History of Tuberculosis

Item

Title: History of Tuberculosis
extracted text: Tuberculosis: Pathogenesis, Protection, and Control
Edited by Batry R. Bloom
© 1994 American Society for Microbiology. Washington, DC 20005

Chapter 2

History of Tuberculosis
Thomas M. Daniel, Joseph H. Bates, and Katharine A. Downes

1958). Mycobacterium bovis was the most
likely infecting organism, and the first hu
man infections may have been with M.
bovis. Since M. tuberculosis infects all pri
mate species, it is also possible that this
species existed in subhuman primates be
fore it became established in humans. .
As centuries and millennia passed, hu
man beings began to live in larger and larger
communities, and with this shift came en
vironmental changes that were associated
with a change in the delicate balance be
tween humans and the tubercle bacillus.
Two alternative theories have been pro
posed to explain the epidemic spread and
subsequent decline of tuberculosis that fol
lowed. The first and widely accepted expla
nation involves the development of geneti
cally determined herd immunity (Stead,
1992). As a rule, parasites are short-lived
compared to their hosts, and this fact gives
parasites a great advantage, since muta
tions can occur in them more frequently
than in their hosts in response to environ
mental pressure. When the host generation
time is much longer than that of the para
site, as is true of humans and the tubercle
bacillus, the host cannot adapt as quickly as
the parasite. Thus, initially the parasite has
a distinct advantage and begins to eliminate
the susceptible members of the species be
fore these individuals can pass on their
genes to progeny. However, since not all

EARLY HISTORY OF TUBERCULOSIS
In the paleolithic period, people lived as
wanderers, did not settle in villages or
permanent locations, and did not congre
gate in large groups. While tuberculosis
may have occurred sporadically, it and
other infectious diseases probably did not
occur in epidemic form. Beginning in about
8000 B.C., humans developed primitive ag
ricultural techniques that allowed settle
ment in permanent sites, and with this
development came the domestication of
cattle, swine, and sheep. In all probability,
tuberculosis occurred more frequently in
this setting, but it nevertheless remained
rare (Clark, 1962). McGrath estimates that
a social network of 180 to 440 persons is
required to achieve the stable host-patho
gen relationship necessary for tuberculous
infection to become endemic in a commu
nity (McGrath, 1988).
Tuberculosis probably occurred as an
endemic disease among animals long before
it affected humans (Steele and Ranncy,
Thomas
M.
Daniel
and
Katharine
A.
Downes • Center for International Health, Case
Western Reserve University School of Medicine,
10900
Euclid
Avenue,
Cleveland,
Ohio
44106.
Joseph It.
Hates • Department of
Medicine, University of Arkansas for Medical
Sciences, John L. McClellan Memorial Veterans’
Hospital, 4300 West 7th Street, Little Rock,
Arkansas 72205.

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TT

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Daniel et al.

STEuropeth;necessaiyenv—■

changes occurred to set off an epidemic that
population that is characterized by in
creased resistance to that particular para came to be called “The Great White
site (Hamilton et al., 1990). Thus, over Plague” (Dubos and Dubos, 1952; Castiglitime, the highly advantageous position en oni, 1933; Webb, 1936; Cummins, 1949). In
joyed by the parasite diminishes, and after the early 1600s, the incidence of tuberculo
successive generations, the once serious sis in England began to increase sharply.
life-threatening infection becomes less dev The epidemic grew over the next two cen
astating. Probably for this reason, no infec turies and spread through Western Europe.
tious disease has ever killed all of its host During this phase of the epidemic, almost
population. Many other factors, such as all Western Europeans became infected
nutrition and overcrowding, contribute to with M. tuberculosis, and about one in four
the incidence of disease in a population, but deaths were due to tuberculosis. In the
genetic factors arc of‘ unquestioned irnpor- ever'cn,arg|»g cities, the increased popula~ from infec
tIGn density provided the necessary envi
tance in the selective mortality
tion.
ronmental conditions for person-to-person
Tuberculosis probably occurred as a spo spread of this airborne pathogen. Such con
radic and unimportant disease of humans in ditions had never been met previously.
their early history. Epidemic spread began
European migrants brought the tubercle ’
* slowly with increasing population density. bacillus with them to North America (Dia
This spread and the selective pressure it mond, 1992).
—Boston,
vwx., xviaaMasFor example, in
has exerted have occurred at different times sachusetts, the mortality rate from tubercuaround the globe. The epidemic slowly losis was as high as 650/100,000 in ISOO^and
spread worldwjde as a result jjf infected it decreased to about 400/100,000 by I860
Europeans traveling to and colonizing dis (Grigg, 1958). In like manner, the tubercu
tant sites (Diamond, 1992). In the 1700s losis death rate in New York was 750 in
and early 1800s, tuberculosis prevalence 1805 and decreased to 400 by 1870. In
peaked in Western Europe and the United Baltimore, it was as high as 400 in 1830
States and was iundoubtedly
’ '
the largest and decreased to 210 by 1900. In the cities
cause of death (reviewed by Bloom
along the northeastern seaboard, each
M
-----Murray,
1992, and’ Graunt,
1662)7and 100
succeeding generation experienced a de
to 200 years later, it had spread in full force creased death rate. By 1904 the tuberculo
to Eastern Europe, Asia., Africa, and South sis death rate in the United States was 188America. Within1 a particular population in it fell to 4/100,000 by 1969. As Western
a defined geographic area, Ithe
’ tuberculosis Europeans moved about the globe, the epepidemic reached its peak wnhi?^“to^
Vears after
’demic of tuberculosis followed them. It
y s alter its beginning and then slowly moved slowly to Eastern Europe As late as
dee med possibly as the more resistam the 1880s, tuberculosis was not common v
host survtvors reproduced.
seen in Russia, and it was relaXelyZom

Tuberculosis Epidemics in Europe and
North America
It is important to recognize that tubercu
losis remained an unimportant disease for
humans regardless of its virulence until in

mon in India at the same time. Cummins
reports (hat tuberculosis was almost un
known within the interior of sub-Saharan
Africa as late as 1908 (Cummins, 1920). It
was essentially unknown in the interior of
New Guinea as late as 1920, when that area
was first explored by Europeans (Brown et
al., 1981).

G

a

o

Chapter 2

vironmental
3idcmic that
reat White
52; Castigliis, 1949). In
f tuberculose sharply,
xt two cen:rn Europe,
nic, almost
le infected
one in four
sis. In the
;ed populassary envii-to-person
. Such condously.
le tubercle
erica (Diaston, Mas
ai tubercu11800, and
10 by 1860
e tubercuvas 750 in
1870. In
)0 in 1830
i the cities
ird, each
eed a detuberculos was 188;
; Western
■e, the ep
them. It
As late as
■ommonly
ly uncomCummins
most un>-Saharan
1920). It
nterior of
that area
Brown ct

Tuberculosis among Indigenous Peoples of
the Western Hemisphere

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History of Tuberculosis

15

chronic pulmonary conditions that were
probably tuberculous in nature. It was only
after the North American Indians were
Although tuberculosis was present in the forced to settle on reservations or to live in
Western Hemisphere in paleolithic times. barracks and prison camps that outbreaks
Native Americans of North America and of tuberculosis were observed. In these
South America had little trouble with tuber settings, contact with white settlers became
culosis prior to the European migration. In frequent, and the crowding promoted air
the immediately pre-Columbian era, about borne transmission of the bacillus. In 1887
60 million persons lived in South and North at the Mount Vernon Barracks, several
Americas, with the great majority living in hundred Apache prisoners were kept in
South America. There were few, if any, close confinement, and the death rate the
large population centers. Buikstra and first year was 54/1,000, rising to 143/1,000 in
Cook reported a review of 14 prehistoric the fourth year. Nearly half of these deaths
human skeletons from eight population cen were due to tuberculosis (Bushnell, 1930).
ters in Illinois dating between 100 B.C. and By 1886, the tuberculosis death rate for
1300 A.D. (Buikstra and Cook, 1981). Some North American Indians reached 9,000/
of these skeletons showed deformities com 100,000 (Ferguson, 1955). These death
patible with tuberculosis, but the lesions rates are the highest ever recorded world
were not diagnostic of tuberculosis. Perzi- wide and exceed by 10 times the peak death
gian and Widmer (1979) described osseous rate observed in Europe in the 17th century.
changes typical of tuberculosis in the ver
tebral skeletal remains of 6 of 290 persons
Tuberculosis in Africa
from an Ohio community dated to 1275 A.D.
Acid-fast bacilli were observed in the
Tuberculosis of the spine is depicted in
lungs of a mummy from southern Peru several figurines dating from the predynasdated from about 700 A.D., and subsequent tic era (prior to 3000 B.C.) of Nilotic North
additional cases of tuberculosis have been Africa (Morse et al., 1964). Some of these
observed in South American mummies (Al figurines appear to have originated from
lison et al., 1973). Deformities suggesting nomadic desert-living tribes. Additional
Pott’s disease among skeletons dating back similar figures and paintings clearly depictto 160 B.C. have been found in Peru. In his ing angular spinal deformities characteristic
review of prehistoric skeletal deformities in of tuberculous spondylitis occur through
Latin America, Ponce describes large num out Egyptian dynastic times. Mummies
bers of prehistoric figures and drawings from several Egyptian sites show skeletal
depicting Pott’s disease (Ponce Sangines, changes typical of tuberculosis (Morse et
1969). Endemic tuberculosis in the pre- al., 1964), and psoas abscesses and fibrotic
Columbian South American setting would pulmonary disease have been observed,
be compatible with the fairly complex soci further supporting the impression that the
ety, densely sited housing, and established skeletal changes were tuberculous in origin.
agriculture that existed among the inhabit Among 10 early dynastic Nubian skeletons,
ants of Peru as long as 6,000 years ago.
spinal disease typical of tuberculosis was
Despite this archaeologic evidence, tu found in 4. These four skeletons came from
berculosis was a rare disease among native two graves, suggesting the familial occur
North American Indians even early into the rence of tuberculosis.
19th century. Priests who explored the
Despite the fact that tuberculosis was
Great Lakes region during this time re spreading rapidly in Europe, Nilotic North
ported rare cases of glandular infection and Africa, and the Americas, it remained es-

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Daniel et al.

sentiaiiy unknown in sub-Saharan Africa as
late as the beginning of the 20th century. A
number of medical observers reported the
complete absence of tuberculosis in the
interior of sub-Saharan Africa. Army med
ical officers from Great Britain noted that
tuberculosis was unknown in those parts of
Africa where European immigration had
not occurred (Cummins, 1920). Livingstone
(185 7) found no tuberculosis in parts of
South Africa, and Lichenstein found none
as fate as the first half of the 20th centurv
(Lichenstein, 1928).
I’uberculosis in Asia and the Pacific Islands

lupus vulgaris, and that of the spine wa.‘
termed Pott s disease. The vertebral fusion
and deformity of the spine that characterize
Pott’s disease have enabled historians to
establish the existence of tuberculosis in
mummies dating from 2000 to 4000 B.C.
As Europe emerged from the Dark Ages,
there was a renaissance not only of the arts
but also of medical science. Observant sci
entists described their world and explored
its nature and mechanisms. This European
intellectual renaissance began in an era of
extraordinarily high tuberculosis preva
lence fueled by the industrial revolution
and the grinding poverty it engendered in
its huddled masses. Hence, it is not surpris
ing that many fundamental concepts of bi
ology emerged in the context of inquiry
about the nature of tuberculosis. Weaving
together stories of individuals whose lives
were dramatically affected by tuberculosis
with accounts of pioneering exploration of
the pathogenesis of this disease, we will
attempt to create a tapestry depicting the
genesis of four areas of knowledge about
tubercu'osis and the human and social con
texts in which the knowledge was acquired.

The Hawaiian Islands had little or no
tuberculosis as late as the 1850s. Wilkinson
remarked upon the rarity of tuberculosis in
India in the first half of the 19th century and
its progressive increase in the middle years
of the 19th century as industrialization in
creased population density (Wilkinson,
1914). Toward the end of the 19th ccv^ry,
India and China experienced peaks in the
incidence of tuberculosis, but as late as
1951, tuberculosis was still unknown
among the island populations cf New
Guinea (Brown et al., 1981). Finally, when
the disease did reach these latter popula
Infectious Etiology of Tuberculosis
tions, it produced the typhoidal illness sc
Tuberculosis (consumption) was com
characteristic of highly susceptible individ
uals having their first experience with tu mon in European cities during the first half
of the 19th century, and one-fifth to oneberculosis.
quarter of all deaths were due to this dis
ease (Waksman, 1964). No one knew what
TUBERCULOSIS AND THE DAWNING
caused tuberculosis. Some doubted that it
OF BIOMEDICAL SCIENCE
was a single disease, so varied were its
manifestations. That it might be contagious
From the time of Hippocrates, tubercuwas a notion that occurred to only a few.
•osis was known as “phthisis,” a term
4 hus, Frederick Chopin was not expecting
derived from the Greek for “wasting
hostility from the inhabitants of Majorca,
away.” The swollen glands of the neck
where he had gone in 1839 to seek relief
were known as “scrofula,” and because
from his symptoms. However, his doctors
newly crowned kings of England and
alerted the residents of the island that the
France were believed to have special heal
famous composer and musician was con
ing powers, the most desired treatment of
sumptive,
public clamor ensued, and his
this “King’s Evil” 'was being touched by landlord turned
him out (Dubos and Dubos,
kings. I uberculosis of the skin was termed
1952; Waksman, 1964).

it of the spine was
rhe vertebral fusion
ne that characterize
abled historians to
of tuberculosis in
000 to 4000 B.C.
rom the Dark Ages,
not only of the arts
ice. Observant scivorld and explored
ms. This European
began in an era of
iberculosis prevadustrial revolution
y it engendered in
-e, it is not surpristal concepts of bi-ontext of inquiry
rculosis. Weaving
duals whose lives
-d by tuberculosis
ing exploration of
disease, we will
stry depicting the
knowledge about
;
in and social conJge was acquired.
Tuberculosis

>tion) was com•ring the first half
one-fifth to one: due to this dis) one knew what
i doubted that it
varied were its
ht be contagious
d to only a few.
as not expecting
nts of Majorca,
:9 to seek relief
ver, his doctors
‘ island that the
sician was connsued, and his
bos and Du bos.

Chapter 2

History of Tuberculosis

17

Frederick Chopin had been a sickly
Nature”
youth. He first developed clinical tubercu thaTc^t' ' ' inin,icab,e to
that
can
be
transmitted
by
“
a
Breath
fa
losis at age 16. Dubos and Dubos fl952)
consumptive]
emits
from
his
Lungs
quote Georges Sand, who accompanied
that may be caught by a sound plrson”
Chopin to Majorca. She recounted that the
( oetsch, 1978; Castiglioni, 1933). More
landlord who expelled them sought dam
than
a century after Laennec’s birth
ages for replastering the house they had
Vdlemm
performed experiments on raboccupied because it was contaminated
Their departure arrangements were compli
injecting infectious sputum and case
cated by the refusal of carriage drivers to ous materia! into healthy animals to pro
transport them and their goods. Thev 1868 'deaSe' TheSe StUdies’ Published in
the firs'; co''
y Maj°r (1945)’ Provided
crossed the .sland with wheelbarrows
They sailed to Barcelona with a shipload of the first convtncmg evidence of the infecous nature of tuberculosis. Gradually, the
pigs, and the inn keeper in Barcelona
charged them for Chopin’s bed, which the infectious nature of tuberculosis became
local authorities required be burned
ItaTv Tn'd
reCO«nized' 4s early as 1699,
aly and later Spam enacted restnctivB
Chopin died of tuberculosis a decade later
quarantine laws, while in Northern Europe
in 1849. He was 39 years old.
A scant 20 years prior to Chopin’s ejec tuberculosis was not widely viewed as a
tion from Majorca, Theophile Laennec public health problem
of a century
published his classic text on diseases of the af°n^arCh,24:
after
Chopin
s
death,TRobert
Koch
made a
chest (Laennec, 1962). While Laennec is
best known to students of medicine for his presentafon to the Berlin Physiological Sodescription of alcoholic cirrhosis of the ciety that changed thinking about fubercu
osis and infectious diseals forever and
ver, his principal interest throughout his
nec with ‘Ub"rculosis- MajOf cred® s Laen'- that can be thought of as establishing the
in al7of ir, J reCOgn,zin8 that tuberculosis, mb ? °>, m,crobi°iogy- He described the
of its forms and anatomic sites is a tubercle bacillus, M. tuberculosis, an orsingle disease (Major, 1945). This view was efflurand kn°Wn tO many aS Koch’s ba
not espoused by most of the pathologists of be h/
co™nc‘ngiy demonstrated it to
s^“ni82S6ew kae"neC d'ed °f ,ubcrculo- Sakufa Ci98S2e c tUberCulosis (Koch, 1932;
was ?hi f Waksman P°in« out that this saxula, 1982, Grange and Bishop, 1982) To
on i s
Te year “ whicb Cboptn devel- cary out his pioneering studies, Koch deejeped staining techniques and was the
11 7670 Ji’erculosis (Waksman, 1964).
hrs
to employ culture or soiid media This
In 1679, Franciscus Sylvius described the
characteristic lung nodules as “tubercula” landmark technical advance allowed the
a fun tUr'nS °,{ lnd,vidual colonies, clearly
tmn to cavities, but virtually all of the great biIfolanHn'a teChniCal advance in micro
Heved the t’,n
8 Rudolf Virchow, be- stanis^’hH1rf-Cnterla f°r pr0of that the or
forJ J , d'SeaSC to be constitutional, a ganism he discovered caused tuberculosis
have been widely adopted and have be
come known as Koch’s postulates He
phthisis m a work on contagion in ISAfi" but ihe b'acfili
“uT necessaly to isolate
the
bac
Ih
from
the body; to grow them in
culosis m^'h6 1Understandin8 that tubergan°sms w
'° ''nfeCtious lnicroor- Holated b '"n ’ and’ by adrainistering the
an,mals> to reproduce the
MarteTon 7
'n 1722 by Bcaiamin same d e.', '
cause of tu^ ?n’'VhO PrOp°Sed that tbe same morbid condition ...” (Koch 19371
of tuberculosis was “animaliculae or cukuTfil^in
culture filtrates cured the disease, a claim

18

Daniel el al.

that was immediately controversial and
promptly discredited. Sadly, Koch refused
to divulge the nature and preparation of the
curative material, an action for v/hich he
was accused of trying to give his govern
ment a monopoly and himself an institute
(Bloom and Murray, 1992). Nevertheless,
th )se filtrates, later partially purified, be
came the principal means of establishing
the presence of infection in an individual,
i.e., the tuberculin skin. test.
Koch’s initial presentation, made to the
physiologists because Virchow refused to
allow him to address the pathologists in
Berlin, was received with gieat excite
ment, and. his observations were rapidiy
confirmed by others. Among those who
heard him was Paul Ehrlich, who has
tened to develop improved staining tech
niques; Ziehi and Neelson quickly made
further refinements, upon which diagnos
tic sputum smears are still based today.
Subsequently, Ehrlich stained acid-fast
bacilli in his own sputum to establish his
personal diagnosis of tuberculosis. Ed
ward Livingston Trudeau, whose own
youthful, nearly fatal bout with tubercu
losis led him to devote his life to the study
and treatment of this disease, learned of
Koch’s work. He established his labora
tory at Saranac Lake, New York, and
repeated and extended Koch’s observa
tions. Fundamental work on tuberculosis
continued at that laboratory for decades,
and when Trudeau's cottage sanatorium
finally closed, its endowment was used to
establish the Trudeau Institute, where re
search on the immunology of tuberculosis
continues to this day.
With the infectious nature of tuberculosis
firmly established and the tubercle bacillus
a pathogen that could be identified in labo
ratories, public health officials urged ac
tions to interdict its spread: the beginning
of the public health movement in the
United States. Coughing and spitting in
public were the subject of regulations and
became socially unacceptable. In hospitals.

the burning of Chopin’s bed linen was re
peated again and again as concern over
fomites grew. In the 1930s, William Wells
injected both common sense and reason
into controlling the transmission of infec
tious particles when he pointed out that the
tubercle bacillus is an airborne, inhaled
pathogen. He emphasized the role of infec
tious droplet nuclei and undertook studies
of their aerial spread. This work culminated
in the classic study by Riley, a pupil of
Wells (Riley et al., 1962). In this study, air
from a tuberculosis ward was delivered
untreated to an animal exposure chamber
and, after UV irradiation, to a control
chamber. Each chamber housed 120 guinea
pigs. No infections occurred in guinea pigs
receiving irradiated air, while 63 animals .
receiving untreated air became infected.
Thus, the aerial spread of tuberculosis was
firmly established. By matching microbial
drug susceptibility patterns, one patient
with tuberculosis laryngitis was identified
as particularly' infectious. Modern parallels
are presented by microepidemics in poorly
ventilated areas, of which few are more
dramatic than the one described by Catan
zaro just 100years after Koch’s demonstra
tion of the tubercle bacillus (Catanzaro,
1932). Ajriong hospital personnel caring for
a patient with unrecognized infectious tu
berculosis in an intensive care unit, primary
infections occurred in 31% of susceptible
exposed individuals, with the attack rate
reaching 77% in persons attending a bron
choscopy. The patient was estimated to be
generating 249 infectious units per h, and
the ventilation in the patient area provided
only 1.2 air turnovers per h.
Resistance to Tuberculosis

The romantic age of the 19th century
glamorized the sallow, wan physical ap
pearance typical of patients with tuberculo
sis. Thus, when Daniel Chester French
began his work on the statue of John Har
vard that remains a notable feature of the

I

en was reicern over
!iam Wells
nd reason
i of infecut that the
3, inhaled
e of infec3k studies
ulminated
i pupil of
study, air
delivered
chamber
a control
20 guinea
linea pigs
5 animals
infected,
losis was
microbial
3 patient
identified
parallels
in poorly
ire more
y Catanmonstratanzaro,
aring for
tious tuprimary
iceptible
ick rate
a broned to be
■ h, and
•rovided

L ; ■

) .
: I

<

f

century
cal ap>erculoFrench
in Harof the

Chapter 2

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History of Tuberculosis

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Harvard Yard, he seized upon the fact that lar disease probably unrelated to his tuber
John Harvard was known to have had tu culosis.
berculosis to model a face “delicatePerhaps the most illustrative example of
' ... and sensitive in expression” (Rich familial tendency toward tuberculosis is the
man, 1977). But this romantic view of Bronte family. This literary British family
tuberculosis belies the facts. The variable shared a passion for learning and writing
course of tuberculosis makes it evident to and a strong predisposition for acquiring
all observers that some individuals are tuberculosis. The Reverend Bronte and his
much more susceptible to the ravages of wife Maria had six children in less than 7
this disease than others. Some tuberculous years: Maria (1813), Elizabeth (1815), Char
patients are hardy and robust while still lotte (1816), Patrick Branwell (1817), Emily
diseased; others suffer more.
(1818), and Anne (1820) (Chadwick, 1914).
John Keats was a remarkable poet who All six children died of tuberculosis before
died of tuberculosis in 1821 at the age of 26. they reached their 40th birthdays.
He met tuberculosis in his family at an early
Less than a year after the birth of Anne,
age; his mother died of this disease when he Mrs. Bronte died at age 39 in 1821. It is
was 14, and his brother later developed unclear whether she died from cancer, a
tuberculosis. Keats studied medicine and postpartum complication, or septicemia.
was torn between it and poetry, for which Three years later, in July 1824, Reverend
he was acclaimed in his lifetime. In the Bronte found himself unable to care for his
summer of 1820 he developed hemoptysis, young daughters, and he sent the four el
which he recognized as his death warrant, dest to a boarding school for the daughters
and from that point his course was steadily of clergy at Cowan Bridge. The harsh regi
downhill. His short life ended in Italy in men, poor diet, and walks in the freezing
February 1821. During his final weeks, his rain did not agree with the young girls’
treatment included phlebotomies, the same “delicate constitutions.” In April of 1825,
ineffective therapy used for Laennec. Al the eldest daughter, Maria, developed the
though Keats succumbed rather rapidly to symptoms of tuberculosis and was sent
what must have been fulminant disease, it home, only to die in May at the age of 12.
is incorrect to think of him as weak or Elizabeth followed, returning home in May
asthenic. As a youth he was robust and to die of the same disease in less than a
athletic. He enjoying wrestling, mountain month at the age of 11.
climbing, and long walking trips over rough
The Bronte family then enjoyed a 23-year
terrain.
hiatus from tuberculosis, during which each
Robert Louis Stevenson’s life and death of the children wrote pieces that became
contrast with those of Keats. Also a writer cornerstones of British literature. In 1848,
acclaimed in his time, Stevenson traveled however, the opium-addicted poet Bran
across the world seeking a benevolent cli well Bronte died from tuberculosis at the
mate where he would find relief from his age of 31 (Fraser, 1988). According to
tuberculosis. He wrote The Master of Bal- Fraser, he might have contracted tubercu
laritrae and other stories published as the losis in the village, “where it was endemic,
Scribner series while a patient at Trudeau’s which would explain the speed with which
cottage sanatorium in Saranac Lake. His it killed Emily and Anne” (Fraser, 1988).
Saranac Lake home is open today as a Other possible sources “were cither Emily
museum. Chronically but never acutely ill, or Charlotte herself, who was carrying a
debilitated by disease of relatively stability, form of chronic fibrotic tuberculosis which
he continued writing and traveling, finally periodically flared up, or Mr. Bronte, who
dying in the South Pacific in 1894 of vascu is believed to have suffered from chronic

Daniel et al.

tubercular bronchitis” (Fraser, 1988). At
b’ts for his studies, feeling it to be the
her brother’s funeral, Ernily Brome, author
animal model that best approximated the
of Wuther'ng Heights, caught a cold that
pathogenesis of human tuberculosis. He
was said to have weakened her in her undertook studies with inbred families of
bereaved state, and in December 1848 she
rabbits, developing strains that “exhibit
succumbed to “galloping consumption” at varying characteristic inherited resistance
the age o ' 30. After iosing her only brother
to tuberculosis, generation after inbred gen
'■md older sister in less than 3 months, Anne
eration” (Lurie, 1964). This work set the
Bronte sadly soon followed, dying in May
stage for the widespread use of inbred lab
of 1849 at the age o: 29, leaving behind her
oratory animals to elucidate genetic aspects
novel Agnes Grey. Only Charlotte Bronte
of many diseases. Studies in twins have
remained Six years later, on July 29, 1854, shown that Lurie’s concepts are applicable
she married for the first time ai the age of
to humans (Comstock, 1978), an observa
38. Her marriage lasted less than a year.
tion not surprising to clinicians and other
While walking on the moors with her hus
observers of oeople, who have long recog
band, she caught a cold that developed into
nized the occurrence of tuberculosis in fam
full tuberculosis, and she died on March 31, ilies.
1855, at the age of 39. The Reverend Bronte
outlived his entire family, dying in 1861 at
the age of 85.
immunology of Tuberculosis
Max Lurie emigrated from Lithuania to
Samuel Johnson suffered from scrofula
the United States in 1908 at the age of 15.
the King’s Evil. In 1712 he was touched by
He entered medical school at Corneil Uni
Queen Aame, whose ancestors, beginning
versity and graduated in 1921, but he did
with King Clovis of France in the fifth
not practice medicine, for he developed
century, claimed the divine power to heal
tuberculosis, making his own diagnosis. Al
this affliction. Knowing that tuberculosis
though medical students were at increased
adenitis usually represents primary infecexposure r;sk of tuberculosis in tnat time,
tion, that its course is often benign, and that
J-urie felt that he was disposed to this
Lurie
primary infection confers immunity against
disease by his family history. His mother
reinfection, it is easy to understand how
had tuberculosis; her father and grandroyal claims of a cure might have gained
mother had died of it.
widespread acceptance.
Beginning his studies while- a patient at
'n 1891, Robert Koch, already famous
the National Jewish Hospital in Denver and
for his discoxTiy of the tubercle bacillus,
continuing ai the Phipps Institute of the
described experiments with guinea pigs that
r University of Pennsylvania, Lurie dedi
extended his earlier observations and
cated his life to studies of the experimental
clearly demonstrated acquired immunity
pathology of tuberculosis. He recognized
following primary infection, and the term
the central role of monocytes and their
“Koch phenomenon” has been applied to
tissue forms (macrophages; in host resis
the results he described (Bothamley and
tance. He understood clearly the differ Grange. 1991). Koch noted that healthy
ences between host responses to initial and
guinea pigs inoculated cutaneously with tu
subsequent infections with mycobacteria.
bercle bacilli healed the primary inocula
He became intrigued with the factors that
tion lesion, only to die later of disseminated
made some individuals and some kindreds
infection. However, a second inoculation
susceptible and others resistant to the rav
of virulent organisms produced a very dif
ages of this infection.
ferent result. The wound became indurated
Lurie chose bovine tuberculosis in rab- in 1 or 2 days and then ulcerated; dissemi-

Chapter 2

to be the
mated the
ilosis. He
amilies of
“exhibit
resistance
•bred genk set the
ibred labc aspects
ins have
pplicable
observand other
ig re cogis in fam-

S

;crofula,
ched by
^ginning
he fifth
to heal
rculosis
/ infecind that
against
id how
gained
famous
acillus,
igs that
s and
munity
e term
lied to
y and
ealthy
ith tuoculainated
dation
y diftrated
•semi

•

History of Tuberculosis

21

nation did not result. When tubercle bacilli note (Chase, 1985, 1988). Chase was en
killed by boiling were used for the initial gaged in the study of contact dermatitis in
inoculation, the same result followed. Koch the laboratory of Karl Landsteiner. Land
noted that a sterile culture filtrate of bacilli, steiner was convinced that cell-fixed anti
which he named tuberculin, evoked the bodies were responsible for this and other
cutaneous induration as well as whole or forms of delayed hypersensitivity. In 1941
ganisms did, and he attributed the hyper and 1942, partly by accident. Chase found
sensitivity thus demonstrated to something that dermal-contact hypersensitivity could
in this filtrate. Indeed, he proposed treating be transferred by cell suspensions. Two
•
tuberculous patients with tuberculin, a mea years later, the observation was extended
sure that failed to have therapeutic benefit.
to tuberculin reactivity induced with myco
The warp thread of acquired immunity bacteria. The science of cellular immunol
was deftly woven into the fabric of the ogy was born, rising from these experi
‘ ' ’ 1 ' ’ history of tuberculosis by Albert Calmette ments with guinea pigs infected with
r-’
and Camille Guerin (Sgkula, 1983). Cal tubercle bacilli.
mette, a French physician with extensive
experience in infectious and tropical dis
Treatment of Tuberculosis
eases, was appointed to the directorship of
the newly founded Pasteur Institute of Lille
Alice Marble was born on September 28, •
■ -*
( t ..... in 1895. He was joined there by Guerin, his 1913, in a settlement named Dutch Flat in
assistant and a veterinarian, in 1897. They Plumas County, California, the daughter of
. i ■ • ’ • knew of Koch’s experiments, of early work a lumberman and a nurse (Davidson and
done by von Pirquet and others on tuber Jones, 1971). By her early teenage years,
culin hypersensitivity, and of the apparent her athletic prowess was manifest, and she
.
1 •success of Pasteur in vaccinating against enjoyed the privilege of participating in
1 rabies. With great hope, they began in 1908 pregame warm-ups of the San Francisco
to attenuate a strain of M. bovis by serial Seals, a minor league baseball team. Her
passage. By 1919 they had completed 230. oldest brother, Dan, concerned about his
passages, and their vaccine strain was 15-year-old tomboy sister, returned home
found to be avirulent in guinea pigs, rab- one evening with a gift for Alice—a tennis
i
bits, cattle, and horses. It was first.givento racquet. He hoped that she would apply
a human in 1921. Without detailing the long herself to a more ladylike sport than base
history of conflicting results from clinical ball.
trials, the efficacy of bacille CalmctteEight months later, Alice Marble won her
.. >
Guerin (BCG) remains unknown today. first tournament, and in 1931 she traveled to
: '■ ■ :■ ' However, it is currently in widespread use the East Coast to participate in the national
'• ■ •
throughout the world.
tennis championships. In less than a year,
' Today, the immunology of tuberculosis is . she was ranked seventh in the national
' • well known. While many important ques senior rankings. A new coach, Eleanor
tions are yet to be answered, it is clear that “leach” Pennant, helped her become ac
T lymphocytes responding to protein anti customed to the grass courts of the east,
gens of mycobacteria and lymphokines, and in 1933 she traveled to Great Britain to
prominently including interleukins 1 and 2, represent the United States in the Wight
gamma interferon, and tumor necrosis fac man Cup. Her skills improved, and her
tor alpha, arc major mediators of protective game, marked by a masculine and powerful
immune responses in tuberculosis. Among style exhibited in volleys and serves,
the contributions of many, the seminal ob seemed near perfection. Then tragedy
servations of Merrill Chase deserve special struck. In 1934, Alice Marble collapsed

22

Daniel et al.

during competition on the tennis court in
tatively severe, it may heal spontaneously”
Stade Roland Garros in Paris. She awoke in
;Pottenger, 1948).
a hospital to a diagnosis of tuberculosis and
The grim prognosis of tuberculosis
the disheartening medical opinion that her
changed dramatically in November 1944,
tennis career was over (Marble and I cather- when a 21-year-old woman with progres
man, 1991).
sive, far-advanced pulmonary tuberculosis
Alice Marble left Paris by wheelchair and
wno had failed to respond to both rest and
sailed on the S.S. Aquitania to Nev/ York
thoracoplasty received the first injection of
where she was greeted by a physician’s
streptomycin, isolated only 11 months pre
assessment that she “would never plav
vious^ by Selman Waksman (Pfuetze et
(emus again.” She returned io her hoTe in
al. , 19',5). She improved during the ensuing
California and then entered Pottenger’s
Sanitarium in Monrovia, California. Dr. - months and was discharged from the
hospital in 1947. She was evaluated in 1954
Pottenger examined her weekly with the
and found to be well and the happy mother
conclusion that she was “doing nicely”
cl three children.
(.Marble and Leatherman, 1991). After c
Equally or more dramatic were the re
weeks, Pottenger declared that she need to
suits ol the first use of isoniazid reported by
stay tor at least another 6 weeks and for
Robnzek and Selikoff in 1952 (Robitzek and
bade any physical activity. Just before her
bc. ikoff, 1952). Of 44 febrile patients, the
21st birthday, she received a 'etter from
temperatures of 42 “subsided promptly and
actress Carol Lombard, urging her to fight
sometimes precipitously.” Weight gams in
I
the medical odds to recover from her distne treated patients were “most spectacu
|
ease.
lar,
with the average weight gain 19.7 lb (1
After ,? months of hospitalization and
lb
453.6 g). Appetites of treated patients
with the covert aid of her tennis coach
Mice Marble fled the sanatorium and re were described as “ravenous,” and a 50%
fused to return. She initiated a gradual mcrease in food consumption on the treat
ment ward was noted. Clearing of tubercle
exercise program and within less than a bacilh from the sputum was noted in most
year had returned to the tennis circuit. She
but not all patients, and radiographic clear
won the U.S. women’s singles tennis cham
ing was observed in half. Side effects were •
pionship in each of the three ensuing years.
mimmai. With these dramatic therapeutic
Stic died in 1990 at the age of 77 withoutresults, the era of successful chemotherapy
having suffered subsequent relapses of tu
lor tuberculosis was launched. The con
berculosis.
quest of tuberculosis seemed imminent.
While rest resulted in the cure of some

patients with tuberculosis, not all of those
afflicted were so lucky. In the prechemo
EBB AND FLOW: THE FAILED
therapy era, the ultimate mortality or pa
CONQUEST
tients admitted to New York State sanatona with tuberculosis in 1938 through 1948
That tuberculosis was disappearing from
was 69% for those with far-advanced dis
tile
United States was recognized by Wade
ease, 23% lor those with moderately ad
Hampton Frost in a landmark paper pub
vanced disease, 9nd 13% for those with
lished posthumously in 1939 (Frost, 1939).
minimal disease (Alling and Bosworth
He used Massachusetts public health data
1960). Pottenger, who treated Alice Mar
ble, notes in his text published in 1948 that irom several preceding decades to project
epidermoiogic trends and to explain chang
tuoerculosis shows great tendency to heal
and, even though quantitatively and quali- ing age-specific tuberculin reactor rates.
C Icarly, tuberculosis had been on the wane

Chapter 2

itaneously”

uberculosis
mber 1944,
th progresuberculosis
'th rest and
injection of
lonths prePfuctze ct
he ensuing
from the
ted in 1954
>py mother
ire the re
eported by
bitzek and
tients, the
•mptly and
it gains in
spectacui 19.7 lb (I
d patients
ind a 50%
the treatf tubercle
d in most
hie clearects were
erapeutic
lotherapy
The con- •
inent. ,,,

.y ■
i-

I . .;

j:d
ing from
yy Wade
per pubt, 1939).
ilth data
• project
1 changr rates,
he wane
t

•

i

•

History of Tuberculosis

23

long before effective therapy was intro prospects for cure or progressive disease
duced. National individual tuberculosis that Alice Marble did, and cur country
case reporting was introduced in the Uniteo lacks facilities to provide for their chronic
States in 1953, and annual data thereafter care and for protection of others fo;m air
documented a steady decline in tuberculo borne spread of their virulent bacilli.
sis incidence. Beginning in 1985, that trend Clearly, there is a need for majcr strides
changed, and on Sunday, July 15, 1990, the forward both in tuberculos’s cont/el and in
headline of the lead story on the front page tuberculosis research.
of the New York Times read, “Tuberculo
sis germ resurges as peril to public health;
REFERENT f S
,
Highest threat in cities; Re-emergence
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histoiy of pulmonary tuberculosis. VI. T-e first
tuberculosis case rates since 1985 mean
fifteen years following diagnose. Am. Rev. R>.:pir
Dis. 81:839-849.
that more than 40,000 cases have occurred
Allison,
M. R., O. Mendoza, and A. Ferzia. 1973.
that would not have happened had histori
Documentation of a case of tuberculosis in precal trends continued.
Columbian America. Am. R'-v. Respit. Dis. 107:
There are many reasons for the resur
985-991.
gence of tuberculosis in the United States. Bloom, B. R., and C. J. L. Murray. 1992. Tuberculo
sis: commentary on a reemergard killer. Science
;
The AIDS epidemic is an important factor,
257:1055-1064.
and infection with human immunodefi
Botlmniey, G. H., and J. M. Grange. 1991. The Koch
ciencyvirus is the single greatest risk factor
phenomenon and delayed hypersensitiviiy: 1891known for progression from primary infec1991. Tubercle 72:7-11.
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Mycobacterial and fungal sensitivity paiterns among
tified by Chase are, of course, destroyed by
remote population groups in P’.pj-i ttew Guinea and
. , this virus. The entry into the United States
in the Hebrides, Solomon and Caroline Isiand. .Am.
of large numbers of persons from countries
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with high tuberculosis prevalence rates has Brudney, K., and J. Dobkin. 1991. Resurgent un e~culosis in New York City. Human immunodeficiency
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and immigrants bring with them the epide
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ease in biocultural perspective, p. 115-139. In J. E.
miology of their homelands. Finally, in
Buikstra (ed.), Prehistoric Tuberculosis D the
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Americas. Northwestern Unive-sity Archeological
. .. measures have collapsed or been aban
Program, Evanston, III.
doned, and facilities to serve high-risk indi Bushnell, G. E. 1930. Epidemiology of Tuberculosis,
viduals are inadequate. Thus, 89% of pa
p. 157. William Wood and Co., Baltimore.
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40:1-96.
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M. W. 1988. Early days in cellular immunol
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J

ft

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Comstock, G. W. 1978. Tnbercnlosis in twins- a rc.

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Lune M. T
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