Contributions of Padua to Nephrology
(Dedicated to Arturo Borsatti)
Am J Nephrol 1999;19:226–233
Santorio Sanctorius (1561–1636) –
Founding Father of Metabolic Balance
Studies
Garabed Eknoyan
Renal Section, Department of Medicine, Baylor College of Medicine, Houston, Tex., USA
Key Words
Renaissance W Sanctorius W Metabolic balance W
Insensible perspiration W Instrumentation
Abstract
The intellectual renaissance of the closing decades of the
sixteenth century provided the fertile ground in which
the budding spirit of scientific inquiry emerged in the
seventeenth century. Direct observation, soon aug-
mented by instrumentation that allowed for quantifica-
tion and, therefore, verification, became the revelatory
medium for the progress of the sciences. In medicine,
progress depended on the application of the exact
sciences of chemistry, mathematics and physics to the
study of function. One of the medical luminaries of this
early scientific revolution was Santorio Sanctorius (1561–
1636), whose principal contributions were his studies on
insensible perspiration and his instrumental inventions.
To study insensible perspiration, he designed a movable
platform attached to a steelyard scale that allowed for
the quantification of changes in body weight of subjects
who partook in their daily activities on the platform. After
years of self-experimentation, he applied his device to
the study of patients. Unfortunately, his records are lost.
What survives is a summary of his observations in a
series of aphorisms published under the title of Ars de
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statica medicina, in 1614; 3 years after he was appointed
Ordinary Professor of Theoretical Medicine in Padua. To
enhance the bedside evaluation of patients, he also
designed instruments to quantify the pulse, temperature,
and environmental humidity. For his pioneering and
detailed balance studies, Sanctorius clearly deserves the
title of founding father of metabolic balance studies.
The challenges to ancient orthodoxy and scholasticism,
increasingly voiced by Renaissance humanists during the
closing decades of the sixteenth century, culminated in
the seventeenth century in a fundamental, and although
dispersed but nevertheless a large scale, attempt to change
the view of the whole of the natural world. One of the
more perplexing and astonishing moments in scientific
thought, the seventeenth century has been appropriately
dubbed ‘The Insurgent Century’ [1]. It was then that the
explanation of the natural world advanced by Aristotle
(384–322 BC), and accepted as dogma for centuries past,
came under scrutiny and considered to be no longer ade-
quate. Once the rationale for direct, rather than textual,
observation of nature became the rule, it quickly became
evident that there were just too many contradictions
between the recorded, often theoretical, descriptions of
the ancients and those that were being actually observed.
Garabed Eknoyan, MD
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Department of Medicine
Baylor College of Medicine
One Baylor Plaza, Houston, TX 77030-3498 (USA)
Tel. +1 713 798 4748, Fax +1 713 790 0681
Stockholms Universitet
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The problem became all the more critical when the power
of observation began to be magnified by the growing use
of instrumentation. The resultant intellectual revolution,
began by the philosophers (Bacon, Descartes) and astron-
omers (Copernicus, Kepler), provided the very founda-
tions of scientific research and the roots of modern
science that was to flourish in the centuries to come [2, 3].
As subjective description was replaced by objective mea-
surements (mathematics, physics), scientific experiments
in the form of repeatable and reproducible phenomena
became possible. In astronomy, what Copernicus (1473–
1543) had demonstrated mathematically, Galileo (1564–
1642) confirmed by repeated, reproducible and quantifia-
ble observation, using instruments to extend the senses. It
was then that experimental tradition became well estab-
lished, and perception, augmented by new instrumenta-
tion, became a constant revelatory medium for the pro-
gress of the sciences.
This new and revolutionary spirit of scientific inquiry
also affected the biological sciences [4]. In medicine,
revolt was channelled against the authority of Galen
(130–200), whose voluminous writings formed the bulk of
the medical texts that were becoming widely available in
their original version following the advent of the printing
press (1454). The rebellion began in anatomy. Andreas
Vesalius (1514–1564), the more famous and better known
of the advocates of the direct observational method in
anatomy, vigorously argued that those who sought medi-
cal truth should put aside medical texts and directly study
the human body [5]. It is ironical that none other than the
principal victim of these attacks, Galen, had advocated
that the path ‘to become expert in all matters of plants,
animals, and metals ... was by personally inspecting them,
not once or twice, but often’ [6]. The difference was that
the method which Galen had professed now became
accepted and vigorously applied. It is also ironical that it
was the very rediscovery of direct observation that deter-
mined the limitations of the anatomical approach that
Vesalius and his contemporaries had advocated. Accurate
knowledge of structure did not provide an understanding
of function, and the dead bodies that were being exam-
ined meticulously did not yield the secrets of life. Indeed,
even when dissection was performed on live bodies, the
secrets of nature remained elusive. Vesalius, who did
resort to vivisection, could not advance the understand-
ing of renal function beyond that of Galen [6, 7]. This is
what Vesalius had to say about renal function: ‘the office
of purgation is most fitly performed by the kidneys ... they
quickly draw the greater part of the serous humor of the
liver toward themselves and strain it from the blood. In
Santorio Sanctorius
order that they may accomplish this more handily, a nota-
ble vein and likewise an artery are extended to the kidney;
the kidney receives the serous humor into a membranous
sinus ... covered by a double tunic ... and expels the urine
off into another sinus which is prolonged as the urinary
passage and constructed like a vein ...’. The recurrent ref-
erence to veins is a central tenet of the teaching of Vesal-
ius who believed that ‘nature gave straight fibers to the
veins, by means of these it draws blood into its cavity’ [8].
Thus, while anatomists gradually evolved a concern for
function, and therefore physiology, their explanations
were structural and remained descriptive but did provide
the fertile grounds on which the new science of physiology
would thrive and prosper.
Progress occurred only when the exact sciences of
chemistry, mathematics and physics began to be applied
to medicine. Explanation of function on a chemical basis
started with Paracelsus (1493–1541), who was in fact one
of the first to attack the ancients and challenge the teach-
ings of Galen [9]. He is considered the founder of the
Iatrochemical School, that was to reach its height in the
work of Jean Baptist van Helmont (1577–1644) and Fran-
ciscus Sylvius (1614–1672). Physics and mathematics
were the two other growing exact sciences to be used in
order to provide an explanation of function [10, 11]. René
Descartes (1596–1650), who did much to encourage the
practice of experimentation, brought the human body, the
‘earthen machine’ as he called it, into the sphere of phys-
ics (iatrophysics) [12]. The language of iatrophysical
medicine became that of mechanics (iatromechanics)
or mathematics (iatromathematics). Giovanni Borelli
(1608–1679) brought to the study of action and move-
ments a knowledge of physics and is considered the foun-
der of the iatromechanical school. While Santorio Sancto-
rius (1561–1636) applied mathematics to the study of
medicine and is considered a founder of the iatromathe-
matical school [13, 14].
This pace in the effort to understand and explain func-
tion, which emerged gradually in the sixteenth century,
increased in the seventeenth century, but remained re-
markably restricted to islands of learning. Interestingly,
by and large most of the scientists who led the scientific
revolution in the seventeenth century were trained or
worked in Padua. Padua, which had emerged from its
medievalism and achieved some degree of fame in the
fourteenth century, came under the protection of Venice
in 1440, an event that would ultimately provide it with
the intellectual freedom which was instrumental in mak-
ing it the most distinguished center of learning in Europe
during the second half of the sixteenth and most of the
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 Fig. 1. Time line showing some of the prominent contemporaries of Santorio Sanctorius in medicine, the sciences and
liberal arts.
seventeenth century. This was perhaps truest of its medi-
cal faculty which was founded in 1250 [15]. The era of
medical science in seventeenth century Padua was an
interlude which exhibits a surprising flash that was funda-
mental to the development of the modern methods of
medical research. It was in this atmosphere that Galileo
and Harvey, the two most celebrated Paduan figures,
were trained to think and solve the problems of the new
sciences. Eminent amongst the early scientific experi-
menters and a figure whose work spans the transition
from the 16th to the 17th century is Santorio Sanctorius, a
contemporary of Galileo and a predecessor of Harvey in
Padua (fig. 1).
228 Am J Nephrol 1999;19:226–233
Santorio Sanctorius (1561–1636)
Santorio Sanctorius was born on March 29, 1561, in
Capodistria, the capital of Istria, then under the rule of
Venice and still known by its Roman name of Justinopolis
(fig. 2). Of patrician descent, and the oldest of four chil-
dren, his father, Antonio, was a Friulian nobleman who
had been appointed Chief of Ordnance of the city and his
mother, Elisabetta Cordonia, was of a prosperous and
noble Istrian family. His connections to nobility were to
come to good stead, both during his childhood education
and subsequent career appointments. His schooling
which began in Capodistria, continued in Venice where
he received private education in the home of family
friends, the powerful Morosinis. In 1575, at the age of 14,
he began his studies at the University of Padua, first in
philosophy and later in medicine (table 1). In 1582, he
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Fig. 2. The house of Santorio Sanctorius in
Justinopolis (now Koper), marked with a
commemorative bust placed in his honor by
Italian physicians characterizing him as
‘First Eminent Teacher of Experimental
Medicine’.
received his degree in medicine at the age of 21, one year
younger than Vesalius had received his in 1537, and three
years younger than Harvey would receive his in 1602,
both from the same school [16–18].
Five years after graduation he seems to have been
recruited to practice medicine in the various courts of
eastern Europe. After some 12 years, he returned to
Venice in 1599 to continue his practice of medicine. In
Venice, he became part of the intellectual circle which
gathered at the home of his childhood friend and class-
mate, Andrea Morosini, and included such luminaries as
Galileo, Fabrizzio de Aquapendente (1537–1619) and
Fra Paolo Sarpi. Shortly after his return to Venice, he pub-
lished in 1602 his first book: Method of Combating All the
Errors which Occur in the Art of Medicine (table 2). It was
this book on differential diagnosis that established his
fame and coupled with the strength of his social connec-
tions led to the invitation to serve as Professor of Theoret-
ical Medicine in Padua in 1611. Galileo, who had served
as Professor of Mathematics (1593–1610) had just left,
Fabrizzio de Aquapendente was then Professor of Anato-
my and teaching in the amphitheater he had built in 1595,
and Harvey who had completed his studies in Padua
(1593–1602) had long left.
The position of First Ordinary Professor of Theoria
had been vacant since 1603. In Santorio, the chair
acquired an experienced practitioner, an investigator of
Santorio Sanctorius
Table 1. Santorio Sanctorius (1561–1636)
1561 Born March 29, Capodistria (Justinopolis, Koper)
Begins studies in Venice (Morosinis)
1575 Begins university studies in Padua
1582 Receives medical degree
1582 Begins medical practice and research studies
1611 Professor of Theoretical Medicine, Padua
1616 President, Collegio Venetio, Padua
1624 Returns to medical practice, Venice
1630 President, Venetian College of Physicians
Chief Health Officer, Venice
1636 Dies on February 22, Venice
Table 2. Bibliography of Santorio Sanctorius
1602 Methodus vitandorum errorum omnium qui in arte medica
contigunt
1612 Commentaria in artem medicinalem Galeni
1614 De Statica medicina
1625 Commenteria in primam Fen primi Canonis Avicennae
1629 Commenteria in primam sectionem Aphorismorum
Hypocratis
1629 De remediorum inventione
1638 De lithotomia seu calculi vesicae consultatio
co-authored with L. Batarourum (posthumous)
De instrumentis medicis (unpublished)
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some consequence, and a creative spirit whose influence
extended well beyond the borders of Padua. As Professor
of the Theory of Medicine, his responsibilities were to
interpret and teach the Aphorisms of Hippocrates, the Art
of Medicine of Galen, and the first part of the Canon of
Avicenna. Over the years he would publish his lectures as
commentaries on the work of all three (table 2). Commen-
taries which had started as student aids for learning had
evolved into scholastic endeavors of some merit in the
modernization of teaching [19], at least until the first half
of the seventeenth century. Amongst the more than 60
extant copies of the Commentaries on Avicenna, the one
by Sanctorius is deservedly famous because it was so
uncharacteristic in its genre for the inclusion of scientific
instruments designed by the author to quantify (pulse,
temperature, humidity) the study of patients. Their inclu-
sion indicates that Sanctorius used them in the teaching of
medicine [18, 20]. However, the book that was actually to
establish his position in posterity as a scientist was a rela-
tively short text on insensible perspiration, titled Ars de
statica medicina and published in Venice in 1614.
During the term of his tenure as Professor of Theoreti-
cal Medicine, he was appointed President of a new college
(Collegio Veneto) in 1616, a position he held for 8 years
until 1624, when at the age of 63 he resigned to return to
the practice of medicine in Venice. In recognition of his
contributions, the Venetian Senate granted him the title
of professor and an accompanying salary for life. The fact
that he had several powerful connections in the Venetian
Senate, including his schoolmate Morosini, no doubt
facilitated this well deserved, but rarely granted honor. In
1630, he was appointed President of the Venetian College
of Physicians and Chief Health Officer to control the
plague that was then ravaging Venice. He died, at the age
of 75, on February 22, 1636, from what is said to be com-
plications of urinary tract disease from which he had suf-
fered for several years. Buried in the Church dei Servi in
Venice, his bones were disinterred during the looting of
Venice on Napoleon’s orders, following the Treaty of
Milan. His bones, entrusted to the Professor of Anatomy
of Padua, were ultimately buried in his home town of
Capodistria, while his presumed skull is preserved in the
Anatomical Museum of Padua.
A man of small stature, with a trim beard, Sanctorius
never married, dedicating all his time to his work. A tire-
less investigator, inspired by the exact sciences, he fo-
cused on selected issues that he studied exhaustively. In
his work he demonstrated unprecedented patience and
perseverance. His studies on insensible perspiration, at
which he worked so assiduously, were superior in ap-
230 Am J Nephrol 1999;19:226–233
proach, design and meticulousness to any others of his
time. A man ahead of his times, who preceded the other
luminaries of the century (fig. 1), Sanctorius was recog-
nized by his contemporaries as one of the major figures of
the seventeenth century and considered the equal of Har-
vey. The Ars de Statica medicina underwent 28 editions
and remained in demand well into the end of the eigh-
teenth century and was translated into Italian, English,
German and French [15, 21].
Scientific Contributions
The principal contributions of Sanctorius were his
studies on insensible perspiration and his instrumental
inventions. The latter is at the very core of his metabolic
studies on insensible perspiration. The instrument he
developed for its study consisted of a movable platform,
attached to a steelyard scale, on which the subject would
partake in daily activities, that allowed for the measure-
ment of changes in body weight (fig. 3). His work began as
one of the first self experimentation studies in which he
would partake a meal set on the table before him until his
weight reached a predetermined quantity. If he then
remained on the balance for a while, he could observe his
weight becoming gradually lighter. He recognized that
this decline in weight represented a loss of matter, the loss
of which he called insensible perspiration. During the
course of the experiment, he would weigh the stool and
urine excreted and subtract them from the final change in
weight to verify the loss attributed to insensible perspira-
tion.
After years of self-experimentation, he applied the
instrument to the study of other subjects. In the letter pre-
senting a copy of De Statica to Galileo, he claims to have
studied more than 10,000 subjects in the span of 25 years
[15]. That would entail the daily study of at least one sub-
ject literally on every single day of the 25 years! It is unfor-
tunate that the data he collected is not preserved and that
he elected to summarize his findings in a series of apho-
risms. While criticized for this shortcoming, it should be
kept in mind that at the time of his studies, he was in
constant movement in Eastern Europe and that data
books, as we conceive them today, were not in fashion.
Additionally, the text is not a mere listing of aphorisms,
such as the forerunner of them all the Hippocratic Apho-
risms. Rather, each aphorism is followed by an explana-
tion, which, in paragraphs of varying lengths, provides the
rationale of the information distilled in the aphorisms.
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 The notion of insensible perspiration was not new [22,
23]. Galen had identified it quite clearly as: ‘mouths
placed on the skin pass out whatever is redundant of
vapors and smoke ... and the other excretion, which has
no name because it is not commonly known, since it
escapes observation ... is insensible perspiration (adelos
diapnoe)’, and was cognizant of its overall metabolic con-
sequences ‘... the amount of urine passed everyday shows
clearly that it is the whole of the fluid drunk which
becomes urine, except that which comes away with the
dejections, or passes off as sweat, or as insensible perspira-
tion’. This was the basis of the central role of bathing and
lustrations in Greek and Roman medicine.
What Sanctorius accomplished was to bring to bear the
scientific method in documenting these earlier observa-
tions by quantifying them by instrumentation, verifying
them by repeated examination, and extending them to the
study of the determinants of its variation. The importance
he attached to the role of insensible perspiration is stated
in Section I, Aphorism II: ‘If a physician, who has the care
of another’s health, is acquainted only with sensible sup-
plies and evacuations, and knows nothing of the waste
that is daily made by insensible perspiration, he will only
deceive his patient, and never cure him’. A general notion
of his concepts can be gleaned from the following quotes.
Section III, Aphorism LXXVI: ‘In the first hours after eat-
ing a great many perspire a pound or near; and after that
to the ninth two pounds; and from the ninth to the six-
teenth scarce a pound.’ Section I, Aphorism VI: ‘If eight
pounds of meat and drink are taken in one day, the quan-
tity that usually goes off by insensible perspiration in that
time, is five pounds.’ Section 1, Aphorism XIV: ‘Sixteen
ounces of urine is generally evacuated in the space of one
night; four ounces by stool, and forty ounces upwards by
perspiration.’ Section I, Aphorism LXXXIX: ‘Vomiting
diverts urine and perspiration.’ Section I Aphorism
Fig. 3. The metabolic balance devised by Santorio Sanctorius for the
XCIV: ‘Those who piss more than they drink, little or study of insensible perspiration. From De Statica medicina, 1690.
nothing perspire.’ Section III Aphorism XIV: ‘Robust per-
sons discharge their food for the most part by perspira-
tion. Those not so strong by urine, and the weak chiefly by
an indigested chyle.’
This is well beyond what Galen and all his successors Statica medicina is the result of studies that must have
had said about insensible perspiration. It is a first effort to been initiated at or about 1582 when the rudiments of the
obtain physiological data and provide a quantitative basis scientific revolution were just beginning to gel. As such,
to pathophysiology by meticulous study and precise in- they were not only innovative, but advanced for their
strumentation [24, 25]. Not only did he study insensible time and laid the basis of all future metabolic studies. In
perspiration, but documented its fluctuations under the our balance experiments today, we handle intakes and
influence of such variables as air, food, age, movement, outputs of the body essentially as Sanctorius did, except
repose, sexual activity and drink. Published in 1612, and for the addition of chemical analysis to what he only char-
by his admission having taken 30 years to complete, De acterized in terms of weight and volume.

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Fig. 4. ‘Lectus artificiosus’ – a mechanical bed for the care of inval-
ids – whose advantages Sanctorius characterizes as especially merito-
rious because the patient can remain comfortably seated in bed; can
defecate in bed through a special foramen; can move the bed position
by the four metal balls suspended from the top; and can be moved
while seated allowing for transportation and change of linen.
To evaluate him by current criteria, his work was clear-
ly novel, acknowledged by his contemporaries, and pro-
vided the stimulus for research by others not only in the
17th century, but well into the 20th century. In fact, his
studies did not reach full fruition until the beginnings of
the 20th century when they were resuscitated by the use of
the matter of perspiration for calculating basal and total
metabolism [26].
232 Am J Nephrol 1999;19:226–233
Fig. 5. ‘Balneatorium’ – a leather bag that allows bathing or hydro-
therapy of the patient in bed. After placing the patient in the bag, the
neck of the sack is drawn together with a string, then cold or hot water
can be poured through a tube at the upper and drained through
another at the lower end of the bag.
Conclusion
Although best remembered for his metabolic studies,
Sanctorius made equally important and original contribu-
tions to instrumental precision in medicine [25]. The bal-
ance he used in his studies was but a forerunner of other
instruments to come. Among others, these included a
thermometer to measure temperature, a hygrometer to
record moisture, a pulsilogium to quantitate the pulse, a
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mechanical bed for the care of incapacitated patients
(fig. 4), and a device to bathe the sick in bed (fig. 5). He
alluded to these instruments in his early publications, and
had intended to publish their detail in a volume that
remained only a manuscript, now lost, De instrumentis
medicis. Ultimately, he incorporated them into his Com-
mentary on Avicenna published in 1625 (table 2).
For all his innovative approach and contributions,
Sanctorius clearly deserves not only the title of founding
father of metabolic studies, but also that of clinical experi-
mentation, objective physiological measurement and
medical instrumentation.

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