JUL 8 1966

OSWALD T. AVERY
                  4
   1877-1955

Reprint from GENE~CS, Vol. 51, No. I, January, 1965. Printed in U.S.A.



Reprint from GENETICS, Vol. 51, No. 1, January, 19865. Prinled in U.S.A.

OSWALD T. AVERY

1877-1955

A MONG the achievements of 0. T. AVERY, who considered himself a micro-
biologist, are two developments that were turning points in biochemistry. He
is responsible for the first demonstrations that complex polysaccharides on the
one hand and deoxyribonucleic acids on the other are responsible for biologically
specific actions-actions which contemporary and expert opinion strongly and
even hotly maintained could only be attributed to proteins. The polysaccharides
of pneumococcus were analyzed to become a classic example of one family of
type-specific cellular antigens, and the deoxyribonucleic acids (DNA) of the
same organism were later shown to be the foundation of the genetic determinants
for this species.

Both of these great developments were first explicitly conjectured, demon-
strated, consolidated and broadened in AVERY'S laboratory, some part in investi-
gation by associates who warmly and frequently expressed their indebtedness to
his advice and example. The academic world these days does not often pause for
sufficient perspective to see how such major advances come about, and a step-
wise grand philosophical development is often not as greatly or as promptly
honored by accolade as the easily grasped concrete discovery about which we
may learn in an academic quarter hour. One must needs pay continual and
watchful attention to the innovator who espouses controversial issues, if only
for the reason that he may never succeed in removing the controversy from the
situation. How ironic that, when the great teachers, be it of laboratory, writing
desk or lecture table, construct a rational and logical view of some broad area,
they usually labor until the matter seems utterly "obvious" to those who come
after. Consequently their harvest is gathered up and enjoyed, without long pause
to consider their labors, methods or originality. Be that as it may, anyone who
has witnessed at close hand this kind of excellence has small taste remaining for
teaching which is stimulatory mainly by its assertiveness. AVERY'S scientific
accomplishments demonstrate that, when men and ideas rub against each other,
the ideas receive maximal polishing if the man is gentle and his principles hard.

OSWALD THEODORE AVERY was born in Halifax, Nova Scotia, in 1877, the son
of a clergyman. After the age of 10 years, he lived in New York City until retire-
ment. His education at Colgate University (A.B. 1900) and medical school in
Columbia University (M.D. 1904) prepared him for a career in which he prac-
ticed medicine only a short time but always remained close to medical problems,
patients and people, contributing personally indeed to the atmosphere and newly
arising tradition of the research hospital at the Rockefeller Institute. Although
other positions and responsibilities were opened to him, he remained there from
19 13 until 1947, taking his diversion in the trends of his work and the flow of a
goodly line of microbiological and medical coworkers, numerous by American

Genetics 51: l-10 January 19G5.


2                          OSWALD T. AVERY

standards, through his workshop. At a later time, more than twenty of his former
associates occupied significant positions in academic microbiology and immunol-
ogy. This group was virtually the only feature of his career of which he would
allow himself to speak almost pridefully, although they were generally referred
to as people who "have been in this laboratory", or simply as his friends, "the
boys".
Honors and learned society appointments came his way, including the Ehrlich
Medal in 1932, the Kober and the Copley Medals in 1945, but they did not come
in autocatalytic profusion, for this scholar admired the facts and logic behind
nature's ways more than he did his own unique talents, and customarily avoided
opportunities for public attention. A number of these honors were for the micro-
biological researches made before his fundamental contribution to genetics at
age 67,
Any attempt to discuss AVERY'S contributions and philosophy will be limited
here to the purpose of illuminating how a major and fundamental identification
of genetically active substance came to be made. A selection of articles representa-
tive of his total major research interests is appended. and it illustrates how insist-
ently throughout his career he sought the explanation of different biological
relationships in chemical terms. The decades from 1930-50 may have been rich
in biochemical achievement, but no one was quicker than AVERY to ask "what is
the substance responsible?" when a new biological phenomenon was encountered,
in laboratory or literature. And the question was viewed in a modern manner,
too-the specificity (now "information") was assumed to reside in individual
molecular structures ("messages") capable of influencing (being "translated")
or interacting with (complex forming, repressing, etc.), cellular enzymes re-
sponsible for growth (biosynthetic systems). The confidence that a substance and
an interaction underlie every manifestation was expressed continually and with
contagious optimism. This was the pattern of a whole biochemical era, but the
places were still few where the interest spanned the whole distance from biology
to chemistry. In AVERY'S laboratory, the joy came from understanding, through
irrestistably marshalled logic, some feature of the behavior of that marvel of
organization, the living cell.
The philosophy and approach are unmistakeably among those now ranked
under the banner of "molecular biology." This latter discipline, if that is what
it is, partakes of much of the same optimism and contagious confidence and has
brought forth brilliant achievements. But it may be more common today to find
joy in the cleverness of bypassing logical steps to reach quick hypotheses, in the
artful disposing of alternative hypotheses; satisfaction may now be taken in the
early and prominent public display of hypothesis and in the anticipated delights
of the conclusions. By moving impulsively and impatiently, we now move swiftly
indeed, but we tend to emphasize the cleverness and authority of the individual
and of his techniques rather than that of the integrated living cell which knolvs
all of the secrets.
AVERY enjoyed all of these intellectual pleasures but saw them as only early
steps and, therefore, disciplined himself to indulge them only in private discourse


                          R. D. HOTCHKISS                   3

and in the laboratory. He saw little value for the nonspecialist to be exposed to
all of the uncertain stages in a development, and perhaps for that day and age
the stimulation of a broad public with vignettes and vistas would have been to
no good purpose. Correspondingly, he felt that science had little need for such
personal detail and reminiscence as we are indulging in here. He was acutely
aware of human fallibility and always ready to assume his own; therefore, his
doubts were not turned outward toward criticism and he quietly ignored that
which he could not believe. He, instead, approached others with generous and
charitable acceptance of their good faith and seriousness. But countless coworkers
and individuals were fortunate enough to obtain a private first-rate appraisal
of their own work and had to be amazed at the way this modest little man could
open out for them its ramifications or the weaknesses in its strategy or logic.
To bring a manuscript, whether joint or personal, to DR. AVERY was to impose
on him a task in which he worked as hard as the author. One's eyes were likely
to be opened to undreamed of ambiguities and pitfalls that nest in the everyday
language. A device he often used was to read aloud the prepared text, in the most
gracious tones, but slyly emphasizing the wrong words, or pausing at the wrong
places, so that new linkages were created, hanging participles were absurdly
exposed, independent thoughts became comically interdependent, and the writer
learned from a subtle master actor how weak the connection between thought
and words can be. The elegance of AVERY'S own speech and writing, of course,
was created by the habitual application of the same process of polishing and
tasting.
The joy of intellectual search was most characteristically expressed in a series
of discourses reenacted by AVERY (in these roles he was called "Fess", for Pro-
fessor) for the benefit of visitor or colleague in the quiet of his little office. These
were well rounded coherent presentations of a segment of pneumococcus lore or
a related topic, and were called within the family "Red Seal records" after the
then top grade of musical recording. In them, he successively played the parts of
narrator, expositor, loyal opposition and finally attorney-in-summation. Even at
the second or third hearing of one of these presentations, one could emerge, eyes
glowing, surprised to find that dusk had fallen outside while the new inner light
was dawning.
These gems of perfection were continually revised and repolished. The highly
organized presentation was a kind of debate with himself, punctuated with
rhetorical questions like, "now, why should that be?" or LLwhat does that all
mean?" The auditor who was moved to try to respond, however, quickly found
himself overwhelmed-and indeed suppressed-by the ongoing flow of well-
rehearsed logic, that even in the voice of the man who seemed merely its spokes-
man, would brook no interference. These dissertations probably played a great
part in concentrating the attention of his younger collaborators on basic problems,
especially those involving "that little gram-positive coccus" which, he felt, pre-
sented in small compass most of the basic questions of biology. Many who were
never coauthors with him in publication were among his research students in this
relationship. For example: I had always felt so deeply that I was an associate of


4                          OSWALDT.AVERY

AVERY, that when preparing this article it was with great astonishment that I
realized for perhaps the first time that we had never published a joint paper. The
same association must have been felt by DRS. FRANK L. HORSPALL and GEORGE
K. HIRST, to mention two virologists among many microbiologists who learned
from him. Does the historian of science who leans heavily upon the printed word
always learn of these vital but undocumented family pedigrees?
The AVERY laboratory in its last two decades was housed in former hospital
ward and auxiliary rooms. The high ceilinged glass paneled rooms seemed deep
and quiet, but in almost every corner was a bacteriologist or medical associate
transferring or examining cultures at a wooden office desk. The apparatus con-
sisted mainly of quiet incubators or water vacuum pumps occasionally squalling
at the single porcelain sink each room possessed. The staff tended to be self-selected
into quiet and busy groups-the latter being the young physicians. With these
latter, some problem from the hospital service was always obtruding into the
picture and requiring some experimental bacteriological detective work, so that
this group and the closely associated group of DRS. LANCEFIELD and SWIFT were
in close microbial control over most of the hospital patients. During the day,
these physicians were often to be found leaning against the tables respectfully
listening to DRS. AVERY or DUBOS, MACLEOD or GOEBEL discuss laboratory
features of bacterial growth and chemistry.
By 1928 it had been well established by particular work of AVERY'S laboratory
that pneumococci fall into true-breeding immunologically specific types and
their routes of infection can be traced by means of their polysaccharide capsules.
Small wonder that the work of GRIFFITH in that year seemed doubtful and con-
trary to all that had been carefully established; for this young English micro-
biologist described transformations that seemed to be conversions of one true-
breeding type into another.
GRIFFITH had already applied the mild selective effect of a specific antiserum
to elicit "rough" nonencapsulated pneumococcal variants from normal "smooth"
encapsulated strains. Trying to modify host response to rough strains by material
from encapsulated cells he reported in 1928 combining living rough-type orga-
nisms with heat killed smooth cultures in another selective environment, the
subcutaneous tissue of the susceptible laboratory mouse. His now well-known
discovery showed that the "capsule remnants" could bring about conversion of
rough-type cells into heterologous smooth types, which would be selected some-
what preferentially in the mouse. The heat killing was thoroughly demonstrated
and systematically intensified until first the heterologous and then the homo-
logous capsular transformations disappeared.
AVERY, and nk4RTIN H. DAWSON in his laboratory, had already considerable
experience in GRIFFITH'S antiserum selection, but could hardly believe the trans-
formation until later in the same year NEUFELD, the original discoverer of these
serotypes, confirmed it. By 1930, DAwson- was writing of the importance
of GRIFFITH'S finding and attempting to extend it, which he soon did, with SIA,
into a test tube transformation, effected by from one to six passages of rough
cultures in media containing antiserum and killed smooth-type cells. Surviving


                           R.D. HOTCHKISS                    5
witnesses do not describe exactly what AVERY was doing at this time, but it is
certain that he closely followed and formatively influenced DAWSON'S work. By
1935: I was myself being excited by his discourses on transformation, and they
included vivid descriptions of the frustrations and difficulties at this stage of the
in uitro multiple passage transformations. They described in detail too the import-
ant contributions made by the young physician ALLOWAY also in AVERY'S labora-
tory, who succeeded in recovering an extractable, alcohol precipitable transform-
ing agent of considerably stabilized activity from the killed smooth cultures.
ALLOWAY was probably the first person to see fibers of precipitated biologically
active crude DNA, but AVERY working in the same room must have been initia-
ting. spurring, and aiding in many of the experiments. It is characteristic that
having perhaps inspired the work with his scientific discourses and having
followed7 influenced or guided it, he would usually not accept co-authorship
unless his manual participation was also very considerable. In this way, both
logic, which belonged to everyone, and actual experimental work, which was
personal, became emphasized as the twin foundations of scientific work. "Ideas",
which can be actual or illusory, original or automatic, fundamental or merely
verbal, almost disappeared from consideration as such.
One can be certain that AVERY was frequently prodding these collaborators as
he did his others by asking, "what is the substance responsible?" DAWSON and
SIA speculated that it might be the capsular substance; ALLO~AY could nearly
exclude this and was inclined to consider it a protein, the type-specific antigen.
These evolving answers themselves were in terms of entities recognized through
AVERY'S investigations and insight. But my personal notes of 1936 record that in
one of his discourses on transformation, AVERY outlined to me that the trans-
forming agent could hardly be carbohydrate, did not match very well with pro-
tein, and wistfully suggested that it might be a nucleic acid! His judgment had
already seen that protein was not likely, and the reasons were probably sound,
if preliminary. In 1938, returning to his laboratory frdm a year in Denmark, I
begged for an opportunity to work on transformation, but he was anxious to
further the work on blood proteins in acute infection, and asked me to wait, say-
ing "we will get to that later." Shortly after, we were all drawn into various
responsibilities by the second great war. But luckily, he and MACLEOD did get
back to the problem, and a new young pediatrician, MACLYN MCCARTY, with
superb biochemical skill helped them to convert ALLOWAY'S extract into a highly
pure DNA, reported in 1944. The coincident virtual discovery and development
of the enzyme deoxyribonuclease gave strong biochemical confirmation of the
elementary analysis presented in the now classic paper.
Subsequent history is probably well enough known. Some of us were still
concerned over the chemical data. MIRSKY pointed out the deficiencies of ele-
mentary analyses in distinguishing between nucleic acid and protein, and pro-
posed a study of nucleoprotein fractions. AVERY continually asked me, as soon as
I was able to help, how protein or nucleic acid could be more explicitly recog-
nized, and I entered on a study (reported only in a symposium paper) showing
that the purine and pyrimidine groupings as well as the elementary composition,


6                          OSWALDT.AVEllY

were those of DNA, but occurred in different proportions than in thymus DNA.
Furthermore, the other candidate groupings, amino acid residues, did not seem
to be present in significant amounts. Later on, physical studies contributed other
correlations with DNA. And HERSHEY and CHASE in 1952 added the elegance of
isotopic differentiation to distinguish the elementary analyses of protein and
DNA in the effective genetic elements of bacteriophage.
  With purification of the specific pancreatic deoxyribonuclease by MCCARTY,
acceptance of the DNA nature of pneumococcal transforming agent became gen-
eral and widespread, The subsequent chemical analyses of DNA's, and the
extension to other transformable bacteria of course brought other kinds of con-
fidence. The development of other transformable traits in pneumococcus added
general significance. All of those advances AVERY followed with enthusiasm and
deep understanding.
  The absorption of these chemical findings into the body of genetic thinking
required the remaining step of accepting bacteria as genetically functioning
organisms. Fortunately, LURIA and DELBR~~CK'S, and DEMEREC'S, studies of
mutations, and the several new modes of genetic transfer in haploid organisms
first seen in the GRIFFITH-AVERY transformations, have made this step a logical
and highly productive one.
1  Although AVERY'S transformation papers include only the barest mention of
i genes and viruses, I can testify that he was well aware of the implications of
i DNA transforming agents for genetics and infection. In fact, he collected, read,
] and commented on, with great interest and some amusement, the conjectures of
( many leading geneticists and biologists about transformation, from 1930 to 1948.
But, since at that time the operational unit-the sperm nucleus or viral particle
! -could not be broken down experimentally into injectable nucleic acids, then for
AVERY it seemed merely clever for him to do so only conceptually, and a rather
vainglorious and irresponsible thing to do: before an impressionable public.
I   In his last two years at The Rockefeller Institute, DR. AVERY began his self-
disciplined withdrawal from participation. At first he would disappear only
when we (by that time only HARRIETT EPHRUSSI-TAYLOR and the writer) were
planning experiments. I believe that he was determined not to be observed in
any of the stages of ageing when he might be losing some of his mental faculties,
as he had seen others do. This precaution was unjustified, for his remarkable
acuity and ability to focus never diminished. But the delight of performing ex-
periments and observing the results he could not forego, and he would appear at
the moment we commenced the work, asking "what are we doing today?" and
start to help. We still enjoyed his influence at the time of discussing and inter-
preting the outcome. But this participation too he began to surrender, especially
in the last year, when I was attempting new chemical analyses, although all of
his friends tried to make him welcome in the laboratories.
  In this deliberate withdrawal, the still-bachelor professor, somewhat lonely
though widely loved, left New York in 1947 and went to live in Nashville with
his brother ROY S. AVERY, a bacteriologist, in company with an old family friend.
In this relaxed atmosphere he came into contact with workers at the Vanderbilt


                           R. D. HOTCHKISS                    7

Medical School and until his death he followed some bacteriological-medical re-
searches going on there with his usual fundamentally directed and stimulating
enthusiasm.                         ROLLIN D. HOTCHKISS

SELECTED BIBLIOGRAPHY ILLUSTRATIVE OF THE WORK OF OSWALD T. AVERY

1, First studies on mechanisms underlying infection
Concerning the bacteremic theory of tuberculosis. J. Med. Res. 23,95 (1910). [with B. WHITE.1
The action of certain products obtained from the tubercle bacillus. A. Cleavage products of
tuberculoprotein obtained by the method of Vaughan. Communication I. The poisonous
substance. J. Med. &s. X,31 7 (19 12). [with B. WHITE.]

2. Recognition of pneumococcal types as basis for etiological and epidemiological
studies.

Varieties of pneumococcus and their relation to lobar pneumonia. 1. exptl. Med. 21, 114 (1915).
[with A. R. DOCH~Z.]

The distribution of the immune bodies occurring in anti-pneumococcus serum. J. rxptl. Med.
21, 173 (1915).

A further study on the biologic classification of pneumococci. J. ex@I. Med. 22, 804 (1915).
Studies on the biology of streptococcus. I. Antigenic relationships between strains of Strepto-
coccus ~ffemoZ~f~c~~. 1. ezpil. Med. 30, 179 (1919). [writh A. R. DOCHEZ, R. C. LANCEPIELD.]

3. Identification of type antigens, demonstration of specific polysaccharide anti-
gens and haptenes.

Soluble substance of pneumococcus origin in the blood and urine during lobar pneumonia.
Proc. SW. ezp. Biol., N.Y. 14,126 (1917). [with A. R. DOCHEZ.]
The elaboration of specific soluble substances by pneumococcus during growth. J. exptl. Med.
26, 477 (1917). Trans. Assoc. Am. Physicians 32, 281 (1917). [with A. R. DOCHEZ.]
Soluble specific substance of pneumococcus. I. expft. Med. 38, 73 (1923). [with M. HEIDEL-
AERGER.]

Immunological relationships of cell constituents of pneumococcus. J. mpfl. Med. 35, 81 (1923).
[with M. HEIDELBERGFSR.]

The soluble specific substance of pneumococcus. Second paper, J. exptl. Med. 40, 301 (1924).
[with M. HEIDEIZERGER.]

Immunological reactions of isolated carbohydrate and protein of pneumococcus. J. ezptl. Med.
42,347 (1925). [with H. J. MORGAN.]

Immunological relationships of cell constituents of pneumococcus. f. ezp~l. Med. 42, 367
(1925). [with M. HEIDELBERGER.]

The solubIe specific substance of pncumococcus. Paper III. f. exptl. Med. 42, 727 (1925).
[with M. HEIDELBERGER.]

Chemical and immunological properties of a species-specific carbohydrate of pneumococci.
f. exp-pfl. Med. 52.895 (1930). [with W. S. TILLETT, 571. F. GOEBEL.]
Chemo-immunological studies on soluble specific substance of pneumococcus. I. The isolation
and properties of acetyl polysaccharide of pneumococcus type I. I. exptl. Med. 58, 731
(1933). [with W. F. GOEBEL.]

4. Biochemical studies on bacterial growth and lysis.
Studies on the enzymes of pneumococcns. [with G. E. CULLEN.]
   I. Proteolytic enzymes. J. exptl. Med. 32,547 (1920).
   II. Lipolytic enzymes: &erase. J. exptl. Med. 32. 571 (1920).
  III. Carbohydrate-splitting enzymes: invertas?, amylase and inulase. J. exptl. Med. 32, 583
     (1920).


8                          OSWALD T. AVERY

  IV. Bactefiolytic enzyme. 1. ezptl. Med. 38, 199 (1923).
Studies on bacterial nutrition. [with T. THJOTTA.]
   II. Growth accessory- substances in the cultivation of bemophilic bacilli. J. qo~l. Med.
     34, 97 (1921).
  III. Plant tissue, as a source of growth accessory substances in the cultivation of Bacillus
     jn~ue~~ue. J. exptl. Med. 34,455 { 1921).
The occurrence of peroxide in cultures of pneumococcus. J. q& MS&. 39,275 (1924). [with
  H. J. MORGAN.]
Growth-inhibitory substances in pneumococcus cultures. J. e.xpzptl. Med. 39, 335 (1924). [with
  H. J. &'hRGAN.]
Studies on oxidation and reduction by pneun~ococcus. [with J. Dii. NEILL.]
   I. Production of peroxide by anaerobic cultures of pneumococeus on exposure to air under
     conditions not permitting active growth. J. exptl. Med. 3.9,347 ( iQ24).
   II. The production of peroxide by sterile extracts of pneumococcus. J. ezptl. Med. 39,
     357 ( 1924).
  III. Reduction of methylene blue by sterile extracts of pneumucoccus. j. exprl. Med. 39,
     543 (1924).
   IV. Oxidation of hemotoxin in sterile extracts of pneumococcus. J. CX&. Med. 39, 745
     (1924),
   V. The destruction of oxyhemoglobin by sterile extracts of pnetrmococcus. I. mptl. Me&
     39, 757 (1924).
   VI. The oxidation of enzy-mes in sterile extracts of pneumococcus. J. exptl. Med. 40, 405
     (1924).
  VII. Enzyme activity of sterile filtrates of aerobic and anaerobic cultures of pneumocuccus.
     J. exptl. Med. 40, 423 (1924).
  VIII. Nature of oxidation-reduction systems in sterile pneumococcus extracts. f. ~zpi&. Med.
     41, 285 (1924).
5. Study of cross-reacting ~~~sac~~a~des. Funda~e~~taI specificity of sugar resi-
dues as dependent on configuration, size and nature.
The soluble substance of Friedlander's bacillus. III. On the isolation and properties of the
  specific carbohydrates from Types A and C Friedlander bacillus. J. exptl. Med. +Si 601
  (1925). [with W. F. GOEBEL.]
A soluble specific substance derived from gum arabic. 3. er&. RZ&. 49, 847 (t929). [with
  M. HEIDELBERGER, W. F'. GOEBEL.]
Chemo-immunological studies on conjugated carbohydrate-proteins. [with W. F. GOEWZ.]
   I. The synthesis of ~~am~nophenol p-glucoside, p-aminophenol &gala&side. and their
     coupling with serum globulin. J. eq&. Med. 50,521 (1929).
   II. Immunological specificity of synthetic sugar-protein antigens. f. ~zptl. Med. 50, 533
     (1929).
   III. Active and passive anaphylaxis with synthetic sugar-proteins. 1. LX&, Med. 50, 551
     (1929).
   IV. The synthesis of the p-aminohenzyl ether of the soluble specific substance of type III
     pneumococcus and its coupling with protein. J. exptl. Med. 54, 431 (1931).
   V. The immunological specificity of an antigen prepared by combining the capsular
     I)olysaceharide of type XII pneumococcus with foreign protein. J, exp& Med. 54,437
     (1931).
   VI. The synthesis of p-aminophenol a-glucoside and its coupling with protein. J. e.rp&
     Med. 55, 761 (1932).
  VII. Imm~I~ologicaI specificity of antigens prepared by combining LY- and p-glucosides of
     glucose with proteins. J. exptl. Med. 55? 769 ( 1932).
  VIII. The influence of the acetyl group on the specificity of hexoside-protein antigens. J.
     exptt. Med. 6#,85 (1934).


                          R. D. HOTCHKISS                    9

  IX. The specificity of antigens prepared by combining the p-amino~henol glycosides of
     disaccharides with protein. 3. exptl. Med. 60, 599 (1934).
6. Specific enzyme attacking capsular substance. Deliberately sought natural
a~ltagonistic agent.
The specific action of a bacterial enzyme on pneumococci of type III. Science, 72, 151 (1930).
  [with R. DUBOS.]
The specific action of a bacterial enzyme on type III pneumococci. Trans. Assoc. Am. Phy-
  siciamzs? 46,216 (1931). [with R. Du~os.J
The protective action of a specific enzyme against type III pneumococcus infection in mice.
  J. exptl. Med. 54, 73 (1931). [with R. DUBOS.]
Decomposition of the capsular polysaccharide of pneumococcus type III by a bacterial enzyme.
  J. exptl. Med. 54,51 (1931), [with R. Duaos.]
The action of a specific enzyme upon the dermal infection of rabbits with type III pneumo-
  coccus, J. exptl. Med. 55,393 (1932). [with R. Dusos and K. GOODNER.]
Experimental type III pneumococcus pneumonia in monkeys. II. Treatment with an enzyme
  which decomposes the specific capsular polysaccharide of pneumococcus type III. 3. exptf.
  n/led. SY, 641 (1934). [with T. F R~CIS, E. E. TERRELL; R. DUBOS.]
7. A blood protein reflecting disease process.
The occurrence during acute infections of a protein not normally present in the blood. I. Dis-
  tribution of the reactive protein in patients' sera and the effect of calcium on the flocculation
  reaction with C polysaccharide of pneumococcus. J. exptl. Med. 73, 137 (1941). [with
  T. J. ARERNETHY.]
The occurrence during acute infections of a protein not normally present in the blood. II.
  Isolation and properties of the reactive protein. 3. exptt. Med. 73, 183 (1941). [with C. M.
  MACLEOD.]
The occurrence during acute infections of a protein not normally present in the blood. III.
  ImnlunoIogical properties of the C-reactive protein and its differentiation from normal blood
  proteins. 3. exptl. Med. 73, 191 (1941). [with C. M. MAcLw)D.]
8. Transformation of bacterial types.
Studies on the chemica1 nature of the substance inducing transformation of pneumococcal
  types. [with M. MCG~RTY, C. M. MACLEOD.]
   I. Induction of transformation by a desoxyribonucleic acid fraction isolated from pneu-
     mococcus type III. 3. exptl. Med. 79, 137 (1944).
   II. Effect of de~xyribonucIease on the biological activity of the transforming substance.
     J. exptl. Med. X3,89 (1946).
  III. An improved method for the isolation of the transforming substance and its applica-
     tion to pneumococcus types II, III, and VI. 3. exptl. Med. 83. 97 (1946).
Riochemical studies of environmental factors essential in transformation of pneumococcal types.
  In Cold Spring Harbor Symp. Quant. Biol. 11, 177 (1946). [with M. MCCARTY, H. E.
  TAYLOR.]

9. Transformation studies carried under cIose association with 0. T. AVERY.
D~WSON, M. H., and R. H. P. SIA. fn vitro transformation of pneumococcal types. I. A
  technique for inducing transformation of pneumococcal types in vitro.  J. exptl. Med. 54,
  681 (1931).
SIA, R. N. P., and M, H. DAWSON. in vitro ~ransforma~on of pneumococcal types. II. The
  nature of the factor responsible for the transformation of pneumococcus types, J. ~xntl. Med.
  54, 701 (19.31).
AI~I.OW~Y. J. L. The transformation in uifro of R pneumococci into S forms of different specific
  types by the use of filtered pneumococcus extracts. 1. ezp& Med. 55, 91 (1932).


10                        OSWALD T. AVERY

ALLOWAY, J. L. Further observations on the use of pneumococcus extracts in effecting trans-
  formation of type in vitro. 1. expel. Med. 57,265 (1933).
HOTCHKISS, R. D. titudes chimiques sur le facteur transformant du pncumocoque. Colloq.
intern. centre natl. recherche sci. (Paris) 8: Ulzitk 6iologic~u~.s doutks de continuitt: g&u%-
  que, 57 (1949).
HOTCHHISS, R. D., and H. EPIIRIJSSI-TAYLOR. Use of serum albumin as source of serum factor in
  pneumococcal transformation. Federation Proc. 10: 346 ( 1952).
TAYLOR, H. E. Additive effects of certain transforming agents from some variants of pneumo-
coccus. I. ~xptl. Med. 89,399 (19-W).