Seattle  T-12;   October 27, 1990
(The Transition from Biochemical to Molecular Genetics, HSS mtgs)

On February 1, 1944....    SLIDE 1  Avery
                                 2  Wyatt
Avery's own understanding
O.T. Avery letter to brother Roy
?cited in McCarty
Important new idea; foundation of modern molecular biology
  and biotechnology
a) gene is DNA
b) use bacteria for new progress in genetics (prior v.v. e.g. 1943)
1) an exptl. assay of "DNA" function OR NUCLEO-PROTEIN
2) specific hypothesis (facit in "directed mutation") gene=DNA
3) use bacteria

How it was CON/RE CEIVED
conceived - see McCarty
received + built upon
telling for efficiency of scientific progress
pros/cons of participant commentary

SLIDES
Avery 1944
JL 1/20/1945
CSH 1947.. Harriet there. McCarty 1946 
Muller 1947
JL 1951..
Hershey 1953  post 1952
SCI 1945-54...

letter to brother
bacterial genetics
CSH
Muller's imprimatur
lively discussion
W+C presented there
+OBI! frequent

SLIDES
McCarty 1985 complexity of issues
JL 1956
JL 1958 NP
NP's

Return to issues
1 DNA transformation system
pn. too hard
B. subtilis in late 50's and CaP in 60's
transfunction + plasmids--> full blown
now shotgun

2 gene=DNA
research and unreasonable doubts  
don't judge by hindsight
when should controversy have been closed?  when counterproductive?
a) diluted interest in chemistry of DNA.  Hardly race --> 1953?
b) frustration to claimants; inequity of credit; ?try harder
c) waste a lot of effort in argument.  If had gone on much longer.
hazards of premature closure...
stop looking for analysis
_________________________
Need one "BELIEVE".
asif -- <<ignores proof

sources of resistance
Levine model 1931 -- a stepping stone!
Northrop & Summer 1936!
Stanley fiasco
EB Wilson volte fall

2 gene=DNA
popularize by plasticity of mechanism.  W&C 53.
theoretical image compelling
By 1958 important to express my own conviction lingering vitalism

shortly thereafter, linkage groups sediment w/DNA; broken by shear
proof
Kornberg 1965
enzymatic replication of virus
Khorana - synthesis of a gene
CHECK

3 use bacteria for genetics
E coli recombination
Salmonella viral transduction
Monod & Jacob many more
biotechnology industry

3 FIRST practical application of DNA knowledge 1980.
YW Kan diagnosis 76?
exploded in that decade

broader consideration
what happened
what does it say about efficiency of science

was there resistance?
unreasonable?
external vs internal factors?

My own biases are tragic inevitability of stumbling blocks to
conception after prior stepping stones.
If only... step out of existing dogmatic framework, jump of the
giant's shoulder
many "postmature" discoveries internalized resistance.
use RKM corr.   SLIDE

Need active engagement and focus of attention a prerequisite  SLIDE
Inattention of geneticist to bacteria 
Why not more remark on the nearly total neglect of Griffith 1928.
(I was only 3 years old at the time).
Even Avery follow up was biochemistry  SLIDE
No genetics tale    
Neglect far greater less than active debate
attention , ferment, dialetic
>>important than static uncritical belief
postscripts of participant observer

Nobel Prize for Avery  (Mac McCarty)
Official history
W Stanley role.  How he was burned.
Back to where to fix the system.  Reduce disincentives.
encourage more critical theory
HoS indisposable for that

Future slides:
tetranucleotide theory and its discordants
WC - Nature 1953; pix them
St   , Avery, McCarty today - oblit'd.
Avery letter to brother
Khorana give support
DNA sequencing
precursor        refs (Sapp)

- extensive notes re Avery
  folder on Dubos...  ?my review
  computing models of assimilation
  new info   repl... transcr...
Schlenk - 1988
tetranucleotide as stepping stone
deoxyribose 1930? DNA as a 4x nucleotide;  cf 1931 monograph
see Chargoff 1955
1945 mtg ashMCC - was Stanley there?