| October 10, 1953
My dear Beale:

.. In response to your of the 7th, I am sending a pre-print of a paper
_ due to appear shortly in the Journal of Immainology. The more detailed
genetic analysis is still in progress, and even those inferences that
could be made from the data in that paper were not emphasized,

At fisst sight, the alternatdon of phases would seem to be closely
analogous to the situation in the Parameciua antigens. It is quite clear
that the alternative phases are each represented by a distinct locus
seemingly quite unlinked to the other, e.g. S. typ ium would be

m* H,)2. te series of "specific " antigens, a, c, dy ehy fg gies.
1, Js ky lvecey Tyee. then consthtute a serdes of alleles, while the
"non-specific" antigens: 1,2; 1,53; 1,7; « jeese are a series

of H, alleles. Phase variation is thus_no
of a shift from one allelic specif ba, another. The-Cchief problem now

is how the alternation of phenotyp ned. This is not finally
settled, and owing to technical 14; ye could prohahly not distinguish
between a determination by cytoflas Kye from that by a third unlinked
locus. However, the evidence to datr as to favor a third alternative,
namely a change of state at the locus4+6. elf. This is seen from experi-

ments of the type:

8S. typhimuriua (

  
   
    

 
 
  
   
   
 
   

, e
a pony (a, H, AX) (with b, eonx
serum for
selection)

  
   

ute have been either H+ #0 and

© evidence for two distinct H loci. (The third possible type
that the sdlective conditions would allow would be u,* H,?, never found. ]

engenders mostly Ag Ht? If we accept the principle [based only on rather

general evidence] that transduction involves only the transmisalon of small
chromosomal. fragments, the difference in the transductions from the two phases
would speak for a differentiation local to the genetie factors. Experinents
are in progress to seek to generalize these findings, and to test the role

of the phase of the recipient cells » but there have heen some difficult
technical probleps. Redently, Bernstein here has confirmed an old and
generally discredited report that the two flagellar phases are generally
distinguishable, phl being inagglutinable, and ph2 agglutinable by certain
basic dyes. This fits nicely the two-locus theory, but we are not yet sure

of ite more general implications.

You will note the exceptional behavior of the stock CDC-157 recorded in
the paper. We have quite good evidence, of a duplication ef Hy fa this stock,
so that it should be represented x,» Hy 9“ rather than H,~ Ho 92 gor typical

PB strains. Howeverg the alternation of b:1,2 is extremely sluggish and has
impeded the final verifica on of this notion in certain derived stocks we
believe to be, e.g., Hy Ay H°5x,

 
aay

 

As 49 so much of this work is still so tentative, may I ask that it not
be quoted as yet (except, of course, for the paper about to appear).

Needless to say, I am deeply interested in your continuing work and look
forward to a further gx¢dk exchange of publications.

 

 

f a ’ ’
' '/ Joshua Lederberg

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