Address of the President
Sir Henry Dale, O.M., G.B.E., at the
Anniversary Meeting, 30 November 194.5

The animal number of Obitumy solices of FeZlows of the Royal Society published
today, and the names which have just been read to us, remind us of the losses
from it,s Fellowship which the Society has suffered during the year now closing.
I propose on this occasion to proceed nest to the presentation of the Medals
for 1945.

Awards of Xedals, 1946

The COPLEYMEDAL isa,wardedtoDr OSWALDTHEODOREAVERY forhiscontributions
to knowledge of the chemical basis of the specific properties of bacteria, particula.rly
of the types of the pneumococcus. . His researches in this field have appeared in
unhurried and orderly sequence over the course of a long and dist,inguished career,
and they have furnished a large and essential constibuent of the framework nom
available for a fundamental science of immunochemistry.

We allow ourselves here to claim Avery as Canadian by birth, though with
acknowledgment that his life's work has been accomplished in the United States
of America, and in the Rockefeller Institute of New York in particular, of which
he has held t.he Membership since 1913.

It was in 1917 that Dochez and Avery demonstrated that cultures of different
strains of the pneumococcus yielded different `soluble specific substances'. From
1923 onwards appeared a remarkable se&s&-papers by Avery, with Heidelberger
a,nd other collaborators, in which it was shown that these specific substances had
t,he nature of complex polysaccharides of highly individual characters. These were
present in the regular capsular envelope characteristic of the pneumococcus in its
virulent forms ; and ea.ch type of such virulent pneumococci, dist,inguishable by its
immunological specificity, was shown to have its own distinct polysaccharide.
Each of these rea,cted, with a like specificity, with the corresponding immune body.
Not that these polysaccharides, the soluble specific substances isolated in chemical
purity, had antigenic properties by themselves. It was only when they were
artificially linked to proteins foreign to the reacting animal body, or reta,ined their
natural linkage with proteins of the bacterial strains producing them, that they
elicited, on injection, the appearance in the blood of specific immune substances,
causink agglutination or lysis of the corresponding organisms; but, with the immune
substances thus erolred, the pure, separated polyssccharides now eshibked the
same specific affinities, each forming a precipitahe w-it.11 the corresponding anti-
SWTl:ll.


124      Anniversary Address by Sir H?Z&y Dale
Here, then, in chemically definite form, were separable, prosthetic, combining
groups such as Paul Ehrlich ha.d long earlier envisaged and prophetically named
' haptenes `. Here also was one of the principal foundation stones of a grea.t building
of immunological chemistry, which, in the hands of Avery's contemporaries and
followers, notably in those of a distinguished fellow-Member of the Rockefeller
Instit,ute, the late Karl Landsteiner, has rapidly included an ever-widening range
of studies of artif%al a.nd natural antigens. Fellows of this Society 1na.y recall that
last year we were privileged to hear Bakerian and Croonian Lectures, by, Professor
Haworth and Dr Harington respectively, both dealing, from somewhat different
angles, with experiments in immunochemistry, and each contribut.ing its own
important extension to a structure of knowledge founded so largely on Avery's
pioneer discoveries.
  Meanwhile, in the hands of Avery and his co-workers, knomledge of the specific
characters of the pneumococci, and of the manner in which these a,re acquired, had
been moving quietly to a new pinnacle of achievement. They had long a.go shon-n
t,hat pneumococci, which, in artificial culture, hare lost the capsules endowing
I  them with virulence and containing the specific polysaccharides, have reverted to
avirulent non-specific types, growing in the rough, wrinkled colonies characteristic
of such defective strains. It had been shown also, by the Me Fred Griffit,h, that
such a degenerate, non-specific pneumococcus, from whatever specific type ib had its
provenance, could be induced by cultiva.tion in a medium prepared from a complete,
virulent type to reacquire a capsule conferring the corresponding specificity. And
now, only last year, Avery, with Macleod and X&arty, has been able to isolate and
to characterize a chemical principle acting in minute dosage as the specific stimulus
to such a transformation. An unencapsulated, avirulent, typeless pneumococcus
derived from a specific &rain of type II, responds to this stimulus by acquiring
and retaining the ca,psule and specific polysaccharide, with the virulence and the
cultural characters, of a fully specific st.rain of type III.[Here surely is a cha.nge to
which, if we were dealing with higher organisms, we should accord the status of a.
genetic variation ; and the substance inducing it-the gene in solut,ion, one is
tempted to call it--appears to be a nucleic acid of the desosyribose type. Whatever
it be, it is something m%ich should be capable of complete description in terms of
struct'ural chemistry2
  It has been a matter for rejoicing to his many admirers, friends and followers in
many countries that Avery, a veteran now among investigators, should thus, on
the eve of his retirement, have attained this new peak of discovery-a fitting climax
to a devoted career of such wide inRuence on the progress of science. Many, we
feel with assumnee, in his own country and far beyond it,, will welcome and approve
our award to Dr Avery in this yea.r of the Royal Society's highest recagnit,ion, its
Copley Neda,l.