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Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
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OCR for page 59
THOMAS FRANCIS, JR.
July 15,1900-October 1,1969
BY JOHN R. PAUL 38
THOMAS FRANCIS, JR., was born in Gas City, Indiana, on July
15, 1900, the son of Thomas and Elizabeth Anne (Cadogan)
Francis. His father had emigrated from Wales shortly before
Thomas, {r., came into the world. He was the third of four
children, but the first to be born in this country.
Thomas Francis, Sr., had studied for the ministry as a young
mans but had decided later to loin his father In the tin mills of
South Wales. He had married Elizabeth Anne Cadogan, a grad-
. . . . . . . . . . . . ~ . . .
uate of a Salvation Army Trainings, School in London. It is
said that she kept "her Salvation Army ideals" throughout her
entire life. At least she strove to do her part in supplying a firm
religious background to her brood of four children.
.
In 1897 the Francis family had been persuaded to visit Amer-
~ca. Their destination was a small colony of Welsh families
which had settled in and about Gas City, Indiana. For a while
this venture was considered to be temporary, but when the
family moved to New Castle, Pennsylvania, and Mr. Francis be-
came associated with the steel mills of that town, it became
permanent. After Thomas Francis, Sr.'s, retirement from the
steel mills he turned again to religious ideals and became or-
~ Prior to his death, the author asked Dr. Dorothy M. Horstmann of the Yale
School of Medicine to make certain revisions in this memoir. The final version
of the memoir owes a great deal to Dr. Horstmann's careful and constructive
review, as well as to the faithfulness with which she adhered to the author's style.
~7
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58
BIOGRAPHICAL ME M OIRS
dained as a lay minister. Henceforth he was known as the
Reverend Thomas Francis. For several years he preached at a
small New Castle church.
Both parents had very definite ideas about the home life of
the Francis family: what it should be and how the children were
to act. There were strict rules of behavior, and yet, in spite
or because of them, the family life was a happy one. As a boy,
Tommy led the normal existence of a lad in a small town en-
vironment in which his natural inclinations included fishing
and baseball. At the local high school he became quite active
in dramatics, which, according to his sister, were usually of the
Shakespearean variety.
With regard to the rest of Tommy's immediate family, I
shall not dwell, although they all enjoyed successful lives. His
younger brother, Herbert, graduated in medicine from Yale.
The bulk of Herbert's professional career was spent at the School
of Medicine, Vanderbilt University, as professor and chairman
of the roentgenology department and also as a consultant to
the Institute of Nuclear Studies at Oak Ridge, Tennessee.
With high school over, where all records maintain that
Tommy was an able student, he attended Allegheny College at
Meadville, Pennsylvania, and received the B.S. degree in 1921.
He entered medical school the following fall. I am not aware
of the reason why he made the decision to study medicine but he
told me often about his choice of a medical school. In this he
was influenced by a brother-in-law (a successful surgeon, Dr.
Edgar R. McGuire of Buffalo, New York), whose views he had
sought during his last years at college. He was advised to con-
sider seriously the idea of applying for admission at the re-
juvenated Yale University School of Medicine, which had been
completely overhauled by Yale's new President, James R. Angell,
who had recently come from the University of Michigan, and by
the new Dean of the Medical School, Dr. Milton C. Winternitz,
who was also a newcomer at Yale from Johns Hopkins.
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THOMAS FRANCIS, JR.
59
Although the Yale medical school was a venerable school of
medicine as far as this country was concerned, having been
founded jointly by the Connecticut State Medical Society and
Yale College in 1810, it had never achieved its hoped for goals
during the nineteenth and early twentieth centuries. Indeed,
prior to World War I, it was definitely a second-rate school with
only a handful of students. And yet, oddly enough, in 1915 it
had on its faculty an unusually distinguished group of men:
Yandell Henderson, as professor of physiology, and Lafayette
Mendel, of vitamin fame, in biochemistry, both members of the
National Academy of Sciences; and two very able and wise
clinicians, George Blumer and Wilder Tileston, in internal
medicine, both members of the Association of American Physi-
clans.
.
But luckily the school made a sudden rightabout-face when
in 1917 Winternitz arrived from Baltimore to assume the posi-
tion of chairman of the Department of Pathology. He had
previously been an associate professor of pathology at the Johns
Hopkins medical school under that dean of pathologists, med-
ical educators, and medical historians, Dr. William H. Welch.
Dr. Welch had been a loyal graduate of Yale College and his
hope was to do something along the lines of a salvage operation
for the Yale School of Medicine. Winternitz was an able emissary
to perform this duty. His move to Yale had come just at the time
when the medical schools of this country were undergoing a
state of ferment. The cause of this was the recent issuance, and
the recognition of the worth, of the Abraham Flexner Report
on Medical Education in the United States and Canada, which
introduced a timely reform that was to go into sharp reverse
within the next fifty years. Flexner's report was beginning to
have its effect in 1917 and Winternitz was quick to take ad-
vantage of this. The recommendations concerned, in part, the
introduction of the full-time system into the clinical depart-
ments of the medical schools of North America—an idea that
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60
BIOGRAPHICAL MEMOIRS
heretofore had been foreign to the rank and file of American
physicians, academic or otherwise.
Within two years of Winternitz's coming to Yale, the medical
faculty, sensing that here was no ordinary professor of path-
ology, elected him dean. His plan for Yale was modeled to a
certain extent along the lines that made the Johns Hopkins
School of Medicine great, that is, close personal contact between
scholars and carefully picked students, and a devotion to re-
search. So Winternitz, having made his decisions, went about
his first task, which was that of gathering together the best
young medical scientists and physicians that he could lay his
hands on to fill the recently created full-time professorships in
the clinical departments: Dr. Francis G. Blake, John P. Peters,
and William T. Stadie from the Hospital of the Rockefeller
Institute in internal medicine, all three of whom were sub-
sequently to become members of the National Academy of
Sciences; and Dr. Edwards A. Park in pediatrics.
It was at this stage, in 1921, coincident with Dr. Blake's ar-
rival at the school as chairman of the Department of Internal
Medicine, that the young Francis, having submitted his appli-
cation, was accepted, and entered the newly rejuvenated Yale
University School of Medicine as a first-year student. He was tak-
ing a chance not to have chosen one of the established and better
known medical schools of this country. But, as it turned out, it
was a chance worth taking. The reason for dwelling so long
in this memoir on his academic background is that I am
convinced that the training the young Thomas Francis received
at Yale opened up a vista of new paths and new opportunities
which he eagerly followed.
All accounts testify that he was a fun-loving, attractive, and
able student, quick to learn and quick to appreciate the idea
that the Yale school was supposed to do something out of the
ordinary—and to act as a spearhead in a movement of reform
OCR for page 63
THOMAS FRANCIS, JR.
61
in medical education for the nation and for Yale University.
Most of the members of the clinical faculties, especially those
in internal medicine and pediatrics, whose combined members
in the 1920s could not have amounted to more than fifteen or
eighteen, had put their hearts and souls into making the new
scheme work. They were determined to put the Yale school on
the map and to establish beyond peradventure that the organiza-
tion of the clinical departments on a full-time basis was not
a theoretical pipe dream.
The young Thomas Francis became keenly aware of the
Intimate attention that was being bestowed on this first small
group of medical students who had been admitted under the
new regime. He soon fell under the spell of the newly appointed
faculty members, who besides being clinicians were inspiring
and high-minded teacher: men such as Francis G. Blake ~ and
lames D. Trask in medicine, and Edwards A. Park and Grover
F. Powers in pediatrics. Dr. Blake was especially quick to recog-
nize Francis's ability and his early grasp of what the school was
supposed to do. As a result, a mutual respect developed that
lasted throughout their lives.
With Dr. Blake he had almost a filial rapport. He admired
Francis Blake as an astute diagnostician, a wise teacher, a
physician and medical scientist of complete integrity, and an
able clinical investigator. Besides, Blake had something akin
to an epidemiological instinct long before that science had re-
ceived the attention in this country that it deserved. This last
characteristic accounted for Blake's being chosen as the first
president to head the Army Epidemiological Board
(AEB)
during the years of World War II and for some years afterward.
~ The fells instructors in the Department of Medicine in the Yale University
School of Medicine of the 1920s who are living today all testify to this estimation
of his character.
, See memoir of Francis G. Blake, by Dr. J. R. Panel, in National Academy of
Sciences, Biographical Memoirs, 28 (1954):1-29.
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62
B I O G R A P H I C A L M E M O I R S
Some of these qualities must have rubbed off on the young
medical student who was eventually to become Dr. Blake's suc-
cessor as president of the AEB Esubsequently the AFEB (Armed
Forces Epidemiological Board)] in the years 1958-1960.
. . ~ ~
When Dr. Francis graduated as an M.D. in 1925, he was
Immediately appointed as an intern on the medical service
of the New Haven Hospital, the next year as resident, and the
next as an instructor in Blake's Department of Internal Medi-
cine. This was a prime example of the apprenticeship type of
~ns~rucr~on In which the professor did not have to preach but
resorted instead to imparting the principles of clinical medicine
by personal example. As a result, the young Dr. Francis was
inspired to set his sights to emulate Dr. Blake, who in turn
recognized that his pupil, having fulfilled his post of house
officer and instructor admirably, had also begun to show signs
of promise as a clinical investigator. Blake's early estimate of
Francis's talents was not far wrong, for sixteen years later Francis
was to become the president of the American Society for Clin-
ical Investigation.
In any event, Blake decided that here was no ordinary young
physician—indeed, Thomas Francis was one who might go far.
So he advised him to prepare himself further by a period of
training at the best contemporary institution that was available
for this kind of instruction, namely, the Hospital of the Rocke-
feller Institute. Blake had no hesitancy in recommending Dr.
Francis to Rufus I. Cole, the director of this hospital, as a prom-
ising candidate. Francis was a young man who possessed all the
talents of an able house officer and the qualifications of a
budding research worker (assets which were highly sought after
by Dr. Cole in any candidate he was to take on as a junior
member of his staff) . This sophisticated center of learning and
research was a far cry from New Castle, Pennsylvania.
Had Francis pursued this course of in-service training to
its obvious end, it should have led him straight down the path
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THOMAS FRANCIS, JR.
63
of an academic career in internal medicine—to an assistant,
then associate, and eventually a full professorship at one of the
full-time medical schools in this country. But other career goals
eventually proved more attractive to him.
Among the group which Dr. Cole had assembled on the
Rockefeller hospital staff at this time were included Drs.
Thomas M. Rivers, William T. Tillett, Oswald T. Avery, Donald
D. Van Slyke, Alfred E. Cohn, Homer F. Swift, and several
others whose names were to rank high during the 1930s—an era
which is understandably considered by some as the age of the
flowering of American Medicine—spelled with a capital M.
It was during this period that the young Thomas Francis
began to gain a feeling of confidence that he had arrived as a
person to be reckoned with in the field of full-time clinical
investigation. Besides his qualifications as an investigator,
his clinical abilities as a young physician also came to the fore
on the the wards of the Rockefeller hospital. He often told me
that he must have been appreciated as "a doctor" at this time.
Among his prominent "private patients" were members of the
Rockefeller family, and for a time he almost rated as their
private physician.
Indeed, during the first half of his lone and distinguished
~ 1_ ~ ~ . . —
~ c~ ~ _
career, ne ala not relinquish the hope that he might be con-
sidered as a suitable candidate for a position as chairman of the
Department of Medicine in one or another of the country's
leading medical schools. This hope was not based on the fact
that he possessed a knowledge of medicine that was of en-
cyclopedic nature, but he felt the important thing was that he
had acquired from his parents and his respected teachers—Drs.
Blake and Cole—the altruistic principles of a physician, as well
as the ideals of clinical medicine and, incidentally, of clinical
investigation—and this was enough. Talents which Dr. Francis
had developed at this time were those that had to do with both
clinical and experimental medicine in infectious disease, micro-
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64
BIOGRAPHICAL ME M OIRS
biology, and epidemiology. He could have filled an academic
position in any of these various fields, as well as a professorship
in internal medicine.
On arrival at the Hospital of the Rockefeller Institute, Dr.
Francis pursued the line of work that he had started under
Dr. Blake at Yale. His interest had been aroused by studies
which had to do with the various types of the pneumococcus,
both rough and smooth varieties, and with the respiratory
diseases including lobar pneumonia, a subject of great interest
in that pre-antibiotic age.
In an article written immediately
after Dr. Francis's death, Colin M. MacLeod said:
"On coming to Avery's laboratory, Francis and William
Tillett worked together on cutaneous and serological reactions
to products of pneumococcus, particularly the specific capsular
polysaccharides and the 'C' or somatic carbohydrate, now known
to be a constituent of the bacterial cell wall. Over the three-
^. ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ^_ _ ~ ~ ~ ~ _ ~ ~ ~ _ ~ _ A ~
year period of their collaboration two remarkable findings came
forth.
"The first of these was that there occurs in the blood of
patients with many acute infections a new substance, not an
antibody in the usual sense, which reacts specifically with the
'C' carbohydrate of pneumococcus to give a precipitation re-
action. During recovery from the disease the 'C-reactive pro-
tein,' as it came to be known, diminishes in amount and within
a few days disappears entirely. This is an enigmatic reaction
whose function in man and animals is still unknown but which
provides a useful clinical test to measure the activity of a variety
of infectious processes, for example the activity of the inflamma-
tory process in rheumatic fever.
"Francis and Tillett also discovered that minute amounts of
specific capsular polysaccharides of pneumococcus injected in-
tracutaneously in man cause the development of specific anti-
bodies and that the antibodies are protective....
"While Francis was in Avery's laboratory, Dubos and Avery
OCR for page 67
THOMAS FRANCIS, JR.
65
had developed their famous studies on an induced enzyme
obtained from a soil bacterium which specifically hydrolyzes
the capsular polysaccharide of pneumococcus Type III whether
the latter is in solution or attached to the living, virulent
pneumococcus." ~
Dr. MacLeod went on to say: "Francis, with Terrell, de-
vised methods for producing Type III pneumonia in monkeys
and published meticulous studies of its clinical course. In
collaboration with Dubos and Avery they then went on to
demonstrate in this experimental disease of primates, which
simulates pneumococcal pneumonia in man, that the S III
enzyme has striking curative properties. Unfortunately, test of
the ~~ ~;~ ~~ · ~ .,
t11C Lll~l-~CULlC erect In man was never carried out.''
~ , ~ . . .. ~ . .
Con nuance or tins line ot Investigation was due to Dr.
Francis's departure from the pneumonia service when he entered
upon his work on influenza. But Francis must have derived
not a little satisfaction from his early work at the Rockefeller
hospital, for in recounting the memory of it some forty years
later in his address entitled "Moments in Medical Virology,"
presented at the First International Congress for Virology in
Helsinki, Finland, he recalled events that had occurred while
he had been working enthusiastically on the transformation of
pneumococcus types. He said:
"So I spent the mornings in the laboratory learning of these
phenomena and the afternoons in the library and on the tennis
court developing a model of the double fault. Being convinced
that the induced change of pneumococcus types in the animal
host was a true bill, I began very primitive efforts to obtain
transformation in the test tube. (It is worth noting that a
healthy air of skepticism surrounded the entire phenomenon—
that probably some live organisms were persisting in the heated,
supposedly, killed preparation.) It became clear that the
~ Colin M. MacLeod, "Thomas Francis, Jr., 1900-1969," Arch. Environmental
Health, 21 (1970):226-29.
OCR for page 68
66
capsular polysaccharide, with all its divine properties, was not
the effective agency. But then it seemed likely that whatever
the transforming principle was, it needed special care and I
began making extracts be freezing and thawing organisms in
BIOGRAPHICAL MEMOIRS
, ~
the cold under relatively anaerobic conditions so as to avoid an
enzymatic destruction of the principle. One day at noon I
thought I was all alone in the lab. I was occupied with the
tedious procedure of freezing and thawing. I had put my head
down on my arms on the desk. Unexpectedly, a quiet voice
said, 'What's the matter, boy?' Startled, I said I hated to see
another pneumonia season start with the great time and at-
tention required for clinical work; that I thought what was in
these flasks was more exciting. Then I received a very sharp
lecture from Dr. Avery reminding me that we were physicians;
that the major concern of this laboratory was lobar pneumonia
and that what was done here was in effect to understand the
disease and to lick the pants off the pneumococcus—a theme that
was developed under Avery and Dubos with the Type III de-
capsulating enzyme. This is a true view of Avery's intellectual
commitment to the clinical problem.
"New lines of effort were freely allowed even if they were
not always enthusiastically supported. I found this when I
studied transformation of the rough Type III to virulent in
rabbits; there was a lot of specificity involved and much work,
but it never was published until later (by others).... Things
were apparently dormant for 10 years.
"Then came the epochal study by Avery, MacLeod and
McCarty in 1944....
"Somewhere in these early days I rode on the train from
New York to Princeton, New Jersey, with two leaders in virology,
Thomas Rivers and Christopher Andrewes, to see a third, Dick
Shope. In those days, virology had not yet descended to the
level of the common man and I listened, as the privileged young
OCR for page 102
100
BIOGRAPHICAL MEMOIRS
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~ , ,
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THOMAS FRANCIS, JR. 103
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. .
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The teaching of epidemiology.
BIOGRAPHICAL MEMOIRS
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Evaluation of gamma globulin in prophylaxis of paralytic polio-
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Immunological and epidemiological problems.
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With L. R. Penner and G. C. Brown. Some observations on the
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With K. W. Cochran and G. C. Brown. Antiviral action of a mold
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With R. F. Korns, R. B. Voight, et al. An Evaluation of the 1954
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Poliomyelitis issue. Univ. Mich. Med. Bull., 21:153-55.
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With A. V. Hennessy and F. At. Davenport. Studies of antibodies
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Edith D. Bodian, C. Larson, et al. Interim report, Public Health
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With K. W. Cochran. Antiviral action of helenine on experimental
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With I. F. Enders, I. A. Bell, I. H. Dingle, et al. Adenoviruses:
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With J. Napier and F. NI. Hemphill. Poliomyelitisschutzimpfung.
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Epidemiology and the future of medicine. University of Tennessee
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With L. Blair, M. Jacobs, et al. The role of the physical therapist
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With F. M. Davenport and A. V. Hennessy. Influence of primary
antigenic experience upon the development of a broad immunity
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1958
A New Year's fantasy. Univ. Mich. Med. Bull., 24:1.
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With F. H. Epstein, W. D. Block, and E. A. Hand. Familial hyper-
cholesterolemia, xanthomatosis and coronary heart disease.
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Influenza in perspective. Am. Rev. Resp. Diseases, 83:98.
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With G. C. Brown. Incidence of heterologous antibodies in virus-
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With B. I. Ned, W. W. Ackermann, and F. H. Epstein. Inhibition
of vaccinial hemagglutinins by sera of patients with coronary
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With E. Minuse, P. W. Willis III, and F. M. Davenport. An at-
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With B. I. Neff, G. L. Brady, and F. H. Epstein. Serologic and
pathologic changes in rats on atherogenic diets. Journal of
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1963
Epidemic influenza. Am. Rev. Resp. Diseases, 88:148.
1964
With A. V. Hennessy, F. M. Davenport, R. J. Horton, and J. A.
Napier. Asian influenza: occurrence and recurrence, a com-
munity and family study. Military Medicine, 129:38.
With F. M. Davenport, A. V. Hennessy, l. Drescher, and J. Mulder.
Further observations on the relevance of serologic recapitula-
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With H. F. Maassab. Influenza virus. In: Viral and Rickettsial
Infections of Man, 4th ea., ed. by F. L. Horsfall and I. Tamm,
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by M. Pollard. New York, Hoeber Medical Division, Harper &
Rowe, Publishers.
With F. H. Epstein, N. S. Hayner, et al. Prevalence of chronic
diseases and distribution of selected physiologic variables in a
total community, Tecumseh, Michigan.
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With F. H. Epstein, L. D. Ostrander, Jr., B. C. Johnson, M. W.
Payne, N. S. Hayner, and I. B. Keller. Epidemiological studies
of cardiovascular disease in a total community. Ann. Internal
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Standards for research in new drug testing. In: Proceedings of the
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\Vith G. C. Brown, H. F. Maassab, and I. A. Veronelli. Detection
of rubella antibodies in human serum by the indirect fluorescent
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With L. D. Ostrander, N. S. Hayner, et al. The relationship of
cardiovascular disease to hyperglycemia. Ann. Internal Med.,
62:1 188.
Standards required in vaccine field trials. In: Proceedings of the
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Off.
With N. S. Hayner, M. O. Kjelsberg, and F. H. Epstein. Carbo-
hydrate tolerance and diabetes in a total community, Tecumseh,
Michigan. Diabetes, 14:413.
With N. S. Ling and T. Krasteff. Transcholesterin, a cholesterol-
binding globulin: serological demonstration of a specific inter-
action between cholesterol and serum globulin. Proceedings of
the National Academy of Sciences, 53:1061.
With E. Minuse, I. L. McQueen, and F. A. Davenport. Studies of
antibodies to 1956 and 1963 equine influenza viruses in horses
and man. l. Immunol., 94:563.
1966
The polyvalent vaccine: reasons for inclusion of earlier virus pro-
totypes and contemporary virus strains into current and future
vaccines. (Read before Division of Biologics Standards Con-
ference on Formulation of Influenza Virus Vaccines. National
Institutes of Health, October 1966.)
1967
With L. D. Ostrander, Jr., B. I. Ned, W. D. Block, et al. Hyper-
glycemia and hypertriglyceridemia among persons with coronary
heart disease. Ann. Internal Med., 67:34.
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Epidemic influenza: immunization and control. Med. Clin. N.
Am., 51:781.
Immunization of selected population groups against influenza.
Archives of Environmental Health, 14:747.
With T. O. Anderson, F. W. Denny, et al. Epidemiologic Studies
for Vaccine Development. U.S. Department of Commerce, PB 176
814, National Bureau of Standards Institute of Applied Tech-
nology.
1968
Transcholesterin titers and their biological significance in experi-
mental atherogenesis in rats. Proc. Soc. Exp. Biol. Med., 128: 197.
Experience with vaccines: general comments. In: Conference on
Cell Cultures for Virus Vaccine Production, Bethesda, Maryland,
November 1967. National Cancer Institute Monograph 29.
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Faktoren der Immunitat gegen respiratorische Infekte. Deutsche
MedizinischeWochenschrift, 94:355.
With F. M. Davenport, E. Minuse, and A. V. Hennessy. Interpreta-
tion of influenza antibody patterns of man. Bull. World Health
Organ., 41 :453.
zenith A. S. Monto, F. M. Davenport, and J. A. Napier. EFect of
vaccination of a school-age population upon the course of an
A2/Hong Kong influenza epidemic. Bull. World Health Organ.,
41:537.
With H. F. Maassab, F. M. Davenport, et al.
Laboratory and clin-
ical characteristics of attenuated strains of influenza virus. Bull.
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gress for Virology. Basel, Switzerland, S. Karger, A.G.
Representative terms from entire chapter:
thomas francis