M Belingheri

Bernardino Ramazzini (1633-1714)

Physicians started to identify and study the effects of metals on the central and peripheral nervous systems during the nineteenth century, when the Industrial Revolution caused a widespread exposure to neurotoxins in the western world. In 1805, John Pearson (1758–1826) coined the term “mercurial erethism” in England, while in 1836 the French physician Louis Tanquerel des Planches (1810–1862) used the term “encéphalopathie saturnine” to indicate neuropsychiatric manifestations of lead-intoxication; 20 years later AugustLouis Delpech (1818–1880) first described the neuropsychological effects of occupational exposure to carbon disulfide [1]. During the twentieth century, the studies of neurologists, occupational physicians and experimental psychologists contributed to the development of occupational neurotoxicology, as an autonomous discipline. It is less known that the first observations on the effects of metals on the nervous system can be found in the “De Morbis Artificum Diatriba” by the Italian physician Bernardino Ramazzini (1633–1714) [2, 3]. In chapter VII (“Diseases of glass-workers and mirror-makers”) of his masterpiece, Ramazzini described the effects of mercury on motor function and mood, stating: “Those who make mirrors, using mercury, become palsied [...]. These workers with grim expression (torvis oculis) contemplate the reflection of their suffering in the very mirrors they have made with their own hands and curse the profession they have had to follow” [4]. Furthermore, in chapter IX, he explained that painters were afflicted by palsy of the limbs, caused by colors of mineral origin containing pigments of mercury, lead and copper [4]. These statements indicate a first medical and scientific acknowledgment that exposure to toxic agents can cause both physical and behavioral alterations; therefore, Ramazzini can be considered as a pioneer of neurotoxicology. Bernardino Ramazzini (Fig. 1) was born in Carpi, Italy, in 1633. After his medical graduation in 1659 in Parma, he started to work as physician in Rome and in the Duchy of Castro, a vassal state to the Papal States. He was forced to leave Rome and return to his hometown, because of a severe malarial infection he contracted. In 1682, he was appointed as Professor of Theoretical Medicine at the University of Modena by the Duke Francesco II d’Este (1660–1694). During this period, he wrote several medical works, especially focused on population studies. His Hippocratic approach and his studies on the relation between nature and human health seem to have been inspired by the English physician Thomas Sydenham (1624–1689) and by the French scholar Guillaume de Baillou (1538–1616). Ramazzini was very familiar not only with the ancient Greek and Roman medical authors but also with coeval physicians and intellectuals, as demonstrated by his correspondence with the German philosopher Gottfried Wilhelm Leibniz (1646–1716). While he lived in Modena, he first described the artesian aquifers, made observations on natural history, and conducted studies on the influence of atmospheric agents during the course of epidemic diseases. In regards to malaria, Ramazzini was one of the first to support the use of the quinine-rich bark cinchona. He was also a poet and often alternated the writings of poem to his medical works [5]. At the end of the seventeenth century, Ramazzini started to investigate the influence of occupations on workers’ health, teaching a class on this subject at the University of Modena. He published the treatise “De Morbis Artificum Diatriba” in 1700, in which he first listed work-related health problems in different occupations. Each chapter of the treatise contains a description of the disease associated with a particular work activity followed by a literature analysis, workplace description, and questions for the workers, disease description, remedies, and advice. He advocated that the rulers should protect the health of workers to preserve the workforce and the productivity of their states. In * Michele Augusto Riva michele.riva@unimib.it

A bone in the heart: the strange case of Pope Urban VIII

The autopsies of the popes have been systematically performed since the sixteenth century. Their reports contain some interesting information not only for historians, but also for modern physicians. In this letter, we want to describe a cardiac anomaly found during the autopsy of Pope Urban VIII, one of the most famous and influential popes in the history of the Catholic Church. Urban VIII (Maffeo Barberini, 1568–1644) reigned from 1623 to his death in 1644, expanding the papal territory and influencing politics of Europe. He also contributed to the artistic renovation of Rome, commissioning artistic works by the greatest sculptors, architects, and painters of that time, such as Gian Lorenzo Bernini (1598–1680) and Francesco Borromini (1599–1667). Nowadays, modern tourists can admire the Barberini coat of arms with three bees on several buildings and fountains in Rome. The young age of Urban VIII, he was aged 55 years when the cardinals elected him in 1623, initially guaranteed good health. He only suffered from a gout attack in 1637 manifested as podagra and other joint pains, probably related to gout [1]. Moreover, Urban VIII reached 76 years of age without severe health problems. Suddenly, in June 1644, his health worsened in a few weeks, and he died, probably due to a cerebrovascular event [1]. At Urban VIII’s death, Giovanni Trullio (1598–1661) performed an autopsy. At that time, Trullio was surgeon at the Hospital of Santo Spirito and Professor of Surgery at the University La Sapienza in Rome. Trained for years in Lyon (France), he was one of the first doctors to support the theories of William Harvey (1578–1657) on the circulation of the blood in Italy. Trullio rapidly developed a high reputation as surgeon in Rome, and for this reason, Pier Battista Borghi, friend of Galileo Galilei (1564–1642), asked a medical consultation from him on the blindness of the Italian scientist. In this case, he excluded a senile cataract, and stated that Galileo’s blindness was the result of a uveitis. Trullio also specialized in treating kidney stones, and in dissecting and embalming rich and famous people, including princes, cardinals, and popes. During the autopsy of Urban VIII, the surgeon found a bone-like formation of triangular shape, similar to the letter “T” (literam T referens), which he was not able to explain with the medical knowledge of that period. Trullio also evidenced the presence of five gallstones (quinque calculi in vesica fellea) about the size of a hazelnut each (singuli magnitudine nucis avellanæ), together with several kidney stones (in renibus multi lapilli exigui) [2]. In the following centuries, anatomists and physicians have debated about the anomaly found in the heart of Urban VIII. In detail, the Danish physician Thomas Bartholin (1616–1680) tried to give an explanation of the pope’s heart bone, stating that “it often appears in old people through the supreme foresight of Nature, so that the blood, otherwise sluggish, is roused into rapid motion as if a pump had been installed,” (“sed frequens id in senibus summa Naturae providentia, ut torpidus alioqui sanguis velut stimulo addito ad motum incitetur,” Cent. 2, Hist. Anat. 45) [2]. According to Bartholin, in the heart of old people, stones naturally develop to support the circulation. Giovan Battista Morgagni (1682–1771), the father of modern anatomical pathology, did not agree with the theory of the Danish anatomist. In Letter 27.19 of his masterpiece “De Sedibus et causis morborum per anatomen indagatis” (1761), Morgagni explained that the pope’s heart bone was an aortic valve calcification, refuting Bartholin’s explanation of its “natural” development [3]. Throughout the nineteenth century, this debate continued, especially sustained by German anatomist Adolf Wilhelm Otto (1786–1845), who believed that it was a fibrocartilaginous mass in the heart wall [4]. The analysis of symptoms of the pope and the findings in his autopsy may suggest some diagnoses to modern physicians. Mitral annular calcification seems to be the most * Michele Augusto Riva michele.riva@unimib.it