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Anatomists Who Were Artists I: Reinier de Graaf

Reinier de Graaf's books in the Bernard Becker Medical Library

Fig. 1: Reinier de Graaf at the age of 25 in 1666Reinier de Graaf (1641-1673), a 17th century Dutch physician, is regarded as the founder of modern reproductive biology (Setchell, 1974; Houtzager 2000; Ankum, Houtzager and Bleker 1996).  Figures 1-11 are illustrations from de Graaf’s first Latin edition on the male urogenital system (de Graaf, 1668) and from the first Latin edition of his collected works (de Graaf, 1677).  Both are in the Bernard Becker Medical Library as part of the James Moores Ball collection of the St. Louis Medical Society.  When I cataloged these rare books 10 years ago, I was stunned by the beauty and seeming accuracy of the anatomical engravings that illustrate both books.  

The English translation: Reiner de Graaf’on the human reproductive organs (1972)

I learned later of a fully illustrated English translation by Jocelyn and Setchell of de Graaf’s Treatise concerning the Generative Organs of Men (De virorum organis generationi inservientibus, 1668) and Treatise concerning the Generative Organs of Women (De Mulierum Organis Generationi Inservientibus, 1672).  The translations lay hidden in Supplement 17 (1972) of the Journal of Reproduction and Sterility.  I have only begun to read Treatise concerning the Generative Organs of Men, but the author’s preface answered my questions on the target audience for the books and who did the illustrations.Fig. 2: De virorum organis generationi, 1768

From de Graaf’s own preface to …men (1668), I learned that these monographs were addressed toward working medical practitioner as well as those doing medical research.

There is more art in the recognition than in the cure of a disease and no one can make a basic judgment about a disease, i.e. about an unnatural disposition of parts of the body, if he is ignorant of the natural disposition of these parts.  In order therefore to gain for myself the knowledge I needed of the body’s individual parts, I put my hand to the knife whenever an opportunity to dissect subjects presented itself.  And not without profit.  For every time I put the genital parts in particular on the table, Nature with its prodigal generosity, presented to my eyes certain things hitherto undiscovered.  Along with other physicians I judged knowledge of these things to be quite indispensable and so did not hide away the treasures I came upon but revealed them freely to everyone interested… (Jocelyn and Setchell, 1972, page 5).

De Graaf states it is he who sketched the illustrations while defending the “decent and modest style” of presenting his discoveries.

All these things are illustrated as clearly and chastely as possible with figures sketched by myself.  If, however, anyone has a nature so disrespectful and lascivious as to try to seize upon what I have made public concerning the genital parts for lewd imaginings and scurrilous jokes, let him pay the penalty for his own wickedness.  … I set out my discoveries in a decent and modest style.  No one therefore can be offended by them in the slightest unless he wants to be.  (Jocelyn and Setchell, 1972, page 6-7).

Jocelyn the classicist and Setchell the biologist give a concise evaluation of De Graaf’s contribution in their translator’s preface.

He was one of the first to establish the testis is formed of a series of tubules [See Figure 4 above] and the first to realize the importance of the tubules.  He was the first to see the efferent ducts, to describe the corpora lutea and to ascribe to the Fallopian tubes their true function.  He also demolished a variety of old wives tales current among anatomists of his day.  He was not the first, as he himself points out to describe the vesicles now called the Graafian follicles, but he set out more fully than his predecessors how they change as they develop.  His main error was in equating the ovum with the vesicle…  He was also in error in thinking that fertilization occurs while the ova are still in the ovary (Jocelyn and Setchell, 1972, page ix).

Early Life and university education

De Graaf’s life was short; he died at 32.  How did he accomplish so much in 32 years?  For an answer, I looked at his life as told by authors of the references below.

Reinier de Graaf was born in Schoonhoven, Holland, to Catharine van Breenen, the daughter of an aristocratic family and Cornelis de Graaf, an architect, engineer, and inventor of a hydraulic machine.  Reinier studied medicine in Louvain (1659), Utrecht (1661), and Leiden (1663-1664) before earning M.D. from The University of Angiers (France) in 1665.  He studied anatomy first with Plemp at Louvain and Isbrand van Diemerbroek at Utrecht.  Although he considered anatomy basic to medicine, he wanted to know about the functions of the organs ("Biographical Note," in  De Graaf, Reinier.  De Mulierum Organis Generationi Inservientibus, 1672, 1965 page 7; Houtzager, 2000, page 125).

At the University of Leiden from 1663-1664, he studied physiology and anatomy under the tolerant nurture of Francois dele Boe Sylvius and Johannes van Horne.  Leiden was the predominant European medical center of the 17th century.  Its university’s rise as an intellectual and scientific center was linked to Holland’s economic power in that century. (Kidd, Modlin, 1999, page 307).  Johannes van Horne welcomed de Graaf and Frederik Ruysch to his anatomy lab where he taught them how to prepare the spectacular anatomical specimens that de Graaf sketched for his publications (Houtzager 2000, page 125). Sylvius was a fine clinician who took small groups of medical students to see patients on the ward in daily bedside instruction.  Later in the day, they did autopsies and observed normal function in healthy patients (Kidd, Modlin, 1999, page 1309). 

Fig. 3 Opera 1677 with Dog apparatus standing live lower leftFig. 4: E Pancreatic duct visible through the duodenal fistula Opera 1677  As the student of Sylvius at Leiden in 1664, de Graaf did physiological experiments on the composition and properties of the pancreatic juice  He obtained the pancreatic juice from a living dog by creating a temporary artificial fistula. Figure 3 shows how the dog looked with the collecting bottle attached.  Figure 4 shows the location of artificial fistula in the pancreatic tissue, the dog’s pancreas and surrounding organs (Ragland, 2008, page 632, Figure 1).  “De Graaf’s account of his unsuccessful attempts to collect pancreatic juice, followed by his eventual success is one of the most interesting passages in the history of the experimental method.” (Fulton, History of physiology p. 167; The Haskell F. Norman Library of Science and Medicine, Vol.1, no. 923)  De Graaf’s results showed the pancreatic juice to be alkaline rather than acid as Sylvius expected.  He published his account in Disputatio medica de nature et usu succi pancreatici in 1664. (Kidd, Modlin, 1999, page 1310). De Graaf’s monograph on the pancreatic juice went through many editions, including English translations in 1671 and 1676. De Graaf went on a study tour to France, where he did demonstrations and autopsies in connection with his work on the pancreatic juice.  There he earned his M.D.   ("Biographical Note," page 9 in De Graaf, Reinier.  De Mulierum Organis Generationi Inservientibus, 1672, 1965) (Garrison-Morton 974).

Scientific work and medical practice at Delft

Fig 5 The testicles of human beings De virorum 1672Fig 6 The testicles of dumb aniimals -De Virorum 1668Reinier de Graaf returned to Holland in 1666. He opened a medical practice in Delft, where he also did research on the anatomy and physiology of the reproductive system.  His monograph on the male reproductive system, published in 1668, was largely a review of existing knowledge of the structure and function of the male genital organs with cases and illustrations that he sketched himself.  Figures 1-2 and 5-6 are from de Graaf’s monograph on men.  Figures 5-6 illustrate his most important observations that the testes of humans and other mammals are composed of tubules that confect semen.  He may not have been aware that Claude Aubery made this discovery earlier in his Testis Examinatus, published in 1658.  He also showed that the testes are not glandular in nature as previously thought (Setchell, 1974, page 3-4); Houtzager 2000, page 125-126; The Haskell F. Norman Library of Science and Medicine, Vol. 1, no. 925).

Fig 9 The Fallopian tubes or women's oviducts, of different shapes  De mulierum Fig 11 Ectopic pregnancy occuring in the Fallopian tube De mulierum in Opera The complementary monograph on the female reproductive system, which came out four years later, was much more than a review of existing knowledge.  The cases he and others were seeing in medical practice were an important part of this groundbreaking book, Treatise on the Generative organs of women, (1672). Figure 11 shows a famous case of of a woman with a pregnancy in the fallopian tube reported by Vassal to the Royal Society in London in 1669 (Vassal, 1669). In contrast, Figure 9 shows the variation in the shape of the fallopian tubes. The pathology helped de Graaf and Bartholin before him to guess at the path of the egg after it left the ovary and where fertilization took place.  Figure 10 illustrates  the case history of a child who had adreno–genital- syndrome (Houtzager 2000, page 126).

Fig 10 The malformed external genitals of an infant De mulierum in Opera 1677The genital parts of women, which we have finished describing, sometimes acquire through some inexplicable fault of Nature such a perverse conformation that even people with some experience have been unable to distinguish the sex of the child…

On 27th June 1670, there was born at Delft an infant, whom, because of the malformation of its genital parts, its parents did not want distinguished until they had consulted experts in the matter.  The experts judged it to be a male because of an apparently perfect male member and swellings hanging like testicles underneath.  The infant was, therefore, called Corneliis.  Struck by a serious illness, Cornelius departed this life on 19th July (Jocelyn and Setchell, 1672, 1972, page 163-164, original pages 299-300)

De Graaf ‘s findings on the sex of Corneliis are summarized in this caption for Figure 9 (Houtzager 2000, page 126).

This displays malformed external genitals of an infant.  A. The clitoris looking exactly like a male penis.  B. The glans of the clitoris laid bare.  CC.  The labia of the pudendum.  DD. Protuberances looking somewhat like testicles. (Jocelynand Setchell, 1672, 1972, page 186 Plate XXIII). 

Fig 7 Ovaries of cows and ewes after coitus De mulieribus in Opera 1677Fig 8 A woman's ovary, with the end of the tube attached  De mulieribus in OperaFigure 8 is de Graaf’s anatomical study of the human egg in the ovary.  Up to the mid-1660s, the prevailing view of the egg was the Aristotelian doctrine which held that “the egg was formed in the uterus as a result of activation of menstrual blood by male semen (Longo, 1996).”  Even William Harvey upholds this view in his Generation of Animals in 1651 (Setchell, 1974, page 7).  In the 1660s Jan Swammerdam, Johannes Van Horne of Leiden, and Niels Stensen of Copenhagen independently developed the new idea “that the 'female testes’ such as the ovaries of birds, were the site of egg formation.”  Their ideas were never published, but de Graaf credits Van Horne for the hypothesis in his monograph on …Women (Longo, 1996).  Based on dissections of ovaries from several mammals as depicted in Figure 7, de Graaf showed that generation takes place in ova pre-existing in the ovary.  He was also the first to notice morphological changes in the ovary after ovulation.  He provided the first description of the ovarian Graafian follicles and the corpus luteum (Houtzager 2000, page 125-126; The Haskell F. Norman Library of Science and Medicine. Vol. 1, no. 925; Longo, 1996; Ankum, Houtzager and Bleker, 1996, page 365).

De Graaf’s treatise on the female anatomy and physiology sparked a dispute with Swammerdam, "who claimed that De Graaf had taken the credit for discoveries which had been made by Horne… and Swammerdam himself.”  In the end they referred the matter to the Royal Society.  Setchell (1974, page 11) took a second look at the works of all three men on the female anatomy.  He concludes that while all three looked at and described the same organs, it was de Graaf that had seen beyond the structure and described their function with great accuracy (Setchell, 1974, page 11). 

Scholarly journals were a new development in de Graaf’s time and so was the microscope.  He  wrote three articles for scholarly journals (de Graaf, Van Dongen, 1672, 1965, Bibliographia Graafiana, page 27-40).  De Graaf’s own work was too early to benefit from the high powered microscope which van Leeuwenhoek developed in 1677 (Ankum, Houtzager and Bleker; Houtzager, 2000, page 125). But it was he who introduced Anton von Leeuwenhoek and his microscope to the Royal Society in a letter shortly before his death in 1673 (Van Dongen, "Introduction," in de Graaf, 1672, 1965, page 36-37, #31; Setchell, 1974 page 12).  

De Graaf was one of an innovative scientific circle at the University of Leiden who continued the anatomic and experimental work Sylvius and van Horne started.  The students that Sylvius and van Horne trained at the University of Leiden in the 1660s, “Ruysch, Steensen, de Graaf, and Swammerdam …, [each] made significant advances in pancreatic, lymphatic, reproductive, and respiratory physiology (Kidd, Modlin, 1999, page 307).”  

References

Ankum, W., H. L. Houtzager, and O. P. Bleker “Reinier De Graaf (1641–1673) and the Fallopian tube.  Research Gate, Human Reproduction Update 1996, Vol. 2, No. 4 pp. 365–369

De Graaf, Reinier. Opera omnia. - [1st edition] - Lugd. Batav. [Leyden] : Ex Officina Hackiana, 1677. Bernard Becker Medical Library (BBML), Level 7

De Graaf, Reinier. Regneri de Graaf Opera omnia. – [2nd edition] - Ludg. [Lyons] : Sumpt. Io. Ant. Huguetan & soc., 1678. Bernard Becker Medical Library, Level 7

De Graaf, Reinier. De virorum organis generationi inservientibus : De clysteribus et : De usu siphonis in anatomia. - [1st ed.] - Lugd. Batav. [Leyden] ; Roterod. [Rotterdam] : Ex officina Hackiana, 1668. (BBML), Level 7

De Graaf, Reinier. De Mulierum Organis Generationi Inservientibus, 1672.  Facsimile with an introduction by J. A. van Dongen. Vol. 13. Nieuwkoop: B. de Graaf, 1965. (BBML), Level 1, Compact Shelving

De Graaf, R. and translated by Christopher Pack as De Succo Pancreatico: or a physical and anatomical treatise of the nature and office of the pancreatic juice. Brook, London (1676). Available to Washington University users through EEB0 Online.

Hook, Diana H. The Haskell F. Norman Library of Science and Medicine. Vol. 1. Jeremy Norman & Company, 1991.

Houtzager, H. L. "Reinier de Graaf." European Journal of Obstetrics & Gynecology and Reproductive Biology 12, no. 6 (1981): 385-387

Houtzager, H. L. "Reinier De Graaf and his contribution to reproductive biology." European Journal of Obstetrics & Gynecology and Reproductive Biology 90, no. 2 (2000): 125-127.

Jocelyn, Henry D., and Brian Peter Setchell. "Regnier de Graaf on the human reproductive organs. An annotated translation of Tractatus de Virorum Organis Generationi Inservientibus (1668) and De Mulierum Organis Generationi Inservientibus Tractatus Novus (1672)." Journal of reproduction and fertility. Supplement 17 (1972): 1-222. (especially page 5, 55-64).

Kidd, Mark, and Irvin M. Modlin. "The luminati of Leiden: from Bontius to Boerhaave." World journal of surgery 23, no. 12 (1999): 1307-1314

Longo, Lawrence D., and Regner de Graaf. "De mulierum organis generationi inservientibus tractatus novus." American journal of obstetrics and gynecology 174, no. 2 (1996): 794-795.

Morton, Leslie Thomas. A medical bibliography (Garrison and Morton): an annotated check-list of texts illustrating the history of medicine. Gower, 1983.

Ragland, Evan R. "Experimenting with Chymical Bodies: Reinier de Graaf's Investigations of the Pancreas." Early science and medicine 13, no. 6 (2008): 615-664.

Setchell, Brian P. "The contributions of Regnier de Graaf to reproductive biology." European Journal of Obstetrics & Gynecology and Reproductive Biology 4, no. 1 (1974): 1-13.

Thiery, M. "Reinier De Graaf (1641–1673) and the Graafian follicle." Gynecological Surgery 6, no. 2 (2009): 189-191.

Vassal, M. “An Account Concerning a Woman Having a Double Matrix; As the Publisher Hath Englished It Out of French, Lately Printed at Paris, Where the Body Was Opened [by M Vassal ].” Philosophical Transactions of the Royal Society of London, 1 January 1669, vol. 4 no. 45-56 969-970.

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