[extropy-chat] Re: Harv's Explanation for Slow Progress

[Robert Bradbury]

Harvey said:

> Yes, the genome got mapped faster than predicted. But since those
>  predictions, we have learned a lot more about genetics. Instead of
giving
>   us all the answers on gene expression,

Actually with respect to normal gene expression it has given us a big
part of
the puzzle.  Transcription factors primarily come in two or three
standard forms
and it is relatively easy to pull them out of the genome sequence.
(They are
small tend not to have introns that interupt the sequence, etc.)

> we now know we have to conquer  mitochondrial DNA

We knew that up front and its quite simple actually.  There is a large
and
expanding database of MtDNA sequences from various species.  Human
MtDNA is actually one of the easier ones since it is one of the
smallest.

> RNA,

Its not a large story -- we know the RNA genomic sequences, where they
are
and what they do.  The only exception to this would be the microRNA
sequences that appear to be largely left over from the "original" genome

(since most appear to influence development).

Still an open question IMO is the degree to which the RNA sequences
contribute to aging.  The sequences coding for RNA within the genome
tend to be repetitive and so the may contribute to improper
recombinational
repair that results in the corruption of the genome over time.

> protein folding,

It was always recognized by molecular biologists that this was going to
be
part of the puzzle.  I have read that the NSF is cranking up the X-ray
crystalography capabilities to ~30,000 proteins/year.  I will believe it

when I see it -- but if so one should have the 3D structures of most of
the proteins within a year or two.

> junk DNA,

Its there (a lot of it).  We know the evolutionary processes that
generate it.
It may have a limited function, perhaps in aligning chromosomes for
mitosis
or meiosis or perhaps in simply absorbing free radicals generated by the

mitochondria.  Lots of other theories to think about (perhaps a role in
the evolution of intelligence?).  But that is what keeps academics
publishing
papers and building up their resumes.

> DNA fragments

I'm not sure what you mean by this.  There are not any fragments to
mention.
The relocation of DNA segments between various chromosomes across the
evolution of species is a very robust science.  It is allowing us to
very accurately
compare differences between say mice, chimps and humans.  It will
eventually
allow us to significantly compare a larger number of species (dozens
probably
within this century).  It also allows a decrease in the cost of
individual genome
sequencing as one can depend on certain amounts of genome similarity
between
different species.

> telomere  loss

I'm not sure why you include this.  It is generally agreed that this is
a cancer
protection mechanism.  We have got 5-8 years of good solid research on
this and I believe Geron is testing drugs to promote this.

> random encoding damage

Yep, its there.  Its the source of most genetic diseases.  It probably
contributes to aging.  It can't easily be fixed until we better
understand
the DNA repair process which involves 120+ proteins.  But we now
*have* the gene sequences for most or all of those proteins!

> duplicate genes on different chromosomes,

An interesting product of evolution (genomic segments get swapped
within chromosomes and between chromsomes).

>  enzymatic expression and repression on genes, controller genes, gene
>  families and other cell factors on DNA expression, [snip]

Yep it is complex!  But can you point out a system with 30,000+ parts
(perhaps 90,000+ if you count splice variants) that is not complex???
It sounds like you are commenting on the fact that you as an individual
may not be able to understand it.  Live with it.  I as an individual
cannot
understand the complete design of a 767 either!

> So my point still stands: As we complete each milestone, we discover
more
> milestones.

Not really.  For example a basic biochemistry text will show you
a wealth of things about biology that we currently know and do
not need to do an infinite amout of additional research on.  Most
of the current milestones being worked on we knew at the start
of the HGP.  It comes down to genes, structure, function,
diseases, therapies (in various orders).

> I don't know if genetic reprogramming is now closer or farther
> away than we thought before we mapped the genome.

Oh it is much closer.  It gets closer every day when a parent of
a child with one of the known 8000+ genetic conditions looks
at a physician and says "Isn't there anything you can do to help
my child".  Completing the HGP (it technically isn't complete yet
because only a few of the chromosomes have what one could
call a "robust" analysis) allows those physicians to identify
problems and develop interventions much more quickly than
they could a decade ago.  The therapeutic methods (from gene
therapies [with a few mis-steps] to rapid drug screening)
are moving along.  [Just recently there was a report of the
discovery of a set of drugs that were effective against the
botulism toxin.]

I have a very clear vision of how to do "genetic reprogramming"
and how it might be done within the next decade.  There are at
least 2 companies that I'm aware of working on some of the
basic technologies required.  The questions that will need to
be asked are more likely to be "What do you want the program
to be?".  The people involved in sports are going to be very
unhappy when one can rewrite the program on demand.

Robert