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Janeury 28, 1965

Dea. Freeman H. Quimby Ref: SB(FHQ:pak)
Chief, Exebiology

Bioscience Programs

Office of Space Science and Applications

National Aeornautics and Space Administration

Washington, D. C. 20546

Dear Freeman:

This is a further reaction to your letter of January 7 with its own very
useful comments on my paper "Signs of Life”. You may be right that the
question of ultrasensitivity in detecting molecular species may have been
“over engineered" in the background of some of my thinking about this
question. Certainly the context of a small lander in which the gear for
collecting samples of more than a few milligrams might have been prohibi-
tively heavy was a leading factor in my earlier thinking. However, even

on further reflection I think I would continue to give considerable weight,
though by no means exclusive attention, to "molecular detection”. Even
when target material is originally quite abundant byt the time we have
isolated and purified the particular classes of substances in which we are
most interested, we are again likely to find ourselves with vanishingly
suall amounts, or rather that the extent to which we can ¢ontinue our
analytical work is often limited by the amout of material at our disposal,
This will be true then even for a fifty thousand pound lander operating in
a jungle of life forms. I think we must also give considerable weight to
the possibility that life is as likely to be rather sparse on Mars as it is
to be extremely abundant. Now it is quite possible that some methods are
unnecessarily sensitive in relation to the purposes for which they are
designed, but I really can't accept the argument that a technique is too
sensitive. After all, even in the contaminated column experiments to which
you refer, the contamination is there whether or not the instrument used for
detection is sensitive enough to tell about it, and a wise conslusion is
more a matter of prudence in interpreting the results and in establishing
the necessary controls than it is in blinding oneself to the sub-threshold
levels of material that may be flowing through out of bounds. Good sensitive
techniques will have taken account of the necessity of clean columns, instru~
ment memories, etc. In like fashion, I would never say, and don't think I
did say, that all crucial data for exobiology must be sought at the molecular
level. I do retain the very strong conviction that the most decisive ques-
tions that we can ask of Martian life - apart from the possible extreme one
of intelligence - do concern the molecular architecture of the system. But

I think you will also note that I would recommend very strongly that all of
the landing experiments which should emphasize, though not be completely
dopdmated by, chemical analysis, should be preceded by very extensive
orbital reconnaisance, which is of course generally quite unable to give
detailed information at this level. If my paper really conveys such an
Dr. Freeman H. Quimby January 28, 1965
Page 2

extreme standpoint, I would be very sorry for it, but I really think that
we both understand one another's position and that the issue of emphasis

on chemical versus other approaches to detection are entirely a matter of
emphasis and are very difficult to deal with outside the framework of a set
of concrete proposals.

I think that you and Orr might be particularly interested to hear of a
remarkably clean result that Dr. Halpern has achieved in our laboratories
along the lines of the gas chromatographic assay of optical activity, namely
the very straightforward resolution of derivatives of D versus L amino acids.
The reagent happens to be trifluoroaceto-L-prolyl, since it turned out that
one of the most convenient sources of an already resolved organic reagent

was itself an amino acid. We are now looking for ways in which this approach
can be used on a wide variety of target material, since it has been designed
so far for individual amino acids. It does look very promising indeed as a
way of picking up the optical activity of submicrogram quantities of substance.

Cordially,

Joshua Lederberg
Professor of Genetics