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OCR for page 183
COLIN MUNRO MACLEOD
January 2S, 1909-February 11, 1972
BY WALSH McDERMOTT
AS A BEGINNER in science, Colin Munro MacLeod was
granted the most wonderful of gifts, a key role in a
major discovery that greatly changed the course of biology.
Great as this gift was, it came not as unalloyed treasure. On
the contrary, for reasons that are not wholly clear even today,
the demonstration by Avery, MacLeoct, ancT McCarty that
deoxyribonucleic acid is the stuff that genes are made of was
slow to receive general acceptance and has never really been
saluted in appropriately formal fashion. The event was origi-
nally recorcled in the now famous paper of 1944 in the
Journal of Experimental Medicine, entitled: "Studies on the
Chemical Nature of the Substance Inducing Transformation
of Pneumococcal Types. Induction of Transformation by a
Desoxyribonucleic Acid Fraction Isolated from Pneumococ-
cus Type III."
The title tells the story; clearly this was an historic
watershed. Sir MacFarIand Burnett states that "the discovery
that DNA COUi] transfer genetic information from one pneu-
mococcus to another heralded the opening of the fielct of
molecular biology."2 Writing in Nature in the month before
MacLeod cried, H. V. Wyatt3 reports it as "generally ac-
cepted" that the field of molecular biology began with the
183
OCR for page 184
184
BIOGRAPHICAL MEMOIRS
appearance of this paper. Lederberg terms the work "the
most seminal discovery of twentieth-century biology."
To make an important individual contribution to one of
history's great scientific achievements was an act of creation
of a special sort. It took place in the decade between
MacLeod's twenty-fourth and thirty-fourth years. He could
have rested on this achievement; he could have continued
with it, thus emphasizing his role; or he could have gone on
to something else. As things worked out, he followed the
last-named roacI, influenced to an undeterminable extent by
World War Il.
But there are other forms of creation in science, and, in
some of these, MacLeod also excelled. Before looking at these
aspects of his life, it is worthwhile to pause a moment over the
question of how he hacT been prepared so that he might make
such great contributions. (Dr. Robert Austrian, in a sensitive
and perceptive piece, has describer! MacLeod's early years.4)
One of eight children of the union of a schoolteacher and
a Scottish Presbyterian minister, the young MacLeod skipper!
so many grades in school that after being accepted at McGill
University he had to be "kept out" a year because he was too
young. His birth on January 2S, 1909 took place in Port
Hastings, Nova Scotia. In his early chil(lhoo(l, he moved with
his family back and forth across Canada from Nova Scotia to
Saskatchewan to Quebec. He obviously was a splendid stu-
dent, for, as related by his sister, Miss Margaret MacLeod, he
skipped the third, fifth, and seventh grades and graduated
from secondary school (St. Francis College, Richmond,
Quebec) when only fifteen years of age. His career as an
educator starter! almost immectiately. While being "kept out"
of school to become old enough for McGill, he was incluced
to leave an office job to serve at the age of sixteen as a
substitute teacher of the sixth gracle in a Richmond school.
He held this job wholly on his own for the entire year. These
OCR for page 185
COLIN MUNRO MACLEOD
185
early signs of superior intellectual capacity were not a part of
the stereotype "infant prodigy." Indeecl a clear sign to the
contrary was the fact that within only a few years he was on
the McGill varsity hockey team then, as now, a most im-
pressive athletic achievement.
After two years of premedical education at McGill, he
entered the Medical School and received his clegree in med-
icine in 1932. In 1934, at the age of twenty-four, after two
years of residency training at the Montreal General Hospital,
he came to New York. Less than ten years later, he would
make his own highly important individual contribution to the
Avery- MacLeocl- McCarty study.
The nature of the reception of this work was to test the
remaining thirty years of his life, for its significance clid not
receive the early attention it might be thought to have
merited. Shortly before MacLeod died, this aspect of the
story formed the basis of several articles in scientific and
popular periodicals.5 He had the chance to see these, but
sadly enough, he did not live to see the most extensive and
authoritative account, published in ~ 976 by R. J. Dubos in his
book, The Professor, the Institute and DNA. 6
There is no intent here to attempt to add to this literature.
The chance of painting a distorted picture is too great for one
who was not close to the situation at the time. Moreover, the
endpoint of "acceptance" is hard to measure, for in science it
floes not occur all at once like a directed plebiscite in a totali-
tarian state. Some highly knowlecigeable scientists perceive
the full significance of a particular discovery right away;
others require longer. It is necessary, however, to cite the
major events in the research itself in order to describe
MacLeocl's clearly definable and individual contribution.
AncI, given that contribution, some mention of what hap-
pened to the recognition of the work is inescapable in telling
the story of MacLeod's career in science. For it is the way the
OCR for page 186
86
BIOGRAPHICAL MEMOIRS
whole story seemed to him that could have had a telling
influence on his subsequent career.
When he first arrived at the Rockefeller Institute,
MacLeod fell under the influence or spell of 0. T.
Avery, or "Fess" as he was called, who was the inspiring
teacher of so many others, including Rene Dubos, Maclyn
McCarty, and the late Frank Horsfal1 and Martin Henry
Dawson.
Some years before, as related by Dubos, an old school
friend of MacL.eod's, Henry Dawson, had been asked by
Avery to investigate the variations in pneumococcal colonial
morphology from "rough" to "smooth" (R/S) then being
studied by Griffith in England. Several years later, when
~~ 1_ 7 _1 , , ~ . ~
~ ,
~rlrIlln aemonslra~ecl Nat one pneumococcus type could be
transformed in vivo into another, in effect a directed and
heritable alteration, Dawson was captivated by the feat.
Working with R. H. P. Sia, he was able to repeat the experi-
ment and to produce the chance 8 newton ho to Han
the project, which was taken up by J. S. Alloway,9 who was
able to show that the substance responsible resided in a thick,
syrupy preparation.
The techniques used by Dawson, Sia, and Alloway were
~ _ . . ~ _ _ ~ ~ ~ _. . ~ ~ . .
not at all reliable. Neither the phenomenon of transforma-
tion nor the harvesting of transforming principle could be
reproduced with a high degree of oredictabilitv. A ohenome-
_ _ r , ,~ 1l . 1 · ~
-- rip ---it --r--~--~~-~~
non ot potentially great blologlc significance had been clearly
identified. Yet without methods to produce it with oredict-
ability and to extract its active principle in ways permitting
precise characterization, any attempts to study the matter
further were bound to be marked by frustration. Neverthe-
less, because of the potential significance of the phenome-
non, Avery decided that the work must go on. He continued
to see the first essential task to be the chemical characteriza-
OCR for page 187
COLIN MUNRO MAt~LEOD
187
tion of the active material, but the available techniques were
obviously not sufficiently reliable to permit such chemical
studies. It was at this point that MacLeod entered the picture
in 1935. By improving the medium and isolating a consist-
ently reproducible rough strain of pneumococci, MacLeod
macle it possible (with Avery's encouragement and counsel) to
move the project from what was the study of a fascinating
phenomenon, but one of irregular occurrence and not pos-
sible to assay, to a predictable one. The critical substance
could then be fully characterized in chemical terms. The
subsequent phase of the study, the actual conduct of these
chemical studies, became the responsibility of McCarty.
Each of the six investigators who worked with Avery thus
made a contribution to the solution of Griffith's mystery, but
it is now fully conceded that the critical contributions were
those made by MacLeod and McCarty under the continuing,
brilliant intellectual stimulation, advice, anct course! of Avery
himself. OcicIly enough, as Dubos has clescribed, although
MacLeod and McCarty worked closely together on the proj-
ect, they were not officially at the Institute at the same time,
for in 1941, at age thirty-two, MacLeod became chairman of
the Department of Microbiology at the New York University
School of Medicine. He left the Institute as McCarty arrived.
As the Medical School of NYU and the Rockefeller labora-
tories are both in the micI- East Side of Manhattan, it was easy
for MacLeod to travel back and forth, and he maintained a
continued and wholly recognized association with the project.
In large measure, however, whether it was realized or not at
the time, he had made his contribution. He had taken an
almost formless, erratic phenomenon and macle it into some-
thing predictable and measurable. This had to be clone, and
he click it. Thus, the problem had been brought to the very
stage at which McCarty's own considerable biochemical ex-
OCR for page 188
188
BIOGRAPHICAL MEMOIRS
pertise was exactly what the situation called for. Two years
later (November ~ 943), the paper was submitted to the
Journal of Experimental Medicine. A
In subsequent years, MacLeod continued to work on this
problem in his laboratory at New York University, first with
M. R. Krauss i~ and R. Austrian, and at a later period with
E. Ottolenghi.~3 It is appropriate to postpone discussion of
these subsequent phases of his scientific career in universities
and government and to dwell for a moment on the story of
how the finding presented by Avery anc! his two younger
colleagues in the 1944 paper was received.
A revolutionary concept, as pointed out by Kuhn,~4 does
not usually increase knowledge by adcling on to it; it is more
apt to replace it. A problem in 1944, and a far greater one
today, is how one can evaluate new research with implied
revolutionary finclings when, as a practical matter, one can-
not employ the techniques necessary to repeat it.
The scientists who read the ~ 944 paper by Avery,
MacLeoct, and McCarty hacI, in theory, two choices: they
couIct accept or deny the validity of the demonstration on the
basis of comprehension, or they could repeat the experi-
ments. To (lo the former requires an intimate knowleclge of
the reliability of the techniques. At first glance that is a state-
ment of the obvious something that occurs on the reading
of any scientific paper. But such is really not the case. Most
of the time, in biomedicine at [least, published experiments
represent logical sequences in a series of experiments on the
same subject. The degree of reliability of the key methods is
known to be understood by those intimately engaged in the
fielct, and the rest take it on faith. When this is not the case
when the results clepend on a new method—if the field is
reasonably in the scientific fashion of the clay, it contains
other workers. These other workers soon clefine the limits of
the technique. Obviously, this system depends on the jucig-
OCR for page 189
COLIN MUNRO MACLEOD
.
.
189
mental decisions of presumed experts, but the scientific com-
munity and the public are protected against prolonged error
by the competitive nature of the studies in a particular field.
It is one part of the familiar "marketplace of ideas."
The trouble with the Avery-MacLeod-McCarty studies
was that the approaches they used did not happen to be
fashionable. They were not part of a race to glory, such as
that described by Watson in the Double Helix.~5 Or, more
accurately, the successful approaches that were used by the
Rockefeller group were far out of the ken of most of those
who were working actively to solve the question. Moreover,
the nucleic acids were not believed to have any biologic activ-
ity nor was their structure well defined. There really was no
community of competing investigators fully armed with the
requisite techniques ready to jump in and repeat the experi-
ments. Indeed, to do this wouicI require assembling a team
with the talents, experience, and expertise of Avery,
MacLeod, and McCarty. What is more, it would have to be
assembled from a markedly constricted biomedical research
community, for by this time the U.S. involvement in World
War IT had begun.
Acceptance of the chemical basis of transformation might
seem to have been slow, although clearly there was no set
period within which it should have occurred. There is now a
small body of published material on this question of accept-
ance by some of the people who were close to the field at the
time. Some of these comments were recorded during the
period in question or a little later; others are present-day
recollections of what was thought at the time. As might be
expected, these reports ranged from outright acceptance of
the role of DNA to a definite interest short of conviction, to, at
the other extreme, a belief that the phenomenon was not
mediated by nucleic acid at all, but by minute amounts of
contaminating protein. Stent believed the work had little im-
OCR for page 190
190
BIOGRAPHICAL MEMOIRS
pact on genetics.l6 Lederberg strongly dissents from this
. ~ . . . .
point ot view anc presents important contemporary citations
in support of that position. 17 Indeed, in the year following the
original report, I. Howard Quellers appears to have cor-
rectly perceived the whole story, as may be seen in his article
in the Annual Review of Biochemistry. Dubos,~9 in his 1976
analysis of the entire record, suggests that one of the factors
in the slow acceptance was the starkly noncommittal way the
results were presented, which was notable even in a scientific
report. In those days at the Rockefeller Institute, there was a
philosophy concerning the style in which experimental re-
sults should be presented. This style was largely initiated by
Avery but was also adhered to with conviction by most of his
younger associates, especially MacLeod. In this style, the key
words were carefully chosen to convey only that which had
been clearly proved and nothing more; any suggested impli-
cations were rigorously excluded. Lederberg also credits this
attribute, which he terms "Avery's own a-theoreticism," with
helping to postpone "the conceptual synthesis that now iden-
tifies 'gene' with DNA fragment."20
Whether or not acceptance was slow, it evolved steadily.
For Lederberg also mentions: "In 1946, at the Cold Spring
Harbor Symposium, where Tatum and I first reported on
recombination in Escherichia coli, we were incessantly chal-
lenged with the possibility that this was another example of
transformation, a la Griffith and Avery."2i
Dubos cites a summary by Andre Ewoff of a 1948 con-
ference in Paris in which the genetic role of the nucleic acids
is obviously accepted. But as Dubos also states:
It took an experiment, outside of the Institute, with a biological system
completely different from that used by Avery to win universal acceptance
for the genetic role of DNA. Using coliphage marked with 32P (restricted to
the DNA component of the virus) and with 35S (restricted to the protein
component), Hershey and Chase at the Cold Spring Harbor Laboratory
OCR for page 191
COLIN MUNRO MAcLEOD
191
showed in 1952 that most of the viral DNA penetrates the infected bac-
terium, whereas most of the protein remains outside. This finding sug-
gested that DNA, and not protein, was responsible for the directed specific
synthesis of bacteriophage in infected bacteria. In reality, the interpreta-
tion of this wonderful experiment was just as questionable on technical
grounds as was the chemical interpretation of pneumococcal transforma-
tion, but those obtained by Avery 10 years before, that the few remaining
skeptics were convinced. The case for the view that DNA iS the essential and
sufficient substance capable of inducing genetic transformations in bacte-
ria was not won by a single, absolute demonstration, but by two indepen-
dent lines of evidenced
In his Nobel Prize lecture,23 Lederberg puts it in essen-
tially the same way. He attributes to Avery and his colleagues
the demonstration that the interpneumococcus transference
of an inherited trait was through DNA, the broadening of the
evidence to Hotchkiss,24 and the reinforcement of this con-
clusion to Hershey and Chase,25 with their proof that the
genetic element of a virus is also DNA. Eventually such situa-
tions right themselves. Today if one looks in elementary texts
on human genetics, the Avery- MacLeod- McCarty ~ 944
paper is cited, in effect, as the historic watershed.26
Little imagination is required for anyone who has ever
been engaged in science to envision what a cleep-seatecl disap-
pointment the relative lack of formal recognition of his key
contribution to the DNA work could be to a scientist, especially
to one who was just starting out in his career. A sense of
having in some way suffered an injustice wouIcl not be at all
unusual. This could well lead to bitterness, particularly as the
years went on and others reaped wide professional and pub-
lic recognition for studies on DNA. But MacLeod would have
none of this. Not for him wouIct be the stereotype of the
unhappy investigator living off scientific "might have beens."
Incleed, as far as I have been able to ascertain, at no time did
he ever publicly express, even by indirection, the thought
that, in the DNA story, he had been slighted in any way.
OCR for page 192
192
BIOGRAPHICAL MEMOIRS
MacLeocT's seven years in Avery's "department" at the
Institute were not all occupied by the work on the pneumo-
coccal transforming factor. On the contrary, he was engaged
in a number of other studies, as may be seen from his sixteen
publications of this period, eleven of which list him as senior
author. Two things are striking in looking over this list today.
First, although a number of different topics appear to be
involved, they almost all clear with host-parasite relations at
the very time antimicrobial therapy was coming on stage, so
that the influence of this intervention in the disease mecha-
nism could also be embraced by the studies. Second, virtually
all were concerned with pneumonia, notably pneumococcal
pneumonia; there was one stucly on the so-called primary
atypical pneumonias just then coming into medical recogni-
tion. Given Avery's preoccupation with pneumococcus, the
fact that MacLeocI, working in his laboratory, publishecl a
number of studies on pneumonia may not seem too surpris-
ing. What is important, however, is that this interest lecI
MacLeod to highly productive studies in his subsequent
career.
MacLeod's start as a university professor coincicled
roughly with the entrance of the United States into World
War IT. Viewed in retrospect, the impact of so pervasive a
force as World War lI was bound to have deep and enduring
effects on a young man just emerging as a leader in science.
From this time on, three characteristics were prominent. He
was forever conscious that the university department he
headed was in a school for the training and education of
physicians, he was deeply convinced of the social value of
unfettered basic scientific research, ant! he felt a responsibil-
ity to contribute what he could to the shaping of public policy
in that interface of government and the universities that
cleveloped so rapidly in importance dating from that time. To
a considerable extent, all three characteristics tendec! toward
OCR for page 209
COLIN MUNRO MAcLEOD
209
training in science and in biomedical science. His interest,
however, was in medical education in its totality; in his few
years as an executive of the Commonwealth Fund, he was
able to concentrate largely on this field. Among his major
accomplishments was the successful effort to convince the
Fund to make a substantial investment in support of the
medical education of black students. Moreover, by no means
opposed to the "Centers of Excellence" concept, he was
nevertheless among the first to encourage the university-
basect medical centers to concern themselves also with the
broacT societal issues of medical care. Probably the most care-
fully written of his analytic essays on the social choices before
us regarding the support of medical education and its sci-
ences is "The Government ancT the University," given as the
ctinner address in 1966 before the Association of American
Physicians.40
These three different phases of MacLeocT's scientific and
professional life were largely sequential. There was his fine
work in the laboratory culminating in the sharply focused
scientific effort with Avery ancT McCarty that led to the iclen-
tification of DNA as the material of heredity. In the second
phase, there was the creativity involved in building a model
basic-science department in a university. He lect in the crea-
tion of an exciting teaching program. He assemblecl a group
of splendid scientists, junior and senior, anct proviclecI the
leadership and the environment in which they could attain
their maximal potential. There was the third and longest
phase in which he pioneered in an area essential to the
proper life of science: science and public policy or the inter-
face between science in the university and in government.
The writer had the opportunity to observe him on many
occasions at work in each of the institutional frameworks in
which he laborecI for so long a period. It was easy to see why
OCR for page 210
210
BIOGRAPHICAL MEMOIRS
he was so much in demand. He was responsible, knowledge-
able, always even-tempered, ant! quick to sense a group ten-
sion that could be allayed by his quick wit.
He had attributes somewhat unusual for a young person
In science—at least in biological science in those clays. He had
a considerable interest in intellectual affairs outside of science
as well as those of science, and he usually appeared willing,
one might almost say eager, to stay up all or half the night in
discussions about them. To these he brought a quick wit and
great gifts as a raconteur particularly as a teller of stories in
Scot's dialect. Perhaps he possessed these behavior patterns,
while others of his cohort in science did not, simply because
he had the physical strength others lackecI. As Robert Aus-
trian has put it:
One of Colin's remarkable attributes was his boundless energy. Despite
the multiplicity of his responsibilities, his endless travels here and abroad,
he never seemed to tire. He required less sleep than most men; and, after
an animated evening of discussion with colleagues lasting into the wee
hours, he could attend a meeting the next day without visible evidence of
the influence of fatigue on his thinking.4t
He had strong characteristics that in another person couIcl
have been defects. What in someone else might have been
unattractive rigidity, in him was an enviable firmness and
responsible consistency. While believing deeply in the social
responsibility of science ant! in the need to work out ways to
apply its useful products, he was equally deeply convinced of
the importance of scientific inquiry of a completely unfet-
tered sort. Even in his manner there were the contradic-
tions his small size, quick movements, and careful groom-
ing might easily get the label of dapper but not in him. In
puzzling over why these apparent paradoxes former] an im-
mensely effective person, one might say that the contradic-
tions were in balance, but it was something more than that, it
was really a matter of a disciplined control.
OCR for page 211
COLIN MUNRO MAcLEOD
2
The greatest paradox of all was in personal relations.
Here he gave much of himself; he hacT a wicle circle of ex-
tremely clevotect friends and was always open to their seeking
of help. He gave much of himself, but he gave very little about
himself. Several people who knew him well have commented
that there seemed to be an extraordinarily large group of
people, each one of whom consiclerec! themselves to have
been a close personal frienc! of MacLeocT.
Although he wouicT not talk of himself in a personal fac-
tual sense, he would get into quite serious discussions about
his philosophical beliefs. His view of life as I heard him ex-
press it on more than one occasion was basest on the concept
of immanence. He was fascinated with this iclea. Unfortu-
nately for a precise discussion, the concept of immanence has
several rather different meanings. My own unclerstancting
from our numerous conversations is that MacLeod's imma-
nence hacT the "Got! is everywhere" meaning. Certainly this
fitted well with his unpretentious and utterly convincing won-
derment about the effective intricacies and orderliness of
living systems a characteristic not so often met with in one
who also was extremely interested in disease and the human
. .
cone lotion.
Describer! in this way, he seems like a paragon of virtues
- something ~ suspect he was, but cannot testify to because of
the familiar phenomenon of our relative ignorance of the
"other sides" of persons we know quite well. ~ cTicT not know
him in his roles as brother, husband, or father. ~ knew him as
an extraordinarily capable member of the scientific commu-
nity and an equally effective leader in the world of science
and public policy. In short, ~ knew him in a certain environ-
ment, ant! it is the particular environment that is especially
concerned in these archives. In the relatively broact confines
of that environment, this is the way he was to me.
Tolstoy believed our method of classifying people by at-
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212
BIOGRAPHICAL MEMOIRS
tributing to each some particular leading quality was all
wrong. He concealed that one could say that someone is more
frequently kind, wise, or energetic than the opposite, but to
him:
Men are like rivers. The water is alike in all of them; but every river is
narrow in some places and wide in others; here swift and there sluggish,
here clear and there turbid; cold in winter and warm in summer. The same
may be said of men. Every man bears within himself the germs of every
human quality, displaying all in turn; and a man can often seem unlike
himself yet he still remains the same man.42
It is on this Tolstoyan scoreboard that the MacLeoc!
career stancis so high, for almost without exception, regarcI-
less of how wide or how coIc! the river, he remained the same
man.
NOTES
1. O. T. Avery, C. MacLeod, and M. McCarty, "Studies on the Chemical Nature
of the Substance Inducing Transformation of Pneumosocial Types,"Journal of Ex-
perimental Medicine, 79(1944):137-58.
2. Sir F. M. Burnet, Changing Patterns: An Atypical Biography (London: Heine-
mann, 1968), p. 81.
3 . H. V. Wyatt, Nature, 23 5( 1972) :86.
4. R. Austrian, "Infectious Diseases Society of America: Colin Munro MacLeod~
1909-1972 ," Journal of Infectious Diseases, 127( 1973) .
5. G. S. Stent, "Prematurity and Uniqueness in Scientific Discovery," Scientific
American, 227(1972):8~93.
6. R. J. Dubos, The Professor, the Institute, and DNA (New York: The Rockefeller
University Press, 1976).
7. F. Griffith, Journal of Hygiene, 27( 1928): 1 13.
8. M. H. Dawson and R. H. P. Sia. "In Vitro Transformation of Pneumococcal
TypesIandII,"%,fournalofExperimentalMedicine,54(1931):681-99,701-10.
9. l. S. Alloway, "The Transformation in Vitro of R Pneumococci into S Forms of
Different Specific Types by the Use of Filtered Pneumococcus Extracts," Journal of
Experimental Medicine, 55(1932):91-99; l. S. Alloway, "Further Observations on the
Use of Pneumococcus Extracts in Effecting Transformations of Type in Vitro,"
Journal of Experimental Medicine, 57(1933):265-78.
10. Avery, MacLeod, and McCarty, "Studies of the Chemical Nature of the Sub-
stance Inducing Transformation of Pneumosocial Types."
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COLIN MUNRO MAtLEOD
213
11. C. M. MacLeod and M. R. Krauss, "Stepwise Intra-Type Transformation of
Pneumococcus from R to S by Way of a Various Intermediate in Capsular Polysac-
charide Production," Journal of Experimental Medicine, 86(1947):439-53; C. M.
MacLeod and M. R. Krauss, "Transformation Reactions with Two Non-Allelic R
Mutants of the Same Strain of Pneumococcus Type VIII," Journal of Experimental
Medicine, 103( 1956):623-38.
12. R. Austrian and C. M. MacLeod, "Acquisition of M Protein by Pneumococci
through Transformation Reactions," journal of Experimental Medicine, 89(1949):
45 1-60.
13. E. Ottolenghi and C. M. MacLeod, "Genetic Transformation among Living
Pneumococci in the Mouse,"Proceedings of the NationalAcademy of Sciences of the United
States of America, 50(1963) :4 17.
14. T. S. Kuhn, The Structure of Scientific Revolutions, 2d ed. (Chicago: University
of Chicago Press, 1970), pp. 93-94.
15. J. D. Watson, The Double Helix (New York: Atheneum, 1968).
16. Stent, "Prematurity and Uniqueness in Scientific Discovery."
17. I. Lederberg, "Reply to H. V. Wyatt," Nature, 239, no. 5369(1972):234.
18. J. Howard Mueller, "The Chemistry and Metabolism of Bacteria," Annual
Review of Biochemistry, 14: 733-47.
19. Dubos, The Professor, the Institute, and DNA.
20. Lederberg, "Reply to H. V. Wyatt."
21. Ibid.
22. Dubos, The Professor, the Institute, and DNA, p. 148.
23. j. Lederberg. 1959 Nobel Prize Acceptance Lecture, Royal Caroline Medico-
Surgical Institute, Stockholm, 29 May 1959.
24. R. D. Hotchkiss, "The Genetic Chemistry of the Pneumococcal Transforma-
tions." Harvey Lecture, 24 January 1954.
25. A. D. Hershey and M. Chase, "Independent Function of Viral Proteins and
Nucleic Acid in Growth of Bacteriophage,'' Journal of General Physiology, 36( 195 1):39.
26. Textbook, Elementary, An Introduction to Human Genetics, ed. H. Eldon Sutton
(New York: Holt, Rinehart and Winston, 1965), p. 70.
27. A syndrome principally produced by mycoplasma.
28. C. M. MacLeod, "Primary Atypical Pneumonia," Medical (clinics of North
America, 27(1943):67~86.
29. C. M. MacLeod, R. G. Hodges, M. Heidelberger, and W. G. Bernhard, "Pre-
vention of Pneumococcal Pneumonia by Immunization with Specific Capsular Poly-
saccharides,"Journal of Experimental Medicine, 82(1945):445-65.
30. R. Austrian, R. M. Douglas, G. Schiffman, et al., "Prevention of Pneumo-
coccal Pneumonia by Vaccination," Transactions of the Association of American Physi-
cians, 89(1976):184.
31. C. M. MacLeod, "Chemotherapy of Pneumococcic Pneumonia," Journal of the
American Medical Association, 1 13( 1940): 1405.
32. MacLeod and Krauss, "Stepwise Intra-Type Transformation of Pneumococ-
cus from R to S by Way of a Various Intermediate in Capsular Polysaccharide
Production"; "Transformation Reactions with Two Non-Allelic R Mutants of the
Same Strain of Pneumococcus Type VIII."
33. Austrian and MacLeod. "Acquisition of M Protein by Pneumococci through
Transformation Reactions."
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214
BIOGRAPHICAL MEMOIRS
34. MacLeod, Hodges, Heidelberger, and Bernhard, "Prevention of Pneumo-
coccal Pneumonia by Immunization with Specific Capsular Polysaccharides; M. Hei-
delberger, C. M. MacLeod, S. J. Kaiser, and B. Robinson, "Antibody Formation in
Volunteers Following Injection of Pneumococci of Their Type-Specific Polysaccha-
rides,"Journal of Experimental Medicine, 83(1946):303-20; R. G. Hodges and C. M.
MacLeod, "Epidemic Pneumococcal Pneumonia. I. Description of the Epidemic,"
American journal of Hygiene, 44(1946):183-92; R. G. Hodges and C. M. MacLeod,
"Epidemic Pneumococcal Pneumonia. II. The Influence of Population Characteris-
tics and Environment," American f ournal of Hygiene, 44( 1946): 193-206; R. G.
Hodges, C. M. MacLeod, and W. G. Bernhard, "Epidemic Pneumococcal Pneumo-
nia. III. Pneumococcal Carrier Studies,"American journal of Hygiene, 44(1946):207-
30; R. G. Hodges and C. M. MacLeod, "Epidemic Pneumococcal Pneumonia. IV.
The Relationship of Nonbacterial Respiratory Disease to Pneumococcal Pneumo-
nia," American journal of Hygiene, 44(1946):231-36; R. G. Hodges and C. M.
MacLeod," Epidemic Pneumococcal Pneumonia. V. Final Consideration of the Fac-
tors Underlying the Epidemic," American journal of Hygiene, 44(1946):237-43; M.
Heidelberger, C. M. MacLeod, R. C. Hodges, W. G. Bernhard, and M. M. DiLapi,
"Antibody Formation in Men Following Injection of 4 Type-Specific Polysaccharides
of Pneumococcus," journal of Experimental Medicine, 85(1947):227-30; M. Heidel-
berger, C. M. MacLeod, and M. M. DiLapi, "The Human Antibody Response to
Simultaneous Injection of 6 Specific Polysaccharides of Pneumococcus," journal of
Experimental Medicine, 88(1948):369-72; C. M. MacLeod, M. Heidelberger, and
M. M. DiLapi, "Antigenic Potency in Man of the Specific Polysaccharides of Types
I and V Pneumococcus and Their Products of Alkaline Degradation," journal of
Immunology, 66(1951):14~49; C. M. MacLeod, M. Heidelberger, H. Markowitz, and
M. M. DiLapi, "Absence of a Prosthetic Group in Type-Specific Polysaccharides of
Pneumococcus," Journal of Experimental Medicine, 94(1951):359-62.
35. Austrian, Douglas, Schiffman, et. al., "Prevention of Pneumosocial Pneumo-
nia by Vaccination."
36. In November 1978, both Heidelberger and Austrian received Lasker Awards
for Heidelberger's work with carbohydrate Polysaccharides and Austrian's clinical
studies establishing the effectiveness of the vaccine.
37. The other members were R. I. Dubos, J. Kidd, M. McCarty, W. McDermott,
A. M. Pappenheimer, and L. Thomas.
38. E. J. Van Syke, Science, 104(1946):559.
39. D. R. Nalin, R. A. Cash, R. Islam, M. Molla, and R. A. Phillips. "Oral Mainte-
nance Therapy for Cholera in Adults." Lancet, ii( 1968):37~73.
40. Transactions of the Association of American Physicians, 99.
41. Austrian, "Colin Munro MacLeod."
42. L. Tolstoy. Resurrection. (New York: The New American Library, Signet
Classic), p. 191.
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COLIN MUNRO MAT LEOD
BIBLIOGRAPHY
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215
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217
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Representative terms from entire chapter:
biographical memoirs
