoptosis in nearby cells (not just neurons). The result is a chain reaction were the death of some neurons induces death in other neurons, and so on, and this "wave of death" is preceded by a faster moving wave of electrical activation.

Would it be possible to preemptively inject any substance that neutralized these effects directly in the neocortex in patients to give one last chance of treating them before cerebral death or the damage of the initial rupture of neurons is already too great to allow a person to make a recovery?

Due to the blood-brain barrier, it is quite difficult to get substances injected into the blood into the brain (though some obviously do, otherwise there would be no psychoactive substances). Injecting into brain tissue directly is possible but probably not useful in an emergency: if you want to inject into cortex directly, you have to inject at ulta-low (yet positive) pressures (otherwise you destroy a lot of tissue just by injecting), and diffusion from the site of injection would be slow. In other words, you would have to drill a thousand holes into someones skull, and inject tiny volumes over the course of minutes each time. You could inject into the ventricles. That can be done quicker and with larger volumes without incurring too much damage, but again, lymphatic flow is very slow, so getting the drug into the tissue would take a long time (hours). So from first principles, you are fighting an uphill battle, and the incline is very steep.

The findings in the paper are interesting in the latter scenario, as they identify the deep cortical layers as the likely drivers of the wave of death (not a surprising finding for various reasons so quite likely true). Deep cortical layers are closer to the ventricles, so access would be a bit better than to the cortex in general.

Interesting idea. Perhaps another possibility is the brain's one last check to see if the situation is salvageable.

A1 is a parent of A2, and A2 a parent of A3.

A1 has a genetic trait that makes old age a terribly painful experience, and the moment of death a horrifying ordeal. Far worse than what most experience.

A2 becomes scared of death. As A2 gets older, they behave chaotically because of the trauma from watching A1 die painfully and the fear that they’ll experience the same fate.

A2 does not take good care of A3.

I hope this example (unscientifically) shows that there are likely some strong trends toward genetic traits that support a peaceful end of life period.

I suspect there are also multigenerational trends toward older members dying before they become a drain on a tribe’s resources. An obvious historically-useful benefit, that now leaves us worried sick about our aging parents (that they’ll slip and fall, and activate the “end of life” phase, where they’d have passed away if it weren’t for medical intervention).

> dying before they become a drain on a tribe’s resources.

Why wouldn't evolution select for members who don't become a drain on the tribe? Why age at all?

Indeed, it's the classical Weismann's fallacy. From Nick Lane's 'Life Ascending':

> The most popular idea, dating back to Weismann in the 1880s, is wrong, as he himself was quick to recognise. Weismann originally proposed that ageing and death rid populations of old worn-out individuals, replacing them with racy new models replete with a new set of genes remixed by sex. The idea invests death with some sort of nobility and symmetry, in service of a greater cause, even if it can hardly aspire to the grandeur of a religious purpose. In this view the death of an individual benefits the species, just as the death of some cells benefits the organism. But the argument is circular, as Weismann’s critics pointed out: old individuals are only ‘worn out’ if they age in the first place, so Weismann presupposed exactly what he was trying to explain. The question remained, what makes individuals ‘wear out’ with age, even if death does benefit populations?

I think it’s likely that the brain’s internal behavior at death doesn’t have a significant evolutionary effect, and instead is just a side-effect of how the brain works in general, which in turn is of evolutionary importance, of course.

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