TO:  Joshua Lederberg
Subject:  Pour memo and inquiries of Sentember 22, 1972 re-
      garding Avery and Griffith.
Date:  September 28, 1972
From:   Al Coburn

    1.  "Conceptual antecedents that mav have inspired his ex-
periments".  Griffith was wedded to bacteria and fascinated with
their behavior.  In 1928 "bacterial variation" was a naughty
word.  Nevertheless, the concept intrigued some who saw it.   For
example, during April 1928 T ran into it when a colony of Staph.
rlureus blew in the window of the brand new lab. on "G" Floor of
P. and S.  nochez was startled and took one blood agar plate of
m-y strep. variant home, saying "Avery will be interested in this".
Ry coincidence that lab.  was soon to be devoted for a decade to
the studies of transforming the pneumococcus by Martin Henry
nawson et al.

    It was also about 1028 that nochez conceived that the hac-
terial flora of the chimpanzee pharynx produced variants when
filterable viruses from persons with "common cold" were intro-
duced into the naso pharynx of the chimp.

   As for the inspiration for Griffith's experiments there
were at least two antecedents.   Griffith was curious about this
phenomenon of variation.  Vas it true or mere1.y an artifact,
as most bacteriologists believed in the early 'twenties?  IIe
no doubt realized that his 1929 findings would not be accepted
by his "peers" and so probably never referred to this work,
certainlv not in the literature or to me.

   3ut curiosity was perhaps the minor motivation.  The major
motivation,  as T learned when T too became enamoured, much later,
was his fascination with the epidemiology of beta hemol,vtic
streptococcus.  As W. Rayes pointed out, in the First Griffith
Memorial Iiecture (see enclosed), "He believed that a proper
understanding of epidemiologic problems could come onl,v from '
more detailed and discriminating knowledge of infectious hact-
erial species and of the nature-of bacterial virulence and var-
iation".  'J'his deep interest of Griffith T dir? not learn until
T too had become intrigued with variants that had what T chose
to call "infectivity for the resniratoqy tract of man' rather
than  "virulence for the mouse".  There is no doubt in my mind
that Griffith saw all of this clearly and that this was the
"concentual antecedent" to his colossal task of identifying
hemolytic streptococcus serologicallS, v by his slide agglutination
method of t#vning.  Whereas the sporadic infection was drab, the
sudden outburst of a streptococcal enidemic was an alluring
challenge.  There is no doubt in m,y mind that Griffith, the
bachelor, was inspired b,v the romance of a concent, i.e. one
variant of Streptococcus pyogenes with great "inf'ectivitv"
(commonly called virulence) for man could produce a devastating


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enidemic.  And believe me when one is inspired with this concent
all other matters seem momentarily insignificant.

   After this Englishman of few pavers nublished his pneumo-
coccal findings, he felt that he had done his thing and had no
stomach to become involved in controversy.  He closed the book
and let posterity be the judge while he concentrated on matters
enidemiological.  Teether he corresponded with Aver%v about the
pneumococcus T never asked and do not know.  Averv regarded
Griffith so highl,y that he accepted his findings(and may have
been the only person so to do).  Accordingly,  Averv devoted
the succeeding decades of his life to its elucidation.   Tn this
connection, there may be correspondence on this point; so T en-
close a copy of a letter from Avery's sister-in-law.  Please
note the postscrint.  At least T have expressed my guess that
you requested on the "conceptual antecedents".

    2.  "Further recollections about the impact" etc.  First,
let me state that for many years ? knew no geneticists.   Tn
fact, J knew on1.v the name of one in Nww York.  His daughter,
who worked at the Rockefeller Institute wore a magnificent,
fawn colored gabardine suit!  Between 1942 and 1946 5 was on
active duty in the Nnvv.  Sut one recollection remains permanent.
Avery presented at the Rockefeller's Friday afternoon conference
his information on DNA RS the transforming factor.   On that oc-
casion, R certain capable chemist-biologist attacked Avery with
such vehemence that it sent Charlie Hoagland and me into a tail-
spin.  The antagonist was not a geneticist.  In fact,  IT do not
believe that the Rockefeller Institute had any geneticists in
its ranks during that era.  9ut it did have nucleic acid chemists
of great renown.

    3.  "fiverlooked by most of his peers".  T,et me try to clar-
ify this puzzlement.  'When T wrote overlooked bv most of his
distinguished peers, T was unhappy with tde word peer - defined
in my Webster's Seventh Tntercollegiate Dictionary as "one that
is of equal standing with another".  Theoreticallv, all full
Members of the Rockefeller Jnstitute were of equal standing, and
actually many 0. f these Members were considered distinguished oer-
sons.  Rut how many of them did not overlook the significance of
Avery's contribution?  'I know of only two, the elderly Rufus Cole
and the youthful Charles Uoagland.  Wendell !I. Stanley, working
at the R.  I. in Princeton did more than overlook.  In 1970 he
finally published his analogy.

  T certain1.v did I& mean, even to suggest, that Avery should
have been awarded a Nobel Prize.  'I know nothing about qualifi-
cations for this great honor.  Like F. Gowland Hopkins, Avery
seemed above the hizrarchy of the ffNobellates" or any other
research physician.  In fact,  T now wonder whether Avery had
only one American peer as a biologist, Theobald Smith. A
couple of years ago Dickinson W. Richards mentioned to me the
name of the scientist (chemist, RS T recall? who served the
Yobel Committee as Avery`s blocking agent.  Perhaps that is the
answer to your question as to "why dvery was not en-Kobelled


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.

much earlier for his work in immunochemistry".  Ply travels in
simple,  clinical medical research circles have not taken me into
the rarefied atmosphere of those recognized RS top notch scientists,

    4.  "Had Avery done his T)NA work in his 50's he of course
could not have bee'n ignored".  On this point may 1 be the devil's
advocate?  Avery worked on the transforming factor from age 51
until compulsory retirement.  Even then he obtained as assistant,
a female geneticist,  since help from this discipline was not
available at R. I.  It was not until she had to leave (? for
marriage) that Aver:7 told me he felt that he had gone as far RS
he could, with his lack of training in genetics, was closing up
the shon and moving South to become R neighbor of his brother
Roy in Nashville.  Your statement,  "he just did not live long
enough thereafter" brings two memories;  (a,) Tiselius gave the
same excuse, (b) in congratulating Nobel T,aureate, P. "e<vton
Rous,  T told him that perhaps more important than doing his
cancer work as a. young man was his ability to live into sen-
escence.  There was no rebuttal, but a, postcard"of than!rs.
At that time,  and only at that late date, Rous told me that
Aver,y should have received R Nobel Medal.   Tt is a matter of
record that Avery did live in good health until 1955, twelve
*vears after nubllshing his work on TDJA as the transforming fac-
tor.  Sut perhaps you meant to indicate that it would have taken
more than twelve vears for Arne Tiselius to get the message!

   Tt seems to me that T will not receive a passing grade in
attemnting to answer your questions.  Tf ever I have the priv-
elege of meeting ,vou, there is one question, as indicated by the
remarks about Avery, on my mind:  Are there men whose thinking
and whose fruits of labor transcend the abi1it.y of their contemn-
oraries to evaluate accurately the significance of their discov-
eries?  T once asked this question of nick Richards.  His prompt
replv was that after all distinguished scientists were only     ,
human.

   T close this by attaching R snapshot of Avery taken in
March of 1943.  Aver-v because of his solemnity was long considered
old and was called "Professor" when he WRS R young man.   rhoto-
graphs make him anpear worried.  Terhxns he always was overwhelmed
by his responsibilities until the spring of 1943.   You will note
from this poor snapshot that Averv has, a hanpy smile.   He had
nailed down DNA for the world to stud)T.  At long last he WRS
pleased.   Vhat R man!

Thank ,vou for your inquiries.

Alvin F.  Coburn !I. n.

APC:acc
Enclosures 4