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Vaccination of the ethnic Greeks (Rums) against smallpox in the Ottoman Empire. Emmanuel Timonis and Jacobus Pylarinos as precursors of Edward Jenner

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ABSTRACT
100 Erciyes Med J 2021; 43(1): 100–6 • DOI: 10.14744/etd.2020.82856
HISTORY OF MEDICINE - REVIEW – OPEN ACCESS
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Theodoros Kyrkoudis1 , Gregory Tsoucalas1 , Vasileios Thomaidis1 , Ioannis Bakirtzis2 , Eleni Nalbandi3 ,
Alexandros Polychronidis4 , Aliki Fiska1
Vaccination of the Ethnic Greeks (Rums) Against
Smallpox in the Ottoman Empire: Emmanuel
Timonis and Jacobus Pylarinos as Precursors of
Edward Jenner
This historical review examined the onset of the vaccination method during the Ottoman Empire. Inoculation was performed
in the regions of Thessaly, Macedonia, and Thrace using folk medicine as a measure against the spread of smallpox/variola
infection. Greek physicians Emmanuel Timonis (1669–1720) and Jacobus Pylarinos (1659–1718) as well as several other
Ottoman scientists of the Greek or Turkish descent pioneered the use and dissemination of variolation and the development
of vaccination before or concurrently with Edward Jenner (1749–1823). During the 19th century in the Adrianople (Edirne)
region and much earlier in Constantinople (İstanbul), vaccination programs used to be implemented as evidenced by various
certificates distributed at that time. Ottoman vaccination documents from the early 20th century and the letter of Lady Mary
Wortley Montagu (1689–1762), dated 1719, have been analyzed, which confirms the extensive use of the vaccination
method. Smallpox was the first disease to have been treated with vaccination method. The difference between the Greek
and Ottoman physicians and Edward Jenner lies in the fact that while the Greek and Ottoman physicians removed fluid from
pustules of an infected person to perform inoculation, Edward Jenner removed fluid from pustules of infected cows, which is
why Edward Jenner’s method was coined vaccination (derived from the Latin word “vacca” meaning “cow”). Further, Turk-
ish physicians Mustafa Behçet Efendi (1774–1834) and Sanizade Mehmed Ataullah Efendi (1771–1826) recommended the
variolation method. It thus appears that the Ottomans provided care to all ethnicities of their Empire. Vaccines were initially
used against smallpox, but the immunization program was eventually extended to other diseases.
Keywords: Emmanuel Timonis, history of medicine, inoculation, Jacobus Pylarinos, Ottoman Empire, vaccination, variolation
INTRODUCTION
The British physician Edward Jenner (1749–1823) was the first to systematically apply vaccination against small-
pox. However, physicians Emmanuel Timonis (1669–1720) from Chios and Jacob Pylarinos (1659–1718) from
Cephalonia are considered to be the pioneers of the inoculation method and had their respective studies published
in 1714 in the English Journal Philosophical Transactions (1, 2).
In 1713, the Royal Society of London announced the invention of an immunization method against smallpox. The
pioneer of this method was physician Emmanuel Timonis from Chios, a Professor at the University of Padua, Italy,
who was also a personal physician of Ottoman Sultan Ahmed III (1673–1736). Two years later, another Greek
physician, Jacob Pylarinos from Cephalonia, made a similar discovery. He was also the head physician of the Tsar
of Russia, Peter the Great (1672–1725). From 1704 to 1707, Jacob Pylarinos worked in Constantinople (İstan-
bul) and later served as a consul in Venice, after which he continued his work as a doctor in Smyrna (İzmir) until
1718 (3). Both of them studied in Padua and held Venetian passports as they both hailed from the Venetian-occu-
pied territories of Greece (Fig. 1a) (4). During his numerous trips, Pylarinos met a Greek villager in Thessaly who
would rub children’s hands on an infected sheep wound to induce immunity. “Every September, some old women
perform vaccinations (inoculations, scarifications) when the heat subsides,” he mentioned in his work (5, 6).
Lady Mary Wortley Montagu (Fig. 2a) (1689–1762), wife of the English Ambassador of Constantinople, had her
6-year-old son inoculated in 1717 in Adrianople (Edirne) after having been informed of the inoculation method
against smallpox by Emmanuel Timonis. While everyone in Turkey saw despair and peril, she discerned glimpses
of promise. Variolation was adopted as a general measure for the public health and “the people there considered
it as self-evident as we consider water today” (7). The method gradually became popular after it was embraced by
the aristocracy and doctors of that time. By the year 1840, a Thracian physician and scholar of the Greek descent
born in Adrianople, Istefanaki Bey (Stefanos Karatheodori, 1789–1867) (Fig. 1b), performed the first official
variolation in Constantinople (8, 9).
Although there are several references for the inoculation method among the populations of China and India,
this historical review studies the origins of the inoculation method in the area of Adrianople and the Ottoman
Cite this article as:
Kyrkoudis T, Tsoucalas G,
Thomaidis V, Bakirtzis I,
Nalbandi E,
Polychronidis A, et al.
Vaccination of the Ethnic
Greeks (Rums) Against
Smallpox in the Ottoman
Empire: Emmanuel Timonis
and Jacobus Pylarinos
as Precursors of Edward
Jenner. Erciyes Med J
2021; 43(1): 100–6.
1History of Medicine,
Anatomy Department, School
of Medicine, Democritus
University of Thrace,
Alexandroupolis, Greece
2School of History and
Ethnology, Democritus
University of Thrace,
Komotini, Greece
3Medical English, School
of Medicine, Democritus
University of Thrace,
Alexandroupolis, Greece
4Department of General
Surgery, School of Medicine,
Democritus University of
Thrace, Alexandroupolis,
Greece
Submitted
22.05.2020
Accepted
29.05.2020
Available Online Date
17.12.2020
Correspondence
Gregory Tsoucalas,
History of Medicine, Anatomy
Department, School of
Medicine, Democritus
University of Thrace,
Alexandroupolis, Greece
Phone: +306945298205
e-mail:
gregorytsoucalas@yahoo.gr
©Copyright 2021 by Erciyes
University Faculty of Medicine -
Available online at
www.erciyesmedj.com
Kyrkoudis et al. Vaccination of the Ethnic Greeks in the Ottoman EmpireErciyes Med J 2021; 43(1): 100–6 101
Empire in general. In support, Ottoman vaccination documents
from the early 20th century have been analyzed and the letter
by Lady Mary Montagu has been cited. Smallpox was the first
disease to be treated with the vaccination method. Edward Jen-
ner has been widely considered as the primary pioneer of the
method, thus neglecting the folk wisdom of the Eastern people
as well as the achievements of the Greek physicians and Otto-
man Administration. A search in the online databases, such as
PubMed/Medline, Scopus, and Google Books, was conducted us-
ing “smallpox vaccination,” “Ottoman Empire and vaccination,”
and “history of vaccination” as keywords. In addition, follow-up
search in Greek and Turkish bibliographies was conducted. Doc-
uments on vaccination (Turkish: Çiçek aşısı) of the relevant period
and Lady Montagu’s letter were also studied.
Lady Montagu’s Letter and the Ottoman Vaccination
Documents
Lady Montagu’s letter, written in April 1717 in Adrianople to
her long-time correspondent Mrs. Frances Hewet, describes her
travels, mentioning that she is now in good health and people in
Edirne have been vaccinated against smallpox since 1717. Since
this practice was extremely successful and widespread in the Ot-
toman Empire, she revealed that she had her son vaccinated as
well (Fig. 2b) (10, 11).
The Ottoman vaccination documents that were researched are
of standard forms, include information related to the identity of
the concerned individual, and have been classified as proof of
public record, verbatim aşı şehadetnamesi (proof of vaccination)
and the affixed French title certificat du vaccine (vaccination cer-
tificate). The blank spaces in these documents have been filled in
by hand as well as sealed and signed by the clerk-in-charge. The
certificates were cut out of a “certificate pad” and contained, on
the upper right-hand corner, a printed numbering system koçan
varakası (certificate sheet) without always having the serial num-
a
bc
Figure 1. (a) Emmanouel Timonis and Jacobus Pylarinos,
engraving from the front cover of their book “Some account
of what is said for inoculating or transplanting the small-
pox” With some remarks thereon του Cotton Mather. Bos-
ton, 1721 (top-panel). (b) Stefanos Karatheodoris, portrait,
lithography by the Hellenic Institute of Venice, by Spyridon
Mavrogenis in his work Bios Konstantinou Karatheodori,
Koromelas Eds, Constantinople, 1868 (bottom-left panel).
(c) Tsalikis Pasas Zoiros Alexandros, portrait, Institute for
Neohellenic Research/NHRF (bottom-right panel)
a
bc
Figure 2. (a) Lady Mary Wortley Montagu with her son in
Constantinople, oil painting by Jean Baptiste Vanmour,
18th century (top-panel, 4 sheets). (b) Lady Montagu, Epis-
tle, 1717 (bottom-left panel). (c) Inoculation tools from
the personal collection of the Turkish professor İlter Uzel
published in Mercan Burcu xıx. yüzyılda Osmanlı’da çiçek
salgınları ve çiçek hastalığı ile mücadele. Kırklareli Üniver-
sitesi. Yüksek Lisans Tezi, 2017 (bottom-right panel)
Kyrkoudis et al. Vaccination of the Ethnic Greeks in the Ottoman Empire
102 Erciyes Med J 2021; 43(1): 100–6
ber imprinted. At the top right-hand corner, there is another
numbering system referred to as aded-i umûmi (general number).
The center of the upper portion of the document is sealed with
the tuğra (the Sultan’s calligraphically written identification com-
plex), which, in this case, belongs to Abdülhamid II (1842–1918)
and a round ornate jewel on the right with the inscription of the
name “el-Muzaffer Daima” (The Perpetual Triumphant). The last
vaccination certificate is different from the others with no Em-
peror’s seal but a writing Devlet-i Aliyye-i Osmaniyye (The High
Ottoman State). These documents are dated between 1903 and
1913 and traced back to Sofilu-Soufli, Kirk Kilise-Saranta Ek-
klissies/Forty Churches, and Balikesir areas, all demonstrating
incidences of family vaccinations (Fig. 3a–c) (12).
The Greek Physicians Pylarinos and Timonis
Meeting in Constantinople, Pylarinos and Timonis developed a
strategical method for dealing with smallpox, which was an epi-
demic scourge at that time. Convinced of the safety and effective-
ness of variolation, they published their studies (5).
In order to protect children against smallpox, some women healers
of the Ottoman Empire (majorly Greek and Caucasian populations)
engrafted fluid from pustules of patients suffering from smallpox
and scarified children’s skin, palms, forehead, and cheeks. During
the smallpox epidemic in 1707 in Constantinople, a noble lady,
mother of four little boys, visited Dr. Jacob Pylarinos. She inquired
whether he approved of her taking the boys to women healers,
to have scarification performed, and to allow the application of
fluid from smallpox pustules in order to protect them against the
lethal disease. This noblewoman’s initiative put Pylarinos in a di-
lemma as an expert answer was expected of him to ease the moth-
er’s worries. Indeed, as he writes in his study published in 1715,
the woman healer to which the noble lady planned on taking her
children “described sufficiently and extensively about the process,
manner, place, time, and details of the vaccination procedure.”
He also notes, “after careful consideration, I concluded that the
method was not incompatible with logic and nature.” Evidently, he
was convinced that it was safe to recommend vaccination to the
children, who in the long run showed effective protection against
the disease. He indicates that the application of the material on the
skin, where the scarification had been performed, “is a completely
natural intervention with no trace of bias.” The grafting of small-
pox is real, pure, and natural because it is performed with purely
natural and visible means. He even compared it to the 18th century
notion of disease therapy “of transplantation magnetism, through
which it is said that diseases are transmitted from one person to
the other” (5, 13).
Pylarinos then collected all the inoculation cases he was moni-
toring, and in 1715, with the permission of the Holy Inquisition
in Venice, he published his study Nova et tuta Variolas Excitandi
per Methodus; Nuper inventa & in usum tracta: Qua rite per acta
immunia in posterum praeservantu ab hujus modi contagio corpo-
ra, literally entitled “A new and safe method for treating smallpox
through grafting; newly invented and easily applied, keeping the
rest of the body successfully unaffected by such an infection.” He
adds that he was publicizing his method owing to its promising
efficacy as a means of protection against the deadly smallpox. He
stated, “We announce a medical practice worthy of being admired
by the scientific community not only for its invention but also for
its effectiveness” (10).
Emmanuel Timonis was the son of a priest from Chios. Most of his
family members were clergy or doctors. The poet Lorentz Mavilis
(1860–1912) and the painter Georgio da Chirico (1888–1978) were
both descendants of his family. He was the Vice-Rector of the Uni-
versity of Padua in 1691 and had completed his PhD from Oxford
(11). F.H. Garrison states in the History of Medicine that his daugh-
ter, Kokona Timoni, was vaccinated by him in 1722 and died much
later of smallpox, proving that the vaccination was not effective (14,
15). Emmanuel Timonis went on to publish two scientific papers,
“Istoria variolarum qua per incisionem excitantum” (History of small-
pox cured by incision) in Constantinople in 1715 and “Tractatus de
nova variolas per trasmutationem excitanti method” (Treatise on the
newest findings concerning smallpox grafting through scarification)
in Leiden in 1721. Emmanuel Timonis’ works have been translated
and published in several languages, including English, Italian, and
French (14). It is well known that Timonis performed experiments
in Constantinople, Chios, and elsewhere, but the significance, in his
case, is that although he studied in Padua and Oxford, the doctor
trusted folk medicine and as a result, the British distrusted his meth-
od (13, 16). This notion also stands true for Pylarinos.
a
b c
Figure 3. (a) Proofs of family vaccination, Soufli, 1903
(top-panel). (b) Proofs of family vaccination, Saranda Ek-
klisies, 1903 (bottom-left panel). (c) Proofs of family vacci-
nation, Balikeser, 1913 (bottom-right panel)
Kyrkoudis et al. Vaccination of the Ethnic Greeks in the Ottoman EmpireErciyes Med J 2021; 43(1): 100–6 103
The two pioneers against smallpox, according to Alivizat, prob-
ably met in Smyrna (17). Pylarinos in the “Introduction” raises
the issue of trust in folk medicine and practical healers, empha-
sizing the perspective that what some considered being magic
and empirically perpetuated had a medical basis. Nevertheless,
the methodical science of medicine was required to record and
systematize these empirical practices in order to prove which of
the practices were right and wrong. He seemed to believe that
medicine should not be prejudiced against empiricism as scien-
tists in the Western Europe believed, but rather it should examine
all cases to identify what concept lies behind the “magic.” Per-
haps because there was no Holy Inquisition in the East, people
exercised these practices more freely. For example, he mentions
the case of a woman making the vaccine herself while trying to
convince his reader on the practicality of this method where the
doctor was called upon to observe and experiment with. In gen-
eral, we could say that the Greeks, being Easterners, appeared
more amenable to practical medicine than the Westerners. Al-
though they were uneducated, laymen are crucial in guiding un-
biased scientists who can examine and codify the data as he did
in the multitude of exemplary incidences he described. In the first
part, he describes the method they followed, symptoms of the
vaccination, and outcome. In the second part, he presented his
own experiments as well as those of Timonis’ as practices that
they noticed were used by the people of the Empire. The de-
scription of their experiments revealed how a scientist functions
through observation in order to arrive at safe outcomes and by
not concealing even a single case in which the vaccination result-
ed in poor outcomes. He did not consider his method a panacea,
but he did believe that everyone must be vaccinated, especially
children (18, 19).
The detailed juxtaposition of both Timonis’ and Pylarinos’ experi-
ments provides a prominence to their excellent collaboration with-
out any trace of antagonism. They seek not only to benefit the
local people but also the entire world, considering that they pub-
lished their results in the West. Pylarinos’ scientific methodology
was also demonstrated in the last part of his study “Aetiologia,”
where he used logic as a guide to draw conclusions from his ex-
periments, thereby enabling the possible treatment of the disease
(18, 19). For some people, Pylarinos is the first immunologist of
the modern world (20).
A French book published in Paris in the year 1756 entitled Recueil
de pieces concernant l’inoculation de la petite vérole, et propres à en
prouver la securité et l’utilité (A collection of documents concerning
the inoculation of smallpox and proof of its safety and usefulness)
reports, on page 9, that Aubry de la Mortaye, a French cosmopoli-
tan traveler who visited his friend Timonis, mentions his technique.
In the next chapter, he says that Timonis learned this technique
from a healer in Filippoupoli, who in turn had learned it from her
ancestors. The healer’s instructions included the use of a laxative
and abstaining from meat, eggs, and wine for 5–6 days before
vaccination. Timonis learned of another method recommended by
a healer in Thessaloniki, who scarified the skin in the shape of a
cross, possibly for religious reasons. Elsewhere, he refers to the
letter written by Timonis to the Royal Society of London as well as
to Mr. Skragenstierna, the royal head doctor of the Swedish King.
In this letter, Timonis describes a method of drawing a blend of
smallpox pus mixed with blood. For vaccination, he selected chil-
dren who were ill, and on the 12th or 13th day of the appearance of
the rash, he pierced the pustules mainly in the feet of the children
using a needle. He describes his technique in detail and concludes
that in his eight years of practicing it, he was pleased with his suc-
cess (21). However, it still remains uncertain where Timonis first
encountered this method against smallpox, despite the multitude of
geographical references available.
From Britain to the World
The method adopted by the Ottoman citizens, published by two
doctors for information of the European medical community, was
brought to Europe by Lady Mary Wortley Montagu, a poet and
wife of the English Ambassador of Constantinople, Edward Wort-
ley Montagu (1678–1761), who served as the Ambassador from
1716 to 1717. When she was informed about the vaccination
procedures against smallpox by the physician Emmanuel Timo-
nis, who had been practicing since 1701, she had her 6-year-old
son vaccinated (22). Through a letter sent in 1717 from Adri-
anople, she helped to forward the application of inoculation in
England as well. She had several scars on her face and had lost
her brother to smallpox. Lady Montagu, who happened to be in
England in 1721 during the smallpox epidemic, had her 2 and a
half-year-old daughter vaccinated against the disease. According
to the Oxford Dictionary of National Biography, “the practice of
inoculating children spread rapidly among those who knew Lady
Mary and who had already been bereaved by the disease. Lady
Mary’s most important activity during the 1720s, for the world if
not for herself, was the introduction of inoculation against small-
pox to Western medicine” (11, 23). The inoculation method,
which was already used by Timonis and Pylarinos, soon gained
popularity and was practiced by several physicians in Europe. In
1721, the famous American surgeon Zabdiel Boylston (1679–
1766), who recognized the importance of the work of the two
Greek physicians, began the application of the inoculation meth-
od in Boston (4, 24). The Genevan physician Théodore Tronchin
(1709–1781), after studying in Cambridge University, introduced
the inoculation method in Switzerland, praising the two Greek
pioneers in his writings (25).
J. Crowford, a British physician, mentioned that the inoculation
method was introduced by both Timonis and Pylarinos. Although
he suggested that all physicians should experiment with the inoc-
ulation method for smallpox, he also proposed the idea that Pyla-
rinos had exaggerated the success ratio. As the variolation results
in Britain showed lower success, Crowford believed that Pylarinos
mostly noted rather than practiced the suggested method (26).
Some researchers also believe that the Turkish population as well
as the Turkish Administration of the Ottoman Empire neglected
to take measures against epidemics at least until the 19th century.
However, the citizens of Turkish origin had sporadically used the
inoculation technique, especially in the regions where Greek and
Circassians resided while the Greek physicians were employed
by the Empire (22, 27). Moreover, it is believed that young wom-
en recruited from Caucasian villages to become spouses of the
Sultan likely promoted this practice and that the Sultan himself
recognized the scars on their body and encouraged promotion of
the method (22).
Kyrkoudis et al. Vaccination of the Ethnic Greeks in the Ottoman Empire
104 Erciyes Med J 2021; 43(1): 100–6
It seems that the first case of smallpox inoculation was performed
in Thessaly (16th century), a region in the middle of the Hellenic
peninsula, and later in Macedonia as a folk method against infec-
tion (28). Based on the observations of Timonis and Pylarinos,
the said method was introduced in England, where deaths from
smallpox averaged roughly 10%–20% in the affected regions (29).
The publication of the two Hellenic papers in the same volume
of Philosophical Transactions supports the view of the possible
collaboration of the two physicians. Meanwhile, both the works
were republished in a common volume in Leiden in 1721 after the
deaths of both the authors (30, 31). A few years later, the method
was embraced by the Greek population, both in the Hellenic pen-
insula and the islands (first adopted in the Ionian island complex
of Heptanesa) as well as in the Asian parts then belonging to the
Ottoman Empire. This fact was sealed by the recommendation of
the Christian Orthodox Patriarch who cherished the method and
proposed it to all the Greeks (32).
Was it the French?
Pylarinos and Timonis were considered as Edward Jenner’s pre-
cursors (30, 31). Jenner was the one who introduced the term
“vaccination,” which was later accepted by the great French mi-
crobiologist Louis Pasteur (1822–1895) (29). However, it seems
that both of them adopted the method of the Greek and Ottoman
physicians, who made critical contributions to the major achieve-
ments of vaccination through bibliography and international con-
ferences (33).
At several times in the history, breakthroughs in medicine were
attributed to only one person. Thus, Edward Jenner has paradoxi-
cally remained in the history as the first physician to have had sys-
tematically applied the vaccination method against smallpox, even
after 80 years of its actual introduction. Jenner used pustules col-
lected from infected cows (variolation vs. vaccination) (34). Thus,
the difference between the Greek and Ottoman physicians and
Edward Jenner lies in the fact that while the Greek and Ottoman
physicians used pustules collected from an infected person in order
to achieve immunization, Edward Jenner used pustules collected
from infected cows, which explains why his method is termed as
“vaccination” (derived from the Latin word “vacca” meaning cow)
(5, 8, 9). However, the initial scientific application of the term
“vaccination” in the European territory should be attributed to the
observational spirit of the Greek physicians Pylarinos and Timonis
as well as the Ottoman citizens and Ottoman State authorities.
The Ottomans always employed Greek physicians in their service,
recognizing their significance but also applied the folk inoculation
method, which was being practiced among the Rums (35).
At this time point, we should mention the Ottomans’ leadership
in preventive medicine and that the vaccination program included
citizens of the Ottoman Empire from all categories. Because epi-
demics affected the entire area, the Sultans sent their physicians,
mostly Greeks, to various conferences in the West and favored
application of epidemic-containment methods (8). It is therefore
important to note that during 19th and 20th centuries, the vaccina-
tion programs were also applied for other diseases, such as rabies
(1882), plague, cholera (1883), dysentery, diphtheria (1900), and
typhoid fever (1915) (8, 13). It was decided in 1840 that all those
applying to the Imperial School of Medicine (Mekteb-i Tıbbiye-i Ad-
liye-i Şahane) should be vaccinated and two officials, under the title
of “vaccinationist,” headed by Dr. Isthefanaki Bey Karatheodori,
were accordingly appointed (36).
The Ottomans
Since the early 15th century, a method of variolation through the
nostrils was recorded in China. However, the first Western phy-
sician to provide an accurate description of smallpox was Ahrun
(610–641), a Greek-speaking Christian Egyptian, who lived in
the city of Alexandria. In the 10th century, the best and earliest
description of smallpox and its differential diagnosis from measles
was provided by one of the most notable physicians and poly-
math Abu Bakr Muhammad ibn-Zakariyya al-Razi (854–925).
Shortly afterwards, reports appeared of the described cutane-
ous variolation in various regions of the Ottoman Empire (37).
A Christian inoculator, Ali Chelepi, widely used this method in
Adrianople around the year 1657, including that on his son (38).
In 1712, physician Edward Tarry of Enfield, who had returned
to England from Pera and Galata, claimed that he had observed
more than 4000 cases of variolated Ottoman citizens. In 1715,
Peter Kennedy, a Scottish ophthalmic surgeon who had visited
Constantinople, also published his observations of variolation
or, in his words, “engrafting the smallpox,” in a book titled An
Essay on External Remedies. On March 7, 1716, the botanist
William Sherard (1659–1728), British Consul at Smyrna, and a
close friend of Pylarinos, sent a letter and printed pamphlet pub-
lished by Pylarinos to his brother James Sherard (1666–1738),
an apothecary and a Fellow in the Royal Society. It seems that
Pylarinos had undertaken, or at least observed, a series of three
successful inoculations in or around the year 1701. Moreover,
Sherard’s letter stated that two sons of John Hefferman, the Sec-
retary to Sir Robert Sutton (1671–1746), the British Ambassador
to Turkey, had been variolated in Constantinople (39). Moreover,
Timonis himself praised the Ottomans for their use of the said
method, which according to his opinion, had been adopted from
the populations of the deeper Asian continent and had been in
use since at least past 40 years before his publication (32).
There were four manuscripts published in the early 20th century
that mentioned inoculation prior to the 18th century in the Ottoman
Empire. They all refer to a mystery man who came to Constanti-
nople and variolated some children. It may have been Ali Chelepi.
One more manuscript of the late 18th century mentioned a female
inoculator who inoculated 50 or 60 children in Adrianople. Al-
though all these events happened in the lands of the Ottoman
Empire, it seems that due to the fact that most of these physicians
were Christians in majority of the populations using the inoculation
method, the scientific discussion became more Eurocentric and as
a result, the Oriental innovations were somehow sidelined (38).
The Ottoman leadership in the field of vaccination was further
demonstrated by the historical creation of the first bacteriological
center in the Eurasian region. On his return from Paris, Zoiros
Alexandros Tsalikis Pasha (1841–1917) (Fig. 1c) brought with
him two hares that had been infected the day before along with
all the equipment required to establish a bacteriology laborato-
ry. Upon his return to the Empire on December 29, 1886, he
wrote a report to the Sultan (cited in Yıldız Palace archives, file
25) and immediately set up the bacteriology laboratory as well as
Kyrkoudis et al. Vaccination of the Ethnic Greeks in the Ottoman EmpireErciyes Med J 2021; 43(1): 100–6 105
the production of the vaccine against rabies. Under the direction
of Zoiros, the laboratory began operating in his clinic, to be lat-
er transferred to Demirkapı on the premises of the old Medical
School. Dr. Zoiros Pasha named the operating room “Dersaa-
dette Daülkelp ve Bakteriyoloji Ameliyathanesi.” This was the
first institution created in the East for the treatment of rabies.
Zoiros Pasha started preparing the vaccine by using materials
collected from the two infected hares and transferring the materi-
als by injecting to other hares. Pasteur’s method of preparing the
first vaccine against rabies administered to infected people was
later announced to the Military Medical School Administration
in Constantinople on June 3, 1887 (8). The center of Zoiros
Pasha did an enviable job against infections. It has been report-
ed that after the transfer of the laboratories from the garden of
the Imperial Medical School to a mansion house in Nisantasi in
1895, 3,750 vaccines against diphtheria were produced in the
year 1899–1900. At about the same time, two more institutes of
microbiology and preventive medicine began operations, namely
the Vaccination Laboratory against smallpox and Imperial Vac-
cination Center in Constantinople. Between 1892 and 1913, a
total of 7,260,784 people were vaccinated (8, 39). Zoiros Pasha
was a great admirer of the French microbiologist Louis Pasteur
and he represented Turkey in several scientific conferences to
share his knowledge of the Ottomans (8).
Considering all these findings together with the concerning issue
of vaccination certificates by the Ottoman authorities revealed
that these documents contained sufficient details on the identity
of the individuals who were vaccinated but the most interesting
information was omitted, viz., diseases that were prevented as a
result of vaccination. The fact that all other certificates, except
for two, are related to only one family may be a strong indication
that vaccination in the Evros region had spread to the popu-
lations. This observation may also be interpreted as a version
of progressive urbanization, since it implies a level of familiarity
with all the modern medicines of that time had to contribute to
the emerging field of disease prevention (39). The center of all
decisions seems to have been Constantinople, where smallpox
appeared as early as in the 12
th
century and also evidenced by
Theodore Prodromos’ collection of poems “Ptochoprodromika”
(1115–1160). It seems that both Timonis and Pylarinos applied
the variolation in the epidemic that broke out in Constantinople
in 1701, following the example of a Greek individual who is
said to have used it in 1660. Many scholars believe that Timonis
was the first to study it. At first, the Turks rejected the method,
but later the Ottoman authorities embraced it and implemented
general variolation programs (40–42). Vaccination of the popu-
lation appears to have been organized and massive, beginning
during the Ottoman Empire and culminating in the 19
th
and 20
th
centuries (37).
Greek newspapers of the time, both in the Greek territory and in
areas of the Ottoman Empire (the Istanbul’s “Postman” and the
Macedonian “Thessaloniki”), extensively covered the vaccination
programs while physicians of the time had developed the appro-
priate inoculation tools (Fig. 2c). In addition to physicians of the
Greek descent, several Ottoman physicians used the variolation
technique, including Mustafa Behçet Efendi (1774–1834) (Fig. 4a)
in 1801, who also translated Jenner’s work from Italian to Turkish,
Sanizade Mehmed Ataullah Efendi (1771–1826) (Fig. 4b) in 1811,
and Hekim Ismail Pasa (1807–1880) (Fig. 4c) in 1845, who ar-
rived from Chios and served as Sultan Abdülmecid’s chief surgeon
and personal physician (8).
Epilogue
The Ottomans provided care to individuals of all ethnicities of the
Empire. The vaccines initially concerned smallpox but were later
extended to other diseases to acquire a broader character, result-
ing into family planning. The pioneers appeared to have been the
Greek physicians of the Ottoman Empire, whom the Ottoman
authorities had the intelligence to employ in their state mecha-
nism. The inoculation method applied through folk medicine by
the laymen of the Ottoman Empire led to its scientific discovery.
Vaccination is one of the brightest chapters in the history of med-
ical sciences. However, the tendency of the Western medicine to
neglect the achievements of Eastern people such as the Greeks
and Ottomans is once more observed in the case of vaccination
against smallpox. In fact, the lone genius paradigm, as in the case
of Edward Jenner, is detrimental to the evolution of a medical
breakthrough.
Figure 4. (a) Mustafa Beh-
çet Efendi, portrait, en-
graving of the 19th century
(left panel). (b) Sanizade
Mehmet Ataullah Efendi,
colorized engraving, be-
ginning of the 20th century
(center). (c) Hekim Ismail
Pasa, portrait as published
in Turkish journal “Milli-
yet” in 1986 (right panel)
a b c
Kyrkoudis et al. Vaccination of the Ethnic Greeks in the Ottoman Empire
106 Erciyes Med J 2021; 43(1): 100–6
Acknowledgments: We would like to thank Mr. Michail Pateli (collector)
for the kind issue of vaccination certificates.
Peer-review: Externally peer-reviewed.
Author Contributions: Concept – TK, GT; Design – TK, GT; Supervision
– AF, AP; Resource – TK, VT, IB; Materials – AF, GT; Data Collection and/
or Processing – AF, GT, VT; Analysis and/or Interpretation – IB, TK, GT;
Literature Search – AF, AP; Writing – GT, EN; Critical Reviews – AF, AP.
Conflict of Interest: The authors have no conflict of interest to declare.
Financial Disclosure: The authors declared that this study has received
no financial support.
REFERENCES
1. Timonis E. An account or history of the procuring the small-pox by in-
cision or inoculation as it has for some time been practiced at Constan-
tinople. Philosophical Transactions 1714; 29(339): 72–82. [CrossRef]
2. Pylarinos J. A new and safe method of procuring the small pox by
transplantation. Philosophical Transactions 1714; 29(339): 393–99.
3. Pentogalos G. Physicians and Medical practice in Kefalonia island. [Ar-
ticle in Greek]. Thessaloniki: USP; 2004.p.133.
4. Pertsianis N. A short story of Vaccination [In Greek]. Nicosia: Self pub-
lication; 2011.
5. Karaberopoulos D. The Folklore use of Vaccination against Variola
virus as the point of origin for the vaccination technique inn 1701 by
Jacobus Pylarinos [Article in Greek]. Folklore medicine and Medical
science, a two-way relationship Congress, Academy of Athens, 2018.
6. Karaberopoulos D. Immunology, yesterday-today-tomorrow. [Article in
Greek]. Arch Hellenic Med 2011; 28(5): 711–2.
7. Allen A. Vaccines, History of the most saving medical discovery [In
Greek]. Athens: Archipelagos; 2009.p.14–30.
8. Κarlikaya E. The vaccination and serums which were prepared in ot-
toman empire with the estabilishments which were produced them.
Balkan Med J 1999; 16(3): 167–78.
9. Unat EK. Osmanlı İmparatorluğu’nda Bakterioloji ve viroloji. Istanbul:
Istanbul Universitesi Cerrahpasa Tip Fak Yayinlari; 1970. p. 11–12,
17, 24–32, 37–49.
10. Letter by Mary Wortley Montagu. Available from: URL: https://www.
theguardian.com/books/2016/aug/18/letter-by-mary-wortley-mon-
tagu-pioneering-travel-writer-up-for-auction. Accessed February 6,
2020.
11. Montague Wortley M. The Turkish Embassy Letters. Chicago: Virago,
1994.
12. Kyrkoudis Th. Pharmacists of Asia Minor, Pontus and Cappadocia.
[Article in Greek]. Thessaloniki: iwrite, 2019: 110.
13. Karaberopoulos D. The first Scientific application of Vaccination by the
Greek physicians Emmanouel Timonis and Jacobus Pylarinos (begin-
ning of the 18th century). [Article in Greek]. Bulletin of the 1st Pediatric
Clinic of the University of Athens 2006; 53: 347–51.
14. Lascaratos J. Emmanouel Timonis (1669-1718 to 1720) Biography
and Work [Article in Greek]. Medical Society of Chios Island: Chios,
2000.p.31–42.
15. Garrison FH. An introduction to the history of medicine: with medical
chronology, suggestions for study and bibliographic data. Philadelphia:
Saunders; 1929.p.372–3, 830–2.
16. Ünver AS. Türkiye’de Çiçek Aşısı ve Tarihi. İstanbul: İstanbul Üniversi-
tesi Tıp Tarihi Enstitüsü, 1948.
17. Alivisatos CN. The First Immunologist, James Pylarino (1659-1718),
and the Introduction of Variolation: (Section of the History of Medi-
cine). Proc R Soc Med 1934; 27(8): 1099–104.
18. Maurelos N. Greek medical philosophers in the Balkans and Europe:
the beginnings of modernity (1664-1727). Proceedings of the 4th Con-
gress of Neogreeks, Komotini, November 2019.
19. Pylarinus J. Nova et tuta variolas excitandi per transplantationem
methodus; Nuper inventa et in usum tracta.[In Latin]. Leiden: Janso-
nius Vander; 1721.
20. Garrison FH, Morton TL. Morton’s Medical Bibliography. Norman JM,
editor. 5th edition. London: Scolar Press, 1991.
21. Montucla JE, Morisot-Deslandes PJ. Recueil de pieces concernant l’
inoculation de la petite Verole & propres a en prouver le securite & l’
utelite. [in French]. Paris: Desaint & Saillant & Vincent, 1756.
22. Dinc G, Ulman YI. The introduction of variolation ‘A La Turca’ to the
West by Lady Mary Montagu and Turkey’s contribution to this. Vaccine
2007; 25(21): 4261–5. [CrossRef]
23. Jenner E. An inquiry into the causes and effects of the variolae vacci-
nae. London: Sampson Low, 1798.
24. Boylston A. The origins of inoculation. J R Soc Med 2012; 105(7):
309–13. [CrossRef]
25. Karaberopoulos D. When was the “first vaccine” invented?. [Article in
Greek]. The News J, Athens 2020; April the 10th: 12.
26. Crawford J. The Case of Inoculating the Small-pox Considered. Lon-
don: Warner T; 1722.
27. Stavropoulos A. A sketch of the health conditions and diseases in the
hellenic area after the fall of the Byzantine empire (1453) until the
Greek revolution (1821). Hist Sci Med 1982; 17(Spec 1): 163–7.
28. Kotsiou A, Michalaki V, Anagnostopoulou HN. Devastating epidemics
in recent ages Greek populations. Acta Med Hist Adriat 2017; 15(2):
283–90. [CrossRef]
29. Huth E. Quantitative evidence for judgments on the efficacy of inocu-
lation for the prevention of smallpox: England and New England in the
1700s. J R Soc Med 2006; 99(5): 262–6. [CrossRef]
30. Poulakou-Rebelakou E, Lascaratos J. Emmanuel Timonis, Jacobus Py-
larinus and inoculation. J Med Biogr 2003; 11(3): 181–2. [CrossRef]
31. Cotsaftis G. Un précurseur, inconnu, de Jenner. [Article in French]. La
Chronique Médicale 1923; 1: 87–9.
32. Vladimiros L. The History of the Hellenic Medicine in Smyrna [Article
in Greek]. Athens: Union of Smyrnaeoi, 2018.
33. Gross CP, Sepkowitz KA. The myth of the medical breakthrough:
smallpox, vaccination, and Jenner reconsidered. Int J Infect Dis 1998;
3(1): 54–60. [CrossRef]
34. Flower DR. Bioinformatics for Vaccinology. Oxford: John Wiley &
Sons, 2008. [CrossRef]
35. Lazarou G. Greek medicine in the near Danube hegemonies. [Article in
Greek]. Athens: GL; 2017.
36. Marcetos S, Trompoukis C, Lascaratos J, Bartzokas Ch. The lead-
ing physician from Chios Emmanuel Timonis and his era. [Article in
Greek]. Chios: Medical Society of Chios; 2000.
37. Karatepe M. The role of Turkish physicians in the vaccination against
typhus during the years of World War I. [Article in Turkish]. Mikrobiyol
Bul 2008; 42(2): 301–13.
38. Alicia G. Globalisation of Variolation: The Overlooked Origins of Im-
munity For Smallpox In The 18th Century. London: World Scientific;
2019.
39. Kexagias Th. Sciences in the Ottoman Empire: The Educational In-
stitutions [Article in Greek]. Critical Science and Education 2006; 4:
77–93.
40. Yenen OS. History and eradication of smallpox in Turkey. Microbiolo-
gy Australia 2014; 9: 156–64. [CrossRef]
41. DE Raymond JF. Querelle de l’inoculation ou préhistoire de la vaccina-
tion, Librairie Philosophique. [In French]. Paris: J Vrin; 1982.
42. Winslow OE. A destroying angel: The conquest of smallpox in colonial
Boston. Boston: Houghton Mifflin Company; 1974.p.89.
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