What are the genes What is the nature of the elements of heredity that Mendel postulated as purely theoretical units Frankly these are questions with which the working geneticist has not much concern himself If the gene is a material unit it is a piece of a chromosome if it is a fictitious unit it must be referred to a definite location in a chromosome Therefore it makes no difference in the actual work in genetics which point of view is taken T H Morgan The Relation of Genetics to Physiology and Medicine Nobel Lecture June 4 1934 Bacterial genetics MCB 140 09 19 08 1 MCB 140 09 19 08 2 DNA RNA protein central dogma of molecular biology MCB 140 2 25 05 3 7 20 MCB 140 09 19 08 4 Today even the layman thinks of resistant bacteria as originating from mutation but when Luria and Delbr ck first got together conventional bacteriologists were by no means clear that microorganisms could be tought about genetically Many believed that resistance was some kind of adaptation induced in a few of the bacteria in a culture by the exposure to the antibacterial agent Max Delbr ck 1906 1981 Salvador Luria 1912 1991 Cold Spring Harbor Laboratory Long Island NY Summer 1941 Judson p 55 MCB 140 09 19 08 5 MCB 140 09 19 08 6 1 The idea smacks of the preMendelian pre Darwinian notion of the inheritance of acquired characteristics Luria damned bacteriology as the last stronghold of Lamarckism Let s all do science in Nevada One Saturday evening Luria went to a faculty dance There watching the fluctuating returns obtained by colleagues gambling on a slot machine he thought of the experiment that would distinguish between resistance induced in bacteria and resistance resulting from previous spontaneous mutation upon which selection acts Judson p 55 Judson p 55 MCB 140 09 19 08 7 MCB 140 09 19 08 8 What Luria perceived was that previous spontaneous mutation would pay out jackpots of resistant bacteria that would fluctuate much more widely in size than those paid out by induction He tried the first experiment on the following morning and wrote off to Delbrueck Delbrueck promptly replied that Luria really ought to go to church Judson p 55 MCB 140 09 19 08 9 MCB 140 09 19 08 10 S Luria M Delbr ck 1943 Mutations of bacteria from virus sensitivity to virus resistance Genetics 28 491 511 What Luria actually did Sample set A 1 Inoculate bacteria into individual cultures 1 bacterium per culture 2 Let it grow up to a large number 7 4 Sample set B 1 Take an aliquot of bacteria and start a culture which will therefore not be clonal 2 Let them grow up to a large number Expose both to phage and count how many phageresistant colonies per culture are found Ask if there is a difference between these two sample sets MCB 140 09 19 08 11 If the production of resistance began only at the moment of exposure to phage then it wouldn t matter whether the bacteria came from many individual cultures or one bulk culture When Luria performed the experiment though the twenty separate cultures showed much wider fluctuations from the average number of resistant colonies indicating that a few of the individual tubes contained resistant bacteria from near the beginning of the overnight growth period Judson p 56 MCB 140 09 19 08 12 2 Brock p 59 MCB 140 09 19 08 13 MCB 140 09 19 08 14 George Beadle left and Edward Tatum right receiving their Nobel Prizes MCB 140 09 19 08 15 MCB 140 09 19 08 16 Beadle and Tatum the rationale In 1940 while teaching at Stanford Tatum reviewed the nutritional growth factor requirements that distinguish related bacterial species This raised the question of whether mutations can lead to nutritional requirements in species that do not already require a growth factor As Beadle was already familiar with Neurospora from his contact with Dodge and Lindegren he recognized it as an ideal organism with which to pursue this question First Neurospora could be grown on a simple minimal medium that contained inorganic salts sucrose and a single vitamin The idea of imposing further nutritional requirements by mutation was plausible Moreover Neurospora cultures were haploid and therefore recognition of recessive loss offunction mutations should be straightforward And most importantly Neurospora had orthodox Mendelian genetics an attribute that would be vital in a continuing dispute about the role of genes the idea still persisted among embryologists that the fundamental information regarding body plan organ systems and the epigenetic features of development lay in the cytoplasm Beadle and Tatum did their experiments in part to convince many sceptical biologists that genes control the fundamental processes of life and not just the final touches of development such as wing shape or eye pigment To show this it was important to use a eukaryote that was simpler than Drosophila and to focus on metabolic functions that could not possibly be considered as final touches Nature Reviews Genetics 3 397 403 MCB 140 09 19 08 17 Nature Reviews Genetics 3 397 403 MCB 140 09 19 08 18 3 Beadle and Tatum the beginnings Thirty points on the midterm so wake up Observing him Tatum writing sequences of reactions on the blackboard I suddenly realized how stupid we had been all these years Here were all those enzymatic reactions already worked out by competent biochemists If our gene enzyme concepts were correct then we ought to be able to identify the genes immediately responsible for specifically known enzyme catalysed reactions So why not reverse the approach Instead of looking for reactions by enzymes controlled by known genes why not look for genes that control already known chemical reactions We might then expect to find mutations characterized by an inability to synthesize essential diffusible substances such as vitamins amino acids and other building blocks of the cell s protoplasm Nature Reviews Genetics 5 949 954 MCB 140 09 19 08 19 Nature Reviews Genetics 5 949 954 MCB 140 09 19 08 20 Ka BOOOM It took Beadle and Tatum only 5 months to find the first 3 nutritional mutants in their irradiated cultures one required pyridoxin another needed p aminobenzoic acid and the third required thiamin The first public announcement of their accomplishment was at a Caltech seminar where Beadle went to recruit people for his research group Not surprisingly his news was a bombshell Norman H Horowitz one of the people he recruited recalls it clearly The talk lasted only half an hour and when it was suddenly over the room was silent The silence was a form of
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