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From: Ellington@Frodo.MGH.Harvard.EDU (Deaddog)
Newsgroups: bionet.molbio.bio-matrix
Subject: Re: Oh foolish supporters of genome sequencing
Message-ID: <5695@husc6.harvard.edu>
Date: 11 Feb 91 21:11:58 GMT
References: <9102111908.AA07006@genbank.bio.net>
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Organization: Molecular Biology, Mass. General Hospital
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In article <9102111908.AA07006@genbank.bio.net> 
gribskov@FCRFV1.NCIFCRF.GOV ("Gribskov, Michael") writes:
> Perhaps a more tightly reasoned argument would be more convincing?

From my point of view, Michael, this is rather like trying to argue against
N-rays or phlogiston:  you point out that there is no evidence to support
their existence, and that's about the end of it.

I am sure that I will see justification for the project at some point, 
but so far none has appeared.  I am truly mystified:  given the ability to 
clone genes by a variety of methods (probing with oligos based on protein
sequences, complementation, hybridization with homologous sequences,
panning, subtraction cloning, etc.) I do not see a need to sequence
the human genome.  I do not see what information will be gained that cannot
be garnered by other, more directed means.  In terms of genetic disease, 
for example, the search for a given gene would still seem to be a directed 
search.

You contend that sequencing genes at random and systematically sequencing
a genome are opposites:  I contend that they are both undirected searches 
and,in the current research climate, such undirected searches should not be 
funded to the detriment of research which has a higher probability of
producing new insights into biology/chemistry/medicine.

While there are genome mapping/sequencing projects whose goals I understand
("we want to know the sequences of all the genes in X, because we have a 
fantastic genetic map of organism X, we already know what many of the genes
do, and we don't have to worry about the 95% of the genome that is essentially 
junk;therefore, the sequence of X's genome is just a way to get at a glut of 
information that we can immediately interpret"), these arguments do not seem
to apply to humans.

Even in this form, though, it is not sequencing "the genome" that is 
important, but sequencing "all the genes that we know are important."  It
seems as though anthrocentricity is driving this project, rather than a true
quest for scientific knowledge.

Consider:  I remember when the sequence of all of SV40 was first 
determined; I also remember when the chloroplast genome was completed.  What
new lines of research have been opened up by this information?  New lines
mind you, that wouldn't have been available had not the sequence of the whole
genome been available.  For example, I am grateful for the sequences of
additional Group I introns from the chloroplast genome, but a more diverse
range of sequences has become available from directed searches of many
different genomes.  

And if you defer to thinking about the sequence of the human genome as a 
tool, then it is a very, very expensive tool.  And again I would suggest 
that finding the mechanism of one gene which causes MS is worth much more 
than knowing  the sequences of all the genes together (when you don't know 
what the genes do and still have to go back and find out). 

> I would certainly
> like to know the names of the ofFfFensive person or persons who "would
> suggest I should just bag my ideals and go off to happily catalogue
> genes at random.  And I am outraged that *alternative service* in
> science may come to mean just that."

David Kristofferson (apologies for mis-spelling, if such is the case) 
makes the point that academics should consider industry as an option.  A 
worthy point and one which I take to heart.  However, he goes on to suggest
that researchers should consider not doing 'real science,' and that a
wealth of (not-'real-science'?) opportunities will be related (just how, we
are not sure) to the Genome Project.

Thus, my obviously fanciful statement is based on:

(1) The contention that scientists should somehow be fulfilled "not doing 
real science," which seems like a self-contradictory sentence, and
(2) The notion that the Genome Project will somehow provide opportunities 
in industry for real or unreal science.  Again, I find this hard to imagine.

IMO (obviously H would be a bit out of place here) the Human Genome 
Project does not have a direction or purpose that would make it more useful
than a telephone book in a forgotten language.

Non-woof

(Look Ma, no flames!  Yet.)

(Michael, for someone who characterized my arguments as "he doesn't like 
it," you should do better than "9 out of 10 top docs support the Genome
Initiative;" rather like a National Enquirer special report.)