Re: *sox18* in the bag

Date: Tue Mar 28 2000 - 10:00:31 MST

Damien Broderick, <>, writes:
> `Sox18,' they said two years ago, `is an endothelian-specific gene which is
> probably involved in transcriptional control of endothelium-specific
> genes.' Tonight's news report sez it's the (or a) key gene controlling
> angiogenesis. Switch it on locally, and you'd get fast growth of blood
> supply where you need it. Switch it off with statins or other antagonists,
> and you stop tumor vascularisation cold. Or so I surmise.

I think there's going to be a backlash against some of the over-promising
of the value of the human genome project and other gene sequencing efforts.
Just knowing a gene's sequence does not automatically give you the ability
to control its activities.

In the first place, since the protein folding problem is not understood,
the gene's sequence gives only a very rough idea of the shape of the
protein it codes for. And similarly it tells very little about the shape
of the other molecules and molecular clusters that it has to interact
with to do its work. You probably don't have enough information to allow
you to synthesize a drug that will mimic the shape of the protein well
enough to block or promote its efforts. You have some hints, but there
is much experimental work needed.

Also, the whole question of gene regulation goes beyond knowing just the
sequence that codes for the gene. What turns it on, what turns it off,
is a complicated interaction of many genes. It will take a long time
even once the HG is in hand to untangle the web of interactions dealing
with any particular function in the cell. (Of course much of this work
is ongoing and doesn't depend on knowing the sequences.)

And then even when we have the ability to control the gene or to
synthesize a duplicate, we still face the questions of clinical delivery,
side effects of the drug, and beneficial or harmful effects elsewhere
in the body of the gene that we may be promoting or blocking.

In short it's a long road starting from the gene sequence to the point
where you have a clinically effective treatment for a related disorder.
Yes, knowing the genetic sequence is of tremendous value in making the
research more effective, but it's not a magic wand that will lead to
instant cures flowing from the lab. As the HGP completes I think we
will start to see a major PR effort to tone down the expectations of
prompt miracle cures.


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