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.
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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
