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William Hunter and lymphatics
Accepted Manuscript Title: William Hunter and Lymphatics Authors: Stuart W. McDonald, David Russell PII: DOI: Reference:
S0940-9602(18)30033-5 https://doi.org/10.1016/j.aanat.2018.03.002 AANAT 51242
To appear in: Received date: Revised date: Accepted date:
24-11-2017 14-3-2018 22-3-2018
Please cite this article as: McDonald, Stuart W., Russell, David, William Hunter and Lymphatics.Annals of Anatomy https://doi.org/10.1016/j.aanat.2018.03.002 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
William Hunter and Lymphatics
Stuart W. McDonald and David Russell
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Anatomy Facility, School of Life Sciences, University of Glasgow, Glasgow, United Kingdom.
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E-Mail: [email protected]
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Historical article Corresponding author: Dr Stuart W. McDonald, Anatomy Facility, School of Life Sciences, University of Glasgow, GLASGOW, G12 8QQ, United Kingdom.
ABSTRACT
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William Hunter along with his brother, John, and their colleagues William Hewson, William Cruikshank and John Sheldon made a large contribution to understanding of lymphatic vessels. Hewson, Cruikshank and Sheldon all carried out mercury injections and made much progress in mapping the distribution of lymphatics in the human body. William Hunter appreciated that lymphatics absorbed fluid from the tissues of the body and that lacteals of the intestine and lymphatics are similar structures. John Hunter carried out an elegant series of experiments that proved that lacteals absorb products of digestion. The Hunters, however, were wrong in dismissing absorption by blood vessels and missed the importance of blood capillaries. William Hewson showed that lymphatics were not confined to mammals but that they are present in reptiles, birds and fish. Hewson also demonstrated that tracheobronchial glands are lymph nodes and not mucus-secreting glands as previously thought. Although William Hunter appreciated that tuberculosis and venereal diseases might involve the regional lymph nodes, he does not seem to have fully grasped that malignant disease might involve the local nodes or the concept that knowledge of lymph drainage could be used to define the likely site of a primary malignancy.
Keywords: William Hunter; John Hunter; William Cruikshank; William Hewson; John Sheldon; University of Glasgow; lymphatics; lacteals; 18th Century; history of medicine
INTRODUCTION
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It is 300 years since the birth at East Kilbride, Lanarkshire, Scotland, of William Hunter (1718 - 1783) (Fig. 1) who, going to London, quickly rose to become one of the great anatomists and man-midwives of the 18th Century. In 1762, Hunter became Physician Extraordinary to Queen Charlotte, consort of George III, and was in attendance at the deliveries of all but the last of their children. William Hunter is remembered for his pioneering work The Anatomy of the Gravid Uterus Exhibited in Figures (1774) and the demonstration that the mother and fetus have separate blood circulations. Hunter, however, is also celebrated as a pioneer in elucidating the lymphatic system, the system of vessels that returns excess fluid from the tissues to the bloodstream. The collection of specimens in which lymphatics have been demonstrated by injection of mercury is one of the highlights of William Hunter’s collection of anatomical specimens on display at the Anatomy Museum of the University of Glasgow. Many of the specimens that show human lymphatics were prepared by William Cruikshank (1745 - 1800) and those showing animal lymphatics are the work of William Hewson (1739 - 1774). Hewson served as assistant to William Hunter from 1762 - 1770 and Cruikshank form 1771 to Hunter’s death in 1783.
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The discovery of lymphatics
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Lymphatics had been known long before the days of William Hunter and his brother, John (1728 - 1793). John Sheldon (1752 - 1808), a former student of both John and William Hunter (Cameron, 2004), in his History of the Absorbent System (1784), gave a good account of the history of the discovery of the lymphatic system and the level of understanding that had been reached by the time of William and John Hunter.
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Erasistratus, working in Alexandria (Garrison, 1921) about 300 BC, had seen lacteals distended with chyle in the mesenteries of recently born goat kids he was dissecting. He thought the chyle was the milk the kids had been suckling. Herophilus, also in Alexandria about the same time (Garrison, 1921), also saw lacteals in young animals and noted that they differed from mesenteric veins by passing to glandular structures (mesenteric lymph nodes) rather than to the portal vein. The Roman physician, Galen (c. 130 - 200 AD), wrote about lacteals, but only reiterated the observation made by Herophilus (Sheldon, 1784). In Pavia in 1622, a physician, Gaspare Aselli (1581 - 1626) (Garrison, 1921), was giving a demonstration to friends of the movements and innervation of the diaphragm on a live dog. When he opened the abdomen to give a better view of the diaphragm, he noticed that the intestines and the mesentery were covered in fine white thread-like lines. Departing from the diaphragmatic experiment to study this unexpected observation and realising from their appearance that they were not nerves as he initially supposed, he cut into one to find that a milky substance oozed out. The dog soon died and the vessels disappeared. Aselli
subsequently sacrificed another dog with negative results but when examining another that had just eaten, he again saw the lacteals, the name he gave these vessels (Rusznyak et al., 1960). Aselli then repeated the study on different species, as he was able, including a positive study in a horse that recently had been fed. In his studies on lacteals, Aselli also demonstrated the presence of valves along their length (Sheldon, 1784).
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After Aselli’s observations, lacteals were also seen by Werner Rolfink (1599 - 1673) in 1616, Marco Aurelio Severino (1580 - 1656) in 1630, by Olaus Worm (1588 - 1654) about the same year, by Guilhelmus Fabricius Hildanus (1560 - 1634) in 1632 (Sheldon, 1784) and by Johann Vesling (1598 - 1649) in 1634 (Cruikshank, 1790). A problem that took some time to solve was difficulty over the destination of the lacteals. Aselli and others thought they passed to a “pancreas” and that, by an ill-defined route, the chyle reached the liver (Sheldon, 1784). The thoracic duct had been seen by Bartolommeo Eustachi (1524 - 1574) in a horse about 1563 (Sheldon, 1784; Cruikshank, 1790), and by Vesling in 1649 (Cruikshank, 1790). Its significance as the main lymphatic trunk draining lymph to the bloodstream, however, was not appreciated until an incidental discovery by Jean Pecquet (1622 - 1674) in 1651 (Hewson, 1774; Garrison, 1921). Pecquet was carrying out a dissection of a dog’s heart (Sheldon, 1784) and, on opening the right atrium and seeing milky chyle within it and tracing it back to its source, found that it had come from the thoracic duct via the subclavian vein (Hewson, 1774). Around 1654, the duct was traced in humans by Olof Rudbeck (1630 - 1702), followed by Thomas Bartholin (1616 - 1680), Isbrand van Diemerbroeck (1609 - 1674) and Christian Johannes Langius (1655 - 1701), and also in a number of land and aquatic mammals. It thus became clear that lymph was transmitted to the bloodstream at the veins at the root of the neck. In the Hunterian Collection, Specimen 12.17 is a particularly fine specimen of a thoracic duct filled with mercury (Fig. 2). Its legend says, “One of the largest and most perfect thoracic ducts perhaps ever injected (1770)” (Marshall, 1970).
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Lymphatic vessels at other sites in the body were first observed by Rudbeck about 1648 and around the same time by Bartholin and George Joyliffe (1621 - 1658) at Cambridge (Cruikshank, 1790; Eales, 1974). It was Bartholin who adopted the term vasa lymphatica. Hewson (1774) recorded that after these early discoveries, Anton Nuck (1650 - 1692) about 1691 injected lymph glands, or nodes to use a more modern term. Nuck is also credited with being the first to carry out mercury injections (Rusznyak et al., 1960). Frederik Ruysch (1638 - 1731) in 1665 further described lymphatic valves. These anatomists, however, only saw lymphatics at particular sites but Johann Friedrich Meckel (1724 - 1774) in the later part of his life gave an overview of the whole system and traced lymphatics in sites where they had not been documented previously (Meckel, 1772; Rusznyak et al., 1960; Janjua at al., 2010). Such was the state of the science when the Hunters became interested in the topic. Some of the features seen by early anatomists were demonstrated in William Hunter’s specimens. Specimen 12.81 shows the lymphatics of the intestine of an antelope (Fig. 3). “The absorbents are still preserved in the state they were found in the dead body., i.e. full of their
own chyle. The arteries and veins are both injected red”. The lymphatics pass to a large lymph node in the centre of the specimen. Specimen 12.85 shows lacteals terminating in a mass of glands at the root of the mesentery, which has been called the “pancreas of Aselli” by the author of the Hunterian catalogue (Marshall, 1970). Techniques of Lymphatic Injection in the 18th Century
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Hunter knew that if an injection made into an artery or a vein ruptured into the surrounding connective tissue, what he called the cellular membrane, it very commonly filled the local lymphatic vessels. Similarly, if a “tube loaded with quicksilver, was pushed, at random, into the cellular substance of a gland (the testicle, for example) the quicksilver would frequently pass into the lymphatics of that part” (Cruikshank, 1790).
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John Sheldon studied with both William and John Hunter (Cameron, 2004) and was William Hunter’s successor as Professor of Anatomy at the Royal Academy. In his History of the Absorbent System (1784), Sheldon expressed his willingness to share his knowledge of techniques for injecting lymphatics. Many of these methods he no doubt learned from William and John Hunter and from William Hewson who was a friend, as well as having been an assistant to William Hunter. Sheldon made some refinements to the methods but, in general, they are likely to be similar to those used by the Hunters, Hewson and Cruikshank. Sheldon used fresh cadavers and, dissecting generally being carried out in the winter, preferred to work between the hours of 10 am and 12 noon and at a north-facing window as this gave a more even illumination. Ordinary windows worked well. Bright light could make lymphatics difficult to discern among the tissues. Oedematous bodies, dropsical was the term Sheldon used, worked well as their lymphatic vessels tended to be distended. Decomposing material if conditions were right was also used. In relatively early stages of putrefaction, gas gathered in lymphatics and made them easier to inject. Sometimes for larger lymphatic vessels, Sheldon used what he called the coarse injection which was a mixture of two thirds yellow resin and one third mutton suet. For a firmer injectate, wax could be added and, for a softer consistency, the proportion of suet could be increased. A number of pigments were employed as required: Prussian blue, flake white, verdigrease (sic), vermilion.
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For most lymphatic work, however, mercury was best as its weight made for easy filling of lymphatics. Interestingly, about the same time as Sheldon published his book, the Italian anatomist Paolo Mascagni (1755 – 1815) produced two important works on the lymphatic system: “Prodrome d’une ouvrage sur le système des vaisseaux lymphatiques” and “Vasorum lymphaticorum corporis humani historia et ichnographia” in 1784 and 1787 respectively (Natale et al., 2017). Mascagni, like Sheldon, also injected with mercury and it was still being used by Sappey (1810 - 1896) in the mid-19th Century (Sappey, 1869). Mercury clearly was expensive and Sheldon, as well as mentioning the requirement for adequate amounts to carry out studies, also described ways of catching and reusing spilled mercury. The lymphatic to be injected was dissected out and then cannulated. It is not entirely clear how mercury injection was carried out by the Hunter brothers and their associates, but the method was rather
cumbersome with the need for an assistant to fill the mercury reservoir while the dissector tied the cannula into the lymphatic. It seems that Sheldon improved the method of injection of mercury by pioneering the use of a curved cannula with a valve mechanism to control the flow of mercury and a more manoeuvrable tube connecting the mercury reservoir and the cannula. Sheldon’s account of the methodology is detailed. He even described how to avoid the mercury interacting with the brass of the apparatus by waxing the inside of the metal tube. An interesting recent account of mercury injection has recently been published by Hendriksen (2015).
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Sheldon also described the methods of mounting wet mercury-injected lymphatic specimens for preservation in glass jars, of drying larger mercury injected dissections and of mounting smaller dried specimens on coloured card in glass bottles. Particular care was taken in grinding the top of the jars and their lids to ensure flat surfaces and air-tight bonds. The types of technique described by Sheldon were almost certainly similar to those employed in making the Hunterian material. The descriptions of a few of the Hunterian specimens correspond to some of the methods Sheldon described.
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Specimen 12.4 was prepared from a “dropsical body” and shows a lacteal with distinct valves dividing into several branches and entering a lymph node.
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Specimen 12.16 shows fine blood vessels in the wall of a lymphatic vessel. This specimen is now in turpentine but had initially been dried.
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Specimen 12.19 (missing) showed the thoracic duct of a child. The red tallow injected into the blood vessels had got into the thoracic duct. The tallow in the duct was melted out in hot water and replaced by mercury. In Specimen 12.29, lymphatics of the testis have been injected with mercury and the specimen is mounted on red paper and maintained in turpentine.
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Specimen 12.92 shows the lymphatics of the large intestine of an ass. The specimen has been dried and varnished. The arteries are injected red and a few of the lymphatics contain mercury (Fig. 4). Specimen 12.98 shows mercury-filled lymphatics of the small intestine and mesentery of a turtle (Fig. 5). The form of the bowel is supported by plaster of Paris filling the lumen.
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The controversy of whether lacteals and lymphatics are similar vessels Impressive though the Hunterian specimens are, and they are well worthy of close study, they are by their nature individual specimens and do not, of themselves, allow visitors to the Museum to understand the scientific debates that were in progress when they were made in the third quarter of the 18th Century. For this we need to consult what William Hunter and his colleagues and their contemporaries wrote about the lymphatic system Hunter and his colleagues realised that lacteals and lymphatics were similar vessels. Cruikshank (1790) wrote, “The late Dr Hunter, particularly, taught this doctrine, and urged
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the following arguments in its favour: The lacteals arise from the surfaces of the intestines, pass through the conglobate glands (lymph nodes), terminate in the thoracic duct, and are beyond dispute, absorbents”. The evidence for this, summarising Cruikshank’s account of Hunter’s views, included that i) both lymphatics and lacteals have similarly thin and transparent coats, ii) both have many valves; iii) they pass to lymph nodes; iv) they do not connect with arteries and cannot be injected from them, v) they terminate ultimately in the same common trunk, the thoracic duct. Cruikshank (1790) continued “Thus a grand system for absorption, in men and quadrupeds, was formed, and the lacteals and lymphatics were blended, under the common name of absorbents. Dr Hunter enjoyed the honour of this discovery for many years.”
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Hewson (1774) also appreciated that lacteals and lymphatics were similar vessels. According to Hewson (1774), Francis Glisson (1597 - 1677) and Friderich Hoffman (1660 - 1742) developed the thesis that lymphatic vessels in general were absorbents. William Cruikshank (1745 - 1800), William Hunter’s erstwhile partner in the Great Windmill Street School of Anatomy, in his book on lymphatics, The Anatomy of the Absorbing Vessels (1790), cited one of William Hunter’s Introductory Lectures. Hunter said, “I think I have proved, that the lymphatic vessels are the absorbing vessels, all over the body; that they are the same as the lacteals; and that these, all together, with the thoracic duct, constitute one great and general system, dispersed through the whole body, for absorption; that this system, only, does absorb, and not the veins; that it serves to take up and convey whatever is to make, or to be mixed with, the blood, from the skin, from the intestinal canal, and from all the internal cavities or surfaces whatever. This discovery gains credit daily, both at home and abroad, to such a degree, that I believe we may now say, it is almost universally adopted: and, if we mistake not, in a proper time it will be allowed to be the greatest discovery, both in physiology and pathology, that anatomy has suggested since the discovery of the circulation!” (Cruikshank, 1790; Marshall, 1970).
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It was an ebullient claim from a normally cautious or, to use a Scottish phrase, canny man. Notice though that he is not claiming to have discovered lymphatics as is sometimes asserted, but that he had discovered their function. Although there is no doubt that William and his colleagues made a substantial contribution to the understanding of this topic, and he was correct that lymphatics, lacteals and the thoracic duct were all parts of the system, he was wrong about the absorption by veins. In the body tissues, blood capillaries and lymphatic capillaries absorb interstitial fluid. In the mucosa of the intestines, it tends to be the lipidassociated chylomicrons that are absorbed by lymphatics (see Senior, 1964) while the watersoluble products of digestion are taken up by the blood capillaries. Hunter should perhaps have been more reticent in his claim. The controversy of whether veins or lymphatics are absorbents In the mid-18th Century anatomical world, a hot debate was whether the lymphatics or the veins were absorbents, as they were called at the time. Alexander Monro (secundus) (1733 1817) of Edinburgh in a pamphlet of 1758 (Monro, 1758) made a vicious attack on William Hunter and among other matters accused Hunter of having stolen the idea that lymphatics are
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absorbent vessels from Monro’s thesis of 1755. As well as testimonies at the time that Hunter had been teaching this doctrine prior to 1755, a set of notes of one of Hunter’s students, Charles White, from 1752 contained a note that “The lymphaticks are like the lacteals, but the lacteals are absorbents; therefore it is highly probable that the lymphaticks are the general absorbents of the body and carry the juices to the duct, the receptaculum and finally to the jugular vein” (Dowd, 1972; Eales, 1974). It is likely that Hunter and Monro reached the same conclusion by reading and independent reasoning. A paper by Ambrose (2007) gives a comprehensive account of the Hunter Monro dispute and also describes that Francis Glisson (1597 – 1677), Regius Professor of Physic at Cambridge, had written in 1654 that lymphatics carried a watery humour from the tissues. Hunter had heard of Glisson’s account by 1762 and wrote that he “had the pleasure and mortification that he (Glisson) gave exactly the same account both of transudation and of absorption so that I can no longer call it, what I really believed it to be, a new opinion”. There is no doubt, however, that Hunter and his associates deepened knowledge of the lymphatic system.
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Before microscopes were invented, the presence of invisible vessels between arteries and veins was merely postulated. Without a microscope, Leonardo da Vinci (1452 - 1519) and Andrea Cesalpino (1519 - 1603) could not see blood capillaries, just small blood vessels becoming thinner and dividing into finer branches. Harvey demonstrated the blood circulation without seeing blood capillaries. Marcello Malpighi (1628 - 1694) was the first to observe blood capillaries in 1661 (Pearce, 2007). William Hunter seems never to have considered that it might be them rather than the veins that were doing the absorption. There was no particular thought that blood and lymphatic capillaries might both be involved in absorption. The question of whether lymphatics were absorbents or whether this was the province of veins was a topic that John Hunter addressed.
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John Hunter made an important contribution to the debate (Palmer, 1837). In 1758-59, he carried out an ingenious set of experiments on a dog, three sheep and an ass. In the dog, he showed that when milk passed into the intestine, the lymphatics became white but that the colour of the blood in the veins was unchanged. Nor could massage of the bowel induce the milky substance to appear in the veins. In the sheep, a preparation of starch stained with indigo was passed into the small bowel and the lacteals soon took up the blue stain. A similar study with similar results had been carried out in 1682 by Martin Lister (1639 - 1712) (Lister, 1683). Later scientific criticism that the blue colour might have been the natural colour of lymphatic vessels was dispelled by a further study a few weeks later by William Musgrave (1655 - 1721) (Musgrave, 1701). In his studies, John Hunter was careful to note that the lacteals at the start of the experiment were colourless. Various ways of administering the blue dye and perfusions were tried but none would induce the dye into the veins. Although the lymphatics turned blue, the veins retained their natural colour. The fifth experiment was on an ass. It first had musk in warm water passed into a length of the intestine secured between ligatures. The lymph smelled strongly of musk whereas a sample of venous blood did not. As in the sheep, starch-water dyed with indigo was passed into the ass’s intestinal lumen with results similar to those in the sheep obtained.
Commenting on these experiments, William Hunter in 1762 said, “Here is a new doctrine proposed in physiology, viz. that the red veins do not absorb in the human body. The fair enquirer after truth will be convinced, by the observations which occurred to me, that the common opinion, that they do absorb, is supported by some proofs that are at least doubtful or equivocal, and that the other opinion is not without plausibility; and that he must allow that my brother’s experiments render it highly probable” (Palmer, 1837).
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John Hunter’s experiments make it clear that the fatty content of the milk was absorbed by the lacteals and was transmitted to the bloodstream via the lymphatic trunks and thoracic duct. It seems that the indigo colorant used for the starch was also absorbed by this route. This led the Hunters to conclude that there was no absorption into veins. Lymphatics in birds, reptiles and fish
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An argument that was put forward in the mid-18th century was that if absorption was from lymphatics rather than veins, then this arrangement would be expected in most species of larger animals, not just humans and mammals but in birds, reptiles and fish. Elucidation of this controversy was part of William Hewson’s contribution. Previous anatomists had tried, and failed, to demonstrate lymphatics in birds, reptiles and fish and thus held the view that absorption in these species must be by veins. John Hunter, however, a number of years before Hewson’s investigations, had seen lacteals containing white chyle in a crocodile and had also dissected out lymphatics and lymph nodes in the neck of a swan (Hewson, 1774). Bartholin may have seen lymphatics in the globe fish (Cruikshank, 1790) and William Cheselden (1688 - 1752) observed lymphatics in a fish in 1713 (Eales, 1974).
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Hewson studied the lymphatics of a turtle (Figs. 6 and 7) in 1763 before he saw them in birds and fish. He termed the turtle an amphibian; today we would call it a reptile. In the large turtle he dissected, Hewson found that, differing from his experience of mammals, there were two thoracic ducts but no lymph nodes. The thoracic ducts and the lymphatic trunks of the neck formed a plexus before they opened into the jugular veins. A particular feature in the turtle was the way the mercury filled a plexus immediately beneath the internal lining of the intestines and demonstrated the lacteals (Fig. 8). By inverting the intestine, Hewson was readily able to demonstrate that the mercury reached the region of the villi.
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For a bird in which to study lymphatics, Hewson chose a goose and examined four specimens (Hewson, 1768). Like the turtle, Hewson found there were two thoracic ducts. In birds, the intestinal lymphatics contained clear fluid. There were no lymph nodes associated with the abdominal lymphatics, although a pair was noted near the thoracic duct in the neck. None of the Museum specimens show lymphatics in birds. In 1768, Hewson visited the Sussex coast to study the lymphatics in fish. He went to “Brighthelmstone”, later known as Brighton. In fish, although the general principles of the arrangement of the lymphatic vessels resembled that of mammals, birds and reptiles, the anatomy was sufficiently different to make Hewson uncertain of how to go about demonstrating them. Working initially on a haddock, he found, however, that along the ventral midline of the body of a fish, there is a single large lymphatic which, once located,
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readily accepted the mercury injection. As in the turtle, the lymphatics in fish seemed to have no valves, or were overwhelmed by the injection, so that lymphatic connections could be relatively easily demonstrated. The thoracic duct divided as it passed towards the head to discharge lymph into the venous system. Hewson gave a detailed description of the layout of the lymphatics and it seemed to be similar in the various fish species he examined: haddock, cod, whiting, plaice, turbot, and skate. As in the turtle, the thoracic duct and the lymphatics of the head region formed a complex plexus before joining the jugular veins by a short lymphatic connection. Also similar to the turtle, Hewson noted a plexus of lymphatics close to the intestinal lining. In cod, turbot and plaice, Hewson observed an intricate plexus of lymphatics between the mucosa and the muscular layer of the intestine. In the turbot, Hewson claimed to have seen a lymphatic plexus within the villi. In the cod, he also found that he could express the mercury into the lumen of the intestine which seems likely to have perpetuated the misunderstanding that the intestinal lumen and the lacteals were in communication.
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Hewson’s discoveries, even after his death, were disputed by Alexander Monro (Eales, 1974) who asserted prior discovery in the turtle, birds and fish but his claims had little substance. The haddock illustrated by Hewson (1769) in his paper in Philosophical Transactions is Specimen 12.122 (Fig. 9). The studies on fish extended beyond the species cited in Hewson’s text as the Museum contains specimens showing lymphatics in the conger eel and ray (Marshall, 1970).
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Controversy over the origin of the lacteals and lymphatics from surfaces
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Cruikshank (1790), describing William Hunter’s views, wrote “The venereal and other poisons passing into lymphatics from the skin, proved their origin from surfaces; and the extravasated injections passing into the same vessels, from the cellular membrane (i.e. the connective tissue), proved, in his (William Hunter’s) opinion, their origin from cells.” Hunter also said that lacteals and lymphatics both “appear” to arise from surfaces, stating that, “if the venereal poison is applied to the surface of an ulcer, and passes into the blood, it passes through the lymphatic vessels, it sometimes inflames their coats, and makes them, in consequence of this, appear in the form of red lines; it frequently inflames the glands through which they pass, and, some time after, shews itself in the constitution, by symptoms peculiar to itself …”. Although a reasonable conclusion at the time, Hunter was incorrect.
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William Hunter thought the lacteals commenced at the internal intestinal surface. Hewson also seemed to accept as largely proven that the intestinal contents were taken up directly into the lacteals at the tips of the intestinal villi. As noted earlier, he was able to express the milky fluid from the intestinal villi in a cod. We now know that in doing this, he must have ruptured an epithelial barrier. Hewson thought lacteals were open at their ends and that this pore was guarded by a “patulous” valve, that is one of a soft texture. Hewson’s concept was that when the small intestine was active after a meal, the villi became engorged with blood. Rather like erectile tissue, the villus stiffened and this held the pore open allowing intestinal fluid to be drawn in and along the lacteal by capillary action. This was a histological problem that was not solved until the advent of resin histological sections and electron microscopy. Even at the
start of our careers in the late 1970s, there was still speculation on the presence of pores, although it was generally appreciated that all material being absorbed by the bowel had to be done through the epithelium, there being junctional complexes between epithelial cells that prevented intercellular movement (Fawcett, 1986).
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The quotation cited earlier from Cruikshank (1790) of one of William Hunter’s Introductory Lectures said that the lymphatic system “… serves to take up and convey whatever is to make, or to be mixed with, the blood, from the skin, from the intestinal canal, and from all the internal cavities or surfaces whatever.” As described above, the understanding of Hunter and Hewson that the lacteals arose from pores at the tips of villi was subsequently found to be incorrect. Similarly the concept of lymphatics arising from internal surfaces has proven to be the subject of controversy and research. Hewson (1774) thought that lymphatics arose from body cavities in a way similar to lacteals arising from the intestines. He also thought that lymphatics drained fluid from body cavities writing, “… we have always found the fluids contained in the different cavities of the body and that contained in the lymphatics exactly agreeing with one another, in their transparency, in their consistence, etc.” (Hewson, 1774).
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One of William Hunter’s specimens (12.42) is that of the lymphatics of the lung of a lioness which died in the Tower of London Menagerie (Fig. 10). At its death, it bled from its mouth and into its intestines (Marshall, 1970). The catalogue entry says, “… The absorbents were full of blood, which in the great trunks was coagulated, and prevented the mercury thrown in by the smaller branches from getting on.” The lymphatic trunks being filled with blood suggested that lymphatic vessels must be open-ended. Observations of blood in lymphatics has led to much research interest in the nature of the uptake of fluid from the linings (serous membranes) which has continued right down to the present time.
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Cruikshank wrote, “… injections thrown into the intestines, or other cavities, in the dead body, never, that I could observe, get into the lacteals or lymphatics, though we know their orifices to be really there: could this have taken place, all the absorbent system would long ago have been compleatly (sic) described” (Cruikshank, 1790).
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Like Hewson, Cruikshank had noted that whenever fluids are extravasated on surfaces, or into cavities, the lymphatics of the surfaces and cavities were found full of a similar fluid. He wrote, “This is better demonstrated, when the fluids mentioned happen to be of a strong colour. This I have repeatedly seen, in animals dying of haemoptoe (haemoptysis), and in the human subject itself, the lymphatics of the lungs, which at other times contain a transparent fluid, turgid with blood, which they had absorbed from the air-cells.” (Cruikshank, 1790). Cruikshank also described that “In animals strangled, or dying of some violent death, the lymphatics about the spleen, and in the cavity of the abdomen in general, are almost always found turgid with blood, though I have never seen, on these occasions, any marks of extravasation of that fluid into the cellular membrane. In peritoneal inflammation, I have demonstrated the lacteals full of blood, though in this inflammation there is little or no swelling, of course no extravation of the blood into the cellular membrane” (Cruikshank, 1790).
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Cruikshank (1790) continued, “I have seen the absorbents of the lungs also loaded with blood, in the peripneumony or inflammation of their substance; and on all these occasions have been induced to believe that the lymphatics arose from the internal surfaces of the arteries and veins.” Presumably this observation may explain why earlier anatomists thought that lymphatics were continuous with the arterial system. Cruikshank, however, had further explanations. “This doctrine is not without its difficulties; for arteries and veins have been distended with injected fluids on many occasions, without the smallest drop of these fluids passing into the lymphatics; and one of the arguments, by which the origin of the lymphatics from surfaces is supported, is, that they cannot be injected from arteries or veins.”
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The entry of erythrocytes into lymphatics and the mechanism by which this occurs remains an on-going controversy 250 years later (see Kazeem and Scothorne, 1982). Courtice et al. (1953) injected blood into the peritoneal cavities of rats, rabbits and guinea pigs and found that erythrocytes seemed to be particularly taken up by diaphragmatic lymphatics and passed to the right lymphatic duct. A number of studies including those by Leak and Rahil (1978) and Negrini et al. (1991) have demonstrated the presence of open stomata between the mesothelial cells of the diaphragm associated with a rich plexus of lymphatic capillaries with rapid uptake of tracers (Abu-Hijleh et al., 1994).
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What other contributions did the Hunter brothers and their associates make to the understanding of the lymphatic system?
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Sheldon reported that he had successfully injected human lacteals with mercury from the bowel to the first intestinal gland. He thought he might have been the first person since Nuck to have done so but discovered that Alexander Monro secundus had injected them while working with Meckel in Berlin. William Hewson subsequently told Sheldon that he had once filled them in a human subject. After the death of Hewson, when Sheldon went to work with Dr Hunter, he saw a specimen of a human lacteal trunk injected from the intestine to the first regional mesenteric lymph node. “Upon inquiry I found that this was the preparation which Mr Hewson had mentioned to me; and it was the only specimen of the human lacteals injected, existing in England at that time. Mr Hewson seems to have considered it as a matter of some difficulty to make such a preparation, since he says in his work on the lymphatic system, ‘I have injected them with mercury even in the human subject.’”
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The following specimens correspond to this description: 12.71; 12.75 (missing); 12.77; 12.78; 12.79 (missing), but there is nothing in the Museum to say whether any of them is the one made by Hewson. As well as documenting lymphatic vessels and their arrangement in several species, Hewson also made a number of other discoveries that extended knowledge or corrected misunderstandings. Hewson noted that lacteals do not always contain white fluid. In a dog a while after a meal it is clear and, in birds, the lacteals always contain clear fluid. He thus regarded the lacteals as the lymphatics of the intestines. Hewson made a detailed study of the lymphatics of the human body and his account is very much what would still be accepted today. Meckel had thought that the lymphatics of the
stomach drained into local veins but Hewson disproved this, demonstrating that lymph from the stomach reached the thoracic duct in common with that from other viscera. There are, however, no specimens of the lymphatics of the human stomach in the Hunterian Collection at Glasgow.
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In Hewson’s time, there was a theory that the black tracheobronchial lymph nodes were glands which secreted mucus into the airways. Hewson, however, showed them to be lymph nodes as they filled with mercury when he injected the lungs. This is illustrated in Specimen 12.40.
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Hewson was uncertain about the lymph drainage of the brain but had consistently failed to find lymphatics. He was correct and the special arrangements for fluid movement in the central nervous system have only in recent times started to become elucidated (see Morris et al., 2016). Hewson also dismissed a view that the pineal gland is a lymph node. CONCLUSION
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William and John Hunter and their colleagues, William Hewson, William Cruikshank and John Sheldon made large contributions to understanding the distribution of lymphatic vessels in the human body and in other species and that lacteals and lymphatics are similar vessels involved in absorbing fluid from the tissues. They were, however, subsequently shown to have some misunderstandings, particularly that blood capillaries as well as lymphatic capillaries absorb fluid from the tissues, and that lacteals, like other lymphatic capillaries, are blind-ended and do not absorb directly from the intestinal lumen. Although William Hunter clearly realised that tuberculosis and venereal diseases might involve the regional nodes, the Hunterian Collection at Glasgow, William Hunter’s writings and lecture notes of his students have little on involvement of regional lymph nodes by malignant disease or the concept that, in the presence of metastatic disease in lymph nodes, knowledge of lymph drainage could be used to define the likely site of a primary tumour.
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ACKNOWLEDGEMENT
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We are grateful for the assistance of Mr Graham Nisbet of the Hunterian Art Gallery.
REFERENCES Abu-Hijleh, M.F., Reid, O., McGadey, J., Scothorne, R.J., 1994. Distribution of mesothelial stomata in the rat. Clin. Anat. 7, 189 – 203. Ambrose, C.T., 2007. The priority dispute over the function of the lymphatic system and Glisson's ghost (the 18th-century Hunter-Monro feud). Cell. Immunol. 245, 7 - 15.
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Cameron, A., 2004. John Sheldon (1752 – 1808) anatomist and surgeon. In: Oxford Dictionary of National Biography. Oxford University Press, Oxford. Courtice, F.C., Harding, J., Steinbeck, A.W., 1953. The removal of free red blood cells from the peritoneal cavity of animals. Austral. J. Exp. Biol. Med. Sci. 31, 215 – 225.
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Cruikshank, W.C., 1790. The Anatomy of the Absorbing Vessels of the Human Body. G. Nicol, London. Dowd, N., 1972. Hunter’s Lectures of Anatomy. Elsevier, Amsterdam.
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Eales, N.B., 1974. The history of the lymphatic system, with special reference to the HunterMonro controversy. J. Hist. Med. 29, 280 – 294.
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Fawcett, D.W., 1986. Bloom and Fawcett: A Textbook of Histology, eleventh edition. W. B. Saunders Co., Philadelphia.
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Garrison, F.H., 1921. An Introduction to the History of Medicine, third edition. W. B. Saunders Co., Philadelphia.
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Hendriksen, M.M., 2015. Anatomical mercury: Changing understandings of quicksilver, blood, and the lymphatic system, 1650-1800. J. Hist. Med. Allied. Sci. 70, 516 - 548. Hewson, W., 1768. An account of the lymphatic system in birds. Phil. Trans. 58, 217 – 226.
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Hewson, W., 1769. An account of the lymphatic system in fish. Phil. Trans. 59, 204 – 215.
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Hewson, W., 1774. A description of the lymphatic system in the human subject, and in other animals. In: Gulliver, G. 1846. The Works of William Hewson, F.R.S.. Sydenham Society, London.
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Hunter, W., 1762. Medical Commentaries. Part I. Containing a Plain and Direct Answer to Professor Monro jun. Interspersed with Remarks on the Structure, Functions, and Diseases of Several Parts of the Human Body. A. Hamilton, London. Hunter, W., 1774. The Anatomy of the Gravid Uterus Exhibited in Figures. John Baskerville, Birmingham. Janjua, R.M., Schultka, R., Goebbel, L., Pait, T.G., Shields, C.B., 2010. The legacy of Johann Friedrich Meckel the Elder (1724–1774): A 4-generation dynasty of anatomists. Neurosurg. 66, 758 – 771.
Kazeem, A.A., Scothorne, R.J. 1982. Studies on hemolymph nodes. II. The regional origin of the afferent lymphatics. J. Anat. 135, 1 – 4. Leak, L.V., Rahil, K., 1978. Permeability of the diaphragmatic mesothelium: The ultrastructural basis for “stomata.” Am. J. Anat. 151, 557 - 592. Lister, M., 1683. An extract of a letter, relating an experiment made altering the colour of the chyle in the lacteal veins. Phil. Trans. 13, 6 - 9.
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Marshall, A.J., 1970. Catalogue of the Anatomical Preparations of Dr William Hunter. University of Glasgow, Glasgow.
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Meckel, J.F., 1772. Nova Experimenta et Observationes de Finibus Venarum ac Vasorum Lymphaticorum in Ductus Visceraque Extretoria Corporis Humani. Fridericum Nicolai, Berolini. Monro, A., 1758. Observations, Anatomical and Physiological wherein Dr. Hunter's Claim to some Discoveries is Examined. Hamilton, Balfour and Neill, Edinburgh.
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Morris, A.W.J., MacGregor Sharp, M., Albargothy, N.J., Fernandes, R., Hawkes, C.A., Verma, A., Weller, R.O., Carare, R.O., 2016. Vascular basement membranes as pathways for the passage of fluid into and out of the brain. Acta Neuropathol. 131, 725-736.
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Musgrave, W., 1701. A letter from Dr William Musgrave F.R.S. to the publisher concerning some experiments made for transmitting a blue coloured liquor in-into the lacteals. Phil Trans 22, 996 – 998.
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Natale, G., Bocci, G., Ribatti, D., 2017. Scholars and scientists in the history of the lymphatic system. J. Anat. 231, 417 - 429.
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Negrini, D., Mukenge, S., Del Fabbro, M., Gonano, C., Miserocchi, G., 1991. Distribution of diaphragmatic stomata. J. Appl. Physiol. 70, 1544 - 1549.
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Palmer, J., 1837. On absorption by veins. The Works of John Hunter F.R.S.. Longman, Rees, Orme, Brown Green and Longman, London, pp. 299 – 314. Pearce, J.M.S., 2007. Malpighi and the discovery of capillaries. Eur Neurol 58, 253 – 255. Rusznyak, I., Foldi, M., Szabo, G., 1960. Lymphatics and Lymph Circulation. Pergamon Press, Oxford.
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Sappey, P.C., 1869. Traité d’Anatomie Descriptive. Adrien Delahaye, Paris. Senior, J.R., 1964. Intestinal absorption of fats. J. Lipid Res. 5, 495 – 521. Sheldon, J., 1784. History of the Absorbent System. T. Cadell and P. Elmsly, London.
LEGENDS
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Fig. 1. William Hunter (1718 – 1783) by Sir Joshua Reynolds, c. 1787. By kind permission of the Hunterian Museum, University of Glasgow. © The Hunterian, University of Glasgow 2017.
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Fig. 2. A corner of the Anatomy Museum and Specimen 12.17, a thoracic duct injected with mercury said in 1770 to be “one of the largest and most perfect thoracic ducts perhaps ever injected”.
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Fig. 3. Specimen 12.81, the lymphatics of the intestine of an antelope. “The absorbents are still preserved in the state they were found in the dead body., i.e. full of their own chyle. The arteries and veins are both injected red. The lymphatics pass to a large lymph node in the centre of the specimen.” In many species, the lacteals terminate in a single node still referred to as the “pancreas of Aselli”.
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Fig. 4. Specimen 12.92, the lymphatics of the large intestine of an ass. The specimen now in fluid had been dried and varnished. The arteries are injected red and a few of the lymphatics contain mercury.
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Fig. 5. Specimen 12.98 showing mercury-filled lymphatics of the small intestine and mesentery of a turtle. The form of the bowel is supported by plaster of Paris filling the lumen.
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Fig. 6. Specimen 12.59, part of the stomach of a turtle with the arteries injected red, the veins black and the lymphatics filled with mercury.
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Fig. 7. Specimen 12.107, showing fine mercury-filled lymphatics of the intestine and mesentery of a turtle.
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Fig. 8. Specimen 12.106, demonstrating the large number of lymphatics in the wall of the small intestine of the turtle. The arteries have been injected red and the veins black.
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Fig. 9. Specimen 12.122. The haddock illustrated by Hewson (1769) in his paper in Philosophical Transactions.
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Fig. 10. Specimen 12.42, the lymphatics of the lung of a lioness which died in the Tower of London Menagerie.
S0940-9602(18)30033-5 https://doi.org/10.1016/j.aanat.2018.03.002 AANAT 51242
To appear in: Received date: Revised date: Accepted date:
24-11-2017 14-3-2018 22-3-2018
Please cite this article as: McDonald, Stuart W., Russell, David, William Hunter and Lymphatics.Annals of Anatomy https://doi.org/10.1016/j.aanat.2018.03.002 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
William Hunter and Lymphatics
Stuart W. McDonald and David Russell
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Anatomy Facility, School of Life Sciences, University of Glasgow, Glasgow, United Kingdom.
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Historical article Corresponding author: Dr Stuart W. McDonald, Anatomy Facility, School of Life Sciences, University of Glasgow, GLASGOW, G12 8QQ, United Kingdom.
ABSTRACT
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William Hunter along with his brother, John, and their colleagues William Hewson, William Cruikshank and John Sheldon made a large contribution to understanding of lymphatic vessels. Hewson, Cruikshank and Sheldon all carried out mercury injections and made much progress in mapping the distribution of lymphatics in the human body. William Hunter appreciated that lymphatics absorbed fluid from the tissues of the body and that lacteals of the intestine and lymphatics are similar structures. John Hunter carried out an elegant series of experiments that proved that lacteals absorb products of digestion. The Hunters, however, were wrong in dismissing absorption by blood vessels and missed the importance of blood capillaries. William Hewson showed that lymphatics were not confined to mammals but that they are present in reptiles, birds and fish. Hewson also demonstrated that tracheobronchial glands are lymph nodes and not mucus-secreting glands as previously thought. Although William Hunter appreciated that tuberculosis and venereal diseases might involve the regional lymph nodes, he does not seem to have fully grasped that malignant disease might involve the local nodes or the concept that knowledge of lymph drainage could be used to define the likely site of a primary malignancy.
Keywords: William Hunter; John Hunter; William Cruikshank; William Hewson; John Sheldon; University of Glasgow; lymphatics; lacteals; 18th Century; history of medicine
INTRODUCTION
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It is 300 years since the birth at East Kilbride, Lanarkshire, Scotland, of William Hunter (1718 - 1783) (Fig. 1) who, going to London, quickly rose to become one of the great anatomists and man-midwives of the 18th Century. In 1762, Hunter became Physician Extraordinary to Queen Charlotte, consort of George III, and was in attendance at the deliveries of all but the last of their children. William Hunter is remembered for his pioneering work The Anatomy of the Gravid Uterus Exhibited in Figures (1774) and the demonstration that the mother and fetus have separate blood circulations. Hunter, however, is also celebrated as a pioneer in elucidating the lymphatic system, the system of vessels that returns excess fluid from the tissues to the bloodstream. The collection of specimens in which lymphatics have been demonstrated by injection of mercury is one of the highlights of William Hunter’s collection of anatomical specimens on display at the Anatomy Museum of the University of Glasgow. Many of the specimens that show human lymphatics were prepared by William Cruikshank (1745 - 1800) and those showing animal lymphatics are the work of William Hewson (1739 - 1774). Hewson served as assistant to William Hunter from 1762 - 1770 and Cruikshank form 1771 to Hunter’s death in 1783.
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The discovery of lymphatics
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Lymphatics had been known long before the days of William Hunter and his brother, John (1728 - 1793). John Sheldon (1752 - 1808), a former student of both John and William Hunter (Cameron, 2004), in his History of the Absorbent System (1784), gave a good account of the history of the discovery of the lymphatic system and the level of understanding that had been reached by the time of William and John Hunter.
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Erasistratus, working in Alexandria (Garrison, 1921) about 300 BC, had seen lacteals distended with chyle in the mesenteries of recently born goat kids he was dissecting. He thought the chyle was the milk the kids had been suckling. Herophilus, also in Alexandria about the same time (Garrison, 1921), also saw lacteals in young animals and noted that they differed from mesenteric veins by passing to glandular structures (mesenteric lymph nodes) rather than to the portal vein. The Roman physician, Galen (c. 130 - 200 AD), wrote about lacteals, but only reiterated the observation made by Herophilus (Sheldon, 1784). In Pavia in 1622, a physician, Gaspare Aselli (1581 - 1626) (Garrison, 1921), was giving a demonstration to friends of the movements and innervation of the diaphragm on a live dog. When he opened the abdomen to give a better view of the diaphragm, he noticed that the intestines and the mesentery were covered in fine white thread-like lines. Departing from the diaphragmatic experiment to study this unexpected observation and realising from their appearance that they were not nerves as he initially supposed, he cut into one to find that a milky substance oozed out. The dog soon died and the vessels disappeared. Aselli
subsequently sacrificed another dog with negative results but when examining another that had just eaten, he again saw the lacteals, the name he gave these vessels (Rusznyak et al., 1960). Aselli then repeated the study on different species, as he was able, including a positive study in a horse that recently had been fed. In his studies on lacteals, Aselli also demonstrated the presence of valves along their length (Sheldon, 1784).
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After Aselli’s observations, lacteals were also seen by Werner Rolfink (1599 - 1673) in 1616, Marco Aurelio Severino (1580 - 1656) in 1630, by Olaus Worm (1588 - 1654) about the same year, by Guilhelmus Fabricius Hildanus (1560 - 1634) in 1632 (Sheldon, 1784) and by Johann Vesling (1598 - 1649) in 1634 (Cruikshank, 1790). A problem that took some time to solve was difficulty over the destination of the lacteals. Aselli and others thought they passed to a “pancreas” and that, by an ill-defined route, the chyle reached the liver (Sheldon, 1784). The thoracic duct had been seen by Bartolommeo Eustachi (1524 - 1574) in a horse about 1563 (Sheldon, 1784; Cruikshank, 1790), and by Vesling in 1649 (Cruikshank, 1790). Its significance as the main lymphatic trunk draining lymph to the bloodstream, however, was not appreciated until an incidental discovery by Jean Pecquet (1622 - 1674) in 1651 (Hewson, 1774; Garrison, 1921). Pecquet was carrying out a dissection of a dog’s heart (Sheldon, 1784) and, on opening the right atrium and seeing milky chyle within it and tracing it back to its source, found that it had come from the thoracic duct via the subclavian vein (Hewson, 1774). Around 1654, the duct was traced in humans by Olof Rudbeck (1630 - 1702), followed by Thomas Bartholin (1616 - 1680), Isbrand van Diemerbroeck (1609 - 1674) and Christian Johannes Langius (1655 - 1701), and also in a number of land and aquatic mammals. It thus became clear that lymph was transmitted to the bloodstream at the veins at the root of the neck. In the Hunterian Collection, Specimen 12.17 is a particularly fine specimen of a thoracic duct filled with mercury (Fig. 2). Its legend says, “One of the largest and most perfect thoracic ducts perhaps ever injected (1770)” (Marshall, 1970).
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Lymphatic vessels at other sites in the body were first observed by Rudbeck about 1648 and around the same time by Bartholin and George Joyliffe (1621 - 1658) at Cambridge (Cruikshank, 1790; Eales, 1974). It was Bartholin who adopted the term vasa lymphatica. Hewson (1774) recorded that after these early discoveries, Anton Nuck (1650 - 1692) about 1691 injected lymph glands, or nodes to use a more modern term. Nuck is also credited with being the first to carry out mercury injections (Rusznyak et al., 1960). Frederik Ruysch (1638 - 1731) in 1665 further described lymphatic valves. These anatomists, however, only saw lymphatics at particular sites but Johann Friedrich Meckel (1724 - 1774) in the later part of his life gave an overview of the whole system and traced lymphatics in sites where they had not been documented previously (Meckel, 1772; Rusznyak et al., 1960; Janjua at al., 2010). Such was the state of the science when the Hunters became interested in the topic. Some of the features seen by early anatomists were demonstrated in William Hunter’s specimens. Specimen 12.81 shows the lymphatics of the intestine of an antelope (Fig. 3). “The absorbents are still preserved in the state they were found in the dead body., i.e. full of their
own chyle. The arteries and veins are both injected red”. The lymphatics pass to a large lymph node in the centre of the specimen. Specimen 12.85 shows lacteals terminating in a mass of glands at the root of the mesentery, which has been called the “pancreas of Aselli” by the author of the Hunterian catalogue (Marshall, 1970). Techniques of Lymphatic Injection in the 18th Century
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Hunter knew that if an injection made into an artery or a vein ruptured into the surrounding connective tissue, what he called the cellular membrane, it very commonly filled the local lymphatic vessels. Similarly, if a “tube loaded with quicksilver, was pushed, at random, into the cellular substance of a gland (the testicle, for example) the quicksilver would frequently pass into the lymphatics of that part” (Cruikshank, 1790).
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John Sheldon studied with both William and John Hunter (Cameron, 2004) and was William Hunter’s successor as Professor of Anatomy at the Royal Academy. In his History of the Absorbent System (1784), Sheldon expressed his willingness to share his knowledge of techniques for injecting lymphatics. Many of these methods he no doubt learned from William and John Hunter and from William Hewson who was a friend, as well as having been an assistant to William Hunter. Sheldon made some refinements to the methods but, in general, they are likely to be similar to those used by the Hunters, Hewson and Cruikshank. Sheldon used fresh cadavers and, dissecting generally being carried out in the winter, preferred to work between the hours of 10 am and 12 noon and at a north-facing window as this gave a more even illumination. Ordinary windows worked well. Bright light could make lymphatics difficult to discern among the tissues. Oedematous bodies, dropsical was the term Sheldon used, worked well as their lymphatic vessels tended to be distended. Decomposing material if conditions were right was also used. In relatively early stages of putrefaction, gas gathered in lymphatics and made them easier to inject. Sometimes for larger lymphatic vessels, Sheldon used what he called the coarse injection which was a mixture of two thirds yellow resin and one third mutton suet. For a firmer injectate, wax could be added and, for a softer consistency, the proportion of suet could be increased. A number of pigments were employed as required: Prussian blue, flake white, verdigrease (sic), vermilion.
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For most lymphatic work, however, mercury was best as its weight made for easy filling of lymphatics. Interestingly, about the same time as Sheldon published his book, the Italian anatomist Paolo Mascagni (1755 – 1815) produced two important works on the lymphatic system: “Prodrome d’une ouvrage sur le système des vaisseaux lymphatiques” and “Vasorum lymphaticorum corporis humani historia et ichnographia” in 1784 and 1787 respectively (Natale et al., 2017). Mascagni, like Sheldon, also injected with mercury and it was still being used by Sappey (1810 - 1896) in the mid-19th Century (Sappey, 1869). Mercury clearly was expensive and Sheldon, as well as mentioning the requirement for adequate amounts to carry out studies, also described ways of catching and reusing spilled mercury. The lymphatic to be injected was dissected out and then cannulated. It is not entirely clear how mercury injection was carried out by the Hunter brothers and their associates, but the method was rather
cumbersome with the need for an assistant to fill the mercury reservoir while the dissector tied the cannula into the lymphatic. It seems that Sheldon improved the method of injection of mercury by pioneering the use of a curved cannula with a valve mechanism to control the flow of mercury and a more manoeuvrable tube connecting the mercury reservoir and the cannula. Sheldon’s account of the methodology is detailed. He even described how to avoid the mercury interacting with the brass of the apparatus by waxing the inside of the metal tube. An interesting recent account of mercury injection has recently been published by Hendriksen (2015).
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Sheldon also described the methods of mounting wet mercury-injected lymphatic specimens for preservation in glass jars, of drying larger mercury injected dissections and of mounting smaller dried specimens on coloured card in glass bottles. Particular care was taken in grinding the top of the jars and their lids to ensure flat surfaces and air-tight bonds. The types of technique described by Sheldon were almost certainly similar to those employed in making the Hunterian material. The descriptions of a few of the Hunterian specimens correspond to some of the methods Sheldon described.
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Specimen 12.4 was prepared from a “dropsical body” and shows a lacteal with distinct valves dividing into several branches and entering a lymph node.
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Specimen 12.16 shows fine blood vessels in the wall of a lymphatic vessel. This specimen is now in turpentine but had initially been dried.
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Specimen 12.19 (missing) showed the thoracic duct of a child. The red tallow injected into the blood vessels had got into the thoracic duct. The tallow in the duct was melted out in hot water and replaced by mercury. In Specimen 12.29, lymphatics of the testis have been injected with mercury and the specimen is mounted on red paper and maintained in turpentine.
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Specimen 12.92 shows the lymphatics of the large intestine of an ass. The specimen has been dried and varnished. The arteries are injected red and a few of the lymphatics contain mercury (Fig. 4). Specimen 12.98 shows mercury-filled lymphatics of the small intestine and mesentery of a turtle (Fig. 5). The form of the bowel is supported by plaster of Paris filling the lumen.
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The controversy of whether lacteals and lymphatics are similar vessels Impressive though the Hunterian specimens are, and they are well worthy of close study, they are by their nature individual specimens and do not, of themselves, allow visitors to the Museum to understand the scientific debates that were in progress when they were made in the third quarter of the 18th Century. For this we need to consult what William Hunter and his colleagues and their contemporaries wrote about the lymphatic system Hunter and his colleagues realised that lacteals and lymphatics were similar vessels. Cruikshank (1790) wrote, “The late Dr Hunter, particularly, taught this doctrine, and urged
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the following arguments in its favour: The lacteals arise from the surfaces of the intestines, pass through the conglobate glands (lymph nodes), terminate in the thoracic duct, and are beyond dispute, absorbents”. The evidence for this, summarising Cruikshank’s account of Hunter’s views, included that i) both lymphatics and lacteals have similarly thin and transparent coats, ii) both have many valves; iii) they pass to lymph nodes; iv) they do not connect with arteries and cannot be injected from them, v) they terminate ultimately in the same common trunk, the thoracic duct. Cruikshank (1790) continued “Thus a grand system for absorption, in men and quadrupeds, was formed, and the lacteals and lymphatics were blended, under the common name of absorbents. Dr Hunter enjoyed the honour of this discovery for many years.”
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Hewson (1774) also appreciated that lacteals and lymphatics were similar vessels. According to Hewson (1774), Francis Glisson (1597 - 1677) and Friderich Hoffman (1660 - 1742) developed the thesis that lymphatic vessels in general were absorbents. William Cruikshank (1745 - 1800), William Hunter’s erstwhile partner in the Great Windmill Street School of Anatomy, in his book on lymphatics, The Anatomy of the Absorbing Vessels (1790), cited one of William Hunter’s Introductory Lectures. Hunter said, “I think I have proved, that the lymphatic vessels are the absorbing vessels, all over the body; that they are the same as the lacteals; and that these, all together, with the thoracic duct, constitute one great and general system, dispersed through the whole body, for absorption; that this system, only, does absorb, and not the veins; that it serves to take up and convey whatever is to make, or to be mixed with, the blood, from the skin, from the intestinal canal, and from all the internal cavities or surfaces whatever. This discovery gains credit daily, both at home and abroad, to such a degree, that I believe we may now say, it is almost universally adopted: and, if we mistake not, in a proper time it will be allowed to be the greatest discovery, both in physiology and pathology, that anatomy has suggested since the discovery of the circulation!” (Cruikshank, 1790; Marshall, 1970).
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It was an ebullient claim from a normally cautious or, to use a Scottish phrase, canny man. Notice though that he is not claiming to have discovered lymphatics as is sometimes asserted, but that he had discovered their function. Although there is no doubt that William and his colleagues made a substantial contribution to the understanding of this topic, and he was correct that lymphatics, lacteals and the thoracic duct were all parts of the system, he was wrong about the absorption by veins. In the body tissues, blood capillaries and lymphatic capillaries absorb interstitial fluid. In the mucosa of the intestines, it tends to be the lipidassociated chylomicrons that are absorbed by lymphatics (see Senior, 1964) while the watersoluble products of digestion are taken up by the blood capillaries. Hunter should perhaps have been more reticent in his claim. The controversy of whether veins or lymphatics are absorbents In the mid-18th Century anatomical world, a hot debate was whether the lymphatics or the veins were absorbents, as they were called at the time. Alexander Monro (secundus) (1733 1817) of Edinburgh in a pamphlet of 1758 (Monro, 1758) made a vicious attack on William Hunter and among other matters accused Hunter of having stolen the idea that lymphatics are
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absorbent vessels from Monro’s thesis of 1755. As well as testimonies at the time that Hunter had been teaching this doctrine prior to 1755, a set of notes of one of Hunter’s students, Charles White, from 1752 contained a note that “The lymphaticks are like the lacteals, but the lacteals are absorbents; therefore it is highly probable that the lymphaticks are the general absorbents of the body and carry the juices to the duct, the receptaculum and finally to the jugular vein” (Dowd, 1972; Eales, 1974). It is likely that Hunter and Monro reached the same conclusion by reading and independent reasoning. A paper by Ambrose (2007) gives a comprehensive account of the Hunter Monro dispute and also describes that Francis Glisson (1597 – 1677), Regius Professor of Physic at Cambridge, had written in 1654 that lymphatics carried a watery humour from the tissues. Hunter had heard of Glisson’s account by 1762 and wrote that he “had the pleasure and mortification that he (Glisson) gave exactly the same account both of transudation and of absorption so that I can no longer call it, what I really believed it to be, a new opinion”. There is no doubt, however, that Hunter and his associates deepened knowledge of the lymphatic system.
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Before microscopes were invented, the presence of invisible vessels between arteries and veins was merely postulated. Without a microscope, Leonardo da Vinci (1452 - 1519) and Andrea Cesalpino (1519 - 1603) could not see blood capillaries, just small blood vessels becoming thinner and dividing into finer branches. Harvey demonstrated the blood circulation without seeing blood capillaries. Marcello Malpighi (1628 - 1694) was the first to observe blood capillaries in 1661 (Pearce, 2007). William Hunter seems never to have considered that it might be them rather than the veins that were doing the absorption. There was no particular thought that blood and lymphatic capillaries might both be involved in absorption. The question of whether lymphatics were absorbents or whether this was the province of veins was a topic that John Hunter addressed.
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John Hunter made an important contribution to the debate (Palmer, 1837). In 1758-59, he carried out an ingenious set of experiments on a dog, three sheep and an ass. In the dog, he showed that when milk passed into the intestine, the lymphatics became white but that the colour of the blood in the veins was unchanged. Nor could massage of the bowel induce the milky substance to appear in the veins. In the sheep, a preparation of starch stained with indigo was passed into the small bowel and the lacteals soon took up the blue stain. A similar study with similar results had been carried out in 1682 by Martin Lister (1639 - 1712) (Lister, 1683). Later scientific criticism that the blue colour might have been the natural colour of lymphatic vessels was dispelled by a further study a few weeks later by William Musgrave (1655 - 1721) (Musgrave, 1701). In his studies, John Hunter was careful to note that the lacteals at the start of the experiment were colourless. Various ways of administering the blue dye and perfusions were tried but none would induce the dye into the veins. Although the lymphatics turned blue, the veins retained their natural colour. The fifth experiment was on an ass. It first had musk in warm water passed into a length of the intestine secured between ligatures. The lymph smelled strongly of musk whereas a sample of venous blood did not. As in the sheep, starch-water dyed with indigo was passed into the ass’s intestinal lumen with results similar to those in the sheep obtained.
Commenting on these experiments, William Hunter in 1762 said, “Here is a new doctrine proposed in physiology, viz. that the red veins do not absorb in the human body. The fair enquirer after truth will be convinced, by the observations which occurred to me, that the common opinion, that they do absorb, is supported by some proofs that are at least doubtful or equivocal, and that the other opinion is not without plausibility; and that he must allow that my brother’s experiments render it highly probable” (Palmer, 1837).
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John Hunter’s experiments make it clear that the fatty content of the milk was absorbed by the lacteals and was transmitted to the bloodstream via the lymphatic trunks and thoracic duct. It seems that the indigo colorant used for the starch was also absorbed by this route. This led the Hunters to conclude that there was no absorption into veins. Lymphatics in birds, reptiles and fish
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An argument that was put forward in the mid-18th century was that if absorption was from lymphatics rather than veins, then this arrangement would be expected in most species of larger animals, not just humans and mammals but in birds, reptiles and fish. Elucidation of this controversy was part of William Hewson’s contribution. Previous anatomists had tried, and failed, to demonstrate lymphatics in birds, reptiles and fish and thus held the view that absorption in these species must be by veins. John Hunter, however, a number of years before Hewson’s investigations, had seen lacteals containing white chyle in a crocodile and had also dissected out lymphatics and lymph nodes in the neck of a swan (Hewson, 1774). Bartholin may have seen lymphatics in the globe fish (Cruikshank, 1790) and William Cheselden (1688 - 1752) observed lymphatics in a fish in 1713 (Eales, 1974).
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Hewson studied the lymphatics of a turtle (Figs. 6 and 7) in 1763 before he saw them in birds and fish. He termed the turtle an amphibian; today we would call it a reptile. In the large turtle he dissected, Hewson found that, differing from his experience of mammals, there were two thoracic ducts but no lymph nodes. The thoracic ducts and the lymphatic trunks of the neck formed a plexus before they opened into the jugular veins. A particular feature in the turtle was the way the mercury filled a plexus immediately beneath the internal lining of the intestines and demonstrated the lacteals (Fig. 8). By inverting the intestine, Hewson was readily able to demonstrate that the mercury reached the region of the villi.
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For a bird in which to study lymphatics, Hewson chose a goose and examined four specimens (Hewson, 1768). Like the turtle, Hewson found there were two thoracic ducts. In birds, the intestinal lymphatics contained clear fluid. There were no lymph nodes associated with the abdominal lymphatics, although a pair was noted near the thoracic duct in the neck. None of the Museum specimens show lymphatics in birds. In 1768, Hewson visited the Sussex coast to study the lymphatics in fish. He went to “Brighthelmstone”, later known as Brighton. In fish, although the general principles of the arrangement of the lymphatic vessels resembled that of mammals, birds and reptiles, the anatomy was sufficiently different to make Hewson uncertain of how to go about demonstrating them. Working initially on a haddock, he found, however, that along the ventral midline of the body of a fish, there is a single large lymphatic which, once located,
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readily accepted the mercury injection. As in the turtle, the lymphatics in fish seemed to have no valves, or were overwhelmed by the injection, so that lymphatic connections could be relatively easily demonstrated. The thoracic duct divided as it passed towards the head to discharge lymph into the venous system. Hewson gave a detailed description of the layout of the lymphatics and it seemed to be similar in the various fish species he examined: haddock, cod, whiting, plaice, turbot, and skate. As in the turtle, the thoracic duct and the lymphatics of the head region formed a complex plexus before joining the jugular veins by a short lymphatic connection. Also similar to the turtle, Hewson noted a plexus of lymphatics close to the intestinal lining. In cod, turbot and plaice, Hewson observed an intricate plexus of lymphatics between the mucosa and the muscular layer of the intestine. In the turbot, Hewson claimed to have seen a lymphatic plexus within the villi. In the cod, he also found that he could express the mercury into the lumen of the intestine which seems likely to have perpetuated the misunderstanding that the intestinal lumen and the lacteals were in communication.
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Hewson’s discoveries, even after his death, were disputed by Alexander Monro (Eales, 1974) who asserted prior discovery in the turtle, birds and fish but his claims had little substance. The haddock illustrated by Hewson (1769) in his paper in Philosophical Transactions is Specimen 12.122 (Fig. 9). The studies on fish extended beyond the species cited in Hewson’s text as the Museum contains specimens showing lymphatics in the conger eel and ray (Marshall, 1970).
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Controversy over the origin of the lacteals and lymphatics from surfaces
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Cruikshank (1790), describing William Hunter’s views, wrote “The venereal and other poisons passing into lymphatics from the skin, proved their origin from surfaces; and the extravasated injections passing into the same vessels, from the cellular membrane (i.e. the connective tissue), proved, in his (William Hunter’s) opinion, their origin from cells.” Hunter also said that lacteals and lymphatics both “appear” to arise from surfaces, stating that, “if the venereal poison is applied to the surface of an ulcer, and passes into the blood, it passes through the lymphatic vessels, it sometimes inflames their coats, and makes them, in consequence of this, appear in the form of red lines; it frequently inflames the glands through which they pass, and, some time after, shews itself in the constitution, by symptoms peculiar to itself …”. Although a reasonable conclusion at the time, Hunter was incorrect.
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William Hunter thought the lacteals commenced at the internal intestinal surface. Hewson also seemed to accept as largely proven that the intestinal contents were taken up directly into the lacteals at the tips of the intestinal villi. As noted earlier, he was able to express the milky fluid from the intestinal villi in a cod. We now know that in doing this, he must have ruptured an epithelial barrier. Hewson thought lacteals were open at their ends and that this pore was guarded by a “patulous” valve, that is one of a soft texture. Hewson’s concept was that when the small intestine was active after a meal, the villi became engorged with blood. Rather like erectile tissue, the villus stiffened and this held the pore open allowing intestinal fluid to be drawn in and along the lacteal by capillary action. This was a histological problem that was not solved until the advent of resin histological sections and electron microscopy. Even at the
start of our careers in the late 1970s, there was still speculation on the presence of pores, although it was generally appreciated that all material being absorbed by the bowel had to be done through the epithelium, there being junctional complexes between epithelial cells that prevented intercellular movement (Fawcett, 1986).
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The quotation cited earlier from Cruikshank (1790) of one of William Hunter’s Introductory Lectures said that the lymphatic system “… serves to take up and convey whatever is to make, or to be mixed with, the blood, from the skin, from the intestinal canal, and from all the internal cavities or surfaces whatever.” As described above, the understanding of Hunter and Hewson that the lacteals arose from pores at the tips of villi was subsequently found to be incorrect. Similarly the concept of lymphatics arising from internal surfaces has proven to be the subject of controversy and research. Hewson (1774) thought that lymphatics arose from body cavities in a way similar to lacteals arising from the intestines. He also thought that lymphatics drained fluid from body cavities writing, “… we have always found the fluids contained in the different cavities of the body and that contained in the lymphatics exactly agreeing with one another, in their transparency, in their consistence, etc.” (Hewson, 1774).
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One of William Hunter’s specimens (12.42) is that of the lymphatics of the lung of a lioness which died in the Tower of London Menagerie (Fig. 10). At its death, it bled from its mouth and into its intestines (Marshall, 1970). The catalogue entry says, “… The absorbents were full of blood, which in the great trunks was coagulated, and prevented the mercury thrown in by the smaller branches from getting on.” The lymphatic trunks being filled with blood suggested that lymphatic vessels must be open-ended. Observations of blood in lymphatics has led to much research interest in the nature of the uptake of fluid from the linings (serous membranes) which has continued right down to the present time.
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Cruikshank wrote, “… injections thrown into the intestines, or other cavities, in the dead body, never, that I could observe, get into the lacteals or lymphatics, though we know their orifices to be really there: could this have taken place, all the absorbent system would long ago have been compleatly (sic) described” (Cruikshank, 1790).
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Like Hewson, Cruikshank had noted that whenever fluids are extravasated on surfaces, or into cavities, the lymphatics of the surfaces and cavities were found full of a similar fluid. He wrote, “This is better demonstrated, when the fluids mentioned happen to be of a strong colour. This I have repeatedly seen, in animals dying of haemoptoe (haemoptysis), and in the human subject itself, the lymphatics of the lungs, which at other times contain a transparent fluid, turgid with blood, which they had absorbed from the air-cells.” (Cruikshank, 1790). Cruikshank also described that “In animals strangled, or dying of some violent death, the lymphatics about the spleen, and in the cavity of the abdomen in general, are almost always found turgid with blood, though I have never seen, on these occasions, any marks of extravasation of that fluid into the cellular membrane. In peritoneal inflammation, I have demonstrated the lacteals full of blood, though in this inflammation there is little or no swelling, of course no extravation of the blood into the cellular membrane” (Cruikshank, 1790).
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Cruikshank (1790) continued, “I have seen the absorbents of the lungs also loaded with blood, in the peripneumony or inflammation of their substance; and on all these occasions have been induced to believe that the lymphatics arose from the internal surfaces of the arteries and veins.” Presumably this observation may explain why earlier anatomists thought that lymphatics were continuous with the arterial system. Cruikshank, however, had further explanations. “This doctrine is not without its difficulties; for arteries and veins have been distended with injected fluids on many occasions, without the smallest drop of these fluids passing into the lymphatics; and one of the arguments, by which the origin of the lymphatics from surfaces is supported, is, that they cannot be injected from arteries or veins.”
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The entry of erythrocytes into lymphatics and the mechanism by which this occurs remains an on-going controversy 250 years later (see Kazeem and Scothorne, 1982). Courtice et al. (1953) injected blood into the peritoneal cavities of rats, rabbits and guinea pigs and found that erythrocytes seemed to be particularly taken up by diaphragmatic lymphatics and passed to the right lymphatic duct. A number of studies including those by Leak and Rahil (1978) and Negrini et al. (1991) have demonstrated the presence of open stomata between the mesothelial cells of the diaphragm associated with a rich plexus of lymphatic capillaries with rapid uptake of tracers (Abu-Hijleh et al., 1994).
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What other contributions did the Hunter brothers and their associates make to the understanding of the lymphatic system?
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Sheldon reported that he had successfully injected human lacteals with mercury from the bowel to the first intestinal gland. He thought he might have been the first person since Nuck to have done so but discovered that Alexander Monro secundus had injected them while working with Meckel in Berlin. William Hewson subsequently told Sheldon that he had once filled them in a human subject. After the death of Hewson, when Sheldon went to work with Dr Hunter, he saw a specimen of a human lacteal trunk injected from the intestine to the first regional mesenteric lymph node. “Upon inquiry I found that this was the preparation which Mr Hewson had mentioned to me; and it was the only specimen of the human lacteals injected, existing in England at that time. Mr Hewson seems to have considered it as a matter of some difficulty to make such a preparation, since he says in his work on the lymphatic system, ‘I have injected them with mercury even in the human subject.’”
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The following specimens correspond to this description: 12.71; 12.75 (missing); 12.77; 12.78; 12.79 (missing), but there is nothing in the Museum to say whether any of them is the one made by Hewson. As well as documenting lymphatic vessels and their arrangement in several species, Hewson also made a number of other discoveries that extended knowledge or corrected misunderstandings. Hewson noted that lacteals do not always contain white fluid. In a dog a while after a meal it is clear and, in birds, the lacteals always contain clear fluid. He thus regarded the lacteals as the lymphatics of the intestines. Hewson made a detailed study of the lymphatics of the human body and his account is very much what would still be accepted today. Meckel had thought that the lymphatics of the
stomach drained into local veins but Hewson disproved this, demonstrating that lymph from the stomach reached the thoracic duct in common with that from other viscera. There are, however, no specimens of the lymphatics of the human stomach in the Hunterian Collection at Glasgow.
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In Hewson’s time, there was a theory that the black tracheobronchial lymph nodes were glands which secreted mucus into the airways. Hewson, however, showed them to be lymph nodes as they filled with mercury when he injected the lungs. This is illustrated in Specimen 12.40.
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Hewson was uncertain about the lymph drainage of the brain but had consistently failed to find lymphatics. He was correct and the special arrangements for fluid movement in the central nervous system have only in recent times started to become elucidated (see Morris et al., 2016). Hewson also dismissed a view that the pineal gland is a lymph node. CONCLUSION
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William and John Hunter and their colleagues, William Hewson, William Cruikshank and John Sheldon made large contributions to understanding the distribution of lymphatic vessels in the human body and in other species and that lacteals and lymphatics are similar vessels involved in absorbing fluid from the tissues. They were, however, subsequently shown to have some misunderstandings, particularly that blood capillaries as well as lymphatic capillaries absorb fluid from the tissues, and that lacteals, like other lymphatic capillaries, are blind-ended and do not absorb directly from the intestinal lumen. Although William Hunter clearly realised that tuberculosis and venereal diseases might involve the regional nodes, the Hunterian Collection at Glasgow, William Hunter’s writings and lecture notes of his students have little on involvement of regional lymph nodes by malignant disease or the concept that, in the presence of metastatic disease in lymph nodes, knowledge of lymph drainage could be used to define the likely site of a primary tumour.
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ACKNOWLEDGEMENT
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We are grateful for the assistance of Mr Graham Nisbet of the Hunterian Art Gallery.
REFERENCES Abu-Hijleh, M.F., Reid, O., McGadey, J., Scothorne, R.J., 1994. Distribution of mesothelial stomata in the rat. Clin. Anat. 7, 189 – 203. Ambrose, C.T., 2007. The priority dispute over the function of the lymphatic system and Glisson's ghost (the 18th-century Hunter-Monro feud). Cell. Immunol. 245, 7 - 15.
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Cameron, A., 2004. John Sheldon (1752 – 1808) anatomist and surgeon. In: Oxford Dictionary of National Biography. Oxford University Press, Oxford. Courtice, F.C., Harding, J., Steinbeck, A.W., 1953. The removal of free red blood cells from the peritoneal cavity of animals. Austral. J. Exp. Biol. Med. Sci. 31, 215 – 225.
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Cruikshank, W.C., 1790. The Anatomy of the Absorbing Vessels of the Human Body. G. Nicol, London. Dowd, N., 1972. Hunter’s Lectures of Anatomy. Elsevier, Amsterdam.
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Eales, N.B., 1974. The history of the lymphatic system, with special reference to the HunterMonro controversy. J. Hist. Med. 29, 280 – 294.
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Fawcett, D.W., 1986. Bloom and Fawcett: A Textbook of Histology, eleventh edition. W. B. Saunders Co., Philadelphia.
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Garrison, F.H., 1921. An Introduction to the History of Medicine, third edition. W. B. Saunders Co., Philadelphia.
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Hendriksen, M.M., 2015. Anatomical mercury: Changing understandings of quicksilver, blood, and the lymphatic system, 1650-1800. J. Hist. Med. Allied. Sci. 70, 516 - 548. Hewson, W., 1768. An account of the lymphatic system in birds. Phil. Trans. 58, 217 – 226.
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Hewson, W., 1769. An account of the lymphatic system in fish. Phil. Trans. 59, 204 – 215.
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Hewson, W., 1774. A description of the lymphatic system in the human subject, and in other animals. In: Gulliver, G. 1846. The Works of William Hewson, F.R.S.. Sydenham Society, London.
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Hunter, W., 1762. Medical Commentaries. Part I. Containing a Plain and Direct Answer to Professor Monro jun. Interspersed with Remarks on the Structure, Functions, and Diseases of Several Parts of the Human Body. A. Hamilton, London. Hunter, W., 1774. The Anatomy of the Gravid Uterus Exhibited in Figures. John Baskerville, Birmingham. Janjua, R.M., Schultka, R., Goebbel, L., Pait, T.G., Shields, C.B., 2010. The legacy of Johann Friedrich Meckel the Elder (1724–1774): A 4-generation dynasty of anatomists. Neurosurg. 66, 758 – 771.
Kazeem, A.A., Scothorne, R.J. 1982. Studies on hemolymph nodes. II. The regional origin of the afferent lymphatics. J. Anat. 135, 1 – 4. Leak, L.V., Rahil, K., 1978. Permeability of the diaphragmatic mesothelium: The ultrastructural basis for “stomata.” Am. J. Anat. 151, 557 - 592. Lister, M., 1683. An extract of a letter, relating an experiment made altering the colour of the chyle in the lacteal veins. Phil. Trans. 13, 6 - 9.
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Marshall, A.J., 1970. Catalogue of the Anatomical Preparations of Dr William Hunter. University of Glasgow, Glasgow.
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Meckel, J.F., 1772. Nova Experimenta et Observationes de Finibus Venarum ac Vasorum Lymphaticorum in Ductus Visceraque Extretoria Corporis Humani. Fridericum Nicolai, Berolini. Monro, A., 1758. Observations, Anatomical and Physiological wherein Dr. Hunter's Claim to some Discoveries is Examined. Hamilton, Balfour and Neill, Edinburgh.
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Musgrave, W., 1701. A letter from Dr William Musgrave F.R.S. to the publisher concerning some experiments made for transmitting a blue coloured liquor in-into the lacteals. Phil Trans 22, 996 – 998.
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Natale, G., Bocci, G., Ribatti, D., 2017. Scholars and scientists in the history of the lymphatic system. J. Anat. 231, 417 - 429.
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Negrini, D., Mukenge, S., Del Fabbro, M., Gonano, C., Miserocchi, G., 1991. Distribution of diaphragmatic stomata. J. Appl. Physiol. 70, 1544 - 1549.
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Palmer, J., 1837. On absorption by veins. The Works of John Hunter F.R.S.. Longman, Rees, Orme, Brown Green and Longman, London, pp. 299 – 314. Pearce, J.M.S., 2007. Malpighi and the discovery of capillaries. Eur Neurol 58, 253 – 255. Rusznyak, I., Foldi, M., Szabo, G., 1960. Lymphatics and Lymph Circulation. Pergamon Press, Oxford.
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Sappey, P.C., 1869. Traité d’Anatomie Descriptive. Adrien Delahaye, Paris. Senior, J.R., 1964. Intestinal absorption of fats. J. Lipid Res. 5, 495 – 521. Sheldon, J., 1784. History of the Absorbent System. T. Cadell and P. Elmsly, London.
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Fig. 1. William Hunter (1718 – 1783) by Sir Joshua Reynolds, c. 1787. By kind permission of the Hunterian Museum, University of Glasgow. © The Hunterian, University of Glasgow 2017.
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Fig. 2. A corner of the Anatomy Museum and Specimen 12.17, a thoracic duct injected with mercury said in 1770 to be “one of the largest and most perfect thoracic ducts perhaps ever injected”.
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Fig. 3. Specimen 12.81, the lymphatics of the intestine of an antelope. “The absorbents are still preserved in the state they were found in the dead body., i.e. full of their own chyle. The arteries and veins are both injected red. The lymphatics pass to a large lymph node in the centre of the specimen.” In many species, the lacteals terminate in a single node still referred to as the “pancreas of Aselli”.
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Fig. 4. Specimen 12.92, the lymphatics of the large intestine of an ass. The specimen now in fluid had been dried and varnished. The arteries are injected red and a few of the lymphatics contain mercury.
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Fig. 5. Specimen 12.98 showing mercury-filled lymphatics of the small intestine and mesentery of a turtle. The form of the bowel is supported by plaster of Paris filling the lumen.
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Fig. 6. Specimen 12.59, part of the stomach of a turtle with the arteries injected red, the veins black and the lymphatics filled with mercury.
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Fig. 7. Specimen 12.107, showing fine mercury-filled lymphatics of the intestine and mesentery of a turtle.
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Fig. 8. Specimen 12.106, demonstrating the large number of lymphatics in the wall of the small intestine of the turtle. The arteries have been injected red and the veins black.
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Fig. 9. Specimen 12.122. The haddock illustrated by Hewson (1769) in his paper in Philosophical Transactions.
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Fig. 10. Specimen 12.42, the lymphatics of the lung of a lioness which died in the Tower of London Menagerie.