SUPPLEMENT VII 



A VIEW OF GENETICS* 



Joshua Lederberg 



Department of Genetics, Stanford Vnirersity School of Medicine 



The Nobel Statutes of 1900 charge each 

 prize-winner to give a pubUc lecture in Stock- 

 holm within six months of Commemoration 

 Day. That I have fully used this margin is not 

 altogether ingenuous, since it furnishes a pleas- 

 ant occasion to revisit my many friends and 

 colleagues in your beautiful city during its best 

 season. 



The charge might call for a historical ac- 

 count of past "studies on genetic recombina- 

 tion and organization of the genetic material 

 in bacteria," studies in which I have enjoyed 

 the companionship of many colleagues, above 

 all my wife. However, this subject has been 

 reviewed regularly (36, 37, 3S, 41, 42, 45, 49, 

 54' 55' 5^) -^^^ ^ hope you will share my own 

 inclination to assume a more speculative task, 

 to look at the context of contempf)rary science 

 in which bacterial genetics can be better under- 

 stood, and to scrutinize the future prospects of 

 experimental genetics. 



The dispersion of a Nobel award in the field 

 of genetics symbolizes the convergent efforts 

 of a world-wide community of investigators. 

 That genetics should now be recognized is also 

 timely — for its axial role in the conceptual 

 structure of biology, and for its ripening yield 

 for the theory and practice of medicine. How- 

 ever, experimental genetics is reaching its full 

 powers in coalescence with biochemistry: in 

 principle, each phenotype should eventually be 

 denoted as an exact sequence of amino acids 

 in protein (79) and the genotype as a corre- 

 sponding sequence of nucleotides in DNA 

 (a, 63). The precise demarcation of genetics 

 from biochemistry is already futile: but when 

 genetics has been fully reduced to its molecular 

 foundations, it may continue to serve in the 

 same relation as thermodynamics to mechan- 

 ics (69). The coordination of so many adja- 



• Received for publication May 14, 1959. Nohci Prize 

 lecture given at the Rova! Caroline Meclicf)-SurRical Insti- 

 tute, Stockholm, May 29, 1959. The Nobel Prize in Physi- 

 ology or Medicine was awarded December H), 1958, 

 jointly to G. W. Beadle, E. L. Tatum, and J. Lederberg. 



cent sciences will be a cogent challenge to the 

 intellectual powers of our successors. 



That bacteria and their genetics should now 

 be so relevant to general biology is already a 

 fresh cycle in our scientific outlook. When 

 thought of at all, they have often been relegat- 

 ed to some obscure byway of evolution, their 

 complexity and their homology with other or- 

 ganisms grossly underrated. "Since Pasteur's 

 startling discoveries of the important role 

 played by microbes in human affairs, micro- 

 biology as a science has always suffered from 

 its eminent practical applications. By far the 

 majority of the microbiological studies were 

 undertaken to answer questions connected 

 with the well-being of mankind" (30). The 

 pedagogic cleavage of academic biology from 

 medical education has helped sustain this dis- 

 tortion. Happily, the repatriation of bacteria 

 and viruses is only the first measure of the re- 

 payment of medicine's debt to biology (6, 7, 8) . 



Comparative biochemistry has consum- 

 mated the unification of biology revitalized by 

 Darwin one hundred years ago. Throughout 

 the living world we see a common set of struc- 

 tural units — amino acids, coenzymes, nucleins, 

 carbohydrates and so forth — from which every 

 organism builds itself. The same holds for 

 the fundamental process of biosynthesis and of 

 energy metabolism. The exceptions to this 

 rule thus command special interest as mean- 

 ingful tokens of biological individuality, e.g., 

 the replacement of cytosine by hydroxymethyl 

 cytosine in the DNA of T2 phage (12). 



Nutrition has been a special triumph. Bac- 

 teria which required no vitamins had seemed 

 simpler than man. But deeper insights (32, 

 61) interpret nutritional simplicity as a greater 

 power of synthesis. The requirements of more 

 exacting organisms comprise just those me- 

 tabolites they cannot synthesize with their 

 own enzymatic machinery. 



Species differ in their nutrition: if species are 

 delimited by tlieir genes, tfien genes must con- 

 trol tlie hiosyntfietic steps tvfiicli are reflected 



S-65 



