A. E. Mirsky 133

ity that the minute quantities of protein that probably remain at-
tached to DNA, though undetectable by the tests applied, are neces-
sary for activity—itsclf an exccedingly sensitive test. Transformation
of pneumococci is a sclf-duplication phenomenon, for the effect
finally observed is not due immediately to the active principle added,
but to the enormously greater quantity of active principle generated
in the course of the experiment. It is, therefore, possible that no more
than a few particles of active principle are required; and if no
more than a few particles of DNA were effective, there would be no
doubt that the active principle consisted of nothing but DNA. In his
work on preparation of the bacteriophage Northrop (1937) recog-
nized that he was dealing with a sclf-duplication phenomenon and
was able to demonstrate that the material which he isolated was
actually the bacteriophage because only a few particles were required
for activity. Actually a very large number of DNA particles (more
than 10%, if a molecular weight of a million is assumed for DNA) are
required for pneumococcus transformation, and the minimal mass of
material is about 2,000,000 times that of the minimal mass of nucleo-
protcin required for phage activity. There is, accordingly, some doubt
whether DNA is itself the transforming agent, although it can be
regarded as established that DNA is at least part of the active prin-
ciple. It should be mentioned that even if DNA itself is the active

Since it is now known that the material derived from the heat-
killed cells that is effective in pneumococcus transformation contains
DNA, this is in itself evidence for considering the process to be es-
sentially a hybridization. In those cells which can be studied cytologi-
cally, all the DNA is localized in chromosomes and the essential role

principle, much more than several particles may be needed,

of chromosomal material in hybridization is well-known. It is remark-—

able in the pneumococcus transformation that part of the DNA-con-
taining material is derived from heat-killed cells, and that before
heing used for “hybridization” it can be examined chemically.