Re: Nature via Nurture: What makes you who you are.

From: Brett Paatsch (paatschb@optusnet.com.au)
Date: Sun Jun 01 2003 - 00:44:52 MDT

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    Phil Osborn wrote:

    > >From: Brett Paatsch (paatschb@optusnet.com.au)
    > Date: Fri May 30 2003 - 21:58:23 MDT
    >
    > (Aside: It seems to me that the popular fixation on
    > DNA seems to be wrong to me. Its DNA *interacting*
    > with proteins which do almost everything that matters
    > in biology. DNA of itself is almost completely
    > uninteresting. The same DNA is in every cell
    > type. Yet what makes different cell types and this
    > applies all the way back to the fertilized egg which
    > contains a cocktail of proteins is the way the
    > proteins interact with the DNA and selectively turn
    > certain genes off and on in turn creating other
    > proteins in the mix both in type and in number. If we
    > knew all the proteins in the maternal oocyte, both
    > number and type, that would be powerful knowledge
    > indeed, because these early proteins are crucial to
    > early development and they do not come from the DNA of
    > the fertilized egg or new individual but from the
    > mother. At this point we don't know what these are).
    > >
    >
    > So, there is a kind of meta-DNA cellular memory? With
    > error checking, one might presume? And the ability to
    > respond to changes? Can we come up with an overall
    > description or characterization of this meta-system?

    I'm not sure about "memory" (as you seem to be using the
    word), but there does need to be *some* proteins in the cell
    to work on the DNA (before the DNA has had a chance to
     produce anything) and to determine what other proteins
    should be produced and when.

    In IVF (some types not standard) there is a technique called
    cytoplasmic transfer where some of the cytoplasm from the
    oocytes of a young women (presumably containing healthy or
    well formed proteins) is extracted and injected into the eggs
    of older women who are having difficulty in achieving
    pregnancy. This is illegal in Oz but not I think in the US.
    Problem (politically) is that in taking some of the cytoplasm
    you also take some of the mitochondria from the younger
    woman and you get two types of mitochondrial dna in the
    resulting infant. So far, so far as I know, this has not produced
    any medical problems in any living infants ) of which there are
    some. The technique has only been around a couple of years I
    think. Point is, defective proteins in the oocytes of the older
    women can be enough to prevent the DNA recipe being
    interpreted and the protein cake being made - no pregnancy
    despite *apparently* viable dna).

    > I continue to be intrigued with the fact that about
    > 99% of the human DNA is considered "junk."

    I don't think the "junk" is 99%. 99% sounds like the popular
    figure often quoted for the difference between humans
    and chimps. Even in that context the 99% is debateable
    and depends on what's being measured.

    > So, if it
    > is "junk", then it could presumably be deleted?
    > Right?

    That's pretty much the point, or one of them, as I understand
    it that Robert's been making about whole genome engineering.
    The challenge is to identify the redundant "junk" or unused
    part of the recipe book so as to better understand what's
    going on. The understanding makes for faster and safer
    playing about.

    The zebra or blow fish (I forget which) is a vertebrate like
    us and so has much of the same instructions for construction
    in its DNA but has far less unused dna (less junk dna).

    > How hard would it be to test this with some
    > organism with a lot of "junk" DNA but a small enough
    > total to make it practical to actually clean out a
    > large proportion of the "junk" and then see if the
    > system still works.

    Some projects to do this are underway already.

    I'm fuzzy on the details without looking them up (which I
    should do but sorry I can't now because of time constraints)
    but Craig Ventner has a group that (I think) is essentially
    trying to produce an organism with the minimal number of genes
    to actually live and reproduce by knocking out redundant genes
    from a simple organism. Probably the nematode worm as it has
    so few genes (900 odd) to begin with.

    Theres another research group led by a guy called Blattner
    that (again from memory) are trying to identify and knock out
    redundant dna from a strain of E.coli. E.coli would be one of
    the prime biotech workhorses in that by modifying its genome
    we have converted it into a sort of factory for the production
    of things like "human insulin", "human growth hormone" and
    erythropoietin that is used in stimulating red blood cell formation.
    All these things are medically useful and are being used as
    treatments for existing medical conditions now.

    How hard/easy is it? Well its getting easier all the time as more
    is known about genes and genomes and comparisons can be
    made between organisms. Sometimes gene cassettes, chunks
    of code from one organism can be recognized to do something
    useful and incorporated into the genome of another organism.
     
    > Might there not be significant advantages in deleting
    > that 99%, assuming that only the 1% is in fact useful?

    The percentages seem wrong to me, but yep, and its
    happening.

    > A lot of the 99% is probably old viral garbage, I
    > hazard. Perhaps some of it is actually used by the
    > cell for blocking viral reproduction in some way, so
    > that we wouldn't discover the use until it mattered?

    I'm not sure to what extent this is the case in humans,
    and we wouldn't be messing about with genomes as
    complex as the mammalian one for this sort of stuff
    initially anyway. But plasmids in bacteria can in some
    cases, just by being in the cell, block out other types
    of similar plasmid which might be carrying viruses.

    > Perhaps, on the other hand, viruses have learned to
    > use some of the "junk," like common subroutines or old
    > .dll's that the OS never uses until you happen to
    > bring in some old program. Removing it might disable
    > those viruses.

    Almost certainly. But a problem with this sort of discussion
    is that those that really understand this stuff well are probably
    grinding their teeth at the oversimplification and errors and yet
    if we don't try and popularise this stuff in ways that make
    sense to non-experts we don't learn. (Apologies to all
    teeth grinders).

    I reckon some of the real "saints" or "storm troopers" in the
    van-guard of transhumanism, those who make a real difference
    in the "meme-wars" are those that can popularise this sort of
    science and in so doing lift (by working on the natural curiosity
    of folk) the average punter's or voters general level of
    understanding. The best form of political "propaganda" around
    stuff like stem cells and gene therapy is, imho, having more
    people actually *understand* better what is going on.

    - Brett Paatsch

    (happy to be educated and corrected on any/all of the above)



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