Lymphatic System

The Lymphatic System

‘Along hidden pathways, unknown to the anatomist, lymph vessels entered the nodes from where it flowed into larger lymphs vessels and finally entered into the thoracic duct’.

Anton Nuck, Adenographia curiosa et uteri foeminei anatome nova (Leiden, 1696), p. 49.[1]

As Loukas et al note, ‘Along with the circulatory system, the lymphatic system makes up an extensive network of vessels transporting fluid throughout the body’.[2] It is, as we know, essential for the immune system. Though lymph nodes had been commented on as early as the fifth century BC by Hippocrates, real understanding of the nature of lymph vessels was an early modern discovery.[3] Worth owned works by some of the most important commentators on the lymphatic system: the Danish anatomist Thomas Bartholin (1616–80), who played such a vital role in teaching anatomy at Copenhagen; and the Dutch anatomist Frederick Ruysch (1638–1731) who, based in Amsterdam, revolutionized the uses of embalming fluid.

Daniel Le Clerc and Jean Jacques Manget, Bibliotheca anatomica sive Recens in anatomia inventorum thesaurus locupletissimus (Geneva, 1685), ii, p. 680, Tab. LXXI: A composite of work on lacteals from Gaspare Aselli (fig. 1); Jean Pecquet (fig. II and III); and Thomas Bartholin (figs IV, V and VI).

In addition, in his compilatory two-volume Bibliotheca anatomica sive Recens in anatomia inventorum thesaurus locupletissimus (Geneva, 1685), edited by Daniel Le Clerc (1652–1728), and Jean Jacques Manget (1652–1742), Worth had access to the works of other noted writers in the field. In the above image, which summarizes some of the most important early modern discoveries on lacteals, figure one is from a treatise on the lacteal vessels by an Italian physician, Gaspare Aselli (1581–1626). Aselli recorded his discovery of the lacteals on 23 July 1622 as follows:

‘On the 23rd of July of that year (1622) I had taken a dog in good condition and well fed, for a vivisection at the request of some of my friends, who very much wished to see the recurrent nerves. When I had finished this demonstration of the nerves, it seemed good to watch the movements of the diaphragm in the same dog, at the same operation. While I was attempting this, and for that purpose had opened the abdomen and was pulling down with my hand the intestines and stomach gathered together into a mass, I suddenly beheld a great number of cords as it were, exceedingly thin and beautifully white, scattered over the whole of the mesentery and the intestine, and starting from almost innumerable beginnings. At first I did not delay, thinking them to be nerves. But presently I saw that I was mistaken in this since I noticed that the nerves belonging to the intestine were distinct from these cords, and wholly unlike them, and, besides, were distributed quite separately from them. Wherefore struck by the novelty of the thing, I stood for some time silent while there came into my mind the various disputes, rich in personal quarrels no less than in words, taking place among anatomists concerning the mesaraic veins and their function. And by chance it happened that a few days before I had looked into a little book by Johannes Costaeus written about this very matter. When I gathered my wits together for the sake of the experiment, having laid hold of a very sharp scalpel, I pricked one of those cords and indeed one of the largest of them, I had hardly touched it, when I saw a white liquid like milk or cream forthwith gush out. Seeing this, I could hardly restrain by delight, and turning to those who were standing by, to Alexander Tadinus, and more particularly to Senator Septalius, who was both a member of the great College of the Order of Physicians and, while I am writing this, the Medical Officer of Health, ‘Eureka’ I exclaimed with Archimedes, and at the same time invited them to the interesting spectacle of such an unusual phenomenon. And they were indeed much struck by the novelty of the thing’.[4]

Aselli’s account is important, not just because it is the first description of lacteal vessels but also because it reminds us that progress in human understanding of lacteals (and much else), came at the expense of the canine and more generally animal population. In Figure 1 in the above image, taken from Aselli’s De lactibus sive lacteis venis, quarto vasorum mesaricorium genere (Milan, 1627), which was posthumously published by Tadinus and Septalius, ‘B’ represents the shadowy ‘milk veins’ which Aselli had discovered.

Anatomical investigation of lymphatic vessels in humans was undertaken by Nicholas-Claude Fabri de Peiresc (1580–1637) and Pierre Gassendi (1592–1655) in the following year. Johann Vesling (1598–1649), professor of anatomy at the University of Padua in the seventeenth century, also focused on human mesenteric lacteals, and produced the earliest illustrations of the human lymphatic system.[5] The English anatomist, Nathaniel Highmore (1613–85) likewise included a chapter on lacteals in his 1651 Corporis humani disquisitio anatomica (The Hague, 1651). However, the next leap forward in understanding of lacteals was by the French scientist Jean Pecquet (1622–74), whose experiments are reproduced by Le Clerc and Manget in figures II and III. Pecquet’s Experimenta nova anatomica had been published in the same year as Highmore’s work (1651), and, as is clear from the image, he had reverted to examining lacteals in dogs, a common practice at the time. In his treatise, Pecquet described the cisterna chyli and the thoracic duct. His Experimenta nova anatomica (Paris, 1651) led to an energetic debate about the nature of the lymphatic system in early modern Europe.[6]

Figures IV, V and VI come from the work of Thomas Bartholin. Bartholin had initially worked on dogs but in 1651 he turned his attention to humans and was able to confirm some of Pecquet’s conclusions – for example that the lacteals connected to the thoracic duct. He published the results of his experiments in 1652 under the title De lacteis thoracicis in homine (Copenhagen, 1652), a copy of which was owned by Worth. As Suy  et al. note, Bartholin initially maintained that some chyle was carried by the lacteal veins to the liver but subsequently ‘dethroned’ the liver when he became ‘fully convinced that all chyle and superfluous serous liquid were evacuated to the heart through the chyle duct … Degrading the liver from blood-forming organ to a mere gall filter profoundly disturbed classic physiology, pathology, and therapy’.[7] Bartholin who had been taught by Vesling at Padua, in turn taught another Danish anatomist, Nicolas Steno (1638–86), who carried on work on the lymphatic  system, identifying the right lymphatic and parotid ducts.

Daniel Le Clerc and Jean Jacques Manget, Bibliotheca anatomica sive Recens in anatomia inventorum thesaurus locupletissimus (Geneva, 1685), ii, p. 717, Tab. LXXV: Ruysch’s work on the valves of the lymphatics.

Despite his large collection of treatises by Ruysch Worth did not have a separate edition of Ruysch’s Dilucidatio valvularum in vasis lumphaticis et lacteis, published at Amsterdam in 1665. However, he had a copy of it in Le Clerc and Manget’s Bibliotheca anatomica and figure 1 in the above image is taken from the compilatory volume. As Irischick et al note, Ruysch explained the image as follows: ‘The lymphatic vessels from anterior, from the side and dissected lengthwise with their valves. A: The lymphatic vessel dissected lengthwise; B: The lymphatic vessel from the side; C: The lymphatic vessel from anterior; aaaa: semilunar valves of the said vessels’.[8] As the image makes clear, Ruysch was particularly interested in the valves of lymphatics, and, as Suy et al note, Ruysche was actually the first person ‘to succeed in demonstrating valves in lymph vessels’.[9]

Ruysch not only dissected them, he also preserved them in his anatomical museum by using intravascular injections. As Loukas et al, note, another Dutch anatomist, Anton Nuck (whose Adenographia (Leiden, 1696) was collected by Worth), likewise used injections (in his case of mercury), to highlight fine lymphatic vessels.[10] Nuck (1650–92) also benefited from the development of the microscope in the second half of the seventeenth century, which further aided the investigation of lymph vessels which, as William Harvey (1578–1657) had ruefully noted, were difficult to see.[11] Steno, Nuck, Marcello Malpighi (1628–94) and Antoni van Leeuwenhoek (1632–1723) all demonstrated new discoveries in the lymphatic system using this device. Worth owned two London editions of Malpighi’s works, a 1686 edition and a posthumous 1687 edition, in which he discussed the function of lymph vessels. He likewise owned a number of works by Van Leeuwenhoek and, as a fellow member of the Royal Society, would have been familiar with Van Leeuwenhoek’s letters to the Society on the subject.

Nuck’s use of the microscope was perhaps not as successful as that of Van Leeuwenhoek, but his new process of vascular injection was to prove important for the demonstration of lymph vessels throughout the body, with the exception, as Suy et al. note, of the brain.[12] Vascular injection had been introduced by Malpighi in 1661 and used by leading anatomists such as Reinier de Graaf (1641–73), in his experiments on the organs of generation.

Like his predecessors, Daniel J. Cunningham (1850–1909), Professor of Anatomy at Trinity College Dublin endeavoured to dissect and prepare his specimens to illustrate his lessons and his textbooks; Cunningham’s Practical Manual of Anatomy (1879), Text-book of Anatomy (1902), and Stereoscopic Studies of Anatomy (1909), which features photographs of his specimens. To do so he experimented with various techniques, ultimately veering away from the standard presentation styles of his time. Most anatomists suspended their potted specimen in fluid and supported them with thread and sometimes panes of glass. Cunningham employed a different method altogether, blurring the lines between specimen and illustration. In a manner that mimicked the white field of the paper in his textbooks, he suspended his precise dissections on a matrix of plaster, which had the effect of specimen emerging from the background, as if an anatomical illustration on a page. His artistry and unconventional format set him apart from his contemporaries. Apart from Andrew Francis Dixon (1868–1936), who—being his student, emulated his presentation methods (see kidney), Cunningham’s specimens are unlike any others in medical heritage collections.

Preserved head of an adult male showing the innervation and vasculature of the face, including the parotid gland. Dissected and prepared by Professor of Anatomy Dr. Daniel John Cunningham. Late 19th century. Courtesy of the Old Anatomy Museum, School of Medicine, Trinity College Dublin.

This masterful dissection of the face of a man by Cunningham shows the facial nerves and their branches, as well the facial blood vessels. Resting in front of the ear is the parotid gland, and below the jaw one can see the submandibular salivary gland. Along with the sublingual gland which cannot be seen on this specimen, the salivary glands are responsible for saliva production. Though not labeled in this dissection, the parotid and submandibular lymphatic nodes are embedded in the parotid and submandibular glands respectively. Cunningham writes:

‘Parotid Gland (glandula parotis). — This, the largest of the salivary glands, is a distinctly lobulated mass of a yellowish or light reddish brown colour, which is placed in a deep recess (the parotid recess) at the side of the head, below and in front of the ear (Fig. 647). It extends up to the zygoma, down to the angle of the jaw or even to a lower level, and backwards to the sterno-mastoid muscle. Internally it lies on the styloid process, and anteriorly its facial process is continued for a variable distance over the surface of the masseter’.[13]

By blending artistry and precision in his preparations, Cunningham retained the humanity of his subjects while providing clear and informative dissections for his students.

Text: Dr Elizabethanne Boran, Librarian of the Edward Worth Library, Dublin, and Ms Evi Numen, Curator of the Old Anatomy Museum, Trinity College Dublin.

Sources

Chason, H. M, and B.W. Downs, Anatomy, Head and Neck, Parotid Gland. [Updated 2021 Jun 17]. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2021 Jan online.

Cunningham, Daniel J. (ed.), Text-book of anatomy : illustrated with 824 wood engravings from original drawings, many printed in colours (Edinburgh and London, 1902).

Foster, M., Lectures on the History of Physiology during the Sixteenth, Seventeenth and Eighteenth Centuries (Cambridge, 1924).

Irschick, Regina, et al. ‘The history of anatomical research of lymphatics. From the ancient times to the end of the European Renaissance’, Annals of Anatomy, 223 (2019), 49–69.

Loukas, Marios, et al, ‘The Lymphatic System: A Historical Perspective’, Clinical Anatomy, 24 (2001), 807–16.

Suy, Raphael, Sarah Thomas and Inge Fourneau, ‘The discovery of the lymphatic system in the seventeenth century. Part 1: the early history’, Acta Chirurgica Belgica, 116, no. 4 (2016), 260–66.

Suy, Raphael, Sarah Thomis and Inge Fourneau, ‘The discovery of the lymphatic system in the seventeenth century. Part II: the discovery of Chyle vessels’, Acta Chirurgica Belgica, 116, no. 5 (2016), 329–35.

Suy, Raphael, Sarah Thomis and Inge Fourneau, ‘The discovery of the lymphatic system in the seventeenth century. Part III: the dethroning of the liver’, Acta Chirurgica Belgica, 116, no. 6 (2016), 390–397.

Suy, Raphael, Sarah Thomis and Inge Fourneau, ‘The discovery of the lymphatic system in the seventeenth century. Part IV: the controversy’, Acta Chirurgica Belgica, 117, no. 4 (2017), 270–78.

Suy, Raphael, Sarah Thomis and Inge Fourneau, ‘The discovery of the lymphatic system in the seventeenth century. Part V: an ode to the nerves’, Acta Chirurgica Belgica, 119, no. 5 (2019), 340–46.

Suy, Raphael, Sarah Thomis and Inge Fourneau, ‘The discovery of the lymphatic system in the seventeenth century. Part VI: the microscopic discovery of the subtle anatomy’, Acta Chirurgica Belgica, 121, no. 1 (2021), 61–8.

Suy, Raphael, Sarah Thomis and Inge Fourneau, ‘The discovery of the lymphatic system in the seventeenth century. Part VII: the rise of vascular injection’, Acta Chirurgica Belgica, March (2021), 1–10.

[1] English translation from A. M. Luyensijk Elshout, ‘Anton Nuck (1650–1692). The “Mercator” of the Body Fluids. A review of his anatomical and experimental studies’ in C. van der Meer, J.V. Meininger and J. Schouten (eds), Circa Tiliam Studiea Historiae Gerrit Arie Lindeboom Septuagenario oblata (Leiden, 1974), p. 157.

[2] Loukas, Marios, et al, ‘The Lymphatic System: A Historical Perspective’, Clinical Anatomy, 24 (2001), 807.

[3] Irschick, Regina, et al. ‘The history of anatomical research of lymphatics. From  the ancient times to the end of the European Renaissance’, Annals of Anatomy, 223 (2019), 50.

[4] Translation from Foster, M, Lectures on the History of Physiology during the Sixteenth, Seventeenth and Eighteenth Centuries (Cambridge, 1924), p. 49.

[5] Loukas, Marios, et al, ‘The Lymphatic System’, 809.

[6] On this see Suy, Raphael, Sarah Thomis and Inge Fourneau, ‘The discovery of the lymphatic system in the seventeenth century. Part IV: the controversy’, Acta Chirurgica Belgica, 117, no. 4 (2017), 270–78.

[7] Suy, Raphael, Sarah Thomis and Inge Fourneau, ‘The discovery of the lymphatic system in the seventeenth century. Part III: the dethroning of the liver’, Acta Chirurgica Belgica, 116, no. 6 (2016), 395–6.

[8] Irschick, Regina, et al. ‘The history of anatomical research of lymphatics’, p. 67.

[9] Suy, Raphael, Sarah Thomis and Inge Fourneau, ‘The discovery of the lymphatic system in the seventeenth century. Part IV: the controversy’, Acta Chirurgica Belgica, 117, no. 7 (2017), 274.

[10] Loukas, Marios, et al, ‘The Lymphatic System’, 810.

[11] Cited in Suy, Raphael, Sarah Thomis and Inge Fourneau, ‘The discovery of the lymphatic system in the seventeenth century. Part IV: the controversy’, p. 271.

[12] Suy, Raphael, Sarah Thomis and Inge Fourneau, ‘The discovery of the lymphatic system in the seventeenth century. Part VI: the microscopic discovery of the subtle anatomy’, Acta Chirurgica Belgica, 121, no. 1 (2021), 67.

[13] Cunningham, Daniel J. (ed.) Text-book of anatomy : illustrated with 824 wood engravings from original drawings, many printed in colours (Edinburgh and London, 1902), p. 959.

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