genome project

Gribskov, Michael gribskov at FCRFV1.NCIFCRF.GOV
Tue Feb 12 11:11:00 EST 1991


I am glad to see that this discussion has, for the most part, returned 
to rational debate.  Dr. Ellingtons's objections to the genome project 
seem to me to fall into 3 categories: financial, systematic, and 
scientific.

1) Financial -- the genome project is cutting into NIH funding for 
   other projects and molecular evolution projects are difficult to get
   funding for.

   While there is some truth to this, I think the bulk of the funding
   for the genome program is new money.  NIH's funding problems can 
   be traced to a number of sources, including the large increase in the 
   number of continuing grants funded several years ago, and a 
   substantial increase in the number of researchers competing for 
   grants.  It seems to me that it is very unlikely that cancellation of 
   the genome program would result in the transfer of the allocated funds 
   to NIH general program.  Congress would probably see a "better" use for 
   them (congressional salaries perhaps, certainly not deficit reduction).

   There are also a number of projects funded previously by the NIH 
   which are now funded by genome project funding, thereby freeing up this
   money for non-genome projects.  Or another way of looking at it: some 
   of the genome project money way already being spent on the same projects
   even before the prject officially existed.

2) Systematic --  the information resulting form the genome project is 
   available by other means and few if any new lines of research will be 
   opened up.  

   To apply this standard to the genome project seems unfair.  Few if any 
   grants describe a problem that can't be tackled by other means.  Most
   merely continue an existing line of inquiry and do not open up new 
   ones.

3) Scientific - too little is known about human genes; the genetic map 
   is too poor to justify sequencing the genome, besides most of the DNA 
   is "junk" anyway. Furthermore the project is anthropocentric, ignoring 
   the genomes of species which are much better characterized genetically.

   Many, if not the majority, of genes can be identified and the 
   identity of the protein product determined by comparison to known genes
   from other organisms.  It is not unreasonable to expect that by the 
   time actual genome sequence is available that most genes will be 
   able to be identified in this way.  My understanding of the current 
   project is the large parts, if not all, of the sequences of the 
   following model systems will be sequenced in the course of the genome 
   project: E. coli, yeast, fly, nematode, and mouse.  These include 
   some of the most well characterized gneetic systems.  Perhaps the 
   project should have been called the "lots of genomes project", but this 
   would have been difficult to sell to congress.  Although we do not 
   understand the function of much of the non-coding DNA, it is really 
   premature to call it "junk".  Only a few years ago, the self-splicing
   introns that Dr. Ellington find interesting would have also been 
   characterized as junk.
                             --------------------
   As to whether the resulting information will be useful, I admit that 
   we won't really know until we have a good piece of it.  The project is
   speculative, as is a lot of good science.  One of my main worries is
   that it is being heavily oversold to congress as a panacaea for human
   disease.  This may ultimately result in a painful congressional backlash. 

   The actual sequencing of genomes is still five years or more down the
   road and we will be in a much better position to judge the value of 
   the project in a few years.  In the meantime, the five year goals of the
   project appear to me to be very justifiable and of wide general use.
   My synopsis gleaned from the U.S. Human Genome Project: FY 1991-1995
   (DOE/ER-0452P) report.  

	1) Complete a fully connected human genetic map with markers
	   2-5 centimorgans apart, each associated with an STS.

	2) Assemble STS maps of all human chromosomes with markers at
	   at 100kb intervals.  Generate overlapping clones with 
           continuity over 2mb.

	3) improve sequencing technology to allow sequencing at a cost
	   of $ 0.50/bp.

	4) prepare a genetic map of the mouse genome based on DNA 
	   markers and physically map one or two chromosomes.

	5) develop effective software and database designs to deal with
	   mapping and sequence data.

	6) support research training of up to 600 pre- and post-doctoral
	   trainees.

The technique of ridiculing a project (by comparison to phlogiston or
N-Rays) would seem to indicate a lack of real arguments.  Creationists 
often ridicule evolution with the same "ohmigosh, it's unimaginable"
in the course of proving that evolution is impossible.  I repeat --
many reputable scientists see some value in the genome project -- not 
all of them are fools.  And no, I do not feel that I need to list them;
Most of us know who they are, anyone can find out by reading a little.

Michael Gribskov
gribskov at ncifcrf.gov




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