UNIVERSITY OFOREGON =”
May 22, 1989

Dr. Joshua Lederberg, President
The Rockefeller University
New York, NY 10021

Dear Josh:

Thanks for your note and the reprints of your Commentary on the human genome
project and the Perspectives on replica plating and indirect selection. And apologies for
the delay in this reply.

Your views on the human genome project make excellent sense and | cannot
understand the enthusiasm of some people. It is surely the least cost-effective and
probably the slowest way of getting an understanding of the working of the human
genome. It is remindful of the issue 30 years ago of how best to explore space - with
humans aboard or not. The same kind of forces that determined that decision again
seem operative. Not only do we see large Federal labs bidding for a piece of the action

but also already | had a Cail from an aerospace company asking about some collaboration

with our Institute. Recently | have seen a lot of questioning of the use of humans in
our space missions. It may take another 30 years before the poor wisdom of the human
genome project is appreciated.

You were generous in your reference in your Perspectives to our replica plating
system. For my part, the interest was in a set-up where we could make replicate prints
of a matrix of colonies onto a variety of test plates. Its use for indirect selection of

mutants did not occur to me, perhaps because | had not been thinking of something with

the resolving power of velveteen.

When | first heard of Cairns recent work | was less skeptical than if it had come

from someone whom | respected much less. Whether he is correct or not in the example

he reported | am undecided. But it has since occurred to me that given the enormous

evolutionary potential of microorganisms and given the great advantage of competence for

post-adaptive mutation,that bacteria may have achieved that ability in afew cases. On
the other hand the advantage may not be so great after all. In effect, post-adaptive
mutation would represent an increase by a factor of 109-108 over spontaneous rates.
Even these apparently large factors may not be large enough to offer the necessary
selective advantage. In any event, post-adaptive mutation along with cold fusion has
enlivened things, even if unreal.

NSTITETE OF MOLECULAR BIOLOGY » UNIVERSITY OF ORFGON + EUGENE, OR 974031220 « TELEPHONE (503) 686-5151

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Dr. Joshua Lederberg
May 22, 1989
page 2

i By re way did you notice Me oan article in Nature on organic carbon in
sedimentary rocks over the last 3, million years (Schidiowski, Nature 333, 313-318,
1988). On the basis of 5G /A86 comparisons he concluded that life was present almost 4
billion years 99 and in an abundance no less than that today. Carbon in contemporary
life is poorer in 3C than in carbonate. But | do not believe he can exclude that the
ancient carbon came from abiotic synthesis. | cannot understand why the relative
abundance has remained constant. His assumption that it has been the result of

limitation by something like phosphater-%gsat sounds unconvincing to me.

It was very good to hear from you and I hope | get to see you again soon.
Best regards,

Corn

Aaron Novick

AN: jip v