Journal of Interdisciplinary History, XLIX:3 (Winter, 2019), 367–395.

Samuel Mark
The Origin and Spread of Leprosy: Historical,
Skeletal, and Molecular Data Leprosy was the scourge of
ancient societies and continued to be a significant health problem in
a number of countries until quite recently. A combination of early
diagnosis and treatment with multi-drug therapy has greatly re-
duced the number of cases of leprosy worldwide, especially in the
last twenty-five years. Today, nearly 83 percent of the more than
200,000 new cases reported annually are from three countries—
India, Brazil, and Indonesia. Nevertheless, many Western countries
have not yet been able to eradicate leprosy completely. In the United
States, the appearance of three strains of M. leprae—SNP subtypes 3K
(nine cases), 3J (one case), and 3M (one case)—indicates that new
cases continue to arrive from abroad. Another occasional source of
infection is apparent contact with armadillos, ranging from Texas to
Florida and Georgia. Hence, leprosy continues to remain a health
concern even in developed countries. Employing a variety of
methods—with attention to both historical sources and molecular
data—this article examines the likely origins of leprosy, indicating
what we can know about the spread of a disease that has social as
well as medical consequences.1
Prior to 2005, India was widely accepted as the country of
origin for Mycobacterium leprae primarily due to detailed descrip-
tions of the progressive forms of leprosy in the Sushruta Samhita,

Samuel Mark is Professor of Maritime Studies, Texas A&M University at Galveston. He is the
author of From Egypt to Mesopotamia: A Study of Predynastic Trade Routes (College Station, 1997);
Homeric Seafaring (College Station, 2005).
The author thanks the anonymous referees for suggestions and comments that greatly
improved this article.
© 2018 by the Massachusetts Institute of Technology and The Journal of Interdisciplinary
History, Inc., https://doi.org/10.1162/jinh_a_01301

1 World Health Organization, “Global Leprosy Update, 2016: Accelerating Reduction of

Disease Burden,” Weekly Epidemiological Record, XXXV (2017), 501, 505 (Table 2); Joshua
Lane et al., “Borderline Tuberculoid Leprosy in a Woman from the State of Georgia with
Armadillo Exposure,” Journal of the American Academy of Dermatology, LV (2006), 714–716; Rahul
Sharma et al., “Zoonotic Leprosy in the Southeastern United States,” Emerging Infectious Diseases,
XXI (2015), 2127–2134.
368 | SAM U EL M AR K

an Indian medical text dating to c. 600 B.C. In 2005, Monot et al.

greatly increased our understanding of M. leprae and our ability to
map it geographically based on the discovery that four single-
nucleotide polymorphisms (SNPs) correlated with general geo-
graphical regions consistent with an origin for M. leprae in either
East Africa or India. In 2009, Monot et al. proposed an origin for
M. leprae in East Africa (henceforth, the East African model) after
comparing Brazilian and Indian genome sequences, allowing them
to define sixteen SNP-subtypes (1A–D, 2E–H, 3I–M, 4N–P). They
proposed that the geographical locations of these subtypes were
consistent with migration patterns of early humans and trade
routes. SNP-subtype 2H was the earliest in East Africa, leading to
2F in Iran and finally 1A in India. Subtype 2F would have evolved
into 3K, leading to 3M in Europe. Since type 3 is associated with
European populations, and only 3K was reported in China, it must
have spread from either Iran or Turkey via the Silk Road, instead
of via maritime routes from India to southern China (Figure 1).2
Weng et al. found that 3K was the most common type of
M. leprae in both coastal and inland provinces of China, whereas
subtypes 1D (seventeen cases) and 1A (one case) appeared only in
the coastal provinces of Guangdong, Fujian, and Guangxi, and only
SNP type 2 (subtype unknown, 1 case) appeared in the autonomous
province of Xinjiang. Based on these data, Weng et al. proposed that
M. leprae could have originated in East Africa and spread to China via
southern maritime routes mainly through Guangzhou in Guangdong
province, a port of entry that likely dates to the Han dynasty (202 B.C.–
A.D. 220). According to Paine, however, ports along the southern
coast of China were importing goods as early as the eighth century
3
B.C.

2 For works that propose leprosy as originating in India, see Dharmendra, “Leprosy in Ancient
Indian Medicine,” International Journal of Leprosy, XV (1947), 424–430; Johs Andersen, Studies in
the Medieval Diagnosis of Leprosy in Denmark: An Osteoarchaeological, Historical and Clinical Study
(Copenhagen, 1969), 10–45, 123; Mark, “Alexander the Great, Seafaring, and the Spread of
Leprosy,” Journal of the History of Medicine and Allied Sciences, LVII (2002), 286–311; Marc Monot
et al., “On the Origin of Leprosy,” Science, CCCVIII (2005), 1040–1042; idem et al., “Compar-
ative Genomic and Phylogeographic Analysis of Mycobacterium leprae,” Nature Genetics,
XLI (2009), 1282–1289.
3 Xiaoman Weng et al., “Molecular, Ethno-Spatial Epidemiology of Leprosy in China:
Novel Insights for Tracing Leprosy in Endemic and Non Endemic Provinces,” Infection, Genetics
and Evolution, XIV (2013), 361–368; Lincoln Paine, The Sea and Civilization: A Maritime History of
the World (New York, 2015), 171–173.
T H E OR IG I N A ND S P R E A D O F LE P RO X Y | 369
Fig.1 Distribution of M. leprae SNP Types and Subtypes from Africa
to Japan.

SOURCES This figure is based on data from Masanori Matsuoka et al., “Genotypic Analysis of
Mycobacterium leprae Isolates from Japan and other Asian Countries Reveals a Global Trans-
mission Pattern of leprosy,” FEMS Microbiology Letters, CCLXI (2006), 150–154; idem et al.,
“Various Genotypes of Mycobacterium leprae from Mexico Reveal Distinct Geographic Distri-
bution,” Leprosy Revue, LXXX (2009), 322–326; Marc Monot et al., “Comparative Genomic
and Phylogeographic Analysis of Mycobacterium leprae,” Nature Genetics, XLI (2009), 1282–1289
(Figure 4); Florence Reibel et al., “New Insights into the Geographic Distribution of Myco-
bacterium leprae SNP Genotypes Determined for Isolates from Leprosy Cases Diagnosed in
Metropolitan France and French Territories,” PLoS Neglected Tropical Diseases, IX (2015),
1–10; Xiaoman Weng et al., “Molecular, Ethno-Spatial Epidemiology of Leprosy in China:
Novel Insights for Tracing Leprosy in Endemic and Non Endemic Provinces,” Infection, Genetics
and Evolution, XIV (2013), 361–368.

Schuenemann et al. challenged the East African model after

comparing five M. leprae samples from medieval skeletons with
eleven modern samples that had longer branch lengths from accu-
mulated substitutions. The authors calculated average distances be-
tween strains. Using a strict clock model, which assumes that all
strains evolve at the same evolutionary rate, they calculated the most
likely divergence date for the most recent common ancestor for all
known M. leprae strains to have been 3,126 years ago, or 1114 B.C.
(within a range of 4,562 to 1,975 years ago, or 2546 B.C. to A.D. 43).
They also calculated a most likely date and date ranges for some SNP
subtypes. Subtype 3K was the oldest (782 B.C., 2157 B.C. to A.D. 389),
followed by 3L (no date or range given) and 3I (A.D. 516, 35 B.C. to
A.D. 908). Branch 1 (1D=A.D. 621, A.D. 46 to 1106; 1B=A.D. 810,
A.D. 292 to 1246; 1A=A.D. 1317, A.D. 959 to 1612) and Branch 2
(2F=A.D. 735, A.D. 466 to 964) possibly diverged at the same time; the
370 | SAM U EL M AR K

latest is branch 4 (4N=A.D. 1045, A.D. 558 to 1467; 4P, 4O=A.D.

1246, A.D. 842 to 1610). A most likely date or date range was not
given for subtype 3J, 3M, 1C, 2E, 2G, or 2H. Schuenemann et al.
proposed that these data supported an origin in India (henceforth,
the Indian model). Additional evidence derived from a skeleton
from India exhibiting lesions diagnosed as leprous, dating to
c. 2000 B.C. This date is consistent with the earliest date in their
date range for subtype 3K of 2157 B.C.4
Singh et al. discovered a second species that caused leprosy,
Mycobacterium lepromatosis. Comparing a near-complete genome
sequence of M. lepromatosis with that of M. leprae, they calculated
a divergence time for the most recent common ancestor for all
M. leprae strains as 3,607 years ago (1592 B.C.) with a range of 5,525
to 2,204 years ago (3508 to 187 B.C.). They also stated that subtype
3K was in a separate branch 0 from all other SNP 3 subtypes.5
The most recent common ancestor for all known strains of
M. leprae has never been found in any species. However, chim-
panzees and some species of monkeys and Eurasian red squirrels
(Sciurus vulgaris) are susceptible to M. leprae, and Eurasian red
squirrels are also susceptible to M. lepromatosis. Hence, some re-
searchers propose that M. lepromatosis and M. leprae diverged from
their most recent common ancestor about 13.9 million years ago,
when each acquired a new host, possibly different species of mon-
keys or apes, or even a rodent vector. Sometime around 1592 B.C.
or 1114 B.C., or within the previously cited date ranges of 3508 to
187 B.C. or 2545 B.C. to A.D. 42, humans were probably first infected
with M. leprae from contact with an infected animal, beginning the
divergences of known SNP types and subtypes. M. lepromatosis also
reached humans in a similar manner at an unknown time and place
as migrations and long-distance trade spread both species of leprosy

4 Verena Schuenemann et al., “Genome-wide Comparison of Medieval and Modern

Mycobacterium leprae,” Science, CCCXLI (2013), 179–183. In genetic divergence, bacteria,
which are asexual, reproduce by dividing into two clones. When a mutation occurs, a single
base pair in a DNA sequence, known as a single nucleotide polymorphism, can be either neutral
or adaptive. Both the ancestral strain (before mutation) and the divergent strain (with muta-
tion) can still exchange genes by horizontal gene transfer—the movement of genetic material
between two adjacent bacteria. As these strains become more and more isolated, gene flow
between them correspondingly lessens and can cease altogether.
5 Pushpendra Singh et al., “Insight into the Evolution and Origin of Leprosy Bacilli from
the Genome Sequence of Mycobacterium lepromatosis,” Proceedings of the National Academy of Sciences
of the United States of America, CXII (2015), 4459–4464.
T H E OR IG I N A ND S P R E A D O F LE P RO X Y | 371
around the world. This interpretation is consistent with both the
East African and Indian models.6
Unfortunately, molecular studies have largely ignored the
earliest historical data for the origin and spread of leprosy; they might
have provided a framework to evaluate the strengths and weaknesses
of each theory. One of the most effective methods to do so is to
compare historical accounts of leprosy with the geographical dis-
tribution of each SNP subtype and molecular data from the earliest
dated skeletons in each region. This strategy not only helps to verify
or refute the accuracy of the date ranges for each strain of M. leprae,
but it also identifies gaps in the molecular data, which can be a factor
in the evaluation of the earliest skeletons diagnosed with leprosy but
not verified molecularly. Molecular analysis of ancient skeletons is
an expensive process, and DNA is often too degraded in ancient
skeletons to confirm a case of leprosy. For these reasons, many of
the earliest skeletons diagnosed with leprosy are still untested.
This review of the historical and molecular data raises the
possibility that M. leprae did not originate in either India or East
Africa but somewhere else, like Myanmar. It also reveals two ob-
stacles in determining a place of origin and spread of M. leprae.
Population migrations throughout the centuries were more complex
than the previously cited molecular studies suggest. Hence, the
sixteen SNP subtypes alone are inadequate to map the origin and
spread of M. leprae in some regions. However, SNP variable number
tandem repeat (SNP VNTR) genome sequencing has been used to
differentiate earlier from later versions of the same SNP subtypes,
though only with caution because the reliability of this technique
for this purpose has yet to be proven. This technique or another
one is necessary to clarify this issue.7
A second obstacle to mapping the origin and spread of M. leprae
is the recent discovery of M. lepromatosis. All of the earlier studies
about the origin and spread of leprosy assumed that ancient med-
ical texts describe only M. leprae, but since both species can de-
velop into all forms of leprosy, and each species could have had a

6 Mark, “Early Human Migrations (c. 13,000 years ago) or Post-Contact Europeans for the
Earliest Spread of Mycobacterium leprae and Mycobacterium lepromatosis to the Americas,” Inter-
disciplinary Perspectives on Infectious Diseases, MMXVII (2017), 1–8; Xiang Han and Francisco J.
Silva, “On the Age of Leprosy,” PLoS Neglected Tropical Diseases, VIII (2014), 1–8 [earlier
interpretations for both species].
7 For an example of VNTR typing see, Sharma et al., “Zoonotic Leprosy,” 2127–2134.
372 | SAM U EL M AR K

different country of origin, the study of these texts must proceed

circumspectly. The use of both historical and molecular data is
warranted.8

LEPROSY Leprosy, or Hansen’s disease, is a slow, progressive, and

highly infectious chronic disease produced by the bacilli M. leprae
and M. lepromatosis. M. leprae t-cell-mediated immunity typically
protects more than 95 percent of a modern population, although
this percentage varies by population to some degree, especially
when first introduced. Seventeen years after the first person was
infected with M. leprae on the island of Nauru in the South Pacific,
35 percent of the population was infected with it. M. lepromatosis
may be even more virulent than M. leprae, since it has a shorter
doubling time.9
The lack of detail in most of the ancient texts means that
we can distinguish only the disfiguring features that developed
during the later stages of lepromatous leprosy from other possible
conditions; thickening of facial skin, hypertrophied lips and nose,
pronounced wrinkles, and a yellow cast are also characteristics of
leonine facies or lion face. Leprosy also removes facial hair (espe-
cially eyelashes and the lateral third of eyebrows), as well as the
ears. When the eyes are infected, blindness sometimes follows.
The absorption of the nasal bones typically makes the bridge of
the nose collapse; further damage to the throat can result in a
hoarse whisper. Concurrently, the hands and feet become swollen
and deformed and lose sensation. Persistent injury, due to this lack
of sensation, and the absorption of bone leads to a loss of fingers
and toes. When ancient texts describe a condition with a combi-
nation of these facial disfigurements, concurrent with a loss of
fingers or toes, lepromatous leprosy is undoubtedly the cause.10
The diffuse form of lepromatous leprosy is rarely discussed
outside of Central America. Diffuse lepromatous leprosy uniquely
invades the endothelial cells, typically leading to a vascular occlusion

8 Mark, “Early Human Migrations,” 2 [both species produce all forms of leprosy].
9 Lalit Bhutani et al., “Leprosy,” Lancet, CCCXLV (1995), 697–703, 698–699; Arthur
Aufderheide and Conrado Rodriguez-Martin, The Cambridge Encyclopedia of Human Paleo-
pathology (New York, 1998), 149 [Nauru Island]; Xiang Y. Han et al., “A New Mycobacterium
Species Causing Diffuse Lepromatous Leprosy,” American Journal of Clinical Pathology, CXXX
(2008), 856–864 [virulence of M. lepromatosis].
10 Bhutani et al., “Leprosy,” 698–699; Mark, “Alexander the Great,” 288.
T H E OR IG I N A ND S P R E A D O F LE P RO X Y | 373
and cyanotic lesions; the resulting swollen or spotted appearance
derives from an inadequate blood supply. These lesions can even-
tually become necrotic, as evidenced by ulceration and discoloration
from gray to black. They are most common on the extremities but
occasionally spread to the chest and back. When first discovered
in Mexican patients, the close association between M. lepromatosis
and diffuse lepromatous leprosy, determined solely on the basis of
molecular data, was attributed to M. lepromatosis as the root cause
and M. lepromatosis the derivative within this region. A later study
comparing historical records and molecular data, however, showed
that both species arrived on European ships, illustrating the impor-
tance of comparing detailed historical accounts with molecular data.
Although both species of leprosy can develop into all of the various
forms, M. lepromatosis seems responsible for the presence of diffuse
lepromatous leprosy more often than does M. leprae, though in some
populations, M. lepromatosis develops into only standard forms of
leprosy.11
Osseous leprous lesions, which typically appear in the later
stages of lepromatous leprosy, are also important in mapping the
spread of the disease. Møller-Christensen noted three pathological
changes to facial bones: endonasal inflammation, atrophy of the
anterior nasal spine, and atrophy and recession of the alveolar process
of the maxilla confined to the incisor region. Endonasal inflam-
matory changes, together with one or both of the other two symp-
toms, were necessary for a diagnosis of facies leprosa (Bergen syndrome
or rhinomaxillary syndrome), but facies leprosa alone does not con-
firm leprosy; some conditions—syphilis, tuberculosis, leishmaniasis,
and cancer—can mimic it.12
According to Møller-Christensen, a relatively firm diagnosis of
leprosy was possible when facies leprosa was accompanied by tibiae
and fibulae exhibiting bilateral and symmetrical periostitis and

11 For a description and discussion of diffuse lepromatous leprosy and early theories about
the evolution of M. lepromatosis, see, Han et al., “Analysis of the Leprosy Agents Mycobacterium
leprae and Mycobacterium lepromatosis in Four Countries,” American Journal of Clinical Pathology,
CXLII (2014), 524–532; Singh et al., “Insight into the Evolution,” 4463; for a revised inter-
pretation, Mark, “Early Human Migrations,” 2–3, 6.
12 Vilhelm Møller-Christensen, “Evidence of Leprosy in Earlier Peoples,” in Don Brothwell
and A.T. Sandison (eds.), Diseases in Antiquity (Springfield, Ill., 1967), 295–306, 300; Donald
Ortner, Identification of Pathological Conditions in Human Skeletal Remains (San Diego, 2003; orig.
pub. 1981), 268 [conditions that mimic facies leprosa].
374 | SAM U EL M AR K

vascular grooves (transverse striations usually on the distal third of

both bones), but a reasonably certain diagnosis also required changes
in the bones of the hands and feet, consisting of bilateral but rarely
symmetrical diaphyseal remodeling. In the hands, the terminal
phalanges erode to points due to concentric resorption, presenting
a tapered appearance beginning at the distal end of a bone. Resorp-
tion continues proximally but rarely extends to the metacarpal;
eventually, only stumps may remain. In the feet, bone absorption
typically begins in the metatarsophalangeal joints at, or near, the
distal end of a metatarsal; the diaphysis gradually thins, sometimes
becoming knife-shaped, until a fine, conical needle of bone appears
at the distal end.13
Frostbite, diabetes mellitus, psoriatic arthritis, and pyogenic
osteomyelitus caused by trauma or ulceration can mimic osseous
leprous lesions in the hands and feet. Thus, the combination of
facial lesions and bilateral lesions in extremities is required to iden-
tify leprosy. The importance of this check on diagnoses is illus-
trated by a skeleton diagnosed with leprosy from burial 11 at the
site of Dryburn Bridge in Scotland, c. 2000 to 1600 B.C. The skeleton
exhibited osseous lesions consistent with facies leprosa, but neither
hands nor feet survived, making a diagnosis impossible. This indi-
vidual, however, was only six-to-eight years old; such extensive
facial lesions in young children lacks a medical parallel. Instead,
bone absorption is typically confined to the incisors. Furthermore,
osseous leprous lesions in children usually arise in endemic popu-
lations. In this case, no evidence exists to suggest that leprosy was
endemic. Tuli noted that osseous lesions from tuberculosis appear
early in life, including facial lesions, developing in the first three
decades. Furthermore, this Scottish skeleton tested positive only
for Mycobacterium tuberculosis, which is consistent with the lesions.14

13 Møller-Christensen, “Evidence of Leprosy,” 298–300.

14 Ortner, Pathological Conditions, 580 [psoriatic arthritis]; R. Ted Steinbock, Paleopathological
Diagnosis and Interpretation (Springfield, Ill., 1976), 208–209 [other conditions]; Andrew Dunwell,
“Cist Burials and an Iron Age Settlement at Dryburn Bridge, Innerwick, East Lothian,” Scottish
Archaeological Internet Report, 24 (2007), 10, 18, 22–23, available at http://archaeologydataservice.
ac.uk/archives/view/sair/contents.cfm?vol=24; Mauro Rubini and Paola Zaio, “Lepromatous
Leprosy in an Early Medieval Cemetery in Central Italy (Morrione, Campochiaro, Molise,
6th–8th century AD),” Journal of Archaeological Science, XXXVI (2009), 2777 [cited as a case of
leprosy]; Mary Lewis, “Infant and Childhood Leprosy,” in Charlotte Roberts et al. (eds), The
Past and Present of Leprosy: Archaeological, Historical, Palaeopathological and Clinical Approaches
(Oxford, 2002), 163–170, 163–164 [osseous lesions and endemic populations], 165 [bone
T H E OR IG I N A ND S P R E A D O F LE P RO X Y | 375
Møller-Christensen’s observations and caveats have stood the
test of time, widely cited in the paleopathology literature. Most
recently, as a case in point, Donoghue et al. stated, “A clear diag-
nosis of leprosy based solely on paleopathology can be made only
if the typical facial changes are found in combination with atrophy
and truncation of the fingers and toes.”15

INDIA The argument that leprosy is mentioned in the Atharva Veda

is controversial. The Atharva Veda is one of four vedas; based on lin-
guistic and archaeological evidence, it could date as late as 500 B.C.
The word for leprosy appears in the Charak Samhita, c. 800 B.C., but
without any mention of symptoms. By c. 600 B.C., the Sushruta
Samhita described the various forms of leprosy in detail. The most
extreme form exhibits a “contraction of the skin, local anesthesia,
a copious flow of perspiration, swelling, and piercing or cutting
pain in the affected part, together with a deformity of the limbs
and hoarseness,” “falling off of fingers,” “sinking of the nose and
ears,” and “redness of the eyes.” The detail of the description sug-
gests that it had been fairly common in parts of India at least and
under observation for a considerable period, which is consistent
with the leprosy mentioned in the Charak Samhita 200 years earlier.
No historical evidence exists for leprosy in India before 800 B.C.16
Individual 1997-1 from Balathal, India (c. 2000 B.C.), and nine
additional skeletons from Harappa, India (c. 1900 to 1300 B.C.),
have been diagnosed with leprosy, but none of them appear to
have undergone molecular testing. According to Robbins et al.,
Individual 1997-1 exhibits osseous lesions consistent with facies leprosa

absorption and incisors]; Surendra Mohan Tuli, Tuberculosis of the Skeletal System (New Delhi,
2010; orig. pub. 1991), 193.
15 For the continued relevance of Møller-Christensen’s observations, see Aufderheide and
Rodriguez-Martin, Cambridge Encyclopedia of Human Paleopathology, 150–154; Ortner, Patho-
logical Conditions, 265–271; Helen Donoghue et al., “A Migration-Driven Model for the
Historical Spread of Leprosy in Medieval Eastern and Central Europe,” Infection Genetics
and Evolution, XXXI (2015), 250–256, 251.
16 Gwen Robbins et al., “Ancient Skeletal Evidence for Leprosy in India (2000 B.C.),”
PLoS ONE, Vol. 4, No. 5 (2009), 1–8, 1 [the Atharva Veda]; Michael Witzel, “Autochthonous
Aryans? The Evidence from Old Indian and Iranian Texts,” Electronic Journal of Vedic Studies,
VII (2001), 1–115, 5–6 [dating the Vedas]. For the Charak Samhita and history of leprosy in
India, see Dharmendra, “Leprosy Indian Medicine,” 424–430; Mark, “Alexander the Great,”
301–302; Kaviraj Kunja Lal Bhishagratna (ed. and trans.), The Sushruta Samhita ( Varanasi, India,
1963), II, 36–40.
376 | SAM U EL M AR K

or with tuberculosis, as well as vertebral ankylosis, which also is

associated with tuberculosis. Nonetheless, Robbins et al. conclude
that since this individual lacks other classical pathognomonic changes
associated with tuberculosis, leprosy was a likely cause of the facial
lesions, but in the process, they fail to exercise this same standard
for leprosy. As previously noted, a definitive diagnosis of leprosy
requires not only pathognomonic changes to the face, which it ex-
hibited, but also changes to the extremities, which it lacked. Facial
lesions and vertebral ankylosis more properly pertain to tuberculosis.
Furthermore, Individual 1997-1 also exhibits anterior wedging on
the C4-C7 and possibly L3-L5 vertebrae, which also imply tuber-
culosis. Hence, no reason exists to prefer a diagnosis of leprosy over
tuberculosis.17
Robbins Schug et al. identified an additional nine individuals
from Harappa, India (c.1900–1300 B.C.), with osseous lesions con-
sistent with leprosy, but eight had only cranial lesions. The ninth
exhibited some postcranial lesions but none unique to leprosy,
allowing for a diagnosis of tuberculosis for all of them, especially
since three other skeletons exhibited lesions consistent with only
tuberculosis. Thus, until these skeletons receive molecular testing,
they should be considered probable cases of tuberculosis. Finally,
although some of these skeletons might date earlier than a most
likely date of 1592 B.C., all of them are older than a most likely date
of 1114 B.C.18
Even if all of these individuals had only tuberculosis, M. leprae
may still have originated in India. If the most recent common ances-
tor of M. leprae came from an animal vector around 1114 B.C., and
subtype 3K diverged around 782 B.C., it must have infected a number
of individuals before doing so. Hence, it would be consistent with
M. leprae appearing in the Charak Samhita, around 800 B.C., leading
to its detailed description in Sushruta Samhita in 600 B.C. Thus, the
historical and most of the molecular data fit together well, but a
major obstacle still stands in the way. The earliest SNP subtype in
India is 1D with a most-likely divergence date of A.D. 621 and date

17 For a description of osseous lesions for Individual 1997-1, see Robbins et al., “Ancient
Skeletal Evidence,” 4–6; for anterior wedging, S. Ansari et al., “Pott’s Spine: Diagnostic
Imaging Modalities and Technology Advancements,” North American Journal of Medical Sciences,
V (2013), 404–411, 405.
18 Gwen Robbins Schug et al., “Infection, Disease, and Biosocial Processes at the End of
the Indus Civilization,” PLoS ONE, Vol. 8, No. 12 (2013), 1–20.
T H E OR IG I N A ND S P R E A D O F LE P RO X Y | 377
range of A.D. 46 to 1106. Therefore, either the most recent common
ancestor and subtype 3K still exist in India but have not yet been
found or both strains once existed but have since disappeared, em-
phasizing the need for molecular testing of ancient skeletal remains.
The possibility remains, however, that instead of describing
M. leprae, as previous studies assumed, the ancient texts describe
M. lepromatosis. A condition similar to diffuse lepromatous leprosy
has been reported in India, but not M. lepromatosis itself, though it
has been found to the east in Myanmar, as has M. leprae SNP type 3
(subtype unknown). Moreover, no publication appears to mention
testing for M. lepromatosis in India; both modern and ancient
samples should be tested for both species of leprosy. Finally, these
divergence dates may be inaccurate. If M. leprae is the strain men-
tioned in ancient texts, and if a representative sample of SNP types
exists in India, then SNP subtype 1A or 1D must date before 800 B.C.,
allowing subtype 2H in East Africa to be the oldest SNP.19

EAST AFRICA If M. leprae originated in East Africa as subtype 2H,

it must have existed there centuries prior to 800 B.C. to allow it
time to spread to Iran, where it diverged into 2F before spreading
to India, where it diverged into 1A or 1D to become common enough
for mention in the Charak Samhita (Figure 1). Major problems in-
clude a lack of historical, archaeological, and skeletal evidence for
leprosy in East Africa or Iran so early, and no evidence exists for
migrations or trade between East Africa and either Iran or India at
that time. The Dutch exported Indian slaves to Africa, as well as
other regions during the seventeenth century, and labor was still
needed even after the abolition of slavery in the British colonies
(1824). More than 1 million people from India, Pakistan, and
Bangladesh immigrated to British East Africa in the final quarter of
the nineteenth century alone. Thus, the SNP subtypes found in East
Africa may have arrived quite late. Furthermore, if subtype 2H is the
most ancient subtype, it should have spread to Egypt (Figure 1). The
ancient Egyptians made direct, possibly annual, trading voyages to
East Africa as early as c. 3000 B.C. and no later than c. 2487 B.C. These
voyages continued, with a few breaks, until sometime during the
reign of Ramses III (1187 to 1156 B.C.). Furthermore, their ships

19 For diffuse lepromatous leprosy in India, see, Singh et al., “Insight into the Evolution,”
4460; for SNP type 3 in Myanmar, Matsuoka et al., “Genotypic Analysis,” 150, 152.
378 | SAM U EL M AR K

carried human cargo, consisting of men, women, and children, back

to Egypt. All of them would have provided an excellent opportunity
to spread leprosy to Egypt throughout the centuries. If subtype 2H
was the most ancient, it should have spread to Egypt, but no evi-
dence exists for it. More sampling is necessary.20

THE MIDDLE EAST AND EUROPE None of the exhaustive studies of

ancient Middle Eastern texts has discovered a condition consistent
with leprosy before 300 B.C. The earliest proposed skeletal evidence
is Individual 416 Ka (c. 2700 to 2300 B.C.), from Karataş, Turkey,
which continues to be cited as a possible case of leprosy. According
to Angel, Individual 416 Ka had injuries that were “the healed result
of gangrene after a crush injury (as from a wooden disk cart wheel)
or might be leprosy.” Besides the feet, the only other lesions on
this skeleton are arthritis in the right hand and spine. As previously
noted, extensive lesions in both feet but none consistent with leprosy
anywhere else on a skeleton, especially the face, disqualifies a diag-
nosis of leprosy. Finally, since no lesions in the feet are unique to
leprosy, these pathologies should carry the primary diagnosis of a
crushing injury.21
Two skeletons from Europe are the next-earliest proposed
leprosy cases. Individual 257 S20 from Hungary (c. 3780 to 3650
B.C.) was an eighteen-to-twenty-two-year-old male with osseous
lesions consistent with facies leprosa. Additional pathologies include
porosity of the occipital bone near the lambdoid suture; pitting on
the mandible below the incisors; porotic vertebral bodies; peri-
ostitis and hypervascularization on the ribs; periostitis on the right

20 Markus Vink, “The World’s Oldest Trade: Dutch Slavery and Slave Trade in the Indian
Ocean in the Seventeenth Century,” Journal of World History, XIV (2003), 131–177 [Dutch
slavery]; Andrew Godley, “Migration of Entrepreneurs,” in Anuradha Basu et al. (eds), The
Oxford Handbook of Entrepreneurship (New York, 2006), 601–610 [1,000,000 immigrants];
Mark, “The Earliest Sailboats in Egypt and Their Influence on the Development of Trade,
Seafaring in the Red Sea, and State Development,” Journal of Ancient Egyptian Interconnections,
V (2013), 28–37, 35–36 [3100 B.C.]; idem, “Notes on Mediterranean and Red Sea Ships and Ship
Construction from Sahure to Hatshepsut,” Journal of Ancient Egyptian Interconnections, VI (2014),
34–49 [2487 B.C. and later trade].
21 Mark, “Alexander the Great,” 294–295 [review of ancient texts]; J. Lawrence Angel,
“Appendix: Human Skeletal Remains at Karataş in Mellink,” in Machteld Mellink and idem
(eds.), “Excavations at Karataş-Semayük and Elmali, Lycia, 1969,” American Journal of Archaeol-
ogy, LXXIV (1970), 245–259, 256; Anne Stone et al., “Tuberculosis and Leprosy in Perspec-
tive,” American Journal of Physical Anthropology: Supplement, CXL (2009), 66–94, 81 [cited as
possible case of leprosy].
T H E OR IG I N A ND S P R E A D O F LE P RO X Y | 379
tibia and fibula; periostitis on the diaphysis of both humeri and on
the medial surface of both radii, affecting both ulnae at the distal
end and both femurs; and a deep cavity on the plantar surface of
the os metacarpal on the right side. The left orbital roof had cribra
orbitalia. Four other individuals also had osseous lesions, but none
was specific to a particular condition. Köhler et al. tested for both
M. tuberculosis and M. leprae, but the results were negative. They
preferred a diagnosis of leprosy because of the facial lesions and
the periostitis on the right tibia and fibula. They rejected tubercu-
losis because of a lack of classic tubercular lesions in the postcranial
skeleton and because tuberculosis rarely affects the cranium, except
in childhood.22
The main obstacle to a diagnosis of leprosy in this case is a lack
of any lesion in the postcranial skeleton unique to leprosy, and de-
spite periostitis in the right tibia and fibula (there is no mention of
the left elements), no vascular grooving is in evidence. As such, the
condition that caused this periostitis was probably the same condi-
tion that caused the extensive periostitis on the other postcranial
elements, which does not indicate leprosy. Although the authors
are correct that tubercular facial lesions are rarer in this age group,
by their own admission they sometimes occur. Furthermore, the
age at which this individual first contracted this condition and the
osseous facial lesions began to develop is unknown; this indivi-
dual could have died as young as eighteen years old. Ortner notes
a fifteen-year-old with similar tubercular facial lesions. Further-
more, the date of this skeleton (3780 to 3650 B.C.) is too early for both
divergence dates—that of M. leprae at 1592 B.C. or 1114 B.C.—or
even for either date range of 3508 to 187 B.C. or 2545 B.C. to A.D. 42.23
Moreover, leprosy is a condition that afflicts populations, but
the next earliest evidence for leprosy is more than three millennia
later. If this dating system is inaccurate, and this individual was
infected with either leprosy species, he must have been infected by
a local animal vector. No such evidence for an animal vector, how-
ever, exists in this region. Yet, given that M. tuberculosis is found in
West Asia as early as 7000 B.C. and in Scotland by 2000 B.C., it could
also have been in Hungary at this time. Furthermore, as Köhler et al.

22 Kitti Köhler et al., “Possible Cases of Leprosy from the Late Copper Age (3780–3650 cal
B.C.) in Hungary,” PloS ONE, XII (2017), 1–25, 10–12.
23 Ortner, Pathological Conditions, 253, Figure 10-42.
380 | SAM U EL M AR K

noted, Individual 257 S20 had cribra orbitalia on the left orbital roof,
indicating a “susceptibility for infections, a weakened immune sys-
tem or haematological disorders.” Such an individual would be
prone to tuberculosis, which could cause the osseous facial lesions
as well as periostitis on the ribs. Tuberculosis can also lead to hyper-
trophic osteoarthropathy, which, though rare, can cause extensive
periostitis on postcranial elements. One possible reason for this indi-
vidual testing negative for both leprosy and tuberculosis is that he had
neither condition. Instead, all osseous lesions could have derived
from a single extensive infection or hematological disorder. Peri-
ostitis can involve multiple bones if an infection is widespread; it is
not fatal unless the infection spreads to organs. Thus, based on the
above data, leprosy is improbable.24
The second case is an adult male from tomb 74, Casalecchio
di Reno in Bologna, Italy (henceforth, Individual T74) (c. 400 to
300 B.C.), whose osseous lesions were diagnosed as leprous. With
regard to facial pathologies, the authors state that Individual T74
had only endonasal inflammatory changes, without facies leprosa; his
additional facial lesions lacked parallels for leprosy. Both feet
showed conical and blade-shape resorption at the distal ends of
the metatarsals and a cup-shaped at the proximal end of one meta-
tarsal, but, as the authors note, on at least three of the metatarsals,
resorption began at the tarsometatarsal joint, which lacks a parallel
for leprosy. Periostitis is present in both the tibiae and fibulae bi-
lateral but apparently without vascular grooving, and the bilateral
periostitis on both femora also lacks a parallel for leprosy. Only
two distal phalanges survived from the hands; one of them exhibits
the beginning of resorption, which can be caused by a secondary
infection. Thus, Individual T74 lacks any classical patterns of osse-
ous leprous lesions, exhibiting numerous lesions inconsistent with
leprosy.25

24 Robbins Schug et al., “Infection, Disease, and Biosocial,” 3 [M. tuberculosis 7000 B.C.];
Köhler et al., “Leprosy from the Late Copper Age,” 6, 12 [cribra orbitalia]; Daniel Wilner,
Radiology of Bone Tumors and Allied Disorders (Philadelphia, 1982), II, 1809 [hypertropic
osteoarthropathy].
25 Valentina Mariotti et al., “Probable Early Presence of Leprosy in Europe in a Celtic
Skeleton of the 4th-3rd Century BC (Casalecchio di Reno, Bologna, Italy),” International
Journal of Osteoarchaeology, XV (2005), 311–325, 313 [date], 315–319 [description of lesions];
Donoghue et al., “Migration-Driven Model,” 251 [cited as possible leprosy].
T H E OR IG I N A ND S P R E A D O F LE P RO X Y | 381
EGYPT The next earliest evidence comes from Egypt, which has
excellent preservation of both texts and human remains, as well as
a rich medical tradition dating back as early as c. 2686 B.C. The
evidence strongly suggests that leprosy did not exist in Egypt before
the Ptolemaic period (323–330 B.C.), though two challenges to this
notion have recently emerged. First, in 2002, Lechat stated, “In
Egypt, Huspati (Horus-Den), a quasi-mythical Thinite king of the
First Dynasty (c. 3500 B.C.), is reported in a papyrus dating from
±1500–1200 B.C. as having suffered from a disease whose signs are
evocative of leprosy.” Lechat did not cite the primary evidence him-
self. Instead, he referred to a work by Scott in 1943, which cited an
1879 English version of Brugsch’s 1859 translation of Berlin papyrus
3038. Brugsch’s only mention of leprosy, however, comes in the
sentence, “This is the beginning of the collection of receipts for
curing leprosy.” Apparently, he translated one word to mean leprosy
without any supporting evidence. Although Wreszinski’s translation
of Berlin papyrus 3038 in 1909 describes a number of conditions,
it describes neither leprosy nor any other condition that resembles
it. No other Egyptian papyri mentions leprosy.26
Second, Ibrahim and Abdul-Kadir stated, “There are Egyptian
records from 1350 B.C. of leprosy among Negro slaves from Sudan
and Dafur.” This idea originated with Munro in 1879, based on
Brugsch’s work, which maintained, without any additional evi-
dence, that as early as Husapti’s reign, “negroes were already carriers
of wood to the people of Egypt. They were already slaves to
them, and this communication between the Egyptians and the negro
races has always been kept up.” Munro’s conclusion—that “as the
immigration of negroes from Northern Central Africa to Egypt
would be infinitely more likely to cause the propagation of a chronic

26 Mark, “Alexander the Great,” 294–295 [no evidence for leprosy before the Ptolemaic
period]; Michel Lechat, “The Palaeoepidemiology of Leprosy: An Overview,” in Charlotte
Roberts et al., (eds.), The Past and Present of Leprosy: Archaeological, Historical, Palaeopathological
and Clinical Approaches (Oxford, 2002), 158; Harold Scott, “The Influence of the Slave-Trade
in the Spread of Tropical Disease,” Transactions of the Royal Society of Tropical Medicine and Hy-
giene, XXXVII (1943), 181; Heinrich Brugsch, A History of Egypt under the Pharaohs (London,
1879; orig. pub. in French 1859), I, 58; Walter Wreszinski, Der grosse medizinische papyrus des
Berliner museums (Pap. Berl. 3038) (Leipzig, 1909); Bayard Holmes and Peter Kitterman, Med-
icine in Ancient Egypt: The Hieratic Material (Cincinnati, 1914) [no mention of leprosy in any
cited papyrus]; John F. Nunn and Eddie Tapp, “Tropical Diseases in Ancient Egypt,” Trans-
actions of the Royal Society of Tropical Medicine and Hygiene, XCIV (2000), 147–153 [no mention
of leprosy].
382 | SAM U EL M AR K

Fig.2 M. leprae SNP Subtypes in Europe, North Africa, the Middle

East, and India

SOURCES This figure is based on data from Marc Monot et al., “Comparative Genomic and
Phylogeographic Analysis of Mycobacterium leprae,” Nature Genetics, XLI (2009), 1282–1289
(Figure 4); Verena Schuenemann et al., “Genome-wide Comparison of Medieval and
Modern Mycobacterium leprae,” Science, CCCXLI (2013), 180–182; Helen Donoghue et al.,
“A Migration-Driven Model for the Historical Spread of Leprosy in Medieval Eastern and
Central Europe,” Infection Genetics and Evolution, XXXI (2015), 253 (Table 1); Sarah Inskip
et al., “Osteological, Biomolecular and Geochemical Examination of an Early Anglo-Saxon
Case of Lepromatous Leprosy,” PloS ONE, X (2015), 16.

disease to the Egyptians than the mere inroads of the latter to carry
such disease to that centre, . . . Egypt first received leprosy from the
Soudan and Darfur”—is fallacious, leaving the earliest evidence for
leprosy in Egypt to remain in the Ptolemaic period (323–330 B.C.).27
The search for the earliest evidence for leprosy there has been
extensive, revealing a clear pattern. Direct sea trade between Egypt
and both East Africa and India was well developed no later than
the reign of Ptolemy Philadelphus (308–246 B.C.) with the earliest
harbor at Myos Hormos (Figure 2). The earliest description of
lepromatous leprosy is attributable to Straton of Alexandria, Egypt
(c. 300 B.C.). West of Myos Hormos, the earliest Egyptian lesions
consistent with leprosy belong to four crania and some disasso-
ciated phalanges from the Dakhleh Oasis, c. 200 B.C. These skeletons
have yet to be tested molecularly, but another one (A.D. 300 to
450) with similar lesions from the Dakhleh Oasis, had M. leprae

27 Sharaf Ibrahim and Abdul-Hamid Abdul-Kadir, “Childrens Orthopaedics in the Tropics,”

in Michael Benson et al. (eds.), Children’s Orthopaedics and Fractures (New York, 2010; orig. pub.
1994), 185; William Munro, Leprosy (Manchester, 1879), 8.
T H E OR IG I N A ND S P R E A D O F LE P RO X Y | 383
SNP type 3. Its skeletal variation, hair structure, mtDNA markers, and
isotopic analysis are consistent with Egyptians living near the Nile.
According to Dzierzykray-Rogalski, the number of remains suggest
that leprosy was either endemic in this part of Egypt or that this oasis
had become a leper colony by 200 B.C. Molecular testing of the ear-
liest skeletons for both M. leprae and M. lepromatosis, however, is still
needed.28
Lucretius (c. 99–55 B.C.) stated that leprosy was found only
along the Nile River in Middle Egypt, suggesting that it spread
northward along the Nile. A generation later, Plutarch (A.D. 45–120)
posited leprosy as originating in Greece during the time of Asclepiades
of Bithynia (c. 40 B.C.). Pliny the elder (A.D. 23/4–79)—a military
officer stationed in Europe and later an official in Gaul, Spain, and
Africa—put leprosy’s origin in Italy within the lifetime of Pompeius
Magnus (106–48 B.C.) after coming from Egypt. The earliest molec-
ularly confirmed case of leprosy (type unknown) in the Mediterranean
region is an individual, also infected with tuberculosis, from the
first century A.D. in what is now Israel.29
Rufus of Ephesus (c. A.D. 98–117), who lived in present-day
Turkey and spent time in Egypt, also described lepromatous lep-
rosy. Patients had the symptomatic leontiasis or lion’s face, sunken
cheeks, thickened lips, and a bad odor, as well as “livid and black
raised areas, especially resembling bruises; some . . . located on the
face, others on the arms, and still others on the legs. It also spreads
to the back, chest, and stomach. At first these raised areas are not
ulcerated, but later they ulcerate in the most hideous manner. This
ulceration is accompanied by the swelling of the lips, by a decay so
extensive that sometimes the ends of the fingers fall off, and the
ulcers never completely heal.” Part of this description, such as the

28 Mark, “Alexander the Great,” 285–311 [Egyptian medicine, Ptolemaic trade, and earliest
evidence of Egyptian leprosy]; Tadeusz Dzierzykray-Rogalski, “Paleopathology of the Ptolemaic
Inhabitants of Dakleh Oasis (Egypt),” Journal of Human Evolution, IX (1980) 71–74 [skeletons c. 200
B.C.]; Joseph Molto, “Leprosy in Roman Period Skeletons from Kellis 2, Dakhleh, Egypt,” in
Roberts et al., (eds.), Past and Present of Leprosy, 179–192 [skeleton A.D. 300–450].
29 Titus Lucretius Carus (ed. Adolphus Brieger), De rerum natura (Lipsiae, 1894), 201
[6.1114-15]; Plutarch (ed. Eric Warmington; trans. Edwin Minar, Jr.), Plutarch’s Moralia
(Cambridge, Mass., 1969), 187 [8.9.731.1B]; Pliny (ed. George Goold; trans. William Jones),
Natural History (Cambridge, Mass., 1980), VII, 270–271 [26.5.7-8]. For Pliny’s life, see M. C.
Howatson and Ian Chilvers, The Oxford Companion to Classical Literature (New York, 1993),
431–432. Carney Matheson et al., “Molecular Exploration of the First-Century Tomb of the
Shroud in Akeldama, Jerusalem,” PloS ONE, IV (2009) 1–13.
384 | SAM U EL M AR K

leontiasis, facial collapse, and missing finger tips, could only be lepro-
matous leprosy. But the livid (cyanotic) areas without ulcers and the
black (necrotic) areas with ulcers are inconsistent with lepromatous
leprosy, though they are consistent with diffuse lepromatous leprosy,
which is most commonly caused by M. lepromatosis. Since these
symptoms are prominent, at least in Egypt and possibly Turkey,
diffuse lepromatous leprosy must have been a relatively common
form of leprosy that has since disappeared there.30
Galen (A.D. 130–200), who was one of the most knowledge-
able and cosmopolitan physicians of ancient times, grew up in
Pergamon and studied in Smyrna, both in western Turkey, and
served as personal physician to a number of emperors in Rome. He
spent extended periods in Corinth, Greece, and Alexandria, Egypt,
and traveled to Cilicia, Palestine, Crete, Cyprus, Lemnos, and Syria.
He proclaimed leprosy to be rare in true Germany, which was east
of the Roman border, as well as among the Mysians (northwestern
Turkey), but endemic to Alexandria.31
Not long after Galen’s death, leprosy became more common.
An individual from Devkesken 6 on the Ustyurt plateau of
Uzbekistan (Figure 2) (A.D. 80 to 240) had SNP subtype 3L, placing
it chronologically between 3K (782 B.C., 2157 B.C. to A.D. 389) and
3I (A.D. 516, 35 B.C. to A.D. 908). Leprosy was endemic to the west,
in Armenia, by A.D. 400; a small leprosarium had emerged there as
early as A.D. 260. It was also endemic as far north as Constantinople
during the reign of Consantius II (A.D. 337–361).32

30 Mark, “Alexander the Great,” 304–305 [discussion of this passage]; Oribasius (ed. and
trans. Ulco Cats Bussemaker and Charles Daremberg), Collectio medica (Paris, 1862), VI, 63–64
[Greek translation into English by author].
31 Howatson and Chilvers, Oxford Companion, 233–234 [Galen’s life]; Galen, “Ad Glauconem
or a Method of Medicine to Glaucon,” in Ian Johnston (ed. and trans.), Galen: On the Constitution
of the Art of Medicine; The Art of Medicine; A Method of medicine to Glaucon (Cambridge, Mass., 2016),
321–559, 555.
32 Alexandra Buzhilova, “The Geography of Leprosy in the Russian Empire: Historical
Evidence for the Dissemination of the Disease,” in Roberts et al., (eds.), Past and Present of
Leprosy, 123–133, 127 [Armenia]; Soren Blau and Yagodin Vadim, “Osteoarchaeological
Evidence for Leprosy from Western Central Asia,” American Journal of Physical Anthropology,
CXXVI (2005), 150–158, 153 [date]; G. Michael Taylor et al., “Mycobacterium leprae Genotype
Amplified from an Archaeological Case of Lepromatous Leprosy in Central Asia,” Journal
of Archaeological Science, XXXVI (2009), 2408–2414, 2413 [subtype 3L]; Timothy Miller and
John Nesbitt, Walking Corpses: Leprosy in Byzantium and the Medieval West (London, 2014), 27
[Constantinople]. See also Susan Holman, “Healing the Social Leper in Gregory of Nyssa’s and
Gregory of Nazianzus’s ‘περὶ φιλοπτωχίας,’” Harvard Theological Review, XCII (1999), 283–309.
T H E OR IG I N A ND S P R E A D O F LE P RO X Y | 385
Notwithstanding the generally accepted view that once leprosy
spread to Italy, it spread throughout Roman Europe, no evidence
confirms it. Donoghue et al., who reviewed the earliest proposed
skeletal evidence for leprosy in Roman Europe, cited only one case
outside Italy from the fourth century. A skeleton from Poundbury
Camp, Dorchester, England, with only the lower ends of both
tibiae and fibulae and both feet surviving, does not permit a
definitive diagnosis of leprosy, especially since the foot lesions
are not bilateral and bilateral vascular grooving does not appear
to be present. A number of conditions could have caused these
lesions. The earliest confirmed evidence for M. leprae in northern
Europe comes from Essex, England. Individual GC96, with sub-
type 3I (A.D. 515, 35 B.C. to A.D. 908), dates between A.D. 415
and 545. However, Sr-isotope analysis suggests that Individual
GC96 was originally from Denmark, although Germany and
France are also possible.33
The earliest texts also indicate a late date for the spread of
leprosy in Europe. In France, the Fifth Council of Orleans
(A.D. 549) set out guidelines for the care of those with leprosy,
using church funds; the Third Council of Lyon (A.D. 583) is-
sued similar guidelines and restricted the movement of those
afflicted.34
This lack of evidence for leprosy even pertains to Italy.
Donoghue et al. note that only one possible case of leprosy is in
evidence prior to the sack of Rome by the Visigoths in A.D. 410 —
from Martellona, dating from the second to third centuries A.D.,
consisting of only the cranium of a four-to-five-year-old with
facies leprosa. Based on its similarity in age and in the pattern of
its facial lesions with the child from Scotland, the Martellona child
probably had another condition, possibly tuberculosis.35

33 Roberts and Keith Manchester, The Archaeology of Disease (Ithaca, 1997; orig. pub. 1983),
147 [leprosy in Roman Europe]; Donoghue et al., “Migration Driven Model,” 251; Rachel
Reader, “New Evidence for the Antiquity of Leprosy in Early Britain,” Journal of Archaeological
Science, I (1974), 205–207 [Poundbury skeleton]; Sarah Inskip et al., “Osteological, Biomolec-
ular and Geochemical Examination of an Early Anglo-Saxon Case of Lepromatous Leprosy,”
PloS ONE, X (2015), 1–22.
34 Agnes Lambert, “Leprosy: Past and Present II,” Nineteenth Century: A Monthly Review,
XVI (1884), 467–489, 468–469.
35 Donoghue et al., “Migration Driven Model,” 251; Mauro Rubini et al., “Paleopathological
and Molecular Study on Two Cases of Ancient Childhood Leprosy from the Roman and
Byzantine Empires,” International Journal of Osteoarchaeology, XXIV (2014), 570–582, 573.
386 | SAM U EL M AR K

Leprosy first appeared in Italy around 106 to 48 B.C., but a

century later, during the reign of Tiberius (A.D. 14–37), Celsus
reported that leprosy was almost unknown in Italy. Furthermore,
Galen (A.D. 130–200) makes no mention of leprosy in Italy. At its
peak, Rome’s population was between 450,000 and 1,000,000
people. The large number of poor residents who lived in the city,
in buildings as high as six stories and without plumbing, would
have created a permanent reservoir for any infectious condition.
These people were also most likely to have been malnourished,
making them even less resistant to infectious pathogens. None-
theless, not a single case of leprosy was ever reported in Rome.
Furthermore, Rome had laws to protect slave owners who unknow-
ingly purchased a slave with a pre-existing condition—whether it
be a fever, tuberculosis, eyesores, or mental disorders—but leprosy
receives no mention. In contrast, leprosy does receive explicit legal
mention in countries where we know that the disease existed.36
Kjellström purports to offer evidence for leprosy in Rome.
Citing Browne’s work of 1975, she wrote that leprosy “must have
been considered a serious health problem since leprosaria were
founded in Rome already in the 4th century.” Browne’s only evi-
dence, however, was a citation by Mercier in 1915 claiming only
that the first hospital in Rome, established in the fourth century,
was sufficiently large to suggest the existence of earlier hospitals.
But Browne says nothing about leprosy itself. This first hospital
in Rome, constructed and run by Fabiola, provided the poor with
free treatment for any condition. In spite of assumptions that lepers
also received treatment there, no evidence for the presence of lep-
rosy in Rome or anywhere else in Italy at this time is available. Not
until Rothari, king of Lombardy (A.D. 643), enacted laws to expel
lepers and seize their property is there any indication that leprosy
was in Italy. Leprosy was either extremely rare in, or altogether
absent from, Roman Europe, at least until the end of its run.37

36 Aulus Cornelius Celsus (ed. T. Page; trans. Walter Spencer), De medicina (Cambridge,
1935), I, 342–343 (3.25.1–3); Glenn Storey, “The Population of Ancient Rome,” Antiquity,
LXXI (1997), 966–978; Mortimer Wheeler, Roman Art and Architecture (New York, 1996), 129
[apartment buildings]; Lechat, “Palaeoepidemiology of Leprosy,” 157–162, 158 [Roman law];
Mark, “Alexander the Great,” 308–309 [laws in India and Egypt].
37 Anna Kjelleström, “Possible Cases of Leprosy and Tuberculosis in Medieval Sigtuna,
Sweden,” International Journal of Osteoarchaeology, XXII (2012), 261–283, 262; Stanley Browne,
“Some Aspects of the History of Leprosy: The Leprosie of Yesterday,” Proceedings of the Royal
T H E OR IG I N A ND S P R E A D O F LE P RO X Y | 387
Based on molecular and archaeological data, Donoghue et al.
proposed that the Avars, a nomadic people from north of the Black
Sea, either first brought leprosy, or re-transmitted it, to eastern and
central Europe (including Hungary), eastern Austria, and Italy in
the sixth century A.D. Since leprosy had spread as far as northwest
Turkey before A.D. 200 and infected an individual in Uzbekistan
between A.D. 80 and 240, it could have already spread to popula-
tions north of these locations and east of the Roman border. If
Galen was right that leprosy (as subtype 3M) had spread so far north
as the present Czech Republic, even if the disease was not endemic
to Rome, it could have been brought across the Rhine with the
first Germanic groups in A.D. 376, as well as by groups like the Alans
farther south, when they crossed the Rhine in A.D. 406. If so, these
continued invasions from the East, which were also migrations,
may have also been waves of vectors, spreading subtype 3M to
central and Western Europe, thereby explaining why the earliest
evidence of endemic leprosy in Roman Europe roughly coincides
with its end.38
SNP subtypes 3I, 2F, and 2G are found in northern Europe.
According to Economou et al., the distribution of these subtypes
is consistent with direct trade between northern European coun-
tries and Constantinople via rivers in western Russia as well as the
Black Sea. By the sixth century A.D., trade was vigorous at sites like
Helgö, Sweden, where archaeologists uncovered exotic goods—a
bronze Buddha from India along with eastern and western coins
from the fifth and sixth centuries. Also, Individual GC96 in
England, who was most likely from Denmark, had the earliest
known example of subtype 3I (A.D. 415 and 545) with a likely diver-
gence date of A.D. 515, diverging either in Denmark or along these
trade routes. Furthermore, Eurasian red squirrels on Brownsea Island
in the English Channel, in Scotland, and in Ireland are also infected
with both M. leprae subtype 3I and M. lepromatosis, and probably have

Society of Medicine, LXVIII (1975), 485–493, 486; Charles Mercier, Leper Houses and Mediaeval
Hospitals: Being the Fitzpatrick Lectures, Delivered Before the Royal College of Physicians, London, 5th and
10th November, 1914 (London, 1915), 4; Timothy Miller, “From Poorhouse to Hospital,” Christian
History Magazine, CI (2011), 16–23 [Fabiola]; Lambert, “Leprosy: Past and Present II,” 468
[Rothari].
38 Donoghue et al., “Migration Driven Model,” 262 [Avars], Table 1 [Czech Republic];
Barry Cunliffe, Europe Between the Oceans, 9000 BC–AD 1000 (New Haven, 2008), 413–421
[invasions and population migrations].
388 | SAM U EL M AR K

been for centuries. These data, and Rufus of Ephesus’ possible de-
scription of diffuse lepromatous leprosy, allow for the possibility that
both species spread contemporaneously via these trade routes to
England. Since M. leprae concealed M. lepromatosis, we need to test
for both species.39
The earliest known examples of subtype 2F are from England,
Denmark, and Sweden; the earliest of them dates between A.D.
1010 and 1160. Subtype 2F has a likely divergence date of A.D.
735 and a date range of A.D. 466 to 964, suggesting that it either
diverged in Turkey, spreading northward and southward, or it
diverged in Iran, spreading northward through Turkey to north-
ern Europe. One case of subtype 2G in Sweden from a cemetery
(c. A.D. 1130 to 1300) is the earliest known example, but no diver-
gence date or date range is available. Since 2G has been found only
in Sweden and Nepal, the most likely scenario is that it diverged
between them, but this wide distribution of just two cases empha-
sizes the need for more sampling from and between these regions
to determine which strain is the earliest.40
Apparent inconsistencies exist. The first is that since southern
England and northern France received similar migrations of
Scandinavians during the early medieval era, both subtypes 3I
and 2F should be in northern provinces of France like Normandy,
but 3M is the lone subtype reported in France. Monot et al.’s
“Comparative Genomic and Phylogeographic Analysis” (2009),
the sole repository of subtypes in France, allots them by country.
If samples were listed by province within countries, patterns would
become clearer. Based on the scenarios above, we would expect
subtype 3I to have been restricted to northern Europe, but the
close proximity of subtypes 3I and 4N in Morocco (Figure 2) sug-
gests that 4N diverged from 3I in this region before spreading
southward to western Africa, and then 4O diverged from 4N.
Moreover, the distribution of subtypes in the Americas indicates
that the Portuguese and Spanish brought subtype 3I and African

39 Christos Economou et al., “Ancient-DNA Reveals an Asian Type of Mycobacterium leprae

in Medieval Scandinavia,” Journal of Archaeological Science, XL (2013), 465–470, Figure 2 [trade
routes]; Cunliffe, Europe Between, 435 [Helgö]; Charlotte Avanzi et al., “Red Squirrels in the
British Isles are Infected with Leprosy Bacilli,” Science, CCCLIV (2016), 744–747; Mark,
“Early Human Migrations,” 3, 5–6 [discussion of both species of leprosy in red squirrels].
40 Schuenemann et al., “Genome-Wide Comparison,” 179–183 [2F data]; Economou,
“Ancient-DNA Reveals,” Table 1 [2G data].
T H E OR IG I N A ND S P R E A D O F LE P RO X Y | 389
Fig.3 SNP Subtypes in the Americas

SOURCES This figure is based on data from Marc Monot et al., “Comparative Genomic and
Phylogeographic Analysis of Mycobacterium leprae,” Nature Genetics, XLI (2009), 1282–1289
(Figure 4); Rahul Sharma et al., “Zoonotic Leprosy in the Southeastern United States,” Emerg-
ing Infectious Diseases, XXI (2015), 2130.

slaves brought subtypes 4N and 4O. Subtype 4P diverged either in

Brazil or Venezuela since it is absent from Africa (Figure 3). This is
the first indication of a major flaw in the SNP dating system because
4O and 4P were stated to have diverged at the same time (4O,
4P=A.D. 1246, A.D. 842 to 1610). If 4P diverged in the Americas,
it did so approximately three centuries later than predicted; these
dates need to be reviewed. The divergence dates may well be cor-
rect, however, meaning that 4O and 4P diverged concurrently
somewhere else, like Spain or Portugal, and 4P migrated to the
Americas but never to Africa or that 4P exists in Africa but in-
adequate sampling has yet to find it.
Sharma et al., discovered two strains of subtype 3I in the
armadillos and humans of the southeastern United States, the
3I-2-v15 strain diverging from the 3I-2-v1 strain. Furthermore,
red squirrels on Brownsea Island are infected with subtype 3I of
virtually the same strain as that from medieval skeletons in both
Denmark ( Jorgen 625, A.D. 1293 to 1383) and England (SK2,
A.D. 1268 to 1263), which is closely related to the strain of 3I in
the United States. Even so, no evidence demonstrates that either
Scandinavians or the English brought leprosy to the southern
United States. However, leprosy in Canada may have arrived
either with immigrants from Brittany or sailors from Normandy; it
390 | SAM U EL M AR K

then traveled to Louisiana, probably with Acadian French settlers

after their expulsion from Canada in 1755. Because northern France
and southern England accepted Scandinavian migrants in the early
medieval era, both countries should have a similar strain of subtype
3I. Furthermore, since the Portuguese imported French marines to
Brazil between 1555 and 1700, some of them from Normandy when
leprosy was still prevalent there, the subtype 3I strain in Brazil may
also have come from France. Thus, the historical data not only allows
for a different interpretation for the spread of subtype 3I to the
Americas; it also illustrates another major hole in our molecular
data. The people of Portugal and Spain were vectors for the spread
of leprosy to many regions during their ages of discovery and colo-
nization, but the SNP subtypes in either country as well as their
changes over time are still something of a mystery. The same is true
for most of Asia.41

CHINA The earliest Chinese texts are problematical. The most

ancient medical text is the Nei Ching. Because it was continually
updated throughout the centuries, we do not know when leprosy
entered into it. The earliest surviving text dates to A.D. 762, but
Bodde dates the passage describing leprosy to the second or first
century B.C. Skinsenes contends that leprosy is the reason why
Po-Niu is described in the Lun Yu (c. 600 B.C.) as behind a screen
when Confucius comes to visit, touching his hand through a
window. The assumption is that Po-Niu was disfigured from chi;
in later times, O chi was a name for leprosy, though it can refer to
any “evil disease.” Numerous diagnoses are possible, including
tuberculosis or nasopharyngeal carcinoma (a facial cancer relatively
common in some Chinese groups). If Po-Niu’s face was disfigured
from leprosy, his hands would also have been disfigured. Since the
two men touched hands, Po-Niu probably was not afflicted with
leprosy.42
41 Sharma et al., “Zoonotic Leprosy,” 2127–2134; Avanzi et al., “Red Squirrels,” 744–747;
Scott, “Influence of the Slave-Trade,” 169–188, 182 [Normandy]; Jonathan Hutchinson, On
Leprosy and Fish-Eating: A Statement of Facts and Explanations (London, 1906), 68 [Portugal and
Spain], 235 [Brittany].
42 Olaf Skinsenes, “Understanding of Leprosy in Ancient China,” International Journal of
Leprosy and Other Mycobacterial Diseases, LIII (1985), 289–307, 289–290 [A.D. 762 and Lun
Yu citations]; Derk Bodde, “Medicine in Pre-Imperial China,” Journal of the American Oriental
Society, CII (1982), 1–15, 10 [date of passage in Nei Ching]; Lu Gwei-Djen and Joseph Needham,
“A History of Forensic Medicine in China,” Medical History Journal, XXXII (1988), 357–400,
T H E OR IG I N A ND S P R E A D O F LE P RO X Y | 391
A bamboo book taken from the tomb of Magistrate Hsi is
widely considered to describe a case of leprosy, often dated to
the latter half of the third century B.C. Leung, however, proposes
that the passage in question could date as early as the fourth cen-
tury B.C.: “The headman A of X village has brought in villager B,
a rank-and-file commoner. His denunciation reads: ‘I suspect li
(leprosy), and I have come along with him (to the Judicial Office).’
We interrogated B. His statement reads: ‘At the age of three, I
suffered from sores on my head, and my eyebrows fell out; but
the nature of the illness could not be determined. There is no
other offence of which I am culpable.’ Then we ordered the phy-
sician C to examine him. His statement says: ‘B has no eyebrows.
The bridge of his nose is gone, his nostrils are rotted, and when I
lanced what is left of his nose, he did not sneeze. His elbows and
knees down to the soles of both feet are defective and suppurating
at one place. His hands have no hair (on the back). When I asked
him to shout, his voice and breath were both feeble. It is leprosy.’”43
As previously noted, Monot et al. proposed that leprosy
spread to China from the west via the Silk Road, which began
at the city of Xi’an in Shaanxi Province and continued through
Gansu Province (Figures 2 and 4). If so, early evidence for leprosy
should exist in these provinces, but none does. Also, if the Silk
Road was such an efficient conduit for leprosy, subtypes 2F, 3K,
and 3L should be in northwestern China, especially since the
western end of the Silk Road was at Samarkand in present-day
Uzbekistan, where the only confirmed case is subtype 3L (A.D. 80
to 240), which is not found in China. Moreover, the Silk Road
was not a road per se but a collection of unmarked and shifting
paths roughly 3,600 km long, some of which passed through deserts
and mountains. Travel by this route was so treacherous that mer-
chants rarely took it all the way, preferring to trade goods with the
nearest village or oasis, passing goods down the line. Hence, instead

367 n. 37 [O chi definition]; Mark, “Nasopharyngeal Carcinoma: A Review of Its Causes and Its
Diagnosis in Skeletal Material,” International Journal of Osteoarchaeology, XVII (2007), 547–562,
550–551.
43 Skinsenes, “Understanding of Leprosy,” 291; Bodde, “Medicine in Pre-Imperial China,”
9; Gwei-Djen and Needham, “A History of Forensic Medicine in China,” 364 [third century
date]; Angela Leung, Leprosy in China: A History (New York, 2009), 22; Gwei-Djen and
Needham, “A History of Forensic Medicine in China,” published the excerpt, translated
by Donald Harper (367).
392 | SAM U EL M AR K

Fig.4 Map of China with Reported Prevalence of Leprosy Published

in 1897

SOURCES This figure is based on James Cantlie, “Report on the Conditions under which
Leprosy Occurs in China, Indo-China, Malaya, the Archipelago, and Oceania: Compiled
Chiefly in 1894,” in Prize Essays on Leprosy (London, 1897), 242–243.

of a conduit, the Silk Road would have been more of a barrier for
a slow-spreading condition like leprosy. Furthermore, the Silk
Road’s peak period of use was between A.D. 500 and 800; the
earliest evidence of trade on it between the west and China are
Byzantine coins from Chinese graves dating to the sixth century
A.D. Finally, leprosy appeared in the West centuries after it emerged
in China.44
Much later, the medical text Lingnan weisheng fang (A.D. 1264) con-
fined leprosy to only the southern provinces of Fujian, Guangdong,
and Guangxi. The sixteenth-century physician Zhiwen stated
that Fujian and Guangdong suffered from it the worst, and in the

44 Valerie Hansen, The Silk Road: A New History (New York, 2012), 8–10.
T H E OR IG I N A ND S P R E A D O F LE P RO X Y | 393
mid-seventeenth century, leprosy was still primarily associated with
the provinces of Fujian, Jiangxi, Guangdong, and Guangxi. Houses
for lepers arose primarily in Fujian, Jiangxi, and Guangdong prov-
inces from the fourteenth through the nineteenth century.45
In 1894, Cantlie sent out questionnaires to physicians about
the prevalence of leprosy and other diseases throughout China’s
provinces and then traveled to the affected regions to treat those
with the disease. He discovered leprosy to be clustered along the
southern coast, especially in Guangdong and Fujian Provinces and
among ethnic Chinese on Taiwan and the Hainan Islands. It was less
prevalent in Guangxi, Jiangxi, and Zhejiang; it was so rare in the
northern provinces that people there believed themselves to be im-
mune to it. Northern Shandong Province was an exception. Leprosy
existed there but not profusely (Figure 4). In 1906, Hutchinson
noted a greater presence of leprosy in southern China but still not
in northern China. He and Cantlie also noted leprosy at a few loca-
tions along the Yangtze River, but it must not have been widespread
because in 1929, the Ministry of Public Health stated that leprosy
had just begun to penetrate the Yangtze River basin and the north-
ern banks of the Yellow River (Figure 4).46
The evidence indicates that leprosy first spread to southern
China in the fourth or third century B.C. Molecular data show that
3K was most common in both coastal and inland provinces. The
appearance of subtypes 1D (seventeen cases) and 1A (one case)
only in the coastal provinces of Guangdong, Fujian, and Guangxi
indicates that subtype 3K arrived first. These data are consistent
with the proposed SNP dating system.47
The earliest evidence of leprosy in Japan emerged during the
Nara period (A.D. 710–784). The earliest known homes for lepers
date to the Kamakura period (A.D. 1185–1333). From Japan, leprosy
spread northward to Korea. A possible description of it dates to 1251
and the earliest detailed description to 1433. In 1445, it was endemic
only to Jeju Island between South Korea and Japan. In 1897, Cantlie

45 Leung, Leprosy in China, 32–33 [Zhiwen and southern China], 98–100 [houses].
46 James Cantlie, “Report on the Conditions under which Leprosy Occurs in China, Indo-
China, Malaya, the Archipelago, and Oceania. Compiled Chiefly in 1894,” in Prize Essays on
Leprosy (London, 1897), 239–413; Hutchinson, Leprosy and Fish-Eating, xi; Leung, Leprosy in
China, 139 [Yangtze River Basin 1929].
47 Weng et al., “Molecular, Ethno-Spatial Epidemiology,” 361–368 [molecular subtypes
and locations in China].
394 | SAM U EL M AR K

noted that the incidence of leprosy was low in the south and
diminished to the north of Korea. Hence, the evidence is consistent
with M. leprae spreading to southern China (3K, 1A, 1D) before
moving to Japan (3K, 1A, 1D, 2) and then Korea (3K, 1A, 2).48

The historical, molecular, and skeletal data indicate that determin-

ing a place of origin for M. leprae is far more complex than sug-
gested by the molecular data alone. Both historical texts and
molecular data suggest that M. leprae spread to both China and
Egypt probably via maritime routes at roughly the same time be-
tween the fourth and third centuries B.C. The earliest diagnosed
skeleton with leprosy between India and China is from Noen
U-Loke, Thailand (c. 300 B.C.), though without molecular con-
firmation. Historically and geographically, India best fits as a point
of origin for M. leprae, but, as noted above, the recorded SNP
subtypes are all too late. The molecular data, however, may be
incomplete as in China where only subtype 3K was originally re-
ported until more extensive sampling by province discovered sub-
types 1D and 1A in some of the maritime provinces. Thus, a similar
method of geographically mapping samples in India by province
and molecularly testing modern and ancient samples for both spe-
cies of leprosy could clarify whether India was the point of origin
for one or both of them. Testing for both species extensively could
also reveal a point of origin for M. lepromatosis and determine
whether M. leprae and M. lepromatosis spread together within cer-
tain ancient populations, such as from Egypt to northern Europe.
Additional modern and ancient sampling would also confirm
or refine the SNP dating system. A comparison of these data with
historical records and the earliest dated molecular data from an-
cient and medieval skeletons seems to support the present dating
system—especially when mapping the spread of leprosy from
southern Egypt to northern Europe. But additional data, even in
these regions, could confirm, modify, or refute this interpretation, as
well as shed light on whether leprosy began spreading to Western
Europe from Italy in the first century B .C . or whether it first

48 Kathryn M. Tanaka, “Contested Histories and Happiness: Leprosy Literature in Japan,”

Health, Culture and Society, V (2013), 99–118; Joon Lew, A Korean Model for the Healing of
Leprosy: The Resettlement Village Movement by Spiritual, Physical & Socio-economic Rehabilitation
for Persons with Leprosy (Seoul, 1993), 27–41; Cantlie, “Conditions under Which Leprosy
Occurs,” 319.
T H E OR IG I N A ND S P R E A D O F LE P RO X Y | 395
arrived with eastern invasions and migrations when the Roman
Empire began to crumble. Skeletal cases from India, dating as early
as 2000 B.C., that tested positive for M. leprae and permitted sub-
types to be determined, would confirm or refute the SNP dating sys-
tem and possibly determine a place of origin for M. leprae. Without
such confirmation, none of the current evidence can confirm that
either species of leprosy invaded India before 800 B.C.
In contrast to the case of India, no evidence suggests that East
Africa was a point of origin for M. leprae. If East Africa were to
have been the point of origin, the present SNP dating system would
have to be incorrect, or all recorded SNP subtypes would have to
be late arrivals from slavery and migration, requiring additional
sampling in East Africa and along trade and migration routes both
through Arabia (no cases recorded), Iran to the east, and Egypt to
the north (presently one case of M. leprae [SNP type 3]).
Typically, a place of origin is genetically diverse. The only
country between China and Egypt that fits this description is
Myanmar where SNP types 1, 2, and 3 and M. lepromatosis have
been found but no subtypes determined. Even if all of the subtypes
were to be found in Myanmar, some of them could turn out to
have been relatively recent arrivals. Because Chinese laborers car-
ried leprosy to various countries in Southeast Asia during the nine-
teenth century, including Myanmar, we have to differentiate
earlier from later subtypes in each country—for instance, the 3K
that spread to China c. 400–300 B.C. from the 3K re-introduced
there in the nineteenth century. Additionally, the direct voyages
to the region that the Europeans had begun to undertake by the
late fifteenth century could have introduced, or re-introduced, SNP
subtypes, possibly 2G, to the region. Although data that locate a
point of origin for either leprosy species are lacking, dated skele-
tons with SNP subtypes and current molecular data illustrate areas
where critical information remains to be collected. Such research
could ultimately lead to a definite point of origin or possibly two
separate points of origin, as well as more accurate mapping of the
initial migration of both species. Considering the impressive number
of SNP subtypes that have been mapped since 2009, most of these
gaps in our knowledge could be filled in a relatively short period.49

49 Cantlie, “Conditions under Which Leprosy Occurs,” 323–358 [Chinese laborers].