March 18, 1953

Dear Jim:

Shank you for eending your sm., just received. I have given it a
hasty reading; Unfprtunatsly, I am so confhundedly tied up with other
mss. and the like that I will not be able to study it closely for
some few days.

I am not sure that I have caught all of the assertions that might
demnd afrtt critical review, but by and large I found nothing I could
disagree with violently.  As you will see from the anclosad abstract,
we have already abandoned the 8i.n&diakage group notion, on essentially
the same criteria as you require. I sm not sum v& thar ona is obliged
to re.ject the M-S linkage, at least from our owh data, but am willing to
accept this is not unreasonable. The crosses mntioned in this abstract
involved the use of l&S, ICTL, and S-TL as selective arkers, respectively.

  What I am less certain of is the ti&ng c i' eLM.nation. Again, I accept
our cmiclusf~ns a8 hyaothetical, and the suggestion that it occurs prior
to zygote fornation has not been csnolusk14 disproved. U the 1951 CSH
paper, however, it is nuent1oned without emphasis that 3&J..-5 crossovers
have baen observed ih the incomplete dlploidq ~hI.ch are, as a rule,
hemizygous for this region.(See table 6, p.42l). Such crossovers would
suggest that one can obtain hemizygo&&tq follow3ng synapsis [i.e. opportu-
nity for crossing 09er'J, and 1 hare ,mre or 16~ corist,ructad the general
pi&rule of post-elimination on this basis. I have tried tu set up an
Gxplicit them-~- based on postelinrination of aq entire chromo5om that
could reconc3.l.e all the facts, but the chief ~tmb1i.n~ block has been
the f iinding that, despite the coyrelation of Mai and Xyl of the kind
illustrated in table 6 and figure 4 (sad rsprtisentlng additional assorted
experi;aents as Well), Ul. aoms out hemizygous, whtie l@l i8 U8U&1y
he terozygous . Thia is not compelling evidence, an:! Lt may be that Ma34
represents an independent chromaome. These factors have also behaved
as a linked set in segregation from "cmp!.~3*~~ d;~,td%id~. h&s would seem
to favor pI a regular, post-el.SU.nation of the &&al-4 but not the Xyl-Mtl
segments of a single group. From this hasty reading, I think I could
endorse your paper much mm whole-heartedly lf it were more  e  licft
about the evidence concerning pre- vs. post-el~.nstio~~ of the "fl al4
segment. It would be fairer, too, I thinks if sme mm of the reserved
tone of your letter were to be transferred to the nqmr as qualifications
on the hypothetical schelne. It puts your co.Uenguas :lt zn unfair disad-
vantage to have to keep in &xi all of ahe facts (good bad and indifferent)
if you choose to submit a hypothesis wh%ch prpo~3d~ 5gnoreti so= of them.
This course is not crontrovertible, but the less so the mre circumpectly
it Is s*%ted.

  I am really very sorry to have to mite this so hastuy, snd am me
my thoughts have not been put down in good order-- I hope you can make
due allowances.

Sihcer ely,

Joshua Lederberg