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REMARKS OP DR. MACLYN NCCARTY AT AVERY GATE ImMonTAL
Ci OY OF SLMELITER 29> ToGsS
It if not cur purpose this afternoon to attempt a
systematic analysis of Avery's scientific contributions and
their impact on modern biological thought. Nor is it feasible

to draw a comprehensive pottrait of Fess and his extraordinary,

“multi-faceted personality. Rather, in this series of presenta-

tions, it ia our hope that, in an informal and less structured
manner, wa can convey the essential spirit of the man, his
work, and its scientific consequences.

There is much more of a central, unifying theme in
Avery's carcer as an investigator than the Bimple fact that he
was preoccupied for the greater part of it with a Gingle group
of microorganisms, the pneumococede His intuitive ability to
select significant problonus for attack, the philosophy of his
approach to their solution, and the stringent demands he made
On scientific evidence before accepting his experimental
findings as final are among the traits that give his work a
Special stamp. The quostione he posed in dealing with the
complex biological svstems with which he worked were character-
istically directed toward a fundamental understanding of the
substances responsible for apecilicity. When faced with the
necessity a year or 80 ayo of prenaring a paper with the rather
forbidding title "Molecular Bioloyy and Medicine", it occurred
to ma that, as much ao he might have dislixed the designation,
Fess was a molecular bioloyist long before the term came into

use. This asscrtion is adequately sunported by the direction

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and development off each of his major lines of investiyation,
involving ao they did the isolation and characterization of
biologically active molecules and efforts to establish the
chemical basis for their specificity.

It ia important to recognize that his explorations of the
underlying biochemical basis involved in the phenomena he

 

studied were motivated by a deep interest in proad biological
problens, 4ncluding, as Colin MacLeod will emphasize, clinical
problems related to disease. One of the lees well-known of the
Professor's major interests was his concern with the host
response to disease processea. This interest finds tts most
| notable expression in his work on the human serus protein now
known ag C-reactive protein. This substance, which is not
present in the blood of normal individuals but makes its
appearance in response to a variety of inflammatory stimuli,
was discovered in his laboratory by Tillett and Francis as a
by-product of the pneumococcal work. The term "Cereactive”
refers to the fact that the protein fortuitously reacts to form
a precipitate with the somatic C polysaccharide of the pneumo-
coccus. His studies of this substance with Abernathy and
MacLeod led to its identification as a protein and characteri-~
mation of many of its propertics, and incidentally one cf the
first isolations of a humanprotein in a highly purified,
homogeneous form. Thus, even his exploration of the hest
response to disease developed along the lines of moleculr biology.
A long succession of students and collaborators had the

intellectual stimulus of learning these approaches to scientific

 
 

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investigation from him by precept. At the same time, there was
the associated enriching experience derived from daily contact
with a most exceptional personality. These latter experiences
are perhaps the most difficult to recapture because of their
subjective nature and personal flavor. Certainly, personal
remingcences are notoriously treacherous, particularly with
sespect to the accurate recollection of details and the temporal
interreaationships of events as the years recede.

It ie my impression that all of Fess's former associates
have a cimilar picture of the major facets of his personality,

It is not surprising, however, that there are differcnces of
opinion and of interpretation with respect to many of his less
familiar characteristics. These co-workers and friencs concur in
the broad outlines, but each has his own private view growing out
of his owm personal relationship with Avery. If these frcmices
are correct, then it is clearly impossible for any one individual
to advance a comprehensive analysis of his character that will
fully satisfy all of his other former colleagues. In any event,
I have no intention of attempting such an analysis. I would
like, however, to touch upon one episode which both describes

one of Avery's traits and illustrates my point concerning the
inherent inaccuracy of personal recollections.

The success story recorded in the subsequent careers of a
long series of Fese's boys establishes beyond doubt his precminent
talent for contributing to the molding and directing cf promisegng
young scientists. Tha techniques by which he achieved this --

and indeed whether anything qualifying as a technique was actually
 

aod we

involved -- has long been a subject of debate. Some of the
things that happened to all aspiring investigators on arrival
in Avery's laboratory are indisputable, however.

The nevphyte was never under any circumstances given a

Fe po nl

 

problem by the Professor and put to work shortly after arrival
on some aspect of pneumococeal bacteriology which fitted into
the overall interests of the laboratory. The process waa a
nuch slower and more painful one «-- moat especially for those
who by training and instinct felt dependent upon direction from
aboveee and was based on the firmly-hneld philosophy that every
worker should select his own problem. This end was achieved
through @ combination of subtly directed reading and a series
of discussions that frequently took the form of monclogucs.

Aa one gained a better integrated impression of the trend
of investivation in his department over the years by reading -«
chiefly from the collection of Gepartmental reprints <- ones
gcasp of the pattern and interrelations of the research on
{he pneumnococcus was greatly enhanced by his oral dissertations
that have becn referred to as Feas's Red Seal Records. They
were virtuoso performances in which, with great logic and
clarity, he would develop his theme, including historical Lacke
gxcund and the rationale of approaches used. The oryanizcation
and phraseoloyy of these vignettes had been composed in his mina
at his lcisure with great care and were used repeatedly in
rresenting tha subject to various aucitors.

The young hopeful, dmpatient to get to work at the

laboratory bench, would et the same tine be completely fascinated
a5e

by these discourses. Soon he would raise questions about
certain aspects of the pneumococcus and ultimately would be
gently maneuvered into suggesting his own problem by outlining
his ideas for answering one of the questions he had himself
raised. In this way, the beginner selected his own problem,
and at the same time could be diverted through the medium of
preliminary discussions from blind alleys and paths that had
already been unsuccessfully followed.

In my own case, it was my recollection that this period
of mixed frustration and intellectual stimulation went on for
about two months. This proves to be a beautiful example of
tricks that can be played by a faulty memory, and in this case
the correction is supplied by a “diary" in the form of
labe-atory notes. I arrived at the Rockefeller Institute on
September 1, 1941 and was greeted by Frank Horsfall who Lac just
that summer returned to the Institute staff after his sojourn
in the Rockefeller Foundation laboratories. Fess did not
return from Maine until after the second week of Saptember and
so my indcetrination (which had been initiated with some reading
material in the spring) was not begun in earnest until the
micdle of the month. This was the start of the period that I
remember as having lasted many weeks, and yet the incontrovertible
evicence of the laboratory notebook reveals that I had carricd
out my first tentative experiments in pneumococcal transcormation
bafore the end of Septenber. By mid-Octoker I was engaged in the
growth of masa cultures of type III pneumococeds for extraction

ef the crude transforming substance,

 
(ENE He Li rm

 

 

aGa

My distorted memory of this period probably has its basie
in the rather special situation that obtained at this time.
Colin MacLeod had left the Rockefeller Institute that summer to
assume hia duties as Professor of Microbiology at New York

University, so that fess was auddenly deprived of his closo

_. Gollaborator of the previous 7 years. Although 2 had at the

outset a latent interest in pneumococcal transformation, and this
Anterest had been. sharply increased by reading and by the Red
Beat. Regorda on the subject, I was much too diffident to propose
to Fesa that I join him on the problem. On his part, he was

restrained from enlisting my aid as a collaborator not only by
his policy of insisting that the newcomer select his own problem
but also, I am sure, by the unknown nature of my abilities as a
laboratory worker. How could he be sure that I would not be
nore of a hindrance than a help? it was this impasse that must
have been respon-ivle for the aberration of memory which causes
mo to recall as severnl weeks what could not have bean nore

than several days. I have no clear recollection of pracisoly
how the impasse was broken, and here the laboratory notes are

of no halp.

There are many other respects in which these old laboratory
notebooks prove their inadequacy, and although they scom culte
thorough and acequately ceseriptive of experimental procedure
‘hey are not very useful in dolineating the evolution of ideas
wor the origin of certain approaches. In particular, I had
looped to plece together fron them a clear record of the crigin

and growth of the igea that the pneumococcal trandorming principle

 
oo Jom

ia composeé of DNA. There is some information on the point,
to be sure, but not enoujsh to reconstruct from this source
alone an eccurate picture of all stages in the development of
the idea. Nor is there any reflection of the negative factors
that werolntroduced on discussion with others, such as the
prevailing biochemical dogma of the time that nucleic acids
from various sources were monotonously alike in composition
and thus unlikely candidates as carriers of specific information.
There are rewards of a different nature to be derived from
a return to the old notebooks, however, and thumbing through
their pages again after twenty-odd years tends to conjure up
memories of episodes and the daily laboratory routine of the
period. One of the gratifying minor aspects of the work with

the pneumococcal transforming system was that /each morning on

 

 

“arrival in the laboratory the results of the experiment of the
day before were waiting in the incubator to be read. Thus,
when things were going well, each day began with a new bit of
4nformation that provided the stimulus and direction for
further experiments. Yeas and I had an unspoken agrecment that
prevented either of us from obtaining a sneak proview of the

i results before the other had arrived. (The old protocols

serve to) recall the image of Fess as we converged on the
4ncubator each morning, and in particular I see his expression,
which was a curious mixture of eager anticipation and of arpre-
henoion for fear something had gone wrong with our complex

\ biological test system ~- which, alas, was all too frequently

L the case. |

A multitude offsuch pictures remain in my memory as I am
oBe

sure they do in the memory of others. Despite the fact that
they may be distorted and blurred by the passage of time,
they remain as testimony of the lasting impact of his
' personality on his associates. This legacy is inextricably
enmeshed in our minds with the more durable and objective
legacy of his scientific accomplishments.

In closing, I would like to express the personal
pleasure that I have derived from the intensified reminiscences
of Dr. Avery stimulated by this occasion and from the oppor-
tunity to talk again with many of his old friends and with
his brother and sister-in-law, Dr. and Mrs. Roy Avery. I
must say, however, that the endless variety of these
reminiscences haga renewed my conviction that it is virtually
impossible in a brief discourse to recapture more than a small

portion of his attributes as a ocicntist and aa a friend.

MMcCarty
September 29, 1965