9/20/54 Chapter Outline

GENETICS AND CHEMOTHERAPY
by
L.L.CAVALLISSPORZA and J. LEDERBERG

1. Introduction to define problem: Example,
clinical failure of sulfonamides in therapy
of gonorrhea.

2. Background information on drugs. Theory of
biological antagoniam. (Appendix with cheni-
cal classification of antibiotics?)

3. tations of iniividual orgen lame
A. Drug tolerance and affiction in mamnals
B. Enzymatic adaptation in microorganisas

(Both physiological and not herdétable)

4. Individual variation (higher animala(and plants))
in response to drugs.
A. 7 Fu. Ratbit/atropine esterase (single gene)
B. DDT resis tance in insects (multiple genes)

5. Drug resistance in aieroblal tions

(Content similar to 1953 review

A. Pre- and post-adaptation theories and

thelr experiuental decision
B. Multi-sfep resis tance
C, Physiology of resistance (mechanisaa} cross-resistance;
secondary effects)

6. Genetic effecte of drugs [other than adaptation]

(matagenics anti-mitotic; removal of cytoplaanis

particles

7. Specific examples of drug resistance in bacteria
and other parasites. Laboratory and clinical studies

8. Resistance as a genetic marker (genetic analysis in
mieroorganigs; mutation and recombination studies)

9. Genetic improvement of antibiotic production

10. Genetie theory and clinical practice in chemotherapy.
A. Gorrelation in lab. ani in practice
B. Synergism and combined therapy
G. Future te in chemotherapy
(Shey /$£ /eehtdtiéds (can resistance be prevented or reversed?
(cross-resistance; pathogenicity of resistant mtants; evolutionary
trends in alorobial popplations; the strategy (vs. tactics) of
chemother apsutic practice.)
The book is inéended primarily roe tiatgen students and practitioners of chemotis rapy who want
a theoretical understaniing of the drug-resistance they inevitably encounter in practice. Howe
ver, resistance w 11] also be stressed as a model of adaptation and evolution in microorganiam.

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pdayord