Paper - Regnier De Graaf 1641-1673

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

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This historic 1940 paper by Catchpole describes what is know about Regnier de Graaf (1641 – 1673) a historic Dutch anatomist, best known for the "Graafian follicle", the preovulatory follicle within the ovary. He was also the first to describe the corpus luteum. H. R. Catchpolewho published 32 research works on reproduction and reproductive cycles.


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Regnier de Graaf.jpg

Regnier de Graaf (1641 – 1673) first observed histologically the corpus luteum in the ovary of a cow by its defining yellow structure. The yellow colour is caused by the accumulation of steroidal hormones.

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



Modern Notes: Graafian follicle | corpus luteum | ovary | rabbit
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Regnier De Graaf 1641-1673

Hubert R. Catchpole, PH. D.

Laboratory of Physiology, Yale University School of Medicine, New Haven, Connecticut

I. Life and Works

The approaching tercentenary of the birth of Regnier de Graaf renders the present time a favorable one to inquire into his life and writings. Amore pressing justification could perhaps be sought in the relative neglect of the accomplishments of a man whose name provides such a celebrated eponym-—the Graafian follicle. Only the briefest biographical sketches and few translations of de Graaf’s publications have appeared in English. Although not to be ranked with the greatest masters of medical science, de Graaf is, nevertheless, a significant and attractive figure. His short career was marked by ingenious experiments on the physiology of the pancreas and by brilliant anatomical researches on the generative systems. In an experiment remarkable for this era, he investigated the mode of generation in the rabbit and is to be credited with the first description of the formation of the corpus luteum. These achievements, coupled with his invention and construction of a highly serviceable syringe, might be considered sufficient reason for assigning him an early position in the phylogeny of the endocrinologist.


Sources

In compiling the following record, I have been most fortunate in having had access to first editions of most of de Graaf’s individual works and to his collected works in Latin from the library of Dr. John F. Fulton. I have also a very useful French translation of the collected works made by an anonymous author and published at Basel probably in 1699 (19). The revised version (3) of his Disputatio medica de natura succi pancreatici was issued in French by the author himself. In English there is a translation of the 1671 Tractatus de succi pcmcreatici natura (4) made by Christopher Pack in 1676 (5), which I have seen as a photostatic reproduction of the copy in the Bodleian Library; and also a brief summarized translation from De mulierum orgawis which appeared in the short-lived British record of obstetrics and surgery of 1848 (12). In 1878 appeared a French translation of the minor work De clysteribus under the title L’z'nstrument de M oliére (8), as a commentary on the more serious side of certain medical practices so ridiculed by Moliére in Le malade imaginaire and other writings. It is prefaced by an excellent biographical notice of de Graaf, which it is diflicult to avoid paraphrasing.

  • The histories of Portal (1770) (36) and of Eloy (1821) (29) include notes on de Graaf and his works. Of other publications relevant to the subject may be cited a medical thesis of the University of Bordeaux by’ Albert Rey (37) dealing with de Graaf in relation to Sylvius de le Boé, an article (Italian) by Vedani (42), a note on the author and a translation in the collection of Fulton (31), and an appreciation in the collection of Stirling (40).

Life

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 the body 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. 1

Works

Passing to a review of his two chief works and first to De virorum, de Graaf expresses a now familiar theme when he says: “ The human body is composed of principles so contrary among themselves that their mere composition convinces us of the necessity of death. His excrements are constantly at war and as soon as one overrides another the whole economy goes to pieces: soon illnesses come in droves, and he finds himself succumbing with insupportable pains. Man, then, cannot be immortal on this earth, but he has the consolation in dying of living again in his children, and God has given him the means of generation not only for a thousand years but even for a species of Eternity—and for this purpose there are certain organs of the human frame fashioned with a structure so delicate that the hand of Providence may therein be witnessed ” (7, p. l).* He described the external male organs with a disquisition on eunuchoidism, cryptorchidism, and several abnormalities, and then proceeded to a minute examination of the arteries, veins, nerves, and lymphatics of the genital parts. Quoting Fallopio, Spieghel, and Vesling as believing the substance of the testes to be glandular, as well as the opinions of Wharton and Vesal, he says: “ The different beliefs of these great men are sufficient to show the difficulty of fully understanding the nature of the testis, because not one among them has found the shadow of the truth. I hold that the testis is no other than a mass of very fine vessels disposed so that if one develops them without breaking, they are found to be more than twenty ells in length ” (7, pp. 54-55). To reveal this, “ make a tight ligature on the vas deferens of the dog or some other animal before coitus, and the testicular vessels will be observed to swell and become visible. Or more simply remove the tunica albuginea of a large dormouse and throw the testes in a basin of water, when the vessels will develop one from the other ” (7, p. 56). Several vessels (the vasa efferentia) leave the testis and pass into the epididymis (7, p. 66), which is in effect “ only a long vessel which by its folding forms a body attached to the back of the testis ” (7 , pp. 65-65). Distally from its origin, this vessel enlarges to become the vas deferens. Its total length is more than five ells in a small animal (7, p. 66). By the method of tying off the vas deferens of a dog before coitus, he shows that the semen is “ engendered and formed in the testes ” (7, pp. 72-73). He speaks of a controversy with his intimate friend Bils over whether the semen is derived from lymph, as Bils believed, or from the blood, and remarks, “ Not having the eyes of a lynx we are unable to see the duplicated lymphatic vessels claimed by Dr. Bils ” (7, p. 75). De Graaf advances the “ incontestable principle ” that the semen is formed from the blood, and it remained only to show


This passage is quoted almost verbatim (and without acknowledgment) in Dionis, Anatomie de l’homme, 1702 (p. 254). He characteristically adds: “ Oftentimes the prospect of pleasure, as much as the desire of Eternising oneself, so inflames the imagination that one precipitately abandons oneself to that natural passion ”! how this material passes from the spermatic artery to the seminal vessels. One theory, that of Lindanus, is that the seminal vessels are a continuation of the arteries “ as he claims to have seen with his own eyes ” (7, p. 77) ; the other, that the arteries “ embrace closely the seminal vessels and transmit to the cavity of the latter the most subtle part of the liquid they contain, while the rest passes to the veins. The first will appear false to any who gives himself the trouble to follow exactly the course of the spermatic artery in the substance of the testes. It branches to the right and the left and makes a number of almost invisible ramifications that hold the seminal vessels tightly together, but never enters their substance” (7, pp. 78-79). To observe them better, a coloured liquid was introduced by means of the syringe. He concluded, “ If the generation of the semen is not performed the first way, it must of necessity be in the second, for the mind of man cannot conceive of a third. In a word, the spermatic arteries dispose the material of the semen in the spermatic vessels in the same way that the hepatic arteries dispose the material of the bile in the hepatic canals ” (7 , p. 80). At this point in his argument, conjecture necessarily enters, and he proceeds, “ When the most subtle part of the blood has entered the seminal vessels, it there receives the animal spirits, all anatomists agree, although none of them know what relationships exist between the nerves and the seminal vessels, and I, no more than they. But if it be proper to theorize in these difficult matters, it is reasonable to suppose that the nerves distributed to the membranes of the testes reach to the tunicae internae of the vessels and there discharge the animal spirits” (7, pp. 80-81). The ultimate fate of the blood vessels was a perpetual puzzle to de Graaf, who was apparently ignorant of Malpighi’s observations on the capillaries, made seven years before. The situation of the seminal vesicles is described, and the fact of their absence in dogs is noted (7, p. 95). The vas deferens and the seminal vesicles enter the urethra by a common duct. From his injection experiments, de Graaf was convinced that the seminal vesicles were a depositary of the semen; and in man they are, indeed, usually found to contain sperm although this is never the case in animals. It is apparently true that, in the dead subject, fluids injected from the testicular end of the vas deferens flow first into the seminal vesicles. De Graaf was deceived by the relatively membranous nature of these bodies into thinking them to be nonglandular (7, pp. 92 and 95). The prostate glands are described as the glandular bodies of Vesalius (7, p. 102). Concerning the function of these, he disposes of the idea that their function is to perfect the semen since “it is only necessary to have wielded the knife a little and to have seen the anatomy of these parts to be convinced that this is improbable, since there is no communication between them and the seminal vesicles whereby fluid could pass (7 , p. 107) ; as to the idea that the liquid of the prostate is bitter and serves as a stimulant to the semen, it is only necessary to taste the liquid in question to know that it is not ” (7. p. 108). He decided that the function of the prostatic fluid was to act as a vehicle for the semen (7, p. 112). Discussing the thesis that there are three kinds of semen, from the testes, seminal vesicles, and prostate, respectively, he quotes passages from Wharton’s Treatise on glands of 1659 in support of this theory and says: “ To parry these arguments, I say, in the first place, that Wharton supposes that which is questionable; namely that castrated animals throw semen. This I deny, for they throw merely the vehicle of the semen.” The further arguments are as expeditiously dismissed. He described the anatomy of the penis, and by injecting water into the corpus cavernosa by way of the arterial supply proved that the primary cause of erection was the blood supply, with the muscular and nervous effects as contributory causes (7, p. 154). .


De virorum orgcmis is furnished with nine plates, comprising‘ twenty-five drawings of the male genital tract and showing the care and usual accuracy with which de Graaf’s dissections were made. It is remarkable that he omits all mention of the median septum of the scrotum, which he can scarcely fail to have seen.


The admirable treatise De mulierum is a monograph wherein the opinions of ancient and modern writers are constantly drawn upon and after discussion accepted or rejected; at the same time evidence from the author’s own dissections is introduced. This work is somewhat more systematized than the earlier one on the male, being“ organized into sixteen chapters (fig. 4), with both a chapter and a subject index.


Index Capitum Cap. 1. Propofitio dicendorum. Pag. I

Cap. I. Dé Pudmdo Mzzliebrio 7 Cap III. De Clitoride. 16 Cap. IV. De Z\{ym}>/923'. 29 Cap. V. De Hymme. . 3; Cap. VI. De Meaty Ummria. 64. Cap. V II. De Vagina Utcri. 74. Cap. VIII. De Ultra. 9 I Cap. IX. De Fluxu Menflruo. 124. Cap. X. De Lzgammtis Uteri. 14.2

Cap. XI. De Vafl5Pfxp;zrm2tibm. 156 Cap. XII. De Yéflibus Mu/icrum jive Ovarm. 1 71

Cap. XIII. De Semim’ Muliebri. 1 4. Cap. XlV. De Vnfis Dcjferentibta My 2?mm five tarum 0*vidzgé?i 611:. 2.2.0

Cap. XV. Dc Ii: qua Ow in Ultra Am’dtmt. 16;

Cap. XVI. Ctmiculamm Gmemtiomm tomp/eflitur. 308

R E fig. 4.

The chapter index from De mulierum organis, 1672.


In a preface, de Graaf announced that the history he proposed was based on new principles, for he maintains that “ all men and animals take their origin from an egg; not from an egg formed in the uterus by the semen, as Aristotle says, nor by a seminal virtue, following Harvey, but from an egg existing before coitus in the female testicles.” The first chapter contains a list of the parts of the female genitalia, arranged in tabular form and grouped into external and internal parts. The latter are subdivided into the principal parts. vagina, uterus, fallopian tubes, and testicles, and the less principal parts, comprising the tunicae, veins, arteries, lymphatics, nerves, and ligaments. The anatomy of the external parts is well described, but de Graaf believed that the hymen was a retraction of the vaginal orifice, rather than a specific membrane, and that the blood that appeared at coitus was due to the breaking of vessels in the violent dilatation that occurred. Concerning the criteria of virginity, he concedes that it would be “ not less useful than curious to know these,” but decides that most of them, “ like the supposed changes in voice and hair, the dimensions of the neck, and the approach of bees, are false and fabulous, and the potions and perfumes used to decide this point but old wives’ tales that scarcely merit refutation” (11, pp. 61-62). The positions of the vagina and uterus are described in relation to surrounding structures. The uterus is not always precisely central, but may be displaced, more often to the right than the left (11, p. 93). It has no cornua or cells, as Galen believed; “ He could never have seen, even in a dream, a female uterus, but only those of cows, sheep and the like.” De Graaf distinguishes the cavity of the uterus from the cervical canal, however, and states that the latter is so narrow in the virgin as scarcely to admit a stiletto. He finds incredible the statement of Riolan that this canal is wide open during the menses. The size of the uterus varies with age, number of children, and other factors; to give at least some idea of this variation, he states that its weight in a new born infant is a drachm and a half, at puberty an ounce and a half, and at maturity somewhat larger, but rarely more than two ounces (11, p. 101). He adds: 1“ Whether the uterus is larger at the time of menses is disputed by several authors; there are those who think that blood collects in the uterus after the last menses till it is full, but in very many women that I have dissected I have never found any considerable differences in the size of the uterus as would be if this were true ” (11, p. 105). The external membrane of the uterus takes its origin from the peritoneum; this sustains the organ in place by virtue of the ligaments that take their origin thence. The blood supply of the uterus is through the ovarian and hypogastric arteries, which anastomoseamong themselves and with those of the opposite side: “ These can very agreeably be seen by inflating with air ” (11, p. 109). The veins may be similarly traced. He concludes that the use of the uterus is to “ receive the germ or principle of the fetus, to nourish it and protect it from external injuries, to give it birth in due time, and to purge the female body ” (11, p. 114).


Regarding the menstrual flow, he begins that “ no physician is ignorant of what it is, but all dispute as to its nature,” a sentiment that still has airing of familiarity. He promises to deal with the subject succinctly, rather than become distracted by small difliculties. And first, he maintains that the flow arises in the uterus, rather than in the vagina, pudendae, or other parts that have been postulated. There is no connection between the moon and menses, “for the former follows an immutable course, while the latter varies ” (11, p. 130). Nor is menses due to a plethora of blood passing into the vessels of the uterus and distending them to the bursting point; “ This is refuted by reason and by frequent dissections: for is it reasonable that blood which following the laws of nature is circulating continuously should stagnate for any space of time in the vessels of the uterus; added to which is the fact that these vessels are inadequate to hold the amount of blood released in these periodic evacuations. I have never seen such distended vessels in a woman dying shortly before the flow, nor read of any anatomist who has ” (11, p. 131). All considered, “ The blood purged so regularly by the uterus depends rather upon a ‘ fermentation ’ than on any plethora, and I am persuaded that this fermentation is not confined to the vessels of the uterus alone but passes in the whole mass of the blood, as witness (the other symptoms of menstruation) when the head feels bad, the feet heavy, and the stomach deranged ” (11, p. 132). The uterus is held by four ligaments: two broad, attached on both sides to the body of the uterus and the vagina, and holding the vessels, tubes, and ovaries; and two round, attached to the body of the uterus where the fallopian tubes take their origin. The four “ vasa praeparantia,” i. e., spermatic or ovarian vessels in the female, comprising the ovarian arteries and veins on both sides, are compared with the corresponding spermatic vessels of the male. The ovarian arteries, although more contorted in the female, are nevertheless not as long as those of the male, which must extend to the scrotum. The distribution of these vessels in the sexes also differs since, whereas in the male there are two branches of which the one goes to the testis, the other to the epididymis, in the female the principal branch goes to the uterus where it anastomoses so completely with the hypogastric artery (i. e., the uterine branch of that artery) that it is difiicult to determine the limits of these and to define whence the ovaries actually are supplied (11, p. 158). The same obtains for the blood supply to the tubes. The branches of the vessels extend to the female testes and not only supply their external substance, but also penetrate inwardly. He refutes those who hold that the spermatic arteries and veins anastomose among themselves for, he argues, “ were they so united before arriving at the testes, the blood, indifferently propelled by the heart, would not enter theparenchyma of the testes or the extremities of capillary vessels (vasorum capillarium extremitates) or other devious paths if an easier way existed” (11, pp. 160-161). De Graaf noted that all the vessels that he described were greatly enlarged in the pregnant condition. The female testes differ greatly from those of the male. “ Their internal substance is a composition of several membranes or small fibres in the interstices of which are found several bodies both natural and unnatural.

Corpus luteum

Always found there are certain small bodies full of a liquid; also, nerves and vessels dividing into an infinity of ramifications. Naturally found, but only after coitus, are globular bodies formed like conglomerate glands and surrounded by a proper membrane. These are yellow in cattle, red in ewes, and grey in other animals. Some days after coitus they are of a very thin consistency and have in their centre a clear liquid surrounded by a membrane; this, disappearing with the liquid, leaves a cavity which is gradually abolished, .and after some months of pregnancy these globes are solid, and after parturition gradually abolished ” (11, pp. 177-178).


This would appear to be the first description of the corpus luteum, and, moreover, fairly accurate as to its successive stages. The “ un natural ” bodies to be found in the ovary include hydatids and stones. De Graaf considered, “ The little vesicles, or the matter contained therein, are the things for which all other parts of the testicles exist ” (11, p. 179). Some have called these vesicles hydatids, but the savant Van Home in his preliminary communication properly calls themeggs, and, following the example of that famous man, we will do so in this work, for they perfectly resemble the eggs contained in the ovaries of birds (.11, p. 180). For these, when small, contain only a littleiclear liquid, similar to that observed in the eggs of females while on the other hand having boiled these latter, they are foundto have the same colour, taste, and consistency as the white of eggs of birds. “ One can assert that the females of all sorts of animals have eggs, since theyrare found not only in birds and in oviparous and viviparous fish, but also in quadrupeds and in women. We have found eggsin rabbits, hares, pigs, sheep, and cows; they are present on the surface of the ovary, and are so distinctly seen as to threaten a speedy exit. They vary in size; in rabbits they are as large as grains of hemp, in sheep and pigs the size of a pea, and in the cow as large as a cherry. But in these same animals are others smaller in size, down to those difficult to discern. Following coitus, the condition changes to one or more of the globular bodies described above. according to the number of fetuses in the animal. I had been led to conjecture that similar eggs occurred in other species that I had not yet dissected, and I begged the savant Stensen to appraise me of his observations in species that I lacked. He did not neglect to reply frankly, saying that he had found eggs of different sizes in deer, guinea pigs, badgers, roe deer, wolves, and asses; in mules even and in other animals ” (11, p. 185).


Stensen must indeed receive credit for having, in 1667, homologized the female testes with true ovaria (38, pp. 116-118). De Graaf continues:

“The eggs are engendered and perfected in the testes, in the same way as the yellow of eggs in the ovaries of birds, by means of blood brought to the testes by the ovarian arteries; thus they are nourished, and when they have reached their natural size they become invested with certain tunics between which, after coitus, a glandular substance is formed, which composes the matter of the globular bodies described above. The function of the testes is, in a word, the same as that of the ovaria of birds, and on this account they could be called ovaries since they bear no conceivable relation to the testes of the male ” (11, pp. 185-186).



Fig. 5. Table 26 from De mulierum organis, 1672: Rabbit ova at successive stages of pregnancy.


Dealing with certain ancient and modern theories regarding the female “ seed ” de Graaf states, “I incline to neither side of this dispute, for I believe that women contribute nothing to generation but the eggs described in the previous chapter ” (11, p. 200). He describes Harvey’s experiments on generation in the fowl and concludes, “ Everything considered, it is not difficult to believe’ that a similar sequence occurs in quadrupeds and women, who have organs destined for the same ends not greatly different from those in the bird ” (11, p. 211). The final paragraph of the XIVth chapter reveals his views on the transfer of the eggs: “ We must conclude that the Fallopian tubes are the true vasa deferentia of women and all female genera, or rather Oviducts that carry the Ova to the Uterus ” (11, p. 255). Thus the name of Fallopio, the discoverer of these canals, became secured to them by de Graaf’s demonstration of their true function. The tubes served first, in his opinion, to carry to the egg either the semen or the “ seminal vapour ” by which the egg is impregnated; in the second place, to receive in their extreme ends the fertilized egg that has now been expelled from the ovary, and to conduct it to the uterus. Few of these stages were, at this time, susceptible of direct proof. De Graaf conceived of the female egg as one of the ovarian vesicles. He imagined, and so pictured these vesicles, as capable of being shelled out of the ovary in their entirety (fig. 5). This concept naturally involved him in several difficulties: why these were not found free in the region of the ovary; how bodies of this size could pass down the tubes, and why bodies that he found in the lower part of the tubes and in the uterus (of the rabbit) might be ten times smaller than the vesicles in the ovary. De Graaf never saw the true mammalian ova, not to be found till 1828 by von Baer. It has been noted that de Graaf was a patron of, and well acquainted with the work of Leeuwenhoeck, and the engraved title page of De mulier-um (fig. 3) shows one of the putti examining a rabbit blastocyst with a magnifying instrument. But blinded by analogy with bird ova, the true egg was missed. There is no hint in de Graaf’s writings of any idea of preformation (26, pp. 48, 164, 165). In the rabbit, although the egg is observed to grow for nine days, the fetus is first encountered as an unformed mass only on the tenth day. Regarding the changes that occur in the uterus, he quotes liberally from the writings of Harvey and Needham dealing with the formation and function of the various fetal membranes. His final chapter deals with “ Generation in the rabbit,” in which he attempts to prove certain hypotheses developed during his dissections of the genital parts of the female. The gift of a sure experimental approach already demonstrated in his work on the pancreas nowhere shows to greater advantage than in this research in which successive and accurately timed stages. in pregnancy are patiently observed. It is convenient to deal with his techniques and findings in the rabbit in a separate note and to pass on to his application of them to the human. These, for reasons largely beyond his control, were mainly unfortunate. He concluded that four incontestable truths had been established:

“first, that those err who claim that virgins as well as women have equally the eggs described above; for the glandular substance that helps them to leave the testes only develops in the vesicles of the eggs after a fertile coitus. Second, that the eggs cannot in the space of two or three days reach the size of a cherry since those of the rabbit moistened with the semen of the male remain three days and those of females that bear longer remain some weeks in the testes, gradually diminishing in size until they are 10 times as small; then, expelled from their thick membranes, are received into the tubes and conducted to the uterus where they grow in the manner related. Third, that there is no such thing as a human fetus three or four days following coitus because the eggs of the rabbit, which only bears its young for 31 days, do not reach the uterus till the third day and one cannot see the little fetus (nubecula) till the ninth day; this must appear much later in the woman who bears longer and whose ova stay limpid for a month. The fourth is that the vulgar opinion that the woman must retain the semenof the male to become pregnant is false, since the rabbit dissected on the twenty-ninth day had rejected all the semen of the male after coitus, yet had eleven fetuses in its uterus ” (11, pp. 327-329).


It is unnecessary to comment more than briefly on the latter part of de Graaf’s essay. He went wrongchiefly through ignorance of the true size and nature of the ovum, and also of the nature of the semen, soon to be elucidated by Leeuwenhoeck; he regarded the action of the semen as necessary, but ephemeral.


In presenting his work to the public, de Graaf concludes: “ Here is our Treatise on the Organs of Women that serve for Reproduction, by the Grace of God achieved with exactitude, presented, not to serve for libidinage, but for the advancement of Truth and Medicine, and to show the wonder of providence and the wisdom of the Almighty, in discovering the miraculous means provided for the propagation and conservation of the human race ” (11, p. '329).

This excellent work is illustrated. by twenty-seven plates com prising about sixty drawings, both gross and detailed, of the female genital parts.

II. CAP. XVI. Cuniculorum Generationem Complectens

De Graaf’s experiments on generation in the rabbit form the final chapter of his De mulierum orgamis. This study is justified by the author in an opening paragraph:

Since the foregoing facts lack ocular demonstration in women, we have had recourse to animals, which breed at a time that can be exactly noted, and which bear many young at one time, so that what escapes in one may be found in another. To this end the rabbit seemed most suitable.* first was dissected a virgin, female:

I found that the ovaries, although small, contained a large number of eggs, very limpid and clear, which, when opened, gave forth a glairy liquid, like the white of an egg. I opened another one-half hour after coitus; the uterine cornua were redder, the eggs practically unchanged. There was no sign of the male semen in either vagina. or uterus. Six hours after coitus the envelopes of the ova 1‘ were red, and on piercing with a needle a glairy liquid issued, then a little blood from the vessels pervading the envelope. There was no vestige of semen.

  • The rabbit was not only suitable, but a most lucky choice since it regularly ovulates 10 hours after coitus, and is the only common domestic animal (excepting the cat and ferret) that does so.
  • Ovorum folliculi, translated: envelope or covering of the eggs.


Twenty-four hours after coitus I dissected another and found in one ovary three, and in the other ovary five, egg envelopes considerably altered. For they were now opaque and reddish, and at their surface a little pimple was manifest. On opening I savsg a very little limpid liquid at their centres, and at their peripheries, a substance reddish and denser.


At twenty-seven hours I found the (P vessels of the) uterus and tubes filled with blood and the funnel-like extremities of the latter embracing the testes. As in the foregoing instance, the surface of each follicle* bore a pimple, whence, on pressing the testicle, a limpid liquid was expressed, which subsequently became denser and redder. There were no ova visible on dissecting the uterus, but its inner tunica was furrowed and a little swollen.


At forty-eight hours I examined another; there were seven and three follicles much changed in the two ovaries respectively. The pimple-like excrescences were- more apparent, and on squeezing a little albuminous liquid appeared, but the red matter was thicker and came out with difficulty.


At fifty-two hours I found respectively one and four changed follicles (immutatos folliculos) ; on dissecting these I encountered a glandular material in the centre of which was a cavity devoid of noticeable liquid. I suspected that the limpid liquid inclosed in its proper membrane was burst asunder or expelled. Wherefore I searched in the uterus and tubes without success; the internal tunica of the cornua was nevertheless very inflated and glistening.


Seventy-two or seventy-three hours after coitus I examined another rabbit and found a further change in that the tubes very closely invested the ovaries; which being retracted I found in the right ovary three follicles, larger and more solid, showing in the middle of their surface a small tubercle like a pimple, pierced with a small hole. On dissection I found their median cavity empty; those tubes by which the ova must pass, I examined diligently and found in the middle of the right tube one, and in the extremity of the same cornua two, very minute ova (duo minutissima ova) shown in the first figure of Table 26 (fig. 5), which though so minute are provided with two membranes, and from which, on piercing with a needle, a limpid liquid escaped, which, though it seemed surprising, is easily demonstrated. In the other ovary were four follicles, three somewhat clear, pierced with a little channel and containing a little clear liquid; the fourth not so transparent and containing no liquid, which persuaded me that the ovum had escaped; I searched in the oviduct and horn of the side and found a single ovum in the horn similar to those described above. Hence it follows that ova proceeding from the testes are ten times smaller than those yet cleaving to the testes; because, while still there, they are surrounded by other matter, the same indeed from which the glandular substance of the follicle arises.


Four days after coitus, I found four and three empty vesicles (globulos folliculos exz'nantos),* respectively, and ova in each cornua larger than the preceding as in figure 2 of Table 26 (fig. 5). These eggs had reached the middle of the horn. I saw more clearly than above, a second egg floating in their interior. I saw in the testes, besides follicles as described above, others that the seminal spirit had not touched, and also four black vesicles filled with a mass of blood. But I have seen these also in other rabbits and do not think them worthy of reflection.


  • The word ‘egg’ has been dropped leaving folliculus, a small bag or sac, which is here conveniently translated as follicle (actually, it is now a ruptured follicle).


Summarizing de Graaf’s findings to this point, it is clear he considered that perhaps only a part of the substance of the “ eggs ” seen in the ovary actually descended to the uterus, although he had previously defended the thesis that the whole “ egg ” was capable of negotiating the lumen of the tube. He established the correspondence between the number of follicles discharged from the ovary and the number of eggs that appeared in the uterus, although his criterion of when the egg actually left the ovary was incorrect. In the rabbit, this occurs regularly ten hours after coitus, so that the picture he saw at twenty-four hours would have been that of recent ovulation, and indeed his description corresponds exactly with this. He established that the discharged follicle progressively fills up with a glandular material, and that after coitus unaffected follicles may still be found in the ovary. As to the eggs actually found in the uterus, these evidently represented successive stages in the formation of the blastodermic vesicle. It is difficult to decide the status of de Graaf’s very earliest ova. It is now known that rabbit ova reach the uterus at 72 hours, and that at this time the diameter of the vesicle is about 0.12 mm. It increases rapidly in size, reaching 0.3 mm. at 96 hours, 1.5 mm. at 120 hours, and 3.0-3.5 mm. at 144 hours. De Graaf pictures the ova at 72 hours as small circles varying from about 0.25 to 0.5 mm. in diameter; at 96 hours they are shown with a diameter of around 1.0 mm.; at 120 hours, as 2.0 mm. or slightly less, and at 144 hours, as 2-3 mm. It is clear that sheer difficulty in draughtsmanship would prevent the exact representation of the smallest vesicles that can be seen by the unaided eye.


Five days after coitus, I observed six empty follicles in the ovaries of another rabbit and the same number of ova in different parts of the uterus without being attached. The internal membrane of these was more apparent than before. The globular bodies were large and their canals admitted the passage of a medium sized bristle.


  • 'Empty’ ; i. e., follicles transforming into corpora lutea in which central cavity is becoming obliterated.


Six days after coitus, I counted six empty follicles intone ovary, but found only five ova in the horn of that side. And the other ovary had four empty follicles but only one ovum was recovered. The reason is that they have either been thrown out of the uterus, destroyed in the follicles, or lost by some accident.

Seven days after coitus, I found in the ovaries several empty follicles, larger, redder, and harder than the preceding, and, besides, tumors or transparent cellules in different parts of the uterus. Inside these were ova larger than before, as in figure 5 of the table. In these, besides a very apparent internal membrane and a most limpid humor, I saw‘ nothing else. It is remarkable that the ova could imbibe so much liquor in so short a time and, from being readily removable, now become difficult to detach from the uterus.


On the eighth day after coitus, I examined two rabbits. Having opened the uteri and remarked the ova, I had to bring all my attention and diligence to their removal, since they broke at the least touch; but after boiling the uterus and ova together, the liquor hardened like the white of an egg.


On the ninth day, I dissected an old rabbit with ovaries twice the size of a young one. I found two empty follicles in the right and five in the left ovaries and also others, paler in color and flattened, which were apparently voided in previous coitus and had not yet become obliterated and reduced to small points; to these was due the increase in the size of the ovary. These bodies of the last coitus were still furnished with protuberances. There were two cellules in the right horn and five in the left; their substance was more transparent than that of the uterus proper and traversed by many arteries and veins. On opening these cellules, the ova could be clearly seen though not. removed. They were filled with a crystal clear liquid in which floated an extremely delicate cloudy spot (nubecula). In other rabbits killed on the ninth day this evaded recognition. But on the tenth day in a rabbit having seven uterine vesicles, each showed on opening an unformed, mucilaginous embryo (rude mucilagineum embryonis) resembling a small vermiculus. The placenta was clearly evident to which the ovum was attached. by means of the chorion (sic). After boiling, the consistency of the eggs was the same as described before. After twelve days, the embryo was so apparent as to render visible certain features, such as two red and two white points in the pectoral region; but the smallness of this little animal did not permit further description.


To summarize, the observations of the rapid growth of the blastocyst and its implantation on the seventh or eighth day areacute, as is also the recognition of the first visible trace of the embryo at the ninth day.


Fourteen days after coitus, the uterine cellules were larger with more and greatly inflated vessels. I recognized also that as the cellules increased in size, they approximated closer to each other. The amniotic and chorionic membranes were attached together, and having broken them, the embryo appeared distinctly as depicted in figure 10, having a large and transparent head with the brain reaching to the tip, prominent eyes, open mouth, and ears becoming apparent. The spine curved towards the sternum as a white line resembling the prow of a ship. Very delicate blood vessels reaching along the. sides of the spine sent ramifications to the back and to the extremities. In the pectoral region, two red spots larger than in the preceding stage formed the rudiments of the ventricles of the heart, to both sides of which two white spots showed the position of the lungs. On opening the abdomen, first was seen the reddish colored liver, then a whitish body to which was attached a mucilaginous mass in the form of a contorted thread representing the rudiments (primordia) of the stomach and intestines. All of which must in time increase and develop to perfection. And not to discourage the reader, I pass over the other dissections which I made day by day, except for that made the day before birth wherein those things that were previously seen indistinctly, now were clearly apparent.


The rabbit which I dissected on the 29th day (i. e., a day or so before parturition) had delivered six weeks previously and, during the last coitus in which it had become pregnant, had rejected a large part of the male semen in the form of a white jelly. It had in its ovaries eleven empty follicles and other smaller ones. We have already seen that the envelopes of the eggs do not disappear completely in the ovaries, but leave certain points there * which accumulate in multiparas, Whose ovaries are large and white. The uterus was no longer divided into cellules, but resembled a stuffed sausage. It had a peristalsis so strong that the fetuses nearest the vagina were forced out enveloped in their membranes and all would have been so expelled had we not extirpated the uterus entirely. The uterus was scarcely thicker than in the nonpregnant animal, differing from the human female. Inside were eleven kicking fetuses, each enclosed in its chorion, but so compressed together that there would seem to be but one chorion enclosing all. The chorion of each fetus received its blood from the umbilico-mesenteric artery and directly overlaid the amnion. To follow the figure of these membranes, I distended the kidney-shaped amnion with air; it contained no enclosed fluid; then I blew into the allantoic cavity by a tube introduced into certain passages in the white part of placenta and found that it consisted of several cellules of which the capacity was scarcely less than that of the fetal membrane. It contained about half a drachm of urine. To determine whence this had arisen, I injected first water, and then air, into the bladder by way of the ureter. But neither the one nor the other penetrated into this membrane.

Corpora albicans

Although there is only one placenta, it has two parts, a red and a white which are both extruded with the fetus. The white portion, placed between the red part and the uterus, is pierced with six or seven channels, and when one blows therein the red part is inflated like a sponge. The placenta has two kinds of vessels receiving two arteries from the aortic trunk and one vein from the hepatic; these subdivide and ramify.


The red and white portions of the placenta that are described may be identified with, respectively, the lobulated ectoplacenta and the deeper, submucous part of the placenta. The latter becomes progressively reduced in size during gestation and is shed with the rest of the fetal membranes. The small foramina therein described probably represent lacunae carrying uterine blood to the placenta and fetus.


The essay on generation in the rabbit ends abruptly with the enunciation of four conclusions applying the findings to human reproduction ; with these we have already dealt.


De Graaf in performing this research evidently must have had access to a respectable group of rabbits: some eighteen autopsies are described and it is implied that at least an equal number were examined to complete the gestation series. However, elsewhere (13, p. 66) he reveals that he had examined more than a hundred rabbits, and, in addition, had kept (and fed) more than forty goats, cows, dogs, cats, and a number of other animals, in order to learn distinctly what occurred after coitus and during gestation.


De Graaf’s fine sense of experimental technique that was apparent when he devised the operation for collection of pancreatic juice shows, in a slightly different direction, in this research also. Here is the ability to plan an experiment on an adequate series of animals to make logical deductions possible from stage to stage; in a field, moreover, where active inquiry is still proceeding, and in which time relations, so accurately used by the author, are still of para mount interest.


I wish to express here my gratitude to Dr. John F. Fulton, not only for the use of his de Graaf first editions, but for his help and suggestions and the many historical reference books in his library. To the librarians of the various libraries mentioned in the Bibliographical appendix, I wish also to extend my thanks for their generous cooperation and interest; I have also been fortunate in having had the items from the library of the late Dr. Harvey Cushing made available to me.

III. Bibliographical Appendix

A list of de Graaf’s works has been compiled from various sources. No elaborate descriptions of the separate items has been attempted, but short explanatory notes have been added when necessary. The following symbols for American libraries have been employed:

DSG Army Medical Library, Washington, D. C.

MdBJ'-W Welch Medical Library, Baltimore, Maryland

PPCP College of Physicians, Philadelphia, Pennsylvania

ICJ John Crerar Library, Chicago, Illinois

MBM Boston Medical Library, Boston, Massachusetts

NN N AM New York Academy of Medicine, New York, New York and for foreign libraries the following abbreviations:

Bibl. Nat. Bibliothéque Nationale, P ris

Bibl. med. neerl. Bibliotheek der nederl. Maéschappij der Geneeskunst, Amsterdam Bodleian Bodleian Library, Oxford

Brit. Mus. British Museum, London

Hunt. Hunterian Library, Edinburgh

Libr. Phys. Surg. Library of the Faculty of Physicians and Surgeons, Glasgow Osler Osler Library, McGill University, Montreal

A few private libraries are also included in the listings as follows: Cushing The library of the late Dr. Harvey Cushing, New Haven Fulton The library of Dr. J. F. Fulton, New Haven

Reynolds The library of Dr. Lawrence Reynolds, Detroit

van Wagenen The library of Dr. G. van Wagenen, New York

Waller The library of Dr. Erik Waller, Lidkoping, Sweden

I. Disputatio Medica De Natura Succi Pancreatici

1.» Disputatio medica de natura et usu succi pancreatici, quam summo numine sub praesidio Clarissimi, Doctissimique viri D. Francisci de le Boe, Sylvii, Medicinae practicae in Inclyta Lugd. Batava Academia professoris, publice ventilandam proponie Regnerus De Graef, Schoonhov. Bat. Ad diem 17. Decemb. loco, horisque solitis. Leyden, Hack, 1664. 18° : 90 pp., 3 pl.

N ote: The DSG copy lacks the half—title page that appears in No. 2. It is bound with Deleboe Sylvius, Disputationum medicarum, 1663, and Lower, Th. Willisii: De febribus vindicatio adversus Edmundum de M eara, 1666. Although listed in the Index catalogue as 18°, the collation (A-C12, D9) suggests that it is probably 12°. (See fig. 6a). .

C opies: DSG, MdBJ-W (photostat of DSG copy).

2. Regneri de Graef, Schoonhovia-Bat. De Succi pancreatici natura et usu exercitatio anatomico-medica. Leyden, Hack, 12°, 1664. (4) 90 pp., 3 folding pl.

Half—tz'tle: Regneri de Graef, De succi pancreatici natura et usu exercitatio anatomico-medica, in Inclyta Lugdunensi Academia, sub praesidio Viri Clariss.


DISPUIATIO Msmca D E Natura S: Ufu

Succi Pancreatici ,

QU .4 M

Summo nuxiliantc Numinc sun PRALSIDXO

Cl.¢rzjYmu, Doéfifitmiquc Viri 1). FRANCISCI DE LE‘. BOE. S Y L V I 1. Medicine: Prafiicae in Inclyta Lugd. Bauvi Acadcmifi Profofforia, [’ubIt:é *L'en::I.md.zm prapanii

Rncnanus Dz Gan-zr, Schoonhou\M! AJ a'zem I 7. Down}. Ina, bvritqltjolitk.

won. 3.41.41’. ExOEic'm3. HACMMI A, 1664.‘

(a)

Title-page of Army Medical Library copy

of Disputatio medica de natura succi pancreatico, 1664. (No. 1)

REGNERI DE GRAEF,

ScHooNHov1A-BAI. D E Succi Pancrcatici NAIURA Er USU EXERCITATIO

ANATOMICOMEDICA.

1 US I’). 5 .4 '1' .14’.

Ex Ofiicina H \CKlAN A, A° cb lac Lxxv.

(b)

Title-page of Fulton copy of De succi paucreatici natura, 1664. (No. 2)

fig. 6.

REGNERI DE GRAEF, D E SUCCI PANCREATICI

NATURA E1‘ Usu

EXERCITATIO

ANATOMI C0-MED.IC A, 1 N Inclyta Lugdunenli Academia, s U B P I; [E 3 ID I 0 Viri Clm:/]I C3“ Exyerimtiflf Fazmcxscx De La Boa Svnvn;

Medicine Praéiicx Profefll Celebcrr.

Przeceptox-is honorandi

Publica eruditorum examini Anna 1 66 4.. 1 7. Decemfirit,

Propofita.

(c)

Half-title page of Fulton copy ‘of the same. (No. 2) 1292 HUBERT R. CATCHPOLE

et experientiss. Francisci De Le Boe Sylvii, Medicinae Practicae Profess. Celeberr. Praeceptoris honorandi Publico eruditorum examini Anno 1664. 17. Decembris, Proposita.

Note: A new title-page has been provided and a half-title added bearing on the verso an ode to de Graef. Text and plates are identical with No. 1. The titles and ha1f—title of N o. 1 and 2 have been given in their entirety for the sake of clarity in differentiating between them. (See fig. 6b and c).

Copies: Fulton, Reynolds (Wi1lughby copy, with ms. notes).

II. TRAITTE DE LA NATURE DU SUC PANCREATIQUE

3. Traitté de la nature et de l’usage du suc pancreatique, ou plusieurs

maladies sont expliquées, principalement les fiévres intermitctentes. Paris, Olivier de Varemies, 1666. 12°: (20) (2) 156 (6) pp., 3 folding pl.

I Note: This is not a French translation of the 1664 Latin dissertation. Both text

and figures have been revised and the section on intermittent fevers has been added. Copies: Fulton; DSG; Bibl. neerl. med.; Bibl. Nat.; Reynolds; Waller.

Translations : Latin

4. Tractatus anatomico—medicus de succi pancreatici natura et usu.

Leyden,Hack, 1671. 8°: (20), 216, (14) pp., 3 pl.

Note: This was reviewed in Philos. Trans., 1671, 6: 3066-3067. It is somewhat revised from the French edition of 1666, but has the same plates. The discourse on intermittent fever is now not a separate section, but constitutes Chapter XI (pp. 164-208). It was reprinted in Leclerc and Manget, Bibliotheca anatomica, 1699, vol.

II, pp.d204-21’,1. Eloy. mentions an edition of 1674, which has not, however, been ocate .

Copies: DSL} (Bound with De viromm organis) ; Fulton (lacking frontispiece) ; PPCP (Bound with De virorum organis) ; Bibl. Nat.; Bibl. med. neerl.; Hunt.; Brit. Mus. (957.m.3); MdBJ—W (2); ICJ; Waller (2); van Wagenen (lacking frontispiece) ; Cushing (2, one bound with De virorum organis).

English

5. De succo pancreatico: or, a physical and anatomical treatise of the nature and office of the pancreatick juice; shewing itsgen— eration in the body, what diseases arise by its vitiation; from whence in particular, by plain and familiar examples, is accurately demonstrated the causes and cures of agues, or intermitting feavers, hitherto so difficult and uncertain: with sundry

other things worthy of note. Translated by Christopher Pack. London, N. Brook, 1676. 8°: (24) 151 [1], 16 pp.

Note: An English translation of the 1671 Latin edition. Pack was a chemist, and styled himself professor of chemical medicine. He practiced (as a quack) in


London under the patronage of Boyle and others and wrote and translated works to promote the sale of his specific.

Copies: DSG; PPCP; Bibl. med. neerl.; Hunt.; MBM; Fulton (photostat of‘ Bodleian copy).

III. 'EPISTOLA AD SYLVIUM

6. Epistola de nonnullis circa partes genitales novis inventis. Ad.

Franciscum de le Boe Sylvium. Leyden, 1668. y N ate: This is mentioned by Eloy; cited, but not fully reviewed in Philos. Trans, 1668, 4: 663. It has been reprinted in Leclerc and Manget, Bibliotheca anatomica,

1699, vol. I, pp. 552-553 (also in the 1685 edition). It is found on the preliminary" pages of De virorum organis (No. 7).

IV. DE VIRORUM ORGANIS, DE CLYSTERIBUS ET DE USU SIPHONIS

7. De virorum organis generationi inservientibus, de clysteribus et

de usu siphonis in anatomia. Leyden and Rotterdam, Hack, 1668. 8°: (32) 234 (14) pp., 11 pl.

N ate: Two distinct variants of this work have been identified; an original edition; and an apparently later reprint bearing the same title-page and date. This reprint may have been made in 1671 or 1672 to coincide with the publication of Tractatus de sncco pancreatico or De mnlierum organis with one or both of which it is frequently bound. The text was reset, but followed the original quite closely and. carried the same pagination.

(a) The original has, on the first page of text, a narrow scroll with an animal motif and the, general heading “ Virorum organis generationi inservientibus ” in:

large italic type (fig. 7a). This same type is used on p. 217 _for the heading “ Usu. siphonis in anatomia.”

(b) The reprint has, on the first page of text, a wide scroll without the animal. motif, and both the headings mentioned in (a) are in a smaller sized italic type. The first three lines of text in De virorum organis divide differently than in the original (fig. 7b). A further difference is a general tendency to shorten the catchwords: thus, “extra” to “ex” (p. 5); “ Testes ” to “Te-” (p. 13); “Tunicae ” to “ Tu- ” (p. 19), and so throughout.

The collections PPCP, MdBJ-W and Cushing have copies of both variants.. Reprinted in Leclerc and Manget, Bibliotheca anatomica, 1699, vol. I, pp. 555-582 Other copies: Fulton; DSG; Brit. Mus. (7641.a.20); Bibl. med. neerl. (p. 58);: Hunt. (p. 158); NNNAM (variant (b)).

Translation: French (partial)

8. L’instrument de Moliére. Traduction du traité de clysteribus.. Paris, Damascéne Morgans et Charles Fatout, 1878. 8° : (2), 125 [2] pp.

Note: This translation contains on pp. 9-40 a biographical note on de Graaf and. the portrait engraved by Edelink has been faithfully reproduced by Durand of Paris.

Copies: Fulton; DSG; Osler (2792); Bibl. med. neerl.; Brit. Mus. (7620.ss.6) ;. MdBJ-W, MBM, etc.


REGNERI on GRAAF,

MEDICI DELPHENSIS:

iTRAC TATUS

DE

Virorum Orgamls Qeuerationir infleriwientilam.


Uicumque humanicorporis \ 1;‘ priinordia animo attentio : riperpendet,hominemne= ‘3 cefl'ario morri obnoxium; efl‘e luce meridiana clarius confpicie__t:' nam przterquam quod ear ta_m varns atque rcpugnantibus prmcipus extruétum fit corpus , ej us eriam excrementa continua pugna inter ie _ef’FerveFcunt: quorum unum , vino in .rc_bus naturalibus commiffo , prxdomrnium capiens , aliud fuperat, ac ‘hominem graviflimis atquG.1flC2f8b111bU$ daniIII

(a)

first page of text of first edition of De virorum organis (No. 7a)


MED1c1’D1~:LI>HENs1s,

TRACTATUS

DE

V iramm Orgzmir Generdtioni infervientibur.



-_ Uicumque humani corpo% 3- ris primordia animo atten tioriperpendet, hominem ~ ‘ ‘ neceflario mortiobnoxiutn e{Te‘luce meridiana clarius confpiciet:

nam preeterquam quod ex tam variis atque repugnantibus principiis extru- ,

étum fit corpus,ejus etxam excrementa continua pugna inter fe efl"ervefcunt: quorum unum, vitio in rebus naturalibus commifl'o,praedominiurn capiens, aliud fuperat, ac hominem graviflimis atque incurabilibus darn A ms’

(b)

first page of text of reprint (1670 or 1672) of De virorum organis (No. 7b)

fig. 7.


V. EPISTOLA AD SCHACHT

9. Epistola ad . . . Lucam Schacht de partibus genitalibus mulierum.

pp. 209-216 in: Tractatns de natnra succi pancreatici, Leyden, 1671. (No. 4).

VI. DE MULIERUM ORGANIS

10. De mulierum organis generationi inservientibus. 12°. front. Leyden, 1672.

Note: The only record that has been located of this edition whose title apparently lacks the designation “ tractatus novus ” that appears in No. 11.

Copy: Bibl. med. neerl. (see p. 93).

11. De mulierum organis generationi inservientibus tractatus novus: demonstrans tam homines et animalia caetera omnia, quae vivipara dicuntur, haud minus quam ovipara ab ovo originem ducere. Leyden, Hack, 1672. 8°: (24), 334, (14) pp., engr. port., 27 pl.

N ote: This was reviewed in Philos. Trans., 1672, 7: 4052-4054, and reprinted in

Leclerc and Manget, Bibliotheca anatomica, 1699, vol. I, pp. 538-637. DSG lists

their two copies as 12°, but the collation would seem to make the 8° designation

more likely. There has been no opportunity to have a comparison made of this and No. 10.

Copies: Fulton; DSG; PPCP; Bibl. med. neerl.; Brit. Mus. (7641.2.21) ;.Hunt.; MdBJ-W (4); ICJ ; Waller; MBM; van Wagenen (lacking port., pp. 331-334, pl. 25, 26, 27) ; Cushing (3, one bound with De virorum organis).

Translation: English (partial)

12. On the female testes, or ovaria. Translated from the original edition of 1688 [sic], by R. Knox for the British record of obstetric medicine and surgery. Manchester, I nwin, 1848. 8° : 8 pp.

Copies: NNNAM; Fulton (photostat of NNNAM copy); Libr. Phys. Surg.; DSG.

VII. PARTIUM GENITALIUM DEFENSIO

13. Partium genitalium defensio. Societati Regiae Londini ad Scientiam naturalem promovendam institutae, dicata. Leyden, Hack,

1673, 8°: (8), 83 pp.

N ote: Reprinted in Leclerc and Manget, Bibliotheca anatomica, 1699, v. I, 662-673.

Copies: PPCP; DSG; Bibl. med. neerl.; Hunt.; Bibl. Nat.; MdBJ-W (4); Waller, Cushing (2, one bound with Tractatns de sncco pancreatico and one with De virornm organis).


VIII. EPISTOLA AI) PLEMPIUM

14. [Epistola] Vopisco Fortunato Plempio . . . pp. 76-83 in: Partium genitalium defensio (No. 13).

Translation: French

15. Lettre a Plempius . . . pp. 115-125 in: L’instrnment de M olie‘re (No. 8).

IX. OPERA OMNIA

16. Opera omnia. Leyden, Hack, 1677. 8°: (32), 717 [3] pp., 41 pl.

Contents: De virorum organis (pp. 1-140, 9 pl.); Epistola ad Schacht de partibus genitalibus mulierum (pp. 141-146); De mulierum organis (pp. 147-427, 27 pl.); Partium genitalium defensio (pp. 429-489); Tractatus anatomico-medicus de succi pancreatici natura et usu (pp. 491-666, 3 pl.) ; Tractatus de clysteribus (pp. 667-702, 1 pl.) ; Tractatulus de usu siphonis in anatomia (pp. 703-719, 1 p1.).

Copies: Fulton; DSG; PPCP; Bibl. med. neerl.; Brit. Mus. (1174.3.4) ; Bodleian; MdBJ-W; MBM.

17. Opera omnia. Lyon, .7. A. Hugnetan et Soc., 1678. 8° : xxiv, 390 pp., 41 pl. ‘

Contents: Tractatus de virorum organis (pp. [i-xxiv], 1-70, 9 pl.) ; Epistola ad Schacht (pp. [71] misnumbered 67-83) ; De mulierum organis (pp. 84234, 27 pl.) ; Partium genitalium defensio (pp. 235-261 [266]) ; Tractatus anatomico de succi pancreatici natura et usu (pp. 267-358, 3 pl.) ; Tractatus de clysteribus (pp. 359-374, 1 pl.) ; Tractatulus de usu syphonis in anatomia (pp. 375-389, 1 pl.) ; [pp. 264, 265 are misnumbered ‘ 260,’ ‘ 261.’].

Copies: DSG; PPCP; Bibl. med. neerl.; Bibl. Nat.; MdBJ-W (3); Waller; MBM; van Wagenen (2).

18. Opera omnia. Novae huic editioni praefixa est brevis narratio de auctoris vita. Amsterdam, Wetstens, 1705. 8°: (26), 537

[1] pp., 41 pl Contents: Tractatus de virorum organis (pp. 1-107, 9 pl.); Epistola ad Schacht (pp. 108-112) ; De mulierum organis (pp. 113-326, 27 pl.) ; Partium genitalium defensio (pp. 327-372); Tractatus anatomico-medicus de succi

pancreatici natura et usu (pp. 373-500, 3 pl.); Tractatus de clysteribus accedit Tractatulus de usu siphonis in anatomia (pp. 501-537).

Copies: Fulton; DSG; PPCP; Brit. Mus. (7641.aa.2); Bibl. Nat.; Bibl. med. neerl.; Hunt.; MdB]-W; ICJ. '


Translations : F rench

19. Histoire anatomique des parties genitales de l’homme et de la femme qui servent a la generation avec un traité du suc pancreatique, des clisteres et de l’usage du syphon composée en Latin par Monsieur Graaf, Medécin & célébre Anatomiste de

la ville de Delft, en Hollande. Et traduit en Francois par Monsieur N. P. D. M. Basel, Emanuel Jean George Konig,

1699. 8°: (16) 104 pp., 9 pl.; (8) 245 [3] pp., 27 pl., 142 [2]

pp., 5 pl. (fig. 8).

Contents: Traité des parties de l’homme (pp. 1-104, 9 pl.) ; Traité des parties des femmes ([8] pp. 1-188, 27 pl.) ; La defense des parties genitales (pp. 189-245) ; Traité du suc pancreatique (pp. 1-110, 3 pl.) ; Traité des clisteres

(pp. 111-132, 1 pl.) ; Petit traité de l’usage du siphon (pp. 133-142, 1 pl.).

Note: The date as given on the title-page, M.DC.LXCIX, is obviously a typographical error. Bibl. med. neerl. reads it as 1669; a note in the Catchpole copy changes the last “ C” to “ X ” to give 1679. But it would seem more reasonable to delete the “ L ” to give 1699. Bibl. Nat. and Brunet give this date and the fact that the Warsaw edition of 1701 (No. 20) is the remainder of this printing would render the later date more probable. The author of this translation, Monsieur

-N. P. D. M. has succeeded in remaining anonymous.

Copies: Catchpole; PPCP; Bibl. Nat. (Ta".7) ; Bibl. med. neerl.; Waller.

20. N ouvelles découvertes sur les parties de l’homme et de la femme qui servent a la generation: avec la deffense des parties genitales, contre les sentiments de quelques anatomistes. Un traité

du pucelage, du pancreas, de l’usage du syphon, & des clysteres. Warsaw, Federic Clonski, 1701. 8° : (16) 104 pp., 9 pl.; (8) 268 pp., 27 pl.; 142 pp., 5 pl.; (2) 32 pp.

Contents: Traité des parties de l’homme (pp. 1-104, 9 pl.) ; Traité des parties des femmes ([8] pp. 1-188, 27 pl.) ; La defense des parties genitales (pp. 189-245); Traité du pucelage (pp. 247(sic)-268); Traité du suc pancreatique (pp. 1-110, 3 pl.); Traité des clisteres (pp. 111-132, 1 pl.); Traité de l’usage du siphon (pp. 133-142, 1 pl.) ; Table des matiéres (pp. 1-32).

Note: For part of the following description I am indebted to Dr. W. B. McDaniel, II, Librarian, College of Physicians, Philadelphia, Pennsylvania: A note by Stockton Hough in the PPCP copy states this to be the remainder of the Basel edition of 1699 (No. 19). A “ Traité dn pucelage ” of unknown authorship has been added, following, and ostensibly continuing the pagination of Traité des parties des femmes and La defense des parties genitales (i. e., after p. 245). A new “ Table des matiéres ” appears at the end of the volume. The “title-page omits mention both of de Graaf and his unidentified translator, Monsieur N..P. D. M.

As frontispiece appears an anonymous portrait——certainly not of de Graaf, and scarcely that of the translator. It does bear some resemblance, however, to the well-known anatomist, P. Dionis, but any conclusion that the latter had anything to do with the publication of this work or with the inserted “ Traité du pucelage ” would be speculative. Brunet (vol. 2, 1786) carries the following note: “ C’est la

réimpression de l’ouvrage qui avait déja paru sous le titre d’Histoire anatomique, etc. Basel, 1699.”


HISTOIRE

ANATOMIQUE

D E s PARTIES GENITALES,

E L’HO z‘};u’o/W3)’ E T 1 0% o DE LA F MME.

QUI SERVENT A LA GENERATION:

AVEC UN TRAITE’ DU SUC

PANCREATIQUILDESCLISTERES ET DE IJUSAGE DU SYPHON.

COMPOSEE’ EN LATIN PAR MONSIEUR Graaf, Mcdécin, & célébrc Anatomiflc dc la Ville dc Delft, cn Hollandc.

1;‘: traduit en Fmngoplc par Monficur N. P. D. M. Enrichic dc quarantc unc Planchcs cn taillc doucc.

‘Q, ..'/’/l/ 5&7 “f,:/r’L 2» A B A L E,

Chcz EMANM-:L]1v.A1~t Gnoncz Kdnxc, M. DC. LXCIX.

15.! Fe vcnd 5 Lyon chez H 1 L A nu: BARXTEL, ma Mcrcicrc it la Conllancc.

fig. 8. Title-page of French translation of Opera omnia, 1699 (No. 19).


Dutch

21. Alle de wercken, so in de ontleed-kunde als andere deelen der medicyne. Amsterdam, Abraham Abrahamse, 1686. 8° : (32) 671 [1] pp.

Contents: Brief aan Silvius [sic] ([*8a-**3a]); Antwoordt van Sylvius ([**3b-**5a]); Voor-reeden ([**5b—8b]); Naauw—keurig onder-soek van de voort-teelende ledematen der mannen (pp. 1-144) ; Een nieuw ontwerp

van de ledematen der vrouwen (pp. 145-400); Verdeediging der voortteelende ledematen (pp. 401-461) ; Ontleet-genees-konstige beschryvinge van d’eygenschap des al-vleesigen saps (pp. 463-623) ; Verhandeling der clysteren

(pp. 625-651) ; Brief aan Plempius (pp. 652-656) ; Korte beschryving van’t gebruyk der spuyt (pp. 657-671).

Copies: Fulton; PPCP; Bibl. med. neer1.§ Hunt.; Brit. Mus. (7421.aa.5).

X. CONTRIBUTIONS AND COMMUNICATIONS TO JOURNALS

22. Arteriae carotides induratae. Miscellanea cnriosa medico physical

Acad. natnrae cnriosornm, sive E/Jhemeridinm medlco-physzl carnm, 1670, 1: 285-286.

23. Monstrosus uterus. M iscellanea cnriosa medlco physica Acad. natnrae cnriosornm, sive Ephemerzdum medzco-physzcarnm,

1670, 1 : 286-288.

24. A specimen of some observations made by a microscope, contrived by M. Leeuwenhoeck in Holland, lately communicated

by Dr. Regnerus de Graaf. Philos. Trans., 1673, 8: 60376038.

XI. DOUBTFUL ATTRIBUTION

25. Geschicht historial rym, of Rumchronyk van der Heer Klaas

Kolyn beginnende met den simberschem vloed en eyndigende met de dood van Graaf Dirk . . . in’t jaar 1156 voorgevalken,

zynde voordsnog met de noodige zoo taal als historikundige aantekeningen opgehelderd door Mr. Gerard van Loon — — -’s. Gravenhaage, P. de Hondt, 1745. fol. : xii, 477 pp.

The catalogue of the Bibliothéque Nationale asserts this to be a “Chronique

rimé de Holland depuis 1’invasion des cimbres jusqu’en l156” and adds “Le veritable auteur de l’ouvrage est Regnerus de Graaf.”

C opy: Bibl. Nat. (2, “ un autre ex. sur gr. papier ”).

XII. Biography And Criticism

26. COLE, F. J. Early theories of sexual generation. Oxford, 1930. 8° : x, 230 pp.


DIoNIs, P. L’anatomie de l’homme suivant la circulation du sang et les derniéres decouvertes. [Paris, Laurent d’Honry],

1704. 8°: 15 11., 710 pp., 1911.

DOBELL, C. Antony van Leeuwenhoek and his “ Little animals.” . . . Collected, translated and edited from his printed works, unpublished manuscripts, and contemporary records. . . . London; John Bale, Sons and Danielsson, Ltd., 1932. 8°: viii, 435 pp.

ELoY, N. F. S. Dictionnaire historique de la médecine ancienne et moderne. Mons, H. H oyois, 1778. 4 vol.

F RIEDENWALD, J., and MoRRIsoN, S. The history of the enema with some notes in related procedures. Bull. Hist. M ed., 1940, 8: 68-114.

FULToN, J. F. Selected readings in the history of physiology. Springfield, Ill., Charles C Thomas, 1930. 8°: xx, 317 pp.

HORNE, J. VAN. Suarum circa partes genitales in utroque sexu observationum prodromus. Leyden, 1668. 12°.

LEONICENUS, J. See PECI-ILIN, J. N. MoLII3:RE, J. B. P. Le malade imaginaire. S trasbonrg, 1674.

PECHLIN, J. N. Metamorphosis Aesculapii et Appollonis pancreatici. Leyden, 1673.

PORTAL, A. Histoire de l’anatomie et de la chirurgie. Paris, Fr. Didot le jenne, 1770-73. 6 vol.

REY, A. De Sylvius a Régnier de Graaf. Quelques considérations sur les idees médicales au xxvii° siécle. These. Bor R deanx, Imprimerie de L’/1cade’mie, 1930. 8° :86 pp. A

SINGER, C. Studies in history and method of science, 1921, 2: 285-343.

STENSEN, NILs. Elementorum myologiae specimen: seu musculi descriptio geometrica. Florence, Typ. sub signo S tellae, 1667. 8°: 3 ll., 123 pp., 7 pl.

STIRLING, W. Some apostles of physiology. London, Waterlow and Sons, 1902.

SWAMMERDAM, J. Miraculum naturae, sive uteri muliebris fabrica. Leyden, 1672. 4°: 4ll., 57 [1] pp.

VEDRANI, ALBERTO. Regner de Graaf. Ill. med. ital., 1920, 2: 138-141.



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