gribskov@FCRFV1.NCIFCRF.GOV ("Gribskov, Michael") (02/13/91)
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@ncifcrf.govLab320@Frodo.MGH.Harvard.EDU ( ) (02/13/91)
In article <9102121616.AA03441@genbank.bio.net> gribskov@FCRFV1.NCIFCRF.GOV ("Gribskov, Michael") writes: > I am glad to see that this discussion has, for the most part, returned > to rational debate. Sorry, I'll try to work on this. > Dr. Ellingtons's objections to the genome project > seem to me to fall into 3 categories: financial, systematic, and > scientific. Actually, I didn't realize my thoughts were that coherent. Many thanks. Let me dig my ditch just a little deeper: 1. Financial--Genome Proponents often suggest that the money is not being stolen from the NIH general program. Even were this true, I see two problems, based on the supposition that the Genome Initiative is "science:" (a) Assume, if you will, that there was an "Easter Egg Initiative" in which a number of researchers were trained to dye eggs. This money was sacrosanct, and grants would only be considered if they related to the general area of egg coloration. Can you not see why there would be a hue (heh) and cry from the scientific community over these funds, even if they wouldn't be turned directly back to other science? Wasted money for bad science is wasted money that does not reflect well on good science. (This is not meant to be as flippant as it sounds; I am trying to convey my position, not my ire. Kee-rist, maybe I will start to use the loathesome smiley.) (b) In the coming years, as we all pay the costs of the S&L bailout, the Iraq war, and a general decline in the American Empire, tax money is going to become very, very scarce. Most Congresspeople are going to look at the TOTAL allotment of moneys for science, and are not going to worry about niceties like Genome Initiative vs. NIH general fund. The privileged position of the Genome Initiative will necessarily make fewer funds available for grants that are, in effect, all competing against each other. If the Genome Initiative is a good thing, let it compete for money with the projects it purports to do (see other of my communiques for clarification). 2. Systematic (what in the world do I mean by that?) -- > 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. But almost all grants have a defined goal. Writing a grant that in effect says, "Let me do this and I'm sure I'll learn something. Really." is the kiss of death. My point is this: (a) Most justifications that have been aired in this forum for the Genome Initiative can clearly (IMO) be done more effciently with a directed approach. (b) No justifications have been provided that the Genome Initiative will open up *new* lines of research. And (c) vague justifications that suggest that "there's something out there" wouldn't stand up to scrutiny by the folks that hand out the money. 3. Scientific--note that Dr. Gribskov doesn't actually answer the points he takes the pains to restate in the intro to this section. He merely points out that we will learn a great deal from sequencing other genomes, a point I have already agreed on. However, other genomes cannot be used to 'bootstrap' our way to sequencing the human genome. Junk is still junk. Waste is still waste. In fact, once we have all those lovely homologous sequences, why bother with sequencing the human genome: that's what hybridization and PCR are for, right? As for the rejoinder about "how do we know it's junk until we sequence it all?" I can only reply that we seem to be doing a bang-up job of figuring out the junk we already got without sequencing the human genome. With self-splicing introns being a good example. We got lots of junk and very few insights. More thinking, less sequencing! How much good science will flow from this waste? Some. How much good science will be sacrificed to this waste? Lots. > 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. I would imagine it horrifies Dr. Gribskov to see that we are in synchrony. See another of my annoying replies for details. > 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. This is the true horror. Once we are on the path to perfidy, there is no stopping. Can you imagine sequencing 10% of the human genome and calling it quits? No way! We will spend 5x more money to get the rest (hey, I give the sequencing technologists some credit). And, more importantly, there will be 600 young researchers whose meat and potatoes are coming from the project. Why? Because that's what we trained them to do! Believe it or don't, I agree with all the interim goals of the Genome Project. This is important science that should be done: but not as the tip of a very slippery slide into the accumulation of bags of silly data. Let these projects compete in the normal grant pool: if they are worthy they will be funded and science will be better off. If not, at least we won't have the built-in impetus to clone and sequence random DNA for no good reason. > The technique of ridiculing a project (by comparison to phlogiston or > N-Rays) would seem to indicate a lack of real arguments. No, it indicates a superabundance of bad humor. And besides, didn't you just go to the trouble of reiterating all my arguments, good or not? Non-woof (I see that I have begun to repeat myself, which means that we have just about exhausted this cycle of argumentation. We will all go quiescent soon; I bid you adieu.)
elliston@av8tr.UUCP (Keith Elliston) (02/13/91)
Just one more thought on the whole genome initiative..... Are we really justified in spending the large amount of $$ and time that it will take to sequence the genome, when we are only interested in the sequence of G's, A's, T's and C's??? Are we ready to ignore any and all base modifications that occur? Do we really know that the only information that is important is the sequence of the four bases, and not any other information. I have not heard any address this issue. Anyone want to give it a shot? Keith Elliston (No Woofs or Non-Woofs.... :) -- Keith O. Elliston elliston@av8tr.UUCP elliston@msdrl.com AA5A N9734U elliston@mbcl.rutgers.edu elliston@biovax.bitnet "Fly because you have to, to keep some semblance of sanity."