Re: Is cryopreservation a solution?

Joao Pedro (jpnitya@mail.esoterica.pt)
Fri, 26 Sep 1997 23:31:09 -0700


Hi!

Henri Kluytmans wrote:
> It seems, you're assuming that aging is only caused by error's in
> the DNA. If I understand correctly you're assuming these error's
> are already present from the beginning (so you're not referring
> to the random error's created by damage to the DNA during life
> itself).

If errors are caused to the DNA during life itself, it's because the
cell's DNA repair is not working well. What I see is an error in the
piece(s) of DNA that codes the repair procedures of the cell, this must
be fixed, and the errors that appear during life itself are a result of
this inherited error.

> Question : Exactly what kind of error's are you having in mind ?

I wish I had an answer but unfortunately no-one on earth knows for sure.
IMHO, there are many genetic errors that affect us after our sexual
peek, they could be a lot of things. Ever hear of the telomerase theory?
There are others, personally I think that if only one error would be the
cause for aging, natural selection would already have solved our aging
problem. See my "Why are We Allowed to Age?" article for more on the
evolution of aging at:
http://homepage.esoterica.pt/~jpnitya/science/why.htm

> The "error's" present in the original DNA are not the only causes
> of aging. In most cases other contributions are more important :
>
> 1) For part of the biochemical processes in the cell the use of
> free-radicals is essential. Because biochemical processes
> are largely determined by statistics (movements of the
> reagents are not controlled but are random), free-radicals
> can drift to places where they can do harm.
>
> 2) Damage created by radiation (high energy photons or
> particle radiation)
>
> 3) The buildup of harmful wasteproducts which are not completely
> removed by the processes in the cell
>
> 4) Maybe I forgot a few other causes ..... ?
>
>
> All these result in :
> -damage to the DNA coding (possibly creating a cancer cell)
> -creation of unwanted cross-bonds
> -damage rendering proteins non-functional
>
>
> However biology is using ways to fight this damage by repair
> mechanisms. Proteins and other cell-parts are constantly
> replaced. The DNA is checked for error's which are corrected. But
> these processes are however not capable (by design!) of correcting
> all the damage. Gradually the accumulating damage is rendering
> the complete cell non-functional (aging of the body).
>
> Therefore (cell-) aging cannot be prevented by only "correcting"
> the "errors" that were present in the original DNA.

Error's occur in all cells, radiation damages the DNA, mutations happen
naturally, free radicals can do damage, etc. However, the cell must be
prepared to deal with these problems. For example, I read recently that
the cells of animals that appear not to age, are more efficient at
dealing with free radicals, they have more powerful anti-oxidants.
I understand what you're trying to say, aging is not because of a few
naughty genes but because of our original's design incapacity to deal
with many of life's situations. I agree, actually I think that our
positions are pretty close, when you write, "redesigning the DNA", I bet
it's not much different than when I talk about correcting errors. Please
note that when I write "correcting errors", I include correcting natural
functions that are not working properly - such as anti-oxidants. Where I
think we might not agree is when I claim that our cells have the DNA not
to age (germ and cancer cells are a good example) and with genetic
engineering we can make the right genes active and turn our somatic
cells into immortal cells.

> Actually, till now, I was automatically assuming the immortality
> of each cell to be necessary for immortality of the body. But
> ofcourse this is not required. Non-functional cell's can be
> replaced by new cell's. However for extreme immortality this
> process will not do away with all damage, because damaged DNA
> will be transferred to the new cell's. After a long enough
> period (a thousand years?) this will result in all cell's having
> error's in their DNA.

Cells can only divide a limited amount of times (did you knew this?),
long before a thousand years, cells will run out of divisions and
eventually die.

> For example, the cells do correct error's in their DNA. They do this
> by comparing the opposing bases of the DNA helices. But if the damage
> is so extensive that a complete basepair is damaged beyond recognision,
> this process will not be able to correct the error.
>
> However MNT will be able to (easily) repair even this damage.
> It will just compare the DNA from several separate neighboring
> cells! There is no existing biological process which can do this.
> That is why I claim that to reach immortality (using only
> genetic code altering) the DNA has to be completely redesigned.
> (Because new, more extensive, repair processes are required.)

Actually there is a biological process that can do what you propose,
I'll call it, "natural cellular selection". If some cells are badly
damaged and cannot repair themselves, they will die. The neighboring
cells would then have more space, nutrients, water and other resources
to divide. They would then be able to divide more times than normally
and would "occupy" the place of the cells that died, they would replace
them. It's like natural selection in the wild. This happens all through
our live, the big problem is that cells can only divide a limited amount
of times and therefore we will eventually die.

> (Ofcourse, nature doesn't want the DNA to be completely fault
> resistant, because then natural evolution would stop. This however
> is no problem for our human future, because artificial evolution is
> much faster than natural evolution.)

I agree completely and I actually mention this in my home page.

> And we haven't even discussed diseases caused by bacteria and
> viruses. Which can be fought enormously effectively by MNT.
> (Because the probes build for fighting diseases in the body can
> be intelligently controlled, and reprogrammed almost instantly
> (by broadcast...) to recognize any new virus or bacterium.

I'm not so optimistic about this, at least in a near future. Have you
ever studied our immune system? It's very complex. Our ability in terms
of creating this "probes" you mention, is still, with my current
knowledge, a long time away in the future. Perhaps one day we can do it
but for the next decades or even centuries we will have to rely on
enhancing our natural defenses and creating a few new simple weapons of
our own (like antibiotics), perhaps giving direct instructions into the
immune system in order to speed the natural process and other procedures
but always having our natural defenses has a landmark. For example, our
immune system recognizes any new virus or bacterium, the problem
sometimes is that the immune response takes too much time. Also,
intelligence means nothing in the world of microorganisms, to fight
millions of virus you don't need intelligence, you need brute force. And
also, why create incredibly complex microscopic machines (which will
surely not be cheap) if there are natural compounds and cells that do
the function well enough? Only when science has advanced so much that
these machines are better than natural "warriors" (which will also
evolve and be artificially enhanced in the future) and that will, IMHO,
only happen in a long time.

> >> Why do I think artificial MNT cell-repair machines are easier to
> >> design? Because you don't have to use DNA gene programming !!
> Joa Pedro replied:
> >No but you will still have to know what to repair, there are countless
> >errors in our genome each of them creating it's own effect, there are
> >several defective proteins and you will have to know what these are in
> >order to repair them.
> When MNT cell-repair machines are used you don't have to alter the
> original DNA. The DNA only has to be checked for new error's caused
> by damage. Unwanted crossbonds have to be detected and removed. And
> non-functional proteines have to be recognized and repaired. This
> should render the cell completely "healthy" again.

I see, like in a sinking boat, instead of filling the hole, you
constantly throw water out of it. Well, as long as it keeps the boat
floating, it's a great idea. The question is, is it easier and/or
quicker than genetic engineer?
Anyway, I think you've missed my point. What I was trying to say is that
for MNT cell-repair machines to act, they will have to know where and
against what to act (how to tell normal from mutant proteins). To know
this, cytogerontology, microbiology and other life sciences must
discover them. Therefore MNT cell-repair machines are dependent on
cytogerontology, microbiology, etc.

> Joa Pedro replied:
> >MNT is highly dependent on microbiology to achieve
> >the purpose you propose.
> Actually, there are different pathways for developing MNT. Personally
> I guess the microbiology pathway is more complicated and therefore less
> likely to succeed first, I favor the STM/AFM pathway. However
> it also seems likely that a hybrid approach can be used.

A hybrid, you mean with both biological and artificial materials? Like a
microscopic Robocop, part man, part machine? Sounds interesting, there
are applications of MNT in many areas of general biology, my main
problem with them is that I think, with my current knowledge, MNT will
take longer to appear than you think.

> >As a conclusion, I think MNT might also play a role in achieving life
> >extension, to repair the damage done to our cells, perhaps even to
> >change our genes (gene therapy is still not achieving great results
> >lately) but the ultimate way to achieve life extension is by correcting
> >our DNA.
> That depends on what you consider ultimate. However I still claim that
> you will have to redesign the complete DNA.

Perhaps I haven't made myself clear, like I mention before, correcting
errors includes making the cell's repair procedures more efficient. I
think I didn't explain this point very accurately in my last message and
that is why I am concentrating on it, so there are no doubts about my
intentions.

> I hope you will see that MNT is the best (only feasible) pathway
> to real immortality.

No, because, like I mention before, as far as I know, it will take much
longer to produce an machine that prevents aging rather than preventing
aging with genetic engineering or other biological procedures.
For example, why create artificial enzymes if there are natural ones
that work? In the same line of reasoning, why create machines to prevent
aging if there are natural ways to do the same? It's a waste of time and
resources. Perhaps you can give me a few examples of present
applications of MNT? Give me some real work, some real nano-machines
that can, in a near future, do what you propose. I can do that for the
path for reaching immortality I which to follow (immortal cells, gene
therapy, genetic engineering, mapping of aging genes, etc).

-- 
         Hasta la vista...

"Life's too short to cry, long enough to try." - Kai Hansen Reason's Triumph at: http://homepage.esoterica.pt/~jpnitya/