EDI

 

Jamary 15, 1953. -
Dear Jack: |

Thank you for returning the reprints, ‘and ‘especially f for your critical
appreciation of Cell Genetics. Neither the logic nor the rhetoric of the
latter has entirely pleased. me; I can only plead that I am sti11 floundering
in the sea of uncritical and traditional thinking out. of which I am trying
to swim. If you are interested enough to discuss genetics with ms, I'll play
the same gama with the rihstoric. You are quite right about commas, and merits...
merits. A born weiter, I hope, ia able to avoid these slips and awkward con-
struations before they happen. I have to go over my writing and extract them
later, and. only hope not to have missed too many.

“left a plethora. of terms adrift doesn't sound quite right; ‘left adrift a
plethora of terma might have been bettar, but not mich. Still I support the.
waage "plothors of teras”; it's: =e “eft ean that makes an unhappy phrase,

- 'Mpaats, equarely on ‘the, hiatus," pores exactly: what. Le says ( (though you refusec
‘to. believe it). Again, . this - 48 not a very pleasant ‘eonstruction—~ Fowler might
havé called Atean example’ of belabored subtility.

Te r may. clarity, the construction, Sporbxidac"or. in. the absence of | a microme]
is a parefithesia,” and should have- been marked as stich. In am a sense, if theis
is no current micronucleus, the genotype ie mull. I'd ‘better requote the para~
graph: "Under certain conditions (or in the absence of.a. micromicleus) the
macronicleus will be regenewated from fraighents of tha ‘previcus macronucleas,
irrespactive(iy?) ofthe genotype of the current micronucleus." The more I look
at this, the worse it xeeks seers, and I am left vith the concl usion that noone
6lse is going to understand it who did not already. What I meant was that the
macronucleus might. regensrate from the old macron. ao that its mamkketk gonsti-
tution could be different from the current micron. This can happen even if.
‘there ig no. iwnlcronucleus at ali. Ordinarily, the macronucleus is reconstituted
from the new migronucleus at sach act of gonjugation or autogamy that ‘would
produces a new aicronuclear genotype. As it stands, the paragraph seems to read
that regensration occurs irrespective of the ‘micronuclear genotype, but. this
was not intended. I must have been so preoscupisd with trying to formulate
some of thess ideas fcr ayself that q did not make sure that their meaning was
‘fully given in the writing. ce Oo

#Radio theory” aa you call it is quite the fad in genetics, » and every thing
else, but under the hame of "Cybernetics".

"candidate mhose. availability..." was written about the time of the conventio:
_ It sounds rather stale now, doesn't it.
It wad the philosophical possibiltties, and not the technical findings of
course, that led me to pick out these papers. I am a little troubled already

_ by. some inconsistencies. The review itself has many of themf S.g.," genetic

diseases simulating vhroses might result from the recrudescence of inherited
iatent viruses...'', when. the whole point of the review was to emphasize the

' formal equivalenceg of these views, rather than the correctness of one inter—

pretation over the other. In the midst of my lectures while trying to decry
What you called dogmatiam, I look over my shoulders and find myself doing ‘hx
mich the same things that are deplored. In practice it is very difficult to
do any work without idealizing one's concepts. We frame our axperiments on the
basis of very insecure working hypothes&s; in order to do them, we have to

‘place the full ‘eight of our confidence on then.

| If your comment on dognatism# refers to the discussion of "replica plating",
as f think it doesa,I think I have to mention some of the history of this problem.
There is a tpemendous amount of uncritical work, some of it over reputable
gignatures, on adaptive mechanisms in bacteria. Most of it 43 bad because the
dritical hypotheses are never clearly stated. I think no cna need dispute that
spontaneous mutations and natural selecticn explain most of the adaptive phenomen:
that have been carefully studied. It ig incorrect to generalize, as I did,
that this is the dnly mechanism that can cperate, The paper is written in this
jtone in order to emphasize the essentiality of disqualifying this mechanism in
detail before adopting poorly founded alternatives. It 13 not a studied dis—

jcussion of "spontaneous mutation” such as 1 have, betimes, put elsewhere. Mutatio:

'
!

j

{ are, of course, never "spontaneous", even in the restricted sense kh which
some natural phenomena are (viz. radioactive disintegration). There must be

a material chemical reaction in the cell underlying the genetic change; the
trouble 1s, we kaow nsxt to nothing of what these reactions area, ox how to
control thom. Unfortunately many bacteriologists, having diseovared that they
could select for certain mutant typea, thought theg had tnducad the mtations.
In every case, so far, where the question has baen properly put, these have
turned out to be selected, and not induced. 4 little progress is being made in
the "axperimental control of spontaneous mitation", but no so much that we can
approach’a particular gene and tell it when to change. Until we have achieved
such a control, the mutations might as well be spontaneous. I would agree that
"spontaneous mutation" has been made an absolute ideal, by H. J. Muller for
example, but this is an overcompensatory response to even less sound claims

of lamarckian effects.

I am not at all diffident about my corpus; in fact I have taken quite
seriously the kind of advices you gave and am approaching the 2 cwt. level you
suggested. I had the same impressions of that photograph as you did; it is a
caricature, and was selected by if one of my colleagues (not Buzzati-‘raverso)
with a certain friendly malice. I enjoyed your peam, without fully appreciating
its relevance-~ not thatbthis is needed,

Thanks for putting me straight about your feelings on the academic life (for-
tunately indeed I found this job which is research, and not too bad financially
either); no, I've never heard of any academic job below an assistant professorship |
(and then some, at times and places) that would be likely to match yours, I shouhd
like to teach myself, more than afew hours a week,

Sincerely,

\Yoshua Lederberg

BoA FAG) gu