A Previously Unknown Path to Corpuscularism in the Seventeenth Century: Santorio’s Marginalia to the Commentaria in Primam Fen Primi Libri Canonis Avicennae (1625)

This paper presents some of Santorio's marginalia to his Commentaria in primam fen primi libri Canonis Avicennae (Venice, 1625), which I identified in the Sloane Collection of the British Library in 2016, as well as the evidence for their authorship. The name of the Venetian physician Santorio Santori (1561–1636) is linked with the introduction of quantification in medicine and with the invention of precision instruments that, displayed for the first time in this work, laid down the foundations for what we today understand as evidence-based medicine. But Santorio's monumentale opus also contains evidence of many quantified experiments and displays his ideas on mixtures, structure of matter and corpuscles, which are in many cases clarified and completed by the new marginalia. These ideas testify to an early interest in chemistry within the Medical School of Padua which predates both Galileo and Sennert and which has hitherto been unknown.

the first time in the Commentaria in primam fen primi libri Canonis Avicennae ("A Commentary on the First Fen of the First Book of Avicenna's Canon," Venice, 1625) a book which, as highlighted by Nancy Siraisi, collects the lectures given by Santorio in Padua during the period 1611-1624 as professor of theoretical medicine (medicinae theoricae primo loco profitensis). 2 Santorio's handwritten annotations, which I have identified in a copy of his book, add substantial new material to our understanding of the development of early modern chemistry and, most notably, to Santorio's ideas on mixtures, corpuscles, and primary and secondary qualities, andat least in one caseon the historical background of the invention of an instrument.

The book
Santorio's own annotated copy of Commentaria is held by the British Library, shelfmark 542.h.11. The book belonged to Sir Hans Sloane (1660-1753), collector and physician, who acquired it in June 1692. 3 Since none of the surviving catalogues of book auctions held in London during the period 1690-1692 contain a particular reference to Santorio, it is likely that Sloane obtained the book by inheriting a collection, or even by purchasing it from a private seller. This hypothesis is compatible with the dispersion of Santorio's original library and manuscripts which, according to my research in the State Archive of Venice, followed soon after the death of Santorio's nephew, the physician Antonio Santori (ca. 1600-1642). The list of books which belonged to the last heir of the Santori family (dated 1772) contains no original books written by Santorio, except a single edition of the Methodus vitandorum  Throughout, the book presents four types of annotations written in pen: (on coll. 5C, 7E, 35E, 126C, 169D-E,  173E, 174A-B, 177B, 178D-E, 185E, 242B-C, 272C-D, 406C-D, 420C-D,  573A, 763 on the inferior margin); 2. Twenty-two corrections or small interpolations into the text (on coll. 19C, 20B,  25A, 33D, 35E, 38E, 64A, 68C, 80C, 90D, 169B, 182D, 248B, 264D, 327C,  448E, 453C, 462C, 513A,  The text block has been cut on both margins and many annotations are written up to the inner hinge, making it difficult to reconstruct some of the Latin text.

Criteria of authenticity
The book bears no signature, so the authenticity of Santorio's notes has been ascertained by adopting three criteria: (a) typology of notes; (b) use of the Latin pronoun nos; and (c) handwriting style.

Typology of notes
The manuscript notes complete the discussion in the printed text or add new elements to it. Most of the time they furnish missing references to the medical literature, both ancient (Aristotle, Galen, Averroes) and modern (Francesco Piccolomini, De mixtione, on col. 169 D-E) or address an otherwise open question (col. 272 C-D). 6 Particularly relevant are those in which Santorio discusses the rapport between qualities and perception (col. 126C), the theory of matter and miscibility of substances (coll. 169D-E, 173E), and, in one case, the process which led him towards the invention of one of his devices, an air humidifier (col. 406C-D). Furthermore, an annotation on Aristotle's Metereologica (IV.1, but wrongly quoted as IV.2) is the object of two different annotations, both used, however, to support the idea that substances undergo qualitative changes even when their physical mass alone has changed (177B-C, 242B-C). Finally, as already mentioned, a large number of notes consist of small corrections of the text or even of substitutions with different words (e.g. 462C: "coguntur <coquntur>"; 550B: "ergo et ex <sic > pituita"; 637A: "vel ex nostro in illu [m] 4 Continued most of which were later sold in London in 1791. He was also a great admirer of his ancestor and had a coin minted (1765) to honour him and his achievement in the field of medicine.

5
In transcriptions throughout this paper, Santorio's annotations appear within pointed brackets. Square brackets denote the expansion of contractions or integration of the text, wherever necessary. Original punctuation has been retained. 6 Santorio does not refer to any specific edition of Piccolomini, but he most likely had in mind the second edition: Francesco Carli Piccolomini, De mixtione, in Librorum ad scientiam de natura attinentium partes quinque, 2 vols. (Venice, 1600), vol. II, fols. 98r-112v (hereafter Piccolomini, De mixtione). <illo in istum>"). Particularly significant is the correction of the text in col. 760B-C, which makes sense of an otherwise impracticable optical experience: visio fit per radios decussatos: ergo non in crystallino, quod probatur per experientiam: quia dum inspicimus per aliquod foramen minus quam sit pupilla: si foraminis medietatem cum aliqua lamina, vel cum charta, exempli causa in parte dextra obturamus, pars dextra <sinistra> obiecti visibilis prius obscuratur, quam sinistra <dextra>: si igitur visio fieret in crystallino, idem eveniret, ut pars dextra <sinistra> obiecti visibilis amitteretur: quia dum radii per pupillae foramen penetrant, primo decussantur in crystallino, deinde retina est illa, quae cogendo radios visorios corrigit decussationem: ergo visio non fit in crystallino. 7 ["The vision is a phenomenon that happens by means of crossed rays, therefore it cannot happen in the lens. This can be proved by empirical trial. When we look through some fissure that is smaller than the pupil, if we cover half of the fissure with some blade or paper, e.g. on the right side, the right <left> part of the visible object becomes obscured before the left <right> one does. Now, if vision happened in the lens, it would have the same outcome, that is to say that the right <left> part of the visible object would be lost. In fact, whilst the rays enter the fissure of the pupil, they are firstly crossed by the lens and it is afterwards the retina that, collecting the visual rays, corrects such crossing. Therefore vision does not happen in the lens."] The attribution to Santorio is strongly supported also by the example of a marginal note on col. 406C-D. Here Santorio gives the exact reference of the passage in Galen (De Methodo Medendi, Bk 9, chap. 14; K X, 648-649) which inspired him to invent his air humidifier. This marginal note reads as follows ( Figure 1): ["Such a vessel has been related by Galen in his Method (bk. 9, chap. 14) where he says that in a hot and dry disease the air must be cold and humid. He places it such that a cold breeze from the Euripus blows on it, calling it Euripus because of the tight channel through which the air comes out."] All these elements strongly suggest that Santorio himself wrote these notes in an attempt to expand some discussions within the text.

The use of the pronoun 'nos'
However, the decisive factor in attributing the notes to Santorio is the variation in the use of the personal pronoun ego (I) and nos (we) in the notes to col. 272C-D, which is in line with the general use of plurale maiestatis (or "the royal we") which Santorio consistently uses throughout his work (respondimus, respondo; addimus, addo; invenimus, and the like). The passage at Col. 272C-D reads as follows:   It appears from this note that Santorio was attempting to complete or supplement his discussion on the division of unequal temperaments (intemperaturae). This discussion has so far remained open, for Santorio's marginalia were not added to subsequent editions of his work.

Handwriting style
The handwriting of the notes is compatible with Santorio's mature style, as appears from several of his letters which I have discovered in various archives in Europe as part of my ongoing project on Santorio. An example is offered in Figure 3.

Date
The precise date of the annotation is unknown, but it can certainly be traced back to the last part of Santorio's life, and most likely to 1630-1636. During this period Santorio was committed to re-editing and revising many of his previous works, starting with the Methodus vitandorum (1630, 1631), the Commentaria in Artem Medicinalem (1630Medicinalem ( , 1632, and the Medicina Statica (1634). 9 Furthermore, the fact that the corrections and annotations in the book are not displayed in any of the close following editions of the Commentaria in Primam Fen Primi Libri Canonis Avicennae support a late dating. 10 This strengthens the idea that Santorio's original copy was sold soon after the death of his nephew, Antonio Santori, who, graduating from the Venetian College of Physicians (Collegio dei medici fisici di Venezia) in 1630, was the only heir able to understand the content and the value of Santorio's annotations. 11 Argument and relevance to early modern science and medicine The marginalia are an integral part of Santorio's theory of matter as it developed after the publication of the Methodi vitandorum errorum omnium qui in arte medica contingunt libri XV ("Fifteen Books of a Method to Avoid all the Errors that Happen in Medicine," Venice, 1603). 8 This note has not been translated, as its purpose is only to display the variation between the pronouns ego and nos. Santorio's approach to the question of mixture and composition of matter has long remained unknown to scholars, who usually refer to the corpuscularian suggestions of Galileo's Discorso intorno alle cose che stanno in su l'acqua (Florence, 1612) for Italy, or to Sennert's Hypomemata physicae (Frankfurt, 1636) for the medical field broadly conceived. For instance, although Antonio Clericuzio has discussed several early corpuscularian theories in Italy before Galileo, in particular by clarifying the contributions of Angelo Sala (1576-1637) to the field of chemistry and the quantification of substances, the name of Santorio is not mentioned. 12 In the eighth book of his Methodus, Santorio actually pre-empts both Galileo and Sennert by adopting a corpuscularian theory in which the four Aristotelian qualities (hot, cold, wet, and dry) are analytically reduced to rarity and density (raritas and densitas) which are related (as cause and effect to one another) to the motion of particles within space (particulae minimae).
12 Antonio Clericuzio, Elements, Principles and Corpuscles: A Study of Atomism and Chemistry in the Seventeenth Century (Dordrecht: Springer, 2000), 20-23. 13 In a slightly different formwhich apparently relies on Heron's Pneumatikathese ideas were held by the theologian and philosopher Paolo Sarpi, Santorio's closest friend. They were especially discussed during the meetings of the so-called Ridotto Morosini, a circle of intellectuals that met at the Morosini house on the Grand Canal in Venice Santorio goes even further and eventually contends that prime matter is threedimensionality itself (trina dimensio quae est ipsamet materia). 14 Unlike Sarpi, however, Santorio corroborated his theory with a series of experiments which encompass the generation of colours, mixtures of natural and artificial substances, the making of glass, and the distillation of urine. 15 In discussing the evidence resulting from these experiments, Santorio points out that there are qualities that do not originate from the classic Aristotelian pattern. For instance, the origin of colours is not due to hot, cold, wet, and dry but is the result of the juxtaposition (iuxtappositio) of glasses; transparency and opacity of crystals in turn depends on the disposition of their smallest parts, not on four qualities. By the same token, properties resulting from the mixture of either natural or artificial substance (gunpowder and ingredients for glassmaking) depend on the exact quantity (proportio ad unguem observata) of their ingredients. Eventually Santorio reveals that the material subjects of such experiments must be considered discrete quantities which change their position in space, for in the distillation of urine heat can cause the aspect of urine to transform from opaque to transparent just by rearranging the disposition of its smallest particles (mutante particularum minimarum situm). 16 Santorio's views influenced other natural philosophers, including Galileo Galilei, Daniel Sennert, and Robert Boyle. 17 His ideas were in fact widely disseminated 13 Continued and which were attended byamong othersboth Santorio and Galileo. Sarpi and Santorio shared many ideas on the structure of matter, but the concept of matter as a series of individual quantities arranged geometrically in space according to position, figure and number (situs, figura, numerus) is first recorded in Sarpi's Pensieri, especially in n. 115, which belongs to a group of notes dating back to 1578; see Luisa Cozzi and Libero Sosio, eds., Paolo Sarpi: Pensieri Naturali, Metafisici e Matematici (Milan and Naples: Riccardo Ricciardi Editore, 1996), 134. According to my research, however, although Santorio retained some of Sarpi's distinctive corpuscular features, his theory was also indebted to Jacopo Zabarella's discussion of the conservation of quantity of matter set out at length in the treatise De prima rerum natura, which is part of the De naturalbus rebus libri XXX (Venice, 1590). 14 Santorio, Methodi vitandorum errorum omnium qui in arte medica contingunt libri XV (hereafter Santorio 1603), VIII.7, fol. 157v, C-D: "substantia igitur quatenus corporea, octo iis differentiis positionis faciet tam varium situm: All the ideas already set forth in 1603 are discussed and further refined in the De elementis, the first part of the Commentaria, where Santorio dwells upon the nature of the elements. In both the main text and the subsequent marginal notes, the corpuscular theory emerges as a distinctive feature of his approach, with names like particulae minimae or even atomi. 19 Although it is not my intention here to set out a full discussion of Santorio's corpuscular ideas, a clarification of some aspects of his thinking might offer a better understanding of the context of the marginalia. Santorio generally supports Avicenna's claim that the property of a mixture is a kind of fifth quality emerging beyond (praeter) the remaining four, whereas the traditional view held that the property of the mixture was due to the prevailing of one element over another. In this, his view strongly diverges from the claims of  (Leiden, Boston, Köln: Brill, 2001). 18 Joachim Jungius was a keen physician, mathematician and logician, whose studiesespecially Logica Hamburgensis (Hamburg, 1638)heavily influenced Leibniz. He was also one of the early modern philosophers to advocate the idea of corpuscularism. Jungius graduated in Padua with Santorio and Cremonini on 22 December 1618 and collected many notes from Santorio's original lectures which will be edited in my forthcoming article. 19 The term atomi, in reference to some optical phenomena as well as the diminished transparency of the air, is used very infrequently by Santorio and only in late works, whereas he seems to have used particulae minimae more often; this term is also witnessed in the marginalia. For the use of atomi see Commentaria in Primam Fen Primi Libri Canonis Avicennae (Venice, 1625), col. 726B: "Nec mirum est, quod vitreus ex se transparens in oculi profunditate gerat vicem cubiculi umbrosi: quia etiam aer ipse in sua immensitate diminuit transparentiam, vel fiat hoc propter atomos, vel propter alias causas." the "Peripatetics"as Santorio calls these philosophers to distinguish their approach from his ownand especially from those of Francesco Piccolomini (1522-1604) who, in his De mixtione (1596, 1600), strongly criticises those who claim that the Aristotelian minima are real corpuscles. 20 According to Santorio, then, the quality of the ingredients we perceive results from the geometrical disposition of corpuscles in space (situs), but it is noteworthy that such a disposition is not fortuitous at all. It actually pinpoints a scheme (figura) that corresponds to a substantial form and is driven by a natural ingenuity (retusum habet ingenium). When corpuscles reach their natural position, they are no longer related to one another by mere contact (juxtappositio) but they form something beyond their specific properties (mixtio). In scholastic terms they are "potentially" (potentialiter) separated but constitute a whole in their "actuality" (actualiter). However carefully Santorio references his explanation to the standard terminology of the Aristotelian minima, both "actuality" and "potentiality" individualise the geometrical configuration of matter, which from this standpoint is no longer part of the Aristotelian continuum. This idea actually introduces an increasing rift between real (geometric) and perceived (qualitative) properties that constitute the argument of the marginal addition on col. 126C. This poses a general question about how to understand the relative capacity of elements (earth, water, fire, and air) in terms of ease or difficulty in being heated and cooled, which Santorio explicitly links to a physical property such as density (densitas) or quantity of matter (copiositas materiae), meaning that the intensity of qualities has already been reduced to a quantitative parameter related to the structure of matter. By advancing down that path, Santorio puts under scrutiny the traditional approach, according to which some elements (water and fire) were considered to hold the property of being cool or hot as an exclusive feature, as we read at col. 126A-C: Cur glacies est frigidior aqua? quia est facta densior, ut dicit Aristototeles 4 Meteorum texto 20 a qualitate terrea, et ut densior, est frigidior, quia materia est copiosior. … Nos tamen dicimus, terram non esse frigidiorem aqua, dicimusque frigiditatem primo convenire aquae: secundario terrae; sed haec consideratio secundaria non tollit, quin summa frigiditas sit quoque in terra: sed primo in ordine convenit aquae, et hoc primo non significat intensionem, et secundario remissionem: quia ut declarabimus ex Galeno et Aristotele ambae qualitates in summo sunt in elementis.
["For what reason is ice colder than water? Because it has been rendered denser by the quality of the earth, as Aristotle states in the Metereologica (bk 4, text 20), and the denser it becomes, the colder it is, because the quantity of matter has increased. Nevertheless, we contend that earth is not colder than water, but that coldness is primarily suited to water and secondarily to earth. Such auxiliary consideration, however, does not prevent <to say> that the maximum coldness might also be found in the earth, but 20 Piccolomini, De mixtione, fol. 108r. that it is primarily suited to water. "Primarily" does not apply here to the intensity <of a quality> and secondarily to its attenuation for, as we shall declare later on, in line with the authorities of Galen and Aristotle, both qualities are found at their utmost degree in <all> the elements."] Santorio's annotates this passage as follows: ["<The same hotness exists in air as in fire: it seems nevertheless to be greater in fire for, whilst the dryness is the file of heat, humidity is its bridle. Likewise, the same coldness exists in water as in earth, and yet water appears to be colder to us, because, whilst humidity is the file of dryness, dryness is the bridle of coldness.>"] Although apparently complex, the meaning of the marginal note is clear and it actually specifies the sense of an otherwise tortuous passage. Despite the fact that water and fire might be seen as holding the primacy of coldness and hotness for themselves, Santorio claims that all the elements actually share the same intensity. That they have been regarded (videtur) as primarily holding such qualities (primo in ordine) is due only to their connection to secondary qualities (humidity and dryness) and according to our experience, but has nothing to do with their real intensity (intensio et remissio) nor with their essence. In other words, hot and cold have become a matter of degree of intensity, and the reader should probably bear in mind that these considerations are consistent with Santorio's invention and use of the thermometer.
Another good example of Santorio's corpuscular approach is provided by the marginal note on coll. 169 D-E and 173B-E which, along with other marginalia, offers a second set of arguments. Here the controversy revolves around the nature of mixtures and the existence of very small particles (particulae minimae). If such entities exist, then the mixture would become nothing but spatial links (relationes) between discrete parts, a solution thatas already seen -Santorio partly accepts. As he carefully specifies in the marginal note, there exists a difference in the way in which particles are connected to one another: in the juxtaposition (iuxtappositio) the smallest bodies (minima) touch one another only at a few points (secundum pauciores partes); in the mixture (in mixtum) they touch at more points (secundum plurimum); whilst in the generation (generatio) all their parts are connected one to another (secundum omnes partes) as they hold the natural position assigned to them by the substantial form. What in the traditional view was a "qualitative" progression has then become a "geometrical" progression based on position. Thus in col. 169D-E: Demum respondemus minima se tangere secundum plurimum: quia si secundum totum se tangerent, fieret generatio, quae est transmutatio totius in totum, et non mixtio.
["We finally reply by saying that <in a mixture> the smallest bodies touch one another in many parts; because if they would touch in all the parts, in fact, there would be a generation, which is a transmutation of whole into whole, not a mixture."] And in the marginal note: ["<In a mixture the parts touch one another in many parts, but in a generation in all the partsin juxtaposition the parts touch one another at a few points and this is the reason why no mixture results by means of juxtaposition. In his book On mixture, our master Francesco Piccolomini condemns Avicenna's opinion that, in the process of making the mixture, the smallest parts touch one another in many parts, for, if one accepts this argument of Avicenna, the temperament would no longer be a unity in the sense of the continuity. Yet, he did not understand Avicenna, whose point in this passage is not about the temperament which has already undergone a change, but which is changing. Indeed he said that, once the process of making the mixture has been completed, the miscible parts no longer touch each other.>"] Santorio puts forward a similar argument in the note on col. 173E, where he dwells again upon the actuality and potentiality of the mixture. A third set of marginalia presents the emergence of properties in natural compounds as the result of physical change in the position (situs) of their particles, explained in terms of change in volume and density of matter. 21 To conclude, I would like to outline what place Santorio's ideas on corpuscles and structure of matter hold in the wider picture of his scientific legacy and how they were linked to his idea of quantification in medicine.
Medical authors have always been interested in the action of corpuscles as an effective way to explain (with Fracastoro, for instance) the mechanism of contagion or the properties of drugs. Santorio made the most of this tradition, adopting the concept of corpuscles as a means to quantify matter and to convert the ideal balance of the body into the observable phenomenon we recognise today as "metabolism." It is truly remarkable that, beyond his undoubted merits in science and early modern technology, Santorio also held very innovative ideas on mixtures and was so fully committed to investigating the structure of matter. This makes the case for a deeper study of early modern chemistry in the medical school of Padua, and the way it developed between the end of the sixteenth and the beginning of the 21 I will deal at length with these notesand with othersin a forthcoming article on Santorio's theory of matter. seventeenth century. It was possibly Santorio who firstly drew the attention of early modern philosophers towards the existence of corpuscles as sensible quantities capable of making sense of the conservation of matter during its transformation. In Santorio's hands the concept of minimum turns into a discrete entity whose existence he substantiated by means of experimental trial, an insight that he passed on to following generations of physicians and scientists (via Mersenne, Beeckman, Boyle, Dodart, Borelli, Baglivi, Glisson, De Gorter, Keill, Lining, Franklin) up to Lavoisier. He was also one of the first (as early as 1603) to pinpoint the inadequacy of the traditional pattern of four qualities, which he replaced with the triplet of number, position, and figure, an achievement which has usually been ascribed to Galileo or Descartes. Santorio's true contribution has been forgotten, but, hopefully, this will soon no longer be the case.