Embryology History - Reinier de Graaf

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Regnier De Graaf (1641-1673}

Regnier De Graaf (1641-1673} was a Dutch embryologist who published works on female genital organs. He was first to describe the "Graafian follicle" in the ovary of mammals, but erroneously believed the entire follicle to be the mammalian oocyte (egg).


Online Editor - The text below is an excerpt from a paper by Catchpole (1940) celebrating the tercentenary of the birth of Regnier de Graaf.[1]

Regnier de Graaf was born at Schoonhaven, a town between Arnheim and Rotterdam, on July 30, 1641, the son of Corneille de Graaf, a celebrated architect and inventor of hydraulic machines, and of Catherine van Brenen. By 1660 he was already studying medicine at Utrecht under Isbrand van Diemerbroeck to whom he referred later as an “ excellent professor to whom I owe the progress I have made in the study of the human body ” (7, p. 205). Removing to Leyden in 1663, de Graaf came at once to the most famous university of the Low Countries and under the tutelage of two noted professors, John van Horne and Francois de le Boé (Sylvius). To judge the nature of the intellectual atmosphere of Leyden in these years, it is sufficient merely to name de Graaf’s contemporaries there: Nils Stensen (Steno), the Danish anatomist and geologist: Frederic Ruysch, the “ Prince of Dutch Anatomists ”; Jan Swammerdam, anatomist and entomologist.

De Graaf was at once infected by the teachings and no doubt by the enthusiasms of Sylvius, and resolved to put the doctrines of his master to the test of experiment; partly, as he relates, “ to satisfy my natural curiosity ” and partly “in response to the importunity of friends at Leyden.’ He says: “ Having satisfied the prayers of my friends, and my own desires, the matter would have rested there had not my master, to whom it were ingratitude to refuse anything, asked me to give it to the public in a small Latin treatise ” (3, preface). This treatise, appearing on December 17, 1664, as de Graaf’s first publication, is the thesis Disputatio medica de natura succi pcmcreatici (1). It is a brief work of ninety duodecimo pages, dedicated to an imposing array of persons - the councillors and senators of Schoonhaven, his own father, and a relative, Ysbrand van‘ Brenen. Herein is described the first production of a temporary pancreatic fistula (31, pp. 146-152). There are three plates, excellently drawn, presumably by the author,-illustrating the pancreas of the dog, the set of instruments necessary for the operation (comprising wild goose quill cannulae, bottles for collecting the juice, pith plugs for the cannulae, and clamps), and finally two pictures of the actual operation. One depicts the opened animal with cannula and bottle in place; the other, the animal standing, with the collecting bottle fixed to its abdomen. There is also shown a bottle for collection of salivary juice, but it is not clear whether the parotid duct was actually cannulated. Thus, at the age of twenty-three, de Graaf had successfully performed an operation that was neglected by experimentalists for 200 years, until again taken up by Claude Bernard. The high esteem in which de Graaf held Sylvius unfortunately caused his ideas on the use, and even his observations on the nature, of the juice to be subordinated to the iatrochemical predilections of the latter. Thus it can be admitted that his speculative conclusions are largely absurd. But his theories respecting the pancreatic juice and on the genesis of intermittent fevers that followed in the French edition had an enormous vogue and confirmed the reputation of their author.

In 1665 de Graaf proceeded to Paris where his fame gained for him the favor of medical circles and the good will of the “ Curious.” He met Habert de Montmor, counsellor of Louis XIV and powerful patron of science; Bourdelot, formerly physician to the Queen of Sweden, who held gatherings of the Académie des C urieux de la Nature every Monday at his house; Jean-Baptiste Denis, physician to the King and an early advocate of blood transfusion, and Chapelain, the somewhat insufferable heroic poet and medical dilettante. The latter seems to have got along surprisingly well with de Graaf; he assisted in the preparation of a French edition of De succi and earned therein an enthusiastic dedicatory address. In this edition the subject matter of the thesis is revised and extended. It appeared in 1666 under the title Traitté de la nature et de l’usage du suc pancreatique, ou plusieurs maladies sont expliquées, principalement les fie?/res intermittentes (3). The three plates in this volume are similar to those in the thesis, but have been redrawn. Thus in the completed operation the dog is now represented as laryngectomised. a step that was described but not pictured in the earlier work. In the textjof both these works, reference is made to discoveries that were new at this time. Such were the discovery of the lymphatic vessels by Bartholin and Rudbeck thirteen years before; of the inferior salivary duct by Wharton in 1656; and of the superior salivary duct by Steno in 1661; also, of the pancreatic canal itself by Wirsung, twenty-three years before. Of the latter, he writes, “ The author of this beautiful discovery, having been unfortunately assassinated by his enemies, as they say, was unable to examine the use of that canal, so happily exposed ” (3, p. 7 *). He mentions Harvey, of whose theory Sylvius had been an early continental partisan (3, p. 5). The pancreas is recognized as a glandular rather than “ fleshy ” organ. To disprove an assertion of Bartholin that the pancreas is the excretory organ of the spleen, as is the gall bladder that of the liver, he splenectomized a dog, after making suitable ligatures; then two months later a pancreatic fistula was made, and pancreatic juice successfully collected. He noticed, too, that a splenectomized bitch was capable of conceiving and bearing a litter (3, p. 5). From his experiments he determined that a half ounce and two drachms of juice could be obtained from a medium-sized dog and two ounces from a large, in the space of seven or eight hours (3, pp. 24-25). As indicative of de Graaf’s philosophical temper we may quote,— “ Knowledge of the parts of thebody is as ‘necessary to ascertain that of their function, as is the knowledge of the function to the judging of their sickness with any certainty ” (3, p. 55). Illustrative of a proper research zeal we read, “ After racking the brain and putting the spirit to all sorts of torture to find a proof that would completely satisfy us, we found a method by the grace of God ” (3, pp. 37-38).

  • A story denied by Portal, but still persisting.

On July 23, 1665, de Graaf received adoctorate of medicine from the University of Angers, and about this time travelled extensively around France. Writing to Sylvius in’ 1668 he said, “In my journeys in France I put all my energies to the dissection of bodies which I found there in sufficiently great quantity; I preferred most to dissect the pancreas and the genital parts since I found there constantly new things, unremarked by anatomists before me. These discoveries I showed to the Curious, who frequently urged me to publish my experiences with the latter ” (6). Scattered references in de Graaf’s Writings and letters form the only record of this period in his life. Thus he mentions dissecting the warm body of a sailor killed by a falling mast at Angers and experienced the peculiar pleasure of sampling human pancreatic juice (3, p. 58). He left France sometime during 1666, actually before the French edition of his book was published, and returned to Schoonhaven to settle some affairs; thence he proceeded to the practice of medicine at Delft. Writing to him there from Paris, in a letter dated December 16, 1666, Fabre says, “ I hear with pleasure that you are working wonders at Delft, after your custom . . . but I am sorry to see you so occupied not yet to have given to your friends the results of your work on the male genitalia . . . have care of your health which is very delicate, and conserve yourself for your friends and the world ” (13, pp. 47-48). De Graaf’s medical responsibilities seem to have been very flexible, for early in 1667 he was back in Paris for a stay of nearly a year. Here during the space of three or four months, the French edition of his book was “ presented to Dr. Bourdelot to be publickly examined, to whose house the most curious‘ wits of the University do frequently resort ” (4, preface). During this period, it having been suggested that animals might live no less without the pancreas than without the spleen, he relates: “ Before all that company we extirpated the spleen and also most exactly the pancreas of a certain dog; the abdomen being again closed, Dr. Bourdelot commanded his servants to keep the dog most diligently, who, notwithstanding all their diligence, in a short time died ” (4, pp. 114-115).

Early in 1668 de Graaf returned to Delft, and in this year were published three treatises in a single volume: De virorum orgcmis generationi insert/ientibus, de clysteribus et de um siphonis in cmqtomia (7). A portrait of the author at the age of 25, drawn by Watelé, and engraved by Edelinck, commonly appears in this volume (fig. 1). This work is inscribed to Habert de Montmor in a dedication dated May 12, 1668, from Delft. 3 The first edition is also prefaced by a letter written by de Graaf to Sylvius (6) on February 20, 1668, summarizing his findings and asking the opinion of his old master, and by Sylvius’ reply, dated the Ides of March. De virorum can be discussed more conveniently later. The other, and shorter, treatises are of some curiosity. De clysteribus treats of the clysters or purges that reached a summit in popular approval in the 17th century (30). Moliére’s hypochrondriac thus sums up the situation: “ This month I have taken eight mixtures and twelve clysters, and in the previous month there were twelve mixtures and twenty drenches——it is no wonder I am not so well this month as I was last ” (34). The history and composition of various purges is described and an instrument pictured whereby they might be self-administered. In a letter dated March 14, 1669,to his countryman, Plemp (14),* who occupied the chair of medicine at Louvain, de Graaf described the construction of this instrument and even mentions a manufacturer, the noted Samuel de Musschenbroeck of Leyden, who, “ in his shop near the church of St. Peter, at the sign of the Oriental Lamp, was prepared to construct it with great care, according to the instructions of de Graaf.” Decided ingenuity was indeed necessary to fabricate a narrow, flexible, water-tight tube, in an age when rubber was unknown, that would moreover be resistant to the atrocious mixture of chemicals that composed the clysters. De Graaf recalls that a somewhat similar device was in use in England for the recondite purpose of introducing tobacco smoke into the intestinal tract (7, p". 212). He describes further an instrument consisting of a length of bird’s intestine, having affixed at either end the feather shaft of a bird, that could be used for the transfusion of blood from animal to animal‘, and was much more convenient than the inflexible metal tubes used by Denis in Paris (7, p. 210).

This letter first appeared as a postscript to the Defensio, 1673. In the Opera omnia and in translations it is appended to De clysteribus, where it more appropriately belongs.

Fig. 1. The Watelé portrait from De 7/irlomm organis, 1668.

The short De usu siphonis was a collection of knowledge on the use of the injection method in anatomy. De Graaf is probably one of the first to construct and figure a syringe of an essentially modern pattern. His instrument had a barrel of -copper or silver, at long bent cannula that screwed on to a leather washer, and a piston packed with thread. A hundred and seventy-five years later, such an instrument was being used almost without modification- De Graaf’s experiments on injection have been so well described by F. J. Cole in The history of; cmatomical infections (38) that it is unnecessary to dwell on them further here. Reprints of this popular trilogy are said to have appeared in 1670 and 1672. A reminder that the author was also a busy practising physician at this time is given by two interesting communications made by letter to Joachim Elsner of Breslau, a member of the Leopold Academy, and which appeared in the first volume of that "Society’s Zvliscellanea C uriosae published in 1670. These are observations on “ Ossification of the carotid artery ” (22) and ‘on “ An abnormal uterus ” (2.3), made on two patients. during the spring of 1669. In 1671 de Graaf published a new treatise in Latin entitled Tractatus ana.tomic0-medicus de succi pancreatici, natum etp mu (4). This is considerably revised from the French Tmitté of 1666 and is the edition that appears in the collected works, and from which all subsequent translations were made. (However, the plates are the same as those in the 1666 edition, and the work is still dedicated to Chapelain. Appended to this treatise is a letter dated May 30, 1671, addressed to Schacht, professor of medicine at Leyden, entitled De partibus genitalibus muliemm (9), in which de Graaf writes: “ You are no doubt surprised that I have not yet published my work on the female genital parts, of which I sent you the plates a year ago; blame the ordinary occupations of one of my profession. The exchange of letters with numerous savants occupy me such that I cannot hope before a year to put the treatise in the form I desire. But lest the intermission arouse the envy of those whom I have allowed to see my figures, to profit at my expense, I have resolved to give to the public a succinct account of these same parts,” There follows a summary of his principal findings. At this time de Graaf was beginning to become involved in an unfortunate disagreement with Swammerdam regarding the priority of certain of his findings. Disregarding for the moment the merits of this quarrel, following the above letter and early in 1672 appeared de Graaf’s culminating work and chief merit to fame entitled: De mulierum organis generationi inservientibus (11) (fig. 3), carrying as subtitle (translated) :1 A new treatise wherein it is demonstrated that man and all those animals that are called V ivipara, these no less than the 07/ipara, derive their origin from the egg. The dedication, dated the Ides of February, 1672, is to Cosimo III, Duke of Tuscany, a Medici prince and patron of science, who had visited Holland in 1669. This volume is adorned with the second (Pinchard) portrait of de Graaf that has survived (fig. 2) ; here he is shown as of a fuller figure and greater maturity than in the Watelé drawing.

Fig. 3. The engraved title-page from the Cushing copy of De nmlierum organis, 1672.

In May 1672, Swammerdam published his M iraculum natnrae, sive muliebris fabrica (41), prefaced by a letter to the Royal Society of London whom he asks to be the judges of his accusation, made therein, that de Graaf had appropriated the discoveriesof Van Horne and himself. This work contains his engraving of the virgin uterus, dedicated to the aged Tulp, the physician of Rembrandt’s “ The anatomy lesson.” The controversy between de Graaf and Swammerdam largely ranged around a preliminary communication of Van Home (32) addressed to Rolfinck in a letter dated March 5, 1668, describing dissections he had performed on both sexes. Later Swammerdam collaborated with him on some drawings, and on the death of Van Home in 1670 had taken a stand against de Graaf on their joint behalf. In reply to the M iracnlum naturae, de Graaf indited a Partium genitalium defensio (13) which appeared early in 1673, also addressed to the Royal Society, which takes up‘ Swammerdam’s charges in great detail. There would seem to be little merit to Swammerdam’s contentions, although the issue is complicated by the fact that the investigations of de Graaf and Van Horne were being pursued simultaneously, and since their circles undoubtedly overlapped it would be absurd to assume complete independence. But the charge of plagiarism can be effectively disposed of, for de Graaf had actively dissected the genital parts since 1665, which dissections he had freely demonstrated to many of the Curious; moreover, his findings and interpretations frequently disagreed with those of Van Horne. In respect of the female ovaries, the contribution of Van Home is freely acknowledged in de Graaf’s book. At the end of the Defemio he answers in polemics a defamatory libel directed against de le Boé Sylvius and himself by an anonymous writer. This might well have been the tract by Pechlin (35) published at Leyden early in 1673 under the pseudonym Janus Leonicenus.

Of the career of de Graaf little further remains to be said. He had married Marie Van ‘Dick in 1672. This year his Catholicism apparently prevented his succession to the chair of Anatomy at Leyden, vacated by the death of Sylvius. On April 28, 1673, he transmitted to the Royal Society of London the first of the long series of letters written by his fellow townsman, Anthony van Leeuwenhoeck, recommending it highly to their interest (28, p. 40). Regnier de Graaf, “ Physician and Celebrated Anatomist of the Town of Delft, in Holland,” died, it is said of the plague, on August 17, 1673, in his thirty-second year.


Catchpole HR. Regnier De Graaf 1641-1673 (1940) Bull. Hist. Med. 8(9): 1261 - 1300.

Cite this page: Hill, M.A. (2019, July 20) Embryology Embryology History - Reinier de Graaf. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Embryology_History_-_Reinier_de_Graaf

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  1. Catchpole HR. Regnier De Graaf 1641-1673 (1940) Bull. Hist. Med. 8(9): 1261 - 1300.