Re: >H Protein Antifreeze

From: Eugene Leitl (eugene.leitl@lrz.uni-muenchen.de)
Date: Sat Jan 08 2000 - 23:02:01 MST


Robert Bradbury writes:

> All of the Mycobacteria and probably some of the ultra-micro bacteria
> strains are probably adaptable. The "control" problem is easy to solve
> since you can engineer in suicide triggers. I think the advantage to

The things autoreplicate within the cell, imposing their metabolic
load. Controlling the bacteria population within the cell without
killing the cell is imo very nontrivial. This is very different from
having a dormant set of genes waiting to be switched on.

> bacteria is that you can really "engineer" them to be high production
> factories.
 
You don't need a lot of antifreeze protein to do its magic.

> > 1) Immunoreaction takes time to gear to full response
>
> You are going to get some inflamation as soon as the proteins get
> displayed in the MHC complexes, that should only be a matter of

Ideally, the proteins stay within the CNS's cells.

> hours after you turn on the protein production. I agree a large
> reaction would take immune system amplification and that would
> take days to weeks.
>
> Now how long you have to worry about this depends on how fast you
> can produce sufficient protein concentration to allow the next stage
> of the cool down. You can't cool down too much while you are still
> producing the protein because you reduce protein production.

Of course. You nuke the immune system, get in your vectors, wait for
tranfecttion to complete, then give your signal intravenously,
incubate for a day or two, then start the suspension.
 
> > 2) Immunoreaction can be supressed (and, with a typical patient, is
> > not in the best shape anyway)
>
> This seems to be a good solution for cryonics but a bad solution for
> long-term gene "enhancements".
 
I don't think nontrivial (going beyond simple metabolism patches) gene
enhancements (once we will be able to do them safely) will be relevant
on the time scale in question. Provided, Singularity is not a figment,
of course.

> > We're talking about the end of your biological life span, something
> > taking few days or weeks at best. The problem is having a quantitative
> > tranfection vector targeting neural tissue without destroying it.
>
> The real trick is "quantitative", one of the reasons the cryoprotectant
> fluids are so viscous is because the concentrations are so high.

It is impossible to load the system with polyols of sufficient
concentration from within. Near-terminally damaged CNS insect larvae
are not. Noncolligative cryoprotectants do not have a measurable
impact on viscosity. Clearly, you still need a hybrid approach,
loading the tissue externally with enough glass formers sufficient to
vitrify a macroscopic organ.

> What you would like is a low concentration fluid that "sticks" once
> inside. Then you could pump it in at low concentrations but it would
> get selectively concentrated to higher and higher levels in the cells.
 
An antifreeze protein doesn't have a native pumping system (unless we
engineer it in), so it would tend to stay in cell lumen. Which is imo
good.
 
> This is the same problem we face in "reversing" aging in adults
> and is something I've devoted a lot of thought to. Biobots with
> supplemental genomes are I think the way to go until nanobots become
> feasible. Cryoprotectant manufacturing vehicles would be an interesting
> application because you don't have the normal approval headaches
> since the person is technically "dead". However, this isn't exactly
> a "booming" market.

Definitely. Also, there are ways to load the brain more efficiently by
using blood-brain barrier perforation. This may involve getting in
goodish quantities of polymers, including biopolymers.



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