November 7, 1952

Dr. Edgar /ltenburg
Departiusent of Biology
Rice Institute
Kouston, Texas

Dear Dr. Altenburg:

I certainly do agree that one can anke an unambiguous definition
for u zane, nanely that it is 2 unit according to the best antiytical
techniques that one chooses to apply. As you say, we cun locate genes
in the nucleus by thels segrezetion fn paraliel with the chromosomes.
T do not belleve that there is strong evidence for the location of
single genas 1n isolation anywhere in the cell, and by this strict
definition, viruses are by no means genss. You will admbt that they
do have genetic components, aud viet it muny vases thay have at least
quasi-genetic functions. Whether a given vircid iu of exogenous origin
is, on the one hand, not easily proven, and on the other not much more
pertinent theh the exogenous origin of chromosomes in the eatablishrent
of hybrid complexes such as Nicotiana, Gossypiun, or Triticum. The lmor-
tant thing 1s whether: the Immorted gunetic material constitutes an adap-
tive or potentially adaptive accretion to the genotype; i.e., whether the
new complex can now constitute a unit for adaptive evolution. I do not
believe that we are it: serious disagreanent, although we may prefer dif-
ferent modes of eapression. My only objection te calling sigma a virus,
for example, is that it may tend to discourage geneticista' interest in
it, juet as its designation es a "genoid" has probably hindered the full-
est application cf microbiological techn@qgues to it. I have expounded
this kind of treatment 4n greater detail in my review, which should be
in print momentarlly, and I will send you a reprint as soon as possible.
you will find that I hive gone to the logical conclusio: of treating the
symbiotic chlorellae not as genes (i.e. units), but as genetically interes-~
ting.

The one point on which I do not fully understand your views is the
distinction of eutocatalysts and genetle factors. The criterion of mta~
tion may be no more than a reflection of the complexity of organization
[the argument is in the review]; Genes have arisen de nove (in the atric-
test sense of the term, from non-living waterial) at least once. I am will-
ing t concede that the chromegenes have an unusually well developed
organization and teghnique of self-perpetuation if provided with the
particular anvironnent of the intact cell, but ths slementary reactions
of this perpetuation can hardly fail to be built up from autocatalyste.
Idc not think that it will be possible tc draw a definitive line between
progressive organizational hierarchies/ which will identify the gene. In
practice it may be sufficient tc characterize ths extremes, but it would
be unfortunate to excludes the pertinence of one for the other.

Yours sincerely

Joshua Lederberg
I may have baen too vague in referring to "similar spectlations"— you
may have had different aspects of your discussion in mind. I had in mind
largely a reversal of Darlington's evolutionary sequence of Johnson's "viréplasm'"
and Darlingten's plasmagene-"provisus"—virus hypotheses. ore particularly,
the following references may be cof iamedints interest to you:
Johnson Je Agr. Res. 642443 1942 (and prev.)
Green Biodynamica II (39}:1-8 1938
lieyer-Abich Biblictheca Blotheoretice 5:1~206 19506
Fallin Symblontician ahd the Crigin cf Species. Williane&Wilkins 1927
Burnet Austr. J. Exp. Biol. Med. Se. 62276; 14:27 1929, '36

alao, Blol. Rev. 9:332 '34
Wollimankanx Ann, Inst. Fasteur 39:769 1925

There are probaply others in the reviev.