In defense of the Genome Boondoggle

Deaddog Ellington at Frodo.MGH.Harvard.EDU
Mon Feb 11 21:46:38 EST 1991

In article <9102111942.AA08834 at> gunnell at FCRFV1.NCIFCRF.GOV 
("Gunnell, Mark") writes:
> Catalogue all human genes! Discover the functions of mapped genes; see 
> genes evolve; evaluate molecular evolution theories and how species 
> find amazing biological phenomena never before observed by human eyes.

Ah, finally some meat.

1) Discover the function of mapped genes.  The Genome Initiative is not
necessary for this.  If the phenotype is important, then a directed effort 
can be made to clone and sequence a given gene.  The sequence of the human
genome can of course be used to find the sequence of genes mapped *after*
the genome sequence has been determined.  However, I submit that mapping/
sequencing which targets a specific human diseases will proceed much 
faster and with less waste than the Genome Initiative itself.  Further, I
submit that theories having to do with developmental biology, organization of 
transcription units, regulatory phenomena, and so forth are most readily
answered by testing specific hypotheses/cloning specific genes.  The
Genome Initiative is massive overkill for these answers (see also (3),

2) See how genes evolve; evaluate molecular evolution theories and how
species originate.  As a card-carrying molecular evolutionist (burn him!), 
I agree that these are indeed mouth-watering problems.  It is sad that
they are receiving so little support now.  But, given the Scourge of AIDS,
this is perhaps understandable.  What is not understandable is why the 
Herculean efforts required to sequence the Human Genome will yield more
information than comparative sequence analysis of limited regions or of
specific genes.  Imagine a grant proposal in which I proposed to sequence
lactate dehydrogenase genes from a huge diversity of organisms; this 
proposal would be at the very bottom of the funding heap.  Yet it would
say an immense amount about how genes evolve.  Imagine a grant proposal in
which I proposed to clone/sequence "all zinc finger proteins from three
developmentally different organisms."  This might be more fundable, would
again yield an immense amount of information about protein evolution 
and perhaps transcription/gene regulation, but would not require the
Human Genome Initiative.

3) Find amazing biological phenomena never before observed by human eyes.
I think not.  The genotype is relatively uninterpretable without
corresponding phenotypes (which is why I support Drosophila, Coli, etc.
sequencing but cannot get behind the human effort).  The only biological
phenomena that I can see being elucidated by the sequence of the human 
genome would be instances where phenotype = genotype; that is,
selfish DNAs such as transposable elements.  A very interesting 
phenomena, but one that would again probably be nuked by a review
section if the experiment proposed was "I want to sequence the human
genome so that I can know the distribution of transposable elements
in an individual human."

So:  back to (one of) my original point(s):  In an era of limited funding,
directed research is essential.  Let each of the putative benefits of the
Genome Initiative be put up against other research proposals.  Let the 
molecular evolutionists who want to study bacterial speciation fight for 
the same money as those that want the sequence of every repetitive 
element on each human chromosome.  Let the developmental Drosophilists 
who are feeling the crunch compete against those who would assert that 
we can decode the series of steps by which an organ takes shape from the 
sequence of the human genome.  Let biological phenomena from neural 
networks to nematodes compete against whatever 'new' biological phenomena
the Genome Initiative will proport to discover.

There is so much *INTERESTING* science to be done.  And so little of it
will come from this genetic telephone book.  The question comes back to
how to get the most bang out of your buck.  For each question you say
the Genome Initiative will answer, I believe I can give you a dozen that
are cheaper and more interesting.  


(Getting less vitriolic, but not less arrogant or obnoxious.  Who knows,
maybe I'll even start using smileys or something.)

(Hmmm.  I actually had a thought.  How about we put a little check-off
box on NIH grant proposals--you know, just like on your tax returns.  "I
would like to earmark $5 for the Human Genome Initiative."  That way,
everyone that thinks it's a great idea can devote some of their funding
to it.  Then they could get discounts on the sequences of genes
of interest when they start flowing out of the sequencing sweatshops.
Just an idea.)   

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