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SUNMARY EEPORT:

Bacterial Genetic Research
Supported by the Research Committee
From Funds Supplied by the Wisconsin

Alumni Research Foundation

by Joshua Lederberg
For the past several years, we have been concerned with olarifying
the genetic life cycle of Escherichia egoli. Until recently, most bac-
terlologists believed that bacteria reproduce only by fission, and are
devoid of any sexual reproductive process. This viewpoint is, in fact,
embodied in the name "Fission Fungi," which is applied to the Class of
pasteria, and in a once-popular definition of bacteria that dietingui shed
them from other living things by their supposed absence of a) "true"
nuclei, and »b) sexual reproduction. Since we can hope to achieve ef-
fective control of activities of the microorganisms, whether in medi-
eine, industry, or agriculture, only if we have a correct and clear
understanding of their biology, it is of more than academic importance
that recent evidence points to the occurrence of more or less typical
nuclei in most bacterial cella, and that a sexual method of reproduction
occurs in at least one bacterial species, Escherichia coli, the common
*eolon bacillus. *

So far, sexuality in E, coli has been studied almost entirely by
purely genetic methods: in particular, it hae been possible to show that,
very occasionally, genetically distinguishable variants are capable of
exchanging and reshuffling their genetic differences, a process techni-
cally described as gene recombination, The detailed features of the
recombination process are such as almost certainly to require the oc-
cagional fusion of cella, ao aa to allow their different genetic de-
terminants to intermingle, prior to thelr segregation in new or ‘re-"
combinations.

Since recombination occurs only between one pair of cells per mil-

lion under the most favorable conditions yet discovered, it is not
difficult to understand why no convincing picture of the morphological
basis of this process has yet been obtained.

Some progress has been made, however, toward the desired unification
of genetic and cytological interpretations, Under certain conditions,
bacterial cells can be propagated from a stage in their life cycle just
following fusion, but without Immediately undergoing segregation, Thus,
these cultures consist of cells which individually carry genetic deter-
minants from the two parents, as can be shown by direct single-cell
{e0lation (4n collaboration with Dr. M. BR. Zelle of Cornell University).
The genetic behavior of these heterozygous cultures shows signs of
aberrancy not yet fully understood, but leavea no question as to their
origin from the union of two parents (1.6., by a sexual process), When
examined cytologically the nuclei of heterozygous cultures are clearly
aifferent from the nuclei of their parents, wt this difficult mlaro-
acopical analysis has not yet progressed to the point where definitive
interpretations are possible,

cycle

Incomplete as it 4s, our new understanding of the genetic life/of
thie bacterium makes possible experimental analyses which could not
hitherto be carried out, One line of research, for example, involves
the patterns of genetic determination of enzyme preduction, Results to
date have shown thet these patterns are rather more complex than would
have been anticipated, and create the opportunity of a long-term study

ef the wayea in which different genetic changes may affect different
aspects of the biosynthesis of bacterial enzymes. In another line of

research, the effects of antiseptic agents on heterozygous bacteria

are being studied. This technique permits the conclusion that some
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antiseptics--such as physical radiations; nitrogen mustard; formaldehyde;
hydrogen peroxide; acetic anhydride, and other chemicals, --kill bacteria
either by virtue of, or in close coincidence to gross genetic damuge,
whereas other bactericides, such aa high temperatures, iodine, basie

dyes, streptomycin, and others kill without associated genetic effects.