Hibernation [was Re: Future of Cryonics]

Robert J. Bradbury (bradbury@www.aeiveos.com)
Tue, 5 Oct 1999 11:31:32 -0700 (PDT)

On Sun, 3 Oct 1999, Ken Clements wrote:

> What if you could be in suspension (for the purpose of not loosing more
> function) and yet not be dead? I do not know the state of current
> hibernation research, but suspect that it would be politically easier
> to get funded than cryonics. I understand that slowing down
> metabolism does not keep deterioration from proceeding,
> but it should be slowed as well.

A quick scan of PubMed (hibernation & squirrels) turns up 805 articles. It doesn't look like they understand the causes of hibernation but it is pretty clear that protein synthesis and RNA turnover are substantitally decreased during hibernation.

So there is at least some funding in this field and they are starting to apply the latest biochemical methods (like differential display) to understand exactly what is going on. I would be very surprised if the mechanisms controling this (like those involved in sexual maturity (leptin), circadian cycles (clock genes) or eating/sleep(orexinB/hypocretin-2) are not discovered within the next 3-8 years.

There is one "catch" with humans however. We have not been engineered to operate well at low temperatures. Squirrels, turtles, bears, some fish, etc. have carefully tuned their genomes so their enzymes operate over a wider temperature range (or they have temperature dependent expression of the enzyme variants adapated to the different temperatures). I believe if you cool humans down too much the heart will stop beating.

The other problem is that until you have relatively automated vital signs observations you probably shouldn't hibernate in anyplace but an intensive care unit. That makes it a pretty expensive nap.

> Suppose you were told that you have a degenerative disease, and are given one
> year to live. Now suppose that a hibernation technology was developed that
> could keep you at one tenth your normal metabolism rate for 24 weeks at a
> time.

I'm pretty sure there are cases on record where people had faulty hormone levels and significantly decreased temperatures. If your core body temperature decreases too much you will lose consciousness. You should be able lower your metabolism at least 10-20% and still survive. The calorie restriction experiments would seem to suggest you might be able to push that to 30-40% (though those animals don't lower their metabolism that much -- they more efficiently utilize the avaialbe resources).

Whether you could push metabolism down to 10% of normal is iffy. An interesting question would be whether you could lower the metabolism to hibernation levels *but* maintain the body at a more reasonable operating temperature (warm it from the outside in instead of the inside out).

The decrease in metabolic activities cited above should retard most diseases as well. You might have to be careful about the bacteria in your gut. If they evolved variants that could be more active at a lower temperature or were more aggressive about invading your cells while your immune system was on standby, then you could be in a very bad situation. Remember, your body could be breakfast, lunch and dinner for the "parasites".

> I think that it is possible that some forms of chemotherapy would be
> more effective if the body temp is low enough so that the fast dividing
> cancer cells stand out against the background of low metabolism body cells,
> and so that the chemical agents are not lost as fast due to general
> metabolism.

If you lower metabolism you are going to lower it for all cells. It is clear however that you cancer cells will get slowed down due to decreased oxygen, glucose and other nutrients.

> I could envision a system in which very low level chemical agents
> bioconcentrate in the fast cancer cells over a long period while you are
> suspended, and then when you are periodically brought up to full metabolism,
> these either kill those cells, or are markers for your immune system to come
> and kill them.

If you really want to target cancer cells you either need markers for proteins preferentially expressed in rapidly dividing tissues (such as the transferrin receptor to bring iron into the cancer cells). People are working on these approaches. The problem is that it is difficult to find cancer-specific vs. cell-division-specific markers. The reason why chemo or radiation are so toxic is that they impact you whole blood production apparatus as well.

Nanobots can target the cancer cells on the basis of temperature differences (and this is covered to some degree in Nanomedcine vol. 1).

> I think that cryonics is a good option for the dead. The point I am
> trying to make is that we should put some thought into the gap between
> the conditions of rapid deterioration (alive, but wasting away) and near
> zero deterioration (cryonics) for those who are not yet dead.

The point is well taken and I'll bet that as soon as the mechanisms for hibernation are known, you will seem them being looked at in humans. It will be a while however for us to have home hibernation kits and vital signs monitors plugged into the global net.