Dear 501:

Rovember 6, lLsB6. '

&?W'S th8 G8l%iUa3 (mat ils -Wits d43SCriptiori; I: heard it

  &?rine3' Ju8t let 0s ~8 8 copy of your manuscrfpt, and reading
it wa$jtJat like being at Cold s;prZng Iiarbour, hearing one line'of
WidenCe after another Uti& one fs almost compelled to say:Stop,
1'11 believe anything you say. It is quite thrilling. Anything new?
There is only one pa&&t which is nut quite clear to me, and timt

ia the detail of the postulated ineohanisna of substrate-enzyme
interncUons, Perticularly between dif'ferent sydtxms. What, M
do you propose ia tha mechanism by which the formation of (i second

enzyme dephtea the first ; why should the presence of exogenous

Es affect this process if the substrates are shyly competing cm

unstable enayme 4olecules? Why &re the ?nzymes less unsttib&iB in the       1

pl"stsnce of azfde? All of theso gueztions BP@ based on this km-

ceptilon of the role of aubstr.hte: that ths precursor suffers random

reversible changes, o ccasianally producing enzymatically syec&ffc

IUO eCul8S, and that theses are stabilized by the presence of the

substrate. Bowetver, it is difficult f'or me to see the role of a

i

second tcompeting substrate 1 in effectfng changes in the rate of the   ;
                                                                        I

reaction of decomposition from E to PT. Perhaps this is too si~~~pll-     i
                                                              '? (
                                                         I
fied a canception; I would ay)?eciate It if you could c.lhrify it ~'0s   : ;
                                                                      ,

You may bca iutsreated that E, preliminary note     k, !
                                                                  \ :

an our bacterial work has appeared fn Nature for Oct. 19. I'm climlping '\ '
an your bandwagan, in a way; in hopes of finding non %sndelian nlggkz


machanisms to account for certain discrepancies in the ratlois of
the various new types that ap,eear in our mixed cultures,  WQ are

going to look at the inherfthnce of B lactose fermentation charwtor;
E. 0011 ( a triple mlant Y-10) was hetivlly irrl.diated, and after
pralfminary cultivation, was spread out oTi IW%Zactose plates.
lk 20,000 CQLCQII~S was a Wn-fermenter, and we are goim to study
the segrsgetion of this character fnto grototrophs when Y-10-L
and another biochemical Pautantfi which is Lplus are crossed, in the
presence and absence of lacstoss.   Rny sugges tfons?
Well, best of luck, iEmnd rek,:,ards to everybody there,

Sincerely,

  Josh,

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