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Anatomy and physiology by Leonardo: The hidden revolution?

Published:November 11, 2015DOI:https://doi.org/10.1016/j.surg.2015.10.001
      As the editor, I hope you will enjoy reading this piece as much as I did. Written by a very enthusiastic, passionate Italian surgeon (aren't the all?), Dr Antonio Sterpetti, a devotee of Leonardo da Vinci, “paints” a picture of the life an influence of Leonardo in our understanding of many aspects of the art of medicine through both the anatomic art an the investigative work of Leonardo. Not only is Dr Sterpetti's hypotheses plausible, the “Italian” English, which I tried to preserve whenever possible, itself is art! Enjoy! Michael G. SarrThe Renaissance (the French term for rebirth; Rinascimento in Italian) was a cultural movement which characterised the Italian and European life from the 14th to the 17th century.
      • Burckhardt J.
      The civilization of Renaissance in Italy.
      • Kehoe T.J.
      • Damerow H.E.
      • Duvall J.M.
      Exploring Western Civilization to 1648.
      • Cantimori D.
      Studi di Storia, Umanesimo, Rinascimento, Riforma.
      • Burke P.
      The Italian Renaissance: Culture and Society in Italy.
      The Italian Renaissance started in Florence and Siena and spread rapidly to Venice, Rome, Genoa, and Milan. Among the many factors contributing to this phenomenon, we should include the economic prosperity which characterised the City-States of North and Central Italy, among the wealthiest in Europe. This prosperity was based on the active trades, which extended all over the areas surrounding the Mediterranean. In all City-States of North and Central Italy, local Princes gave their strong support to the development of almost any form of culture.
      • Burckhardt J.
      The civilization of Renaissance in Italy.
      • Kehoe T.J.
      • Damerow H.E.
      • Duvall J.M.
      Exploring Western Civilization to 1648.
      • Cantimori D.
      Studi di Storia, Umanesimo, Rinascimento, Riforma.
      • Burke P.
      The Italian Renaissance: Culture and Society in Italy.
      Leonardo da Vinci (born in Vinci, Italy, in 1452; died in Amboise, France, in 1519) is probably the artist and scientist who represents the “ideal” man of the Italian Renaissance. The philosopher Pico della Mirandola in his “De hominis dignitade” of 1486 listed the characteristics of the mission of human beings as: intelligence and thinking, to understand the beauty of the world created by God.
      • Fumagalli M.
      • Brocchieri B.
      Pico della Mirandola.
      For his treatise, Pico della Mirandola was excommunicated by the Roman Catholic Church. Leonardo tried always to understand the mechanisms which characterised the manifestations of nature described by Pico della Mirandola.
      • Mignano M.
      Leonardo.
      Leonardo was painter, sculptor, architect, scientist, mathematician, poet, inventor, astronomer, geologist, historian, and cartographer. In all his activities, he showed fertile imagination, far above the horizons of his times.
      • Mignano M.
      Leonardo.
      • Santi B.
      Leonardo.
      • Clayton M.
      Leonardo's medicine years.
      • O'Malley C.D.
      • Sounders C.M.
      Leonardo on the human body: the anatomical, physiological and embryological drawings of Leonardo da Vinci.
      • Bortolon L.
      The life and times of Leonardo.
      • Boa G.
      Leonardo e l'anatomia.
      His mind and personality seem to be superhuman, especially when we consider the method of study of his times, when superstition and logics tried to move together in an anarchistic march. Vasari,
      • Vasari G.
      Vita dei più eccellenti pittori, scultori ed architetti italiani, da Cimabue insino i giorni nostri.
      an historian of his times, described Leonardo as an humble, mysterious man, whose favorite past time was to go to markets and buy birds in cages; soon thereafter, Leonardo set the birds free, watching them flying away, with a mysterious smile in his lip, possibly that same uncatchable smile he painted in some of his most famous works like “La Gioconda,” “Saint John The Baptist,” and “The Virgin of the Rocks.”

      A painter with interest in anatomy
      • Mignano M.
      Leonardo.
      • Santi B.
      Leonardo.
      • Clayton M.
      Leonardo's medicine years.
      • O'Malley C.D.
      • Sounders C.M.
      Leonardo on the human body: the anatomical, physiological and embryological drawings of Leonardo da Vinci.
      • Bortolon L.
      The life and times of Leonardo.

      Leonardo started as a student in the “Bottega” of Verocchio, a well-known painter in Florence. Those “Botteghe” were present in all major cities in Italy and represented a sort of university college, where students learned also architecture, engineering, and mathematics. Close relationships and exchanges of ideas were shared between the Botteghe of different cities. Through such exchange of ideas, Leonardo became well-known in a very short time all over Italy.
      Leonardo started in the Bottega at a young age: some say at the age of 10, others at the age of 16.
      • Mignano M.
      Leonardo.
      • Santi B.
      Leonardo.
      • Clayton M.
      Leonardo's medicine years.
      • O'Malley C.D.
      • Sounders C.M.
      Leonardo on the human body: the anatomical, physiological and embryological drawings of Leonardo da Vinci.
      • Bortolon L.
      The life and times of Leonardo.
      Leonardo was an excellent student, and by the age of 19, he was allowed officially to start his independent activity. Verrocchio had a special interest to reproduce exactly in his paintings the structures of the muscle and the skin; these were times when visual perspectives and action were an obligation in art to better reflect the real world. Many artists performed anatomic studies, but those studies were limited to the superficial structures. Leonardo performed studies in humans, including post-mortem dissections in Florence at the age of 20 years; being an artist, he was granted “special permission” to perform human dissections.
      The interest of Leonardo in the relationship between anatomy and physiology is evident in several anatomic studies about the flexion–extension of the arm and hand (Fig 1). His observations learned in these anatomic studies are reflected in several of his paintings, where the action of the hands have special meaning and importance, like in “The Virgin of the Rocks” (Fig 2) or in “Saint John the Baptist” (Fig 3). The “supposed” movement of the index finger gives “real-time action” to all in the scene of the Last Supper, when Jesus says to his Apostles, “One of you will betray me.”
      Figure thumbnail gr1
      Fig 1The position of the hands was very important to give movement to the painting. Specific anatomic studies were performed by Leonardo as shown in the drawing from the Royal Collection. Windsor Castle (with permission).
      Figure thumbnail gr2
      Fig 2The Virgin of the Rocks (ca 1485; Oil on panel; Louvre Museum, Paris). The detailed anatomic studies are reflected in the perfection of the position of the hands, which give movement and feelings to the entire picture.
      Figure thumbnail gr3
      Fig 3Saint John the Baptist (ca 1515; oil on walnut wood; Louvre Museum, Paris) is one of the last paintings of Leonardo. The saint has the same enigmatic smile one can see in other paintings of Leonardo. The saint points to the Paradise. It seems that Leonardo want to tells us that he knows what the Paradise is.
      Leonardo's interest went beyond simple physiology, and he tried to understand the correlation between anatomic changes and diseases. In this way, he was possibly one of the first to create a form of surgical pathology, overcoming the old theories in which diseases were identified as an imbalance in the humours.

      A mysterious man
      • Vasari G.
      Vita dei più eccellenti pittori, scultori ed architetti italiani, da Cimabue insino i giorni nostri.
      • De Mazzeri S.A.
      Leonardo. L'uomo ed il suo tempo.
      • Santi B.
      Leonardo. I protagonisti dell'arte italiana.
      • Lomazzo G.P.
      Idea del tempio della pittura.

      Leonardo's vision of the world was essentially logical, using an empiric method of study, unusual for his times and for many centuries after. He wrote, “no human investigation can be said to be true science, if it can not be demonstrated by mathematics…” and “…nature is driven by the intelligence of its laws.”
      Despite this fact, his life has been always surrounded by mystery and curiosity. Leonardo was left-handed. In those days, all left-handed children in Italy were not allowed to write with the left hand, and they had to write with the right hand. This rule was applied in all major teaching centres. Leonardo, however, was the illegitimate child of a rich notary from Florence, and he grew up in a small village (Vinci) not far from Florence, almost in clandestinity. His education was entrusted to his uncle and to a priest, who did not correct this peculiarity, allowing Leonardo to write freely with the left hand. All his writings can be read only at the mirror, because he wrote with the left hand and from the right to the left. Leonardo, not rarely, wrote enigmatic phrases to increase the interest and encourage the thinking of his students.
      To his “logics,” he often added his “not understandable” imagination and curiosity. In all his works, from engineering to painting, he was revolutionary.

      The revolution in painting
      • Vasari G.
      Vita dei più eccellenti pittori, scultori ed architetti italiani, da Cimabue insino i giorni nostri.
      • Santi B.
      Leonardo. I protagonisti dell'arte italiana.
      • Lomazzo G.P.
      Idea del tempio della pittura.
      • Beltrami L.
      Documenti e memorie riguardanti la vita e le opere di Leonardo da Vinci in ordine cronologico.
      • Baroni C.
      Tutta la pittura di Leonardo.

      All the personages in the paintings of Leonardo express humanity and feelings, thanks to the many small details. The differences between his paintings and those made before him are surprising. He influenced directly Michelangelo Buonarotti (with whom he had many discussions and disputes) and Raffaello, who went to visit him in Florence. Raffaello changed completely his style of painting after seeing Leonardo and his works. Freud, the father of psychoanalysis, once said, “each of the paintings of Leonardo is a treatise of psychology.”

      The history of his anatomic drawings5-8,9,11-14,19

      Leonardo, supported by his genuine desire to understand the intrinsic mechanisms of nature, became very interested, not only in the superficial anatomic structures, mainly muscles and skin, but also in the internal organs. His interest did not remain confined to the anatomy per se; he tried to understand the role of each organ and its anatomy in the human body. Mondino de Liuzzi performed the first “public” human dissection in Italy in 1315. In 1319, Mondino de Liuzzi published the textbook “Anhotomia,” which represented the only textbook of anatomy accepted in all medical faculties in Europe for almost 200 years. The then accepted anatomic theories were the ones proposed by Galen formulated almost 1,000 years before. Findings in animals were extrapolated directly to the human body. The few drawings in the textbook “Anhotomia” were very schematic and drawn by people who never saw a human dissection.
      • Pasini G.
      Mondino de Liuzzi. Anhotomia. Bibliografia dei lavori che danno informazioni su Mondino.
      Leonardo planned to write his textbook “De humanis corpore” with many anatomic illustrations. He stated, “You can explain for many hours, with much knowledge and many details, the characteristics of an anatomic structure: well, you will never reach the accurateness of a well done drawing.” He started to make anatomic drawings with many annotations, as a preparation to the final version of the textbook. The textbook was supposed to consist of 120 “quaderni,” explaining for each organ and surroundings the detailed anatomy, physiology, and pathology with notes on the comparative anatomy with animals. The textbook was supposed to be completed initially in the winter of 1510 and then later in 1516. He started to make drawings and annotations, probably, at the age of 20. He continued this work with alternating attention until he was 60 years old.
      Unfortunately, he never completed this work, and the textbook was never published. At his death, all the books of Leonardo were passed, in heritage, to one of his two loyal disciples, Fabrizio Melzi, who followed him to Rome and to France, and who guarded them until his own death. Later, all his drawings and annotations were bought by the architect and sculptor Pompeo Leoni (1533–1608), who worked for the Spanish government for many years. He divided all the annotations according to the subject of study. Leoni died in Madrid in 1608. No information exists about the anatomic drawings of Leonardo from when they were bought by Leoni until 1621, when they were in possession of the agency of Thomas Howal of London.
      Why this agency bought the drawings and who commissioned such an affair? No one knows.
      Still, they were bought by the King Charles II (1680?) and since then they have been well-preserved at Windsor Castle, outside London. Other drawings and annotations by Leonardo are located in the Instut de France in Paris. Today, about 8,000 pages of the drawings and annotations by Leonardo are known. It has been said that probably the total number of pages left to Fabrizio Melzi at Leonardo's death in 1519 was probably more like 100,000. In 1966, two new “Codici” were found in an old library in Madrid.
      We should note that London, Paris, and Madrid have been centres of power and development in the history of Europe.

      Leonardo: a stubborn and compulsive researcher
      • Vasari G.
      Vita dei più eccellenti pittori, scultori ed architetti italiani, da Cimabue insino i giorni nostri.
      • Santi B.
      Leonardo. I protagonisti dell'arte italiana.
      • Lomazzo G.P.
      Idea del tempio della pittura.

      Anonimo Gaddiano Manuscript. Biblioteca Nazionale di Firenze 1540.

      My hypothesis described above is based in part on the fact that Leonardo was very meticulous as well as scrupulous in his investigations. It has been said that he did not finish many of his works, because some of his paintings and statues are not complete (“Saint Jerome in the Wilderness” [Fig 4]; “The Adoration of Magi” [Fig 5]; The Statue “Great Horse” [Fig 6]). The reason for such a matter was that Leonardo was very revolutionary for his time as well as innovative in all his works; apparently, many of the influential people who commissioned the paintings did not “understand” the painting and refused to support economically the continuation of the painting, so that Leonardo was forced to stop work on the painting and never completed the work.
      Figure thumbnail gr4
      Fig 4A, Detailed anatomy of the muscle structures of the neck. Royal Collection. Windsor Castle (with permission). B, St Jerome in the Wilderness (ca 1480; tempera and oil on walnut panel; Vatican Museum, Rome) depicts St Jerome who lived as a hermit in the desert. In the right hand, the saint holds a rock with which he beats his chest in penance; in front of him, a lion, his loyal companion after he extracted a thorn from its teeth. Leonardo painted the work in a period of deep depression. The history of this painting is not clear. Legends says that it was divided in four pieces which were found by the uncle of Napoleon (a Cardinal) in several humble shops. Probably the sad atmosphere created by the painting was not liked by who commissioned the painting, and Leonardo was forced had to stop work on this piece, which he never finished.
      Figure thumbnail gr5
      Fig 5Adoration of Magi (1481; oil on wood; Galleria Uffizi, Florence). This work is also unfinished, because the priests who commissioned the painting did not like it and stopped all financial support to finish the work. In the centre are the Holy Mary and Jesus Child—two calm, peaceful figures; all around there is surprise, intense emotions in the faces of the people, like they are assisting to a revolution, to something extreme. There is the essence of the mission and message of Christ “a peaceful revolution.” The priests commissioned a more traditional painting by Filippino Lippi.
      Figure thumbnail gr6
      Fig 6A and B, Preparatory drawings for the Great Horse (1481–1485). The work was commissioned by the Duke of Milan (Ludovico il Moro) who asked for the creation of the largest statue of horse in the world in honor of his father. Leonardo had completed all the work with a clay model about 7 meters tall and 20 meters long. The horse was admired deeply by the population of Milan. The final step consisted on the fusion of 100 tons of bronze. In those days, Milan was attacked by foreign enemies, and unfortunately, the Duke preferred to use the bronze to make cannon balls rather than for the horse. The Duke was defeated, and his enemies entered in Milan. They used the “Gran Cavallo” as target to test their crossbows, destroying the model.
      Matteo Bondello, a novelist, saw him working at the fresco “The Last Supper,” and he wrote, “early in the morning, at the sunrise, he started to work on the Cenacolo (Last Supper) and he painted until the sunset, without eating or drinking, just painting…. Other times, he remained to watch the fresco for four-five hours, judging and examining the figures in silence.”
      In some of his annotations, he wrote, “now it is time to stop working, otherwise the soup gets cold.”

      Methods of study
      • Keele K.D.
      Leonardo da Vinci s views on atherosclerosis.
      • Keele K.D.
      Leonardo da Vinci on movement of heart and blood.
      • Keele K.D.
      Leonardo da Vinci elements of the science of man.
      • Boon B.
      Leonardo da Vinci on atherosclerosis and the function of the sinuses of Valsalva.
      • Sterpetti A.V.
      The revolutionary study on blood circulation by Leonardo were too advanced for this time to be published.

      Leonardo performed many studies in animals, mainly cows, and probably in 30 human dissections. He analysed accurately the anatomy of the fresh specimens. From his annotations, we can hypothesise that he also performed studies in animal specimens, obtained after in vivo fixation with different substances designed to study the heart and the blood vessels in more physiologic conditions, as concerns blood pressure and vascular compliance. He made several wax casts of the bull heart in attempt to analyse the details of the internal surface and the movement of the valves.
      From these wax casts, he made glass models to study the hydraulic characteristics of the blood flowing through the heart and its valves using this in vitro model to mimic the human circulation.
      These methods of study were quite revolutionary in times when the heart and its functions was reproduced in anatomic drawings with schematic sketches, made by people, the “experts,” who never experienced first hand an actual anatomic dissection.
      According to Bonn,
      • Boon B.
      Leonardo da Vinci on atherosclerosis and the function of the sinuses of Valsalva.
      Bellhouse
      • Bellhouse B.J.
      Velocity and pressure distribution in the aortic valve.
      published a series of experiments on the mechanics of the aortic valve in 1969 using a transparent model of the aorta with a flexible valve perfused by water. Adding small particles mixed in the water made the patterns of the flow visible, whereby Bellhouse concluded that only minimal reversal in blood flow was required to close the valves completely, preventing regurgitation, because eddy currents in the valvular sinus allowed the leaflets to already begin to approximate during the later stage of the systole.
      In 1991, Robicsek
      • Robicsek F.
      Leonardo da Vinci and the sinuses of Valsalva.
      showed that Leonardo performed almost 450 years before the same sophisticated experiments of Bellhouse with a similar technique and with similar conclusions. Because of his special interest in engineering and hydraulics, Leonardo worked on many projects in Milan, Venice, and Rome involving redirections of major rivers, draining of marshes, and the buildings of dams and water channels. In all these projects, he introduced many interesting innovations. He studied the dynamics of the water flow in rivers, using colours to show the flow patterns, defining the continuous stress on the lateral walls of the river determined by the flow of the water “which is not direct, but tortuous like a snake… the water is continuously bouncing against the banks … and as time passes the course of the river gets more and more tortuous.”
      Along similar lines, Leonardo applied unusual, modern technology to determine the movement of several joint structures of the human body, using special machines and models made for this purpose.

      Heart and blood circulation
      • Kehoe T.J.
      • Damerow H.E.
      • Duvall J.M.
      Exploring Western Civilization to 1648.
      • Cantimori D.
      Studi di Storia, Umanesimo, Rinascimento, Riforma.
      • Keele K.D.
      Leonardo da Vinci s views on atherosclerosis.
      • Keele K.D.
      Leonardo da Vinci on movement of heart and blood.
      • Keele K.D.
      Leonardo da Vinci elements of the science of man.
      • Sterpetti A.V.
      The revolutionary study on blood circulation by Leonardo were too advanced for this time to be published.
      • Bellhouse B.J.
      Velocity and pressure distribution in the aortic valve.
      • Robicsek F.
      Leonardo da Vinci and the sinuses of Valsalva.

      When Leonardo was writing his theories about the heart and the circulation, common knowledge about these matters was unclear and full of mysticism and superstition at the same time (Fig 7, Fig 8). He writes, “the heart is a muscle which contracts spontaneously.” He understands that the aorta provides blood, “calor,” and “energy” to all the body through the arterial blood which goes up to the skin through the capillaries. He examined in detail the bronchi out to their smallest ramifications, noting that each of them was accompanied by a small branch of the pulmonary artery. On the basis of these observations, he hypothesised that the bronchial arteries receive “freshness” from the bronchi, which are full of air. In such a way, the venous blood receive “freshness” in the lung before returning to the heart. This observation and subsequent theory were a revolutionary concept in times when the majority of the scientists thought that the venous blood arrived to the left ventricle through “invisible pores” in the septum. Leonardo, however, did not contradict this theory directly, probably being afraid to be “too much in the future.” Recently, several groups have had doubt on whether Leonardo really identified the bronchial circulation
      • Mitzner W.
      • Wagner E.
      On the purported discovery of the bronchial circulation by Leonardo da Vinci.
      ; however, he described clearly the oxygenation of the venous blood in the lungs. He also studied in detail the anatomy of the coronary artery and veins, coming to the conclusion that the “heart feeds itself.”
      Figure thumbnail gr7
      Fig 7Anatomy of the heart. Royal Collection, Windsor Castle.
      Figure thumbnail gr8
      Fig 8A and B, Studies on the movement of the cardiac valves.
      He noted that both atria contract when the ventricles dilate, explaining the movement of blood from the atria to the ventricles. The right atrium and ventricle are larger than those on the left.
      He was very interested in the hemodynamics which follow the heart contractions and studied very carefully the anatomy of the valves, which “are covered by endocardium at the top and muscles on the bottom.” Similar attention was given to the aortic and pulmonary valves. On the basis of the findings from his “in vitro” studies, he concluded that all 4 valves should open and close completely, otherwise the heart will not function adequately.

      Pulmonary circulation and chronic obstructive pulmonary disease

      When he was painting a fresco in the Church Santa Maria Novella, a middle aged man was preparing the colors for his frescos. The man, breathing the steam from the colours, manifested a severe form of chronic pulmonary obstructive disease, with severe restrictive disease, and consequent dyspnea at rest.
      • Burckhardt J.
      The civilization of Renaissance in Italy.
      • Burke P.
      The Italian Renaissance: Culture and Society in Italy.
      • Vasari G.
      Vita dei più eccellenti pittori, scultori ed architetti italiani, da Cimabue insino i giorni nostri.
      • De Mazzeri S.A.
      Leonardo. L'uomo ed il suo tempo.
      Leonardo made him pose as model for Saint Jerome in the Wilderness. The painting shows Saint Jerome, who lived the life of hermit in the desert, in severe sufferance. In the right hand, he holds a rock with which he beats his chest in penance. The muscles of the neck, chest, and face are shown in spasmodic contraction. When the man died, Leonardo performed an autopsy to understand the reasons for such a sufferance. He found, among other anatomic alterations, emphysema of the lungs, and annotated the possibility of correcting these alterations.

      Atherosclerosis

      In Florence, he met an old man in Santa Maria Nuova (ca 1505), who “was more than 100 year old.” He described the man as “wise, happy despite his advanced age … when he died, I performed an autopsy to understand the reason for his happy elderly.”
      • O'Malley C.D.
      • Sounders C.M.
      Leonardo on the human body: the anatomical, physiological and embryological drawings of Leonardo da Vinci.
      • Bortolon L.
      The life and times of Leonardo.
      • Boa G.
      Leonardo e l'anatomia.
      “I made an autopsy to understand the causes of this peaceful death, and I found that it was caused by weakness though the failure of the blood and of artery that feeds the heart and the other lower members.” In another set of annotations, he made clear the concept of atherosclerosis, and its correlation with aging “when the vessels become old they lose the straightness of their branching and become more folded or tortuous” and “one ask why the vessels in the old acquire great length and those which were formerly straight become tortuous and their coat thickness so much as to occlude and prevent the movement of the blood.” Leonardo performed also an autopsy in a two year old child in whom he found “all the arteries are soft and straight…differently from an old man.”
      Based on his previous hydrodynamic studies on the flow of water in the rivers, Leonardo made several assumptions, talking about “the continuous stress on the wall of the arteries” and about “the lack of nourishment in the medial wall of the artery, distant from the blood which nourish it.”

      Cirrhosis and portal hypertension

      He described accurately a case of portal hypertension with liver cirrhosis: “the artery and the vein which go from the spleen to the liver become so large that they block the blood coming from the mesenteric vein; the latter vein dilates so much and become so tortuous like a snake, that the liver dries and becomes like frozen bran, either in colour or consistency.” Leonardo thought that the changes in the liver were secondary to the dilation of the veins and not the cause. However, in another occasion, he writes that “the liver is nourished by the blood coming from the porta.” The importance of the hepatotrophic factors coming from the portal vein to the liver was recognized and acknowledged really only around 1980, when patients who had portocaval shunts suffered from liver failure and hepatic encephalopathy.

      Balducci G, Sterpetti AV: A short history of portal hypertension and portocaval shunts. J Gastroenterol Hepatol. In press.

      Development of the fetus
      • O'Malley C.D.
      • Sounders C.M.
      Leonardo on the human body: the anatomical, physiological and embryological drawings of Leonardo da Vinci.

      Leonardo performed anatomic dissections of the pregnant cow, describing first the development of the fetus. There is also the possibility that he performed an autopsy in a pregnant woman. These studies were revolutionary.

      Other important discoveries

      In the drawings and annotations of Leonardo, there are so many discoveries that it almost impossible to list all of them. He drew one of the first pictures of the thyroid gland in a human being and of the recurrent laryngeal nerve in an animal. He studied in detail the anatomy of the ocular bulb and of the optic nerve. His notions of neuroanatomy were also far advanced for his times.

      Why did not publish Leonardo his work? A hypothesis
      • Vasari G.
      Vita dei più eccellenti pittori, scultori ed architetti italiani, da Cimabue insino i giorni nostri.
      • De Mazzeri S.A.
      Leonardo. L'uomo ed il suo tempo.
      • Santi B.
      Leonardo. I protagonisti dell'arte italiana.
      • Lomazzo G.P.
      Idea del tempio della pittura.
      • Beltrami L.
      Documenti e memorie riguardanti la vita e le opere di Leonardo da Vinci in ordine cronologico.
      • Murphy C.
      God jury.
      • Magnano M.
      Leonardo. I Geni dell'arte.

      In those days, to be innovative was not as simple as today. The Inquisition was a reaction to any innovation that could jeopardise the power of the Roman Catholic Church. While in Rome, such reaction was under the power of the Pope, while in many other countries, including Spain, Portugal, France, and Germany, it was under the power of the King. Torture was a method to make the presumed guilty confess his sins. One can image that the torture was so violent that at the end, all suspicions became “real.” In this environment, the people in power could use the Inquisition for several reasons, theological, political, economic, and most importantly, personal if any new idea threatened their rule.
      In the early years of the 1500s, the Inquisition became more and more severe in response to any new ideas and challenges to the old way coming from Germany, where there was an increasing intolerance for the power of Rome, an intolerance that a few years later (1517) led to the “95” theses in Wittenberg by Martin Luther against the Indulgences, which officially started the Protestant Reformation. As consequence, the Roman Catholic Church became more and more intolerant of any form of innovation that could be perceived as challenging the Church. Already, the Inquisition had “dealt with” many people who fit the Church's definition of “a religious heretic”: more than 80,000 women and 20,000 men were burnt alive, because they were considered to be a sorcerer or witch. A book, written by two monks, “Malleus Maleficarum,” which was a best seller specified the characteristics of a witch. To understand the misogyny that became the basis of many of these persecutions, the two monks wrote erroneously that the word femina derives from fe minus (fides minus, or “less faith”) and that women were more predisposed to be possessed by the demons, because they are “inferior.” Under these Church doctrines, all women who were intelligent or who could read were considered to be possessed by demons; likewise any new idea in religion was considered heresy, and was followed by persecutions, which not rarely were politically oriented.
      Possibly because of this church doctrine, Leonardo spent the major part of his life in the North of Italy (Florence, Milan, Venice, Bologna, Cesena, Padua) where there was a more liberal spirit for the acceptance of new ideas and theories and the power of the church was less oppressive.
      From ages 62 to 65, Leonardo spent 4 years in Rome (1514–1517) following Pope Leon X. He had a close friendship with the brother of the Pope, Giuliano dei Medici. In Rome, Leonardo experienced all the problems related to the new cultural situation. There was a continuous friction between rich and influential people who supported progress and innovations, and more conservative groups who did not accept any form of change. Martin Luther was having increasing success in Germany arguing that the request for money from the populace by the Church to forgive sins (Indulgences) was not right; indeed the Indulgences were the greatest source of support for the Church.
      In Rome, Leonardo continued work on an old project “the utilization of the solar energy.” Through a system of mirrors, he used the solar energy to boil water in a rudimentary engine, which was supposed to move a wheel. The people working with him, for unknown reasons, refused to work on the project.
      Despite the fact that he was not allowed officially to perform autopsies in Rome, at night Leonardo performed dissections in two major hospitals. He was accused to be a sorcerer by the neighbors, and his laboratory was destroyed completely.
      In this period, the Pope asked Leonardo to make a present for the king of France, who he was supposed to meet in Bologna. Leonardo made a robot: a lion of natural size, which could walk toward the King. The lion stopped in front of the king, and the chest of the lion opened offering flowers to the guest. The king was so favourably impressed by the robot that he asked again Leonardo to go to France to work for him. (Leonardo had a special interest in robots and he made projects for several different types of robots: domestics, military, etc.)
      Finally in 1516, Leonardo decided to accept the job offered by the king of France and moved to Amboise, with two of his loyal disciples. From 1517 to 1519, despite having at least two loyal disciples full time at his services, he did not write any annotations.
      One might hypothesize that Leonardo probably decided not to publish all his works, despite having enough time and support to do so. In his annotations near the drawings about the heart and blood circulation, he wrote “I could tell more, if I was allowed to do so.” In other words, I believe that Leonardo might have understood that his theories were too advanced for his times and might have been afraid that his work was too innovative and too far away from the classic knowledge and could generate great problems, leading to an unstable situation. He or somebody else?
      Another important fact to be considered is that Leonardo was well-known all over Europe, not only in the universities, but also among powerful and rich people who strove to court his friendship. The king of France asked Leonardo many times to go and work in France; at that time the king of France was one of, if not the most powerful person in Europe, and he was considered almost “holy.”
      The work done by Leonardo was well-known in all universities and paintings groups in Italy; his anatomic drawings and the annotations by Leonardo had been seen, admired, and studied.
      The anatomic and scientific work of Leonardo was verified by the visit of the Cardinal Aragona and his followers in Amboice. The cardinal Aragona was a close friend of the Pope Giulio II and, later, of the Pope Leone X. He belonged to a powerful Spanish family, the family Aragona, who had lost the Kingdom of Naples. The cardinal was striving to win back the Kingdom of Naples under the influence of his family by taking advantage of his friendship with the Pope. The cardinal made a long cultural trip to North Europe and decided to go and visit Leonardo in France in 1518. The report of this visit was very detailed and brought back as an “official report” to Rome: “Leonardo showed us three paintings…This gentleman has made so detailed anatomic drawings, of muscles, nerves, veins, joints, of bowel, either of men or women, never done before. He has also studied the nature of water, he has developed several different machines. All his studies are summarised in an infinite number of books, which, when they will be published, they will very useful.” Few months later, the cardinal Aragona died at the age of 45, a few months before Leonardo's death.

      Questions without answers

      There are many questions about the history of the drawings of Leonardo that do not have and maybe cannot have an answer.
      • 1.
        One question rises recurrently when analysing the uncertain situations which followed the destiny of all the annotations by Leonardo: why they were never published? And if not quite later, by others, like his disciples? For instance the anatomic drawings were published only in 1900. Scientists in London and Windsor Castle (Windsor Castle is about 10 miles away from the center of London) knew very well the value of those drawings and annotations: it has been proven historically that the English Royal Family showed the drawings to the famous anatomist William Hunter (ca 1759), who was very much impressed.
      • 2.
        Why did Leonardo or his disciples, not publish his work? Was he not allowed to do so? In the annotations of the drawings of the heart and blood circulation he writes, “I could tell more, if I was allowed to do so.” We have only to guess what he means by these words.
      • 3.
        Why did the architect Pompeo Leoni buy all the annotations of Leonardo, including the anatomic ones and the ones describing the study on the flight of birds? As an architect and sculptor, one might expect him to have been interested only in those relative to his field.
      • 4.
        Why was nobody else interested to buy those manuscripts, when the importance of the work of Leonardo was well-known?
      • 5.
        Why did Pompeo Leoni divide so accurately all the annotations of Leonardo according to the subject of study? Did he want to publish the work? Why he did not do so?
      • 6.
        Why did Pompeo Leoni, as soon as he bought the annotations of Leonardo, go to live in Madrid, bringing with him all the annotations, already divided and catalogued?
      In those days, the most powerful countries in Europe were England, France, and Spain.
      Were those drawings and annotations divided between the 3 most powerful countries in Europe, to control, each for his field, the gradual development of knowledge which could derive from the annotations of Leonardo, avoiding the uncontrolled development of a revolutionary, scientific thought?
      And it should be noted that 90% of the annotations of Leonardo are still missing.

      The hidden medical revolution: The hypothesis

      To give some kind of possibility to the above mentioned hypothesis, we should be able to find correlations between the major medical developments after the death of Leonardo and his drawings. It is quite sure that, if this was a “hidden revolution,” it may be difficult to find a direct relationship. But if we find a correlation between the “presumed” knowledge in those drawings and future major medical developments, that hypothesis, even if it can not be demonstrated scientifically, has a right to be proposed.

      Andreas Van Wesel
      • O Malley C.D.
      Andreas Vesalius of Bruselles.
      (1514–1564)

      Van Wesel was born to a rich family with a close relationship with the Emperor Charles V. He was educated in Leuven and Paris, and in 1538 (very young at the age of 24) he became Professor of Surgical Anatomy in the prestigious University of Padua. In 1543 (at the age of 29), he published the textbook “De Humani Corporis Fabrica,” which was a revolution in the concept of Anatomy, relegating to a secondary place the older theories of Galen. He asked the Bottega of Tiziano, a well-known painter in Venice, to make the drawings for his textbook. Tiziano knew very well Leonardo and his work. There is much dispute among historians if Andrea Van Wesel saw and was inspired by the drawings of Leonardo. Vesalio (the Latin name for Van Wesel) left Padua just a short time after the publication of his work and went to work in Madrid. For unknown reasons (someone suggested he went to be purified from his sins),
      • O Malley C.D.
      Andreas Vesalius of Bruselles.
      he was sent in pilgrimage to the Holy Land. He died in 1564, when the ship which brought him back from the Holy Land sank near the island of Zante, Greece.

      William Harvey
      • Andrew G.
      Harvey's heart.
      (1578–1657)

      In 1628, Harvey published the book “Exercitatio Anatomica de Motu Cordis and Sangunis in Animalibus,” in which he described the blood circulation in detail. This book began a revolution in the ideas of how the blood circulated and in the function of the heart. Harvey had a close relationship with the English Royal Family, because he married Elisabeth Browne, daughter of Lancelot Browne, personal physician of both Queen Elisabeth I and King James I. Later, Harvey became physician for the Royal Family. He was one of the members in charge of the Royal College of Physicians. Did he see the anatomic drawings and annotations of Leonardo? Was he inspired by those studies? We know for sure that 10 years before the publication of the anatomic textbook “Exercitatio,” the anatomic drawings and annotations of Leonardo were brought to London.
      Who decided and commissioned this international affair? Was the Royal College of Physician which was very powerful and very well organised behind this?

      Marcello Malpighi
      • Minelli G.
      All'origine della biologia moderna.
      (1628–1694)

      Malpighi was professor of Theoretical Medicine at the University of Bologna and was elected member of the London Royal Society of Medicine. In 1661, he published the textbook “De Pulmonibus Observationes Anatomicae,” in which he described the concept of the oxygenation of the venous blood in the lungs before it returns to the heart, completing the previous theory of William Harvey. The annotations and drawings of Leonardo were well-known in Bologna, where Leonardo spent several months. Interesting enough, Malpighi knew very well the botanic studies made by Leonardo, but he made no mention about the previous studies of Leonardo on the pulmonary circulation. Malpighi had very difficult times with his colleagues in Bologna, and also subsequently in Messina; however, he always had the support from the London Royal Medical Society which in 1669 published in English all his works.

      Giovanni Battista Morgagni
      • Bynum W.F.
      • Bynum H.
      Dictionary of medical biography.
      (1682–1771)

      Morgagni was professor of Theoretical Medicine in the prestigious University of Padova. His was nominated Professor thanks to the strong and continuous support by Lorenzo Tiepolo, a famous painter. In 1674, Morgagni become a member of the Royal College of Physicians of England. We know that the drawings of Leonardo were well-known among the painters of Venice: the painters had a strong influence in the Government of Venice, which controlled the University of Padua. In 1691, he published the book “De Sedibus et Causis Morborum per Anatomen Indagatis,” which represents one of the major developments in medicine. Similar to Leonardo, Morgagni gave evidence that for each disease there was a correlated anatomic change, overcoming the old theories which considered the diseases as the result of an imbalance in the humours of the body. In the third volume of the “De Sedibus,” Morgagni described a case of liver cirrhosis, with characteristics similar to the case described by Leonardo. In 1740, he published some other studies, very similar to those of Leonardo, on the aortic valves and described in the detail the sinus that he named Valsalva, in honour of his teacher Antonio Maria Valsalva.

      William Hunter
      • Kerr J.M.
      William Hunter, his life, personality, achievements.
      (1718–1783)

      Hunter was an outstanding anatomist and obstetrician. He taught anatomy to John Hunter, his younger brother, who became one of the greatest surgeons in modern medicine. In 1762, he assisted Queen Charlotte in the delivery of her baby and became famous immediately all over London, after which he was chosen as personal physician of Queen Charlotte in 1764. In 1766, he was elected a fellow of the London Royal Society of Medicine. Because of his close relationship to the Royal Family, he was able to observe and to study the anatomic drawings and annotations by Leonardo. He tried to make public the importance of the drawings and annotations of Leonardo. For reasons that remain unknown, he entered in open criticism of some of the thoughts of the Royal College of Physicians. His greatest work was “Anatomy Uteri Humani Gravidi.” The influence of the drawings of the development of the fetus in the uterus by Leonardo appear to be evident in the work of Hunter.

      Charles Darwin
      • Desmond A.
      • Moore J.
      The life of Charles Darwin.
      (1809–1892)

      In 1859, Darwin published his famous “On the origin of the species,” in which he specified many concepts about the theory of evolution of animal and vegetables species based on his personal experience around the world. The theories about the evolution of the different animal species based on a natural selection had circulated around England for almost 100 years. The grandfather of Charles Darwin, Erasmus Darwin had published a book on this topic as well (Zoonomia). The popularity of the various theories on evolution was based on a reaction from the general public to the Anglican Church, which tried to control very closely the teaching in the different universities.
      The Anglican Church did not allow teaching of the theories of the evolution. Two universities, the University of London and the University of Edinburgh (where Darwin graduated), agreed to teach the theories of the evolution despite the Anglican church. In the drawings of Leonardo, there is a close comparison between the skeleton of several animals and that of a human being, in which it seems clearly demonstrated the theory of evolution. Did those drawings influence the diffusion of the theory of the evolution in England and the consequent dispute to limit the power of the Anglican Church?
      In conclusion, there are many questions that cannot be answered in this article, and many of my assumptions remain just assumptions. But, there is another important message we can get from the history of Leonardo. The progress of science requires the ability to correlate art and science. A scientist, a surgeon, should be an artist, at least in her or his soul.

      References

        • Burckhardt J.
        The civilization of Renaissance in Italy.
        1878 (Trans S.G.C. Middlemore, CT)
        • Kehoe T.J.
        • Damerow H.E.
        • Duvall J.M.
        Exploring Western Civilization to 1648.
        Kendall/Hunt Publishing Company, Dubuque, IA1997: 411-436
        • Cantimori D.
        Studi di Storia, Umanesimo, Rinascimento, Riforma.
        1976 (Minerva Ed, Torino, Italy)
        • Burke P.
        The Italian Renaissance: Culture and Society in Italy.
        Princeton University Press, Princeton1999
        • Fumagalli M.
        • Brocchieri B.
        Pico della Mirandola.
        Ed Piemme, Milano1999
        • Mignano M.
        Leonardo.
        in: Geni dell'Arte. Mondatori, Milano2007
        • Santi B.
        Leonardo.
        in: Protagonisti dell'Arte Italiana. Scala Group Ed, Florence2001
        • Clayton M.
        Leonardo's medicine years.
        Nature. 2012; 484: 314-316
        • O'Malley C.D.
        • Sounders C.M.
        Leonardo on the human body: the anatomical, physiological and embryological drawings of Leonardo da Vinci.
        Henry Schuman, New York1952
        • Bortolon L.
        The life and times of Leonardo.
        Paul Hamlin, London1967
        • Boa G.
        Leonardo e l'anatomia.
        (Thesis) University of Milan-Bicocca Press, Milan, Italy, 2012
        • Vasari G.
        Vita dei più eccellenti pittori, scultori ed architetti italiani, da Cimabue insino i giorni nostri.
        1550 (Lorenzo Tormentino Ed- Florence)
        • De Mazzeri S.A.
        Leonardo. L'uomo ed il suo tempo.
        1999: 500 (Ed Rizzoli, Milano, Italy)
        • Santi B.
        Leonardo. I protagonisti dell'arte italiana.
        Scala Group, Florence2001
        • Lomazzo G.P.
        Idea del tempio della pittura.
        1590 (Milan)
        • Beltrami L.
        Documenti e memorie riguardanti la vita e le opere di Leonardo da Vinci in ordine cronologico.
        1919 (Milan)
        • Baroni C.
        Tutta la pittura di Leonardo.
        1952 (Milan)
        • Pasini G.
        Mondino de Liuzzi. Anhotomia. Bibliografia dei lavori che danno informazioni su Mondino.
        Istituto per la Storia dell'Università di Bologna, Bologna1992
      1. Anonimo Gaddiano Manuscript. Biblioteca Nazionale di Firenze 1540.

        • Keele K.D.
        Leonardo da Vinci s views on atherosclerosis.
        Med Hist. 1973; 17: 304-308
        • Keele K.D.
        Leonardo da Vinci on movement of heart and blood.
        Education University Press, London1952
        • Keele K.D.
        Leonardo da Vinci elements of the science of man.
        Education University Press, London1983
        • Boon B.
        Leonardo da Vinci on atherosclerosis and the function of the sinuses of Valsalva.
        Neth Heart J. 2009; 17: 496-499
        • Sterpetti A.V.
        The revolutionary study on blood circulation by Leonardo were too advanced for this time to be published.
        J Vasc Surg. 2015; 62: 259-263
        • Bellhouse B.J.
        Velocity and pressure distribution in the aortic valve.
        J Fluid Mech. 1969; 37: 587-600
        • Robicsek F.
        Leonardo da Vinci and the sinuses of Valsalva.
        Ann Thorac Surg. 1991; 52: 328-335
        • Mitzner W.
        • Wagner E.
        On the purported discovery of the bronchial circulation by Leonardo da Vinci.
        J Appl Physiol. 1992; 73: 1196-1201
      2. Balducci G, Sterpetti AV: A short history of portal hypertension and portocaval shunts. J Gastroenterol Hepatol. In press.

        • Murphy C.
        God jury.
        Mariner Books, New York2012: 150
        • Magnano M.
        Leonardo. I Geni dell'arte.
        Mondadori Arte, Milan2007
        • O Malley C.D.
        Andreas Vesalius of Bruselles.
        University of California Press, San Francisco1964
        • Andrew G.
        Harvey's heart.
        Icon Books, Cambridge, England2001
        • Minelli G.
        All'origine della biologia moderna.
        Jaca Books, Milan1987
        • Bynum W.F.
        • Bynum H.
        Dictionary of medical biography.
        Greenwood Press, Westport Connecticut-London2007
        • Kerr J.M.
        William Hunter, his life, personality, achievements.
        Scott Med J. 1957; 2: 372-378
        • Desmond A.
        • Moore J.
        The life of Charles Darwin.
        Bollati Boringhieri, Turin2009