April 13, 1954

Dr. J. Monod
Institut Pasteur
28 rue du Dr. Roux
Paris ¥V°, France

Dear Jacques:

Thank you for the culture of "W-1301-1", received here only yesterday,
and for your letters of April laand 2, which arrived earlier but while I
was away at Bethesda (where your own vieit had made a Beting impression!)

I mst admit my sincere respect for your conscientious letter of the 2a.

I d not, however, believe there is any moral issue involved at all; had
you chosen not to send your culture, I could not criticize you for it
("Judge not lest ye be judged" according to Scriptus@@), but I am delighted
at this indication of your interest in a collaborative approach, such as
you had suggested during our very pleasant meeting here at Madison.

Perhaps some embarrassment could have been prevented had I sent some
cultures by Air rather than Surface Mail, as I did on March 23. I hope you
will have received them by now-- thay were W-2417, as explained with the
package, and W-478, which is, of course, M- V,P Het. I hope you will not
have too many difficulties with the latter. It is not as fruitful, as it
seems, as it was at first, but should still be entirely workable. We have
still not clarified all of the peculiarities of elimination in the non-dis-
junction stocks, and you will have to anticipate that such markers as Mal,
S, Lp, and some Gal factors but not others, will invariably be fount in hemi-
zygous condition, usually ret&ining the markers from the F- parent, but often
enough from the F+ or from both. Also, as recounted especially in my paper
in the 1951 CSH, any other marker is likely to be found occasionally in the
homozygous rather than heterozygous state, so that each diploid must be
regarded as a personality of itself.

As to "%-1301/1", there has been time only for a first plating on FMB
lactose. In my hands this culture is distinctly lactose—positive, albeit
considerably weaker than wild type. Some colonies seemed to ferment more
weakly than others; these will be sorted out and tested for constitutive
activity. It seems to me possible that Lac,” may accentuate the effect of
lactose in inhibiting the constitutive formation of lactase, as can readily
be tested. I am not surprised that the stock is lactgse-positive for the
following reasons:

1) Boris has retested the activation fagor of Lac, induced by methyk
galactoside, and found it high, but not abnormallyso. his revalidates ay

older experiment with butyl-galactoside induction, on which some doubt was
cast (in a pbst~card that I hope you received at Berkeley) on the possibility
that the released butanol may have activated.

2) I had a chance to study my older experimental notes and found some
forgotten fragments. You will recall that Cst’ acts as a partial suppressor
of Lac. I had prepared a Lac, Lacy”, and by selection on lactose had

secured Ag a suppressor "reversion" which was a weak lactose-positive, but
still glucose negative. This was then used in crosses to test whether the
auppressor was separable from Lac,. No Lac™ Glut were found among several
hundred prototrophs of the backcross to wild type, which was the basis of

the conclusion that ¢é¥ "Cst" (or at least this suppressor!) was very closaiy
linked to Lac,. Unfortunately, the cultures seem to have been discarded

before they were adeq/uately test#ed for constitutive activity. At any rate,
we have again taken up this approach for evaluating the incidence and genetic
behavior of the Cst mutation. [Would you agree to rename this Lac, with alleles

Lac

i and Lac, or soms similar arrangement 7)

If a reprint of the constitutive paper was sent, I appear to have lost it,
and would greatly appreciate another.

With best wishes from all of us,
Yours sincebey,

i f
t Fag:
eT fat She

Joshita Lederberg

we