Graaf, Regnier De

(b. Schoonhoven, Netherlands, 30 July 1641; d, Delft, Netherlands, 21 August 1673)

medicine, anatomy, physiology.

De Graaf began his medical studies in 1660 at Utrecht and continued them at Leiden, where he was a student of Franciscus Sylvius and Johannes van Horne. One of his fellow students was Jan Swammerdam; their friendship was later transformed into violent hostility as a result of priority disputes. As early as 1664 de Graaf published a work on the pancreatic juice; it was immediately translated into Frence and reprinted many times. After a period in France he received an M.D. degree at Angers in 1665. He established himself as a well-known practicing physician in Delft and privately did scientific research. In spite of his international reputation de Graaf held no university posts, presumably as a result of his being a Roman Catholic. According to a tradition reported by Antoine Portal, he was proposed as successor to Sylvius, but he refused the offer. During this period the Netherlands was involved in successive wars with England and France, a circumstance which did not prevent a remarkable artistic, philosophic, and scientific flowering. Living in Delft at the same time were Anton van Leeuwenhoek and the painter Vermeer. De Graaf was friendly with Leeuwenhoek, whom he introduced to the Royal Society of London in 1673 by a letter which is still preserved.

De Graaf is rightly considered one of the creators of experimental physiology. His reputation was great in his own lifetime, as is evident from the many editions and translations of his works which followed each other in rapid succession. In the eighteenth century Hermann Boerhaave praised him, and Portal devoted twenty pages to him in his Histoire de l’anatomie et de la chirurgie. In the nineteenth century Claude Bernard held him in very high esteem and dedicated his meditations on the role of the experimental physiologist to him.

De Graaf published works on very diverse subjects; he also devised the method of the pancreatic fistula. He is known, though, through the term “Graafian follicle,” which commemorates his crucial role in the accurate and concrete description of the anatomy and physiology of the female mammalian reproductive organs. The problem of reproduction was vigorously debated around 1665. Many famous writers of the period devoted their works and their speculations to the problems of generation and claimed priority in bitter disputes. Only the name of de Graaf remains. In 1668 he had published a treatise on the male reproductive organs which was immediately reprinted several times; but its contents, showing little originality, are all but forgotten. On the other hand, his treatise on the female reproductive organs constitutes an important step in the history of biology.

For the female mammalian gonad de Graaf adopted the name “ovary,” a term proposed at the time by such authors as van Horne and Swammerdam. During this period there appeared the completely new technique of injecting vessels with colored substances, an invention claimed by many, particularly by Swammerdam, who reproached de Graaf with having stolen it from him. The quarrel, often conducted with great bitterness, was sent in letters to the Royal Society for arbitration. According to a story spread by Leeuwenhoek twenty years later, de Graaf died from the exhaustion brought on by the polemic; but it is much more likely that he died of an epidemic illness.

It is easier to grasp the originality of de Graaf’s discoveries from his illustrations than from his text. He examined and dissected the ovaries of numerous mammals, including the human, and he succeeded in isolating the ovarian vesicles with their envelopes. In the cow he described the ovary before and after mating and ascertained that its structure changed. He was thus the first to discover the morphological changes of the female gonad which accompany its physiological functions. De Graaf established that the vesicles disappeared to make room for a “glandulous substance projecting from the female testicle.” Hence he was the first to recognize the glandular nature of the corpus luteum, a fundamental discovery that was not definitely established until around 1900 and that played an essential role in the development of modern sexual endocrinology. It is beyond doubt that de Graaf correctly depicted the stigma of the corpus luteum, which indicates rupture of the ovarian follicles. His only error was not recognizing the rupture of the follicle. Instead, he supposed that the follicle in its entirety constituted the egg expelled into the Fallopian tube.

The mammalian egg was not discovered until 1827, by Karl Ernst von Baer. The phenomenon of ovulation or follicular rupture was clarified in the course of extended research and debate throughout the nineteenth century but was not definitively established until the first years of the twentieth century. It is remarkable that de Graaf followed the progress of pregnancy in the rabbit from mating until birth. He left several plates illustrating it and was fully aware that the egg traveling in the tube was smaller than the ovarian follicle, but he was unable to explain this, not having observed the follicular rupture. It is very instructive to compare de Graaf’s book on the female reproductive organs with the writings of his contemporaries and competitors. One can then see the fundamental differences between the precise details given by de Graaf and those of his colleagues, which are frequently inexact and allow free rein to an often unbridled imagination.

De Graaf’s iconography deserves special mention. His likeness was engraved in 1666 by Gérard Edelinck, one of the most celebrated portraitists of the age, and is the frontispiece in a number of editions. A portrait of 1672 has likewise become well known. There is also a drawing of great artistic merit, attributed to Verkolje, which probably represents de Graaf in his laboratory, in the act of dissecting a cadaver. As a second frontispiece to his books there are some symbolic engravings of great iconographic interest. The one in the work on the pancreatic juice (1671) long held the attention of Claude Bernard, who considered it a symbol of experimental physiology in the service of medicine. The plates representing ovaries and internal reproductive organs have been reproduced, particularly in W. M. Bayliss’ treatise, which, around 1920, constituted a veritable summa of general physiology. In 1943 the famous American endocrinologist and historian of medicine G. W. Corner published a translation of the most important chapters concerning the ovary along with the relevant plates. The present author has published a detailed commentary on these figures and believes that even today the physiology of the ovary can be illustrated by utilizing de Graaf’s plates without modification.

BIBLIOGRAPHY

I. Original Works. Complete bibliographies of de Graaf’s writings are in the articles by Barge and Daniels. Collections of his works include Opera omnia (Lyons, 1678; Amsterdam, 1705, with a short biography). Individual writings mentioned in the text are De succi pancreatici natura et usu exercitatio anatomico medica (Leiden, 1664); De virorum organis generationi inservientibus, de clysteris et de usu siphonis in anatomia (Leiden-Rotterdam, 1668); Tractatus anatomico-medicus de succi pancreatici natura et usu (Leiden, 1671); and De mulierum organis generationi inservientibus tractatus novus... (Leiden, 1672).

II. Secondary Literature. On de Graaf or his work, see J. A. J. Barge, “Reinier de Graaf, 1641–1941,” in Mededeelingen der Nederlandsche Akademie van Wetenschappen, Afdeeling Letterkunde 5 , no. 5 (1942), 257–281; W. M. Bayliss, Principles of General Physiology (London, 1924), p. 882, cf. p. 253; A. M. Cetto, “Un portrait inconnu de Régnier de Graaf,” in Ciba-Symposium,5 (1958), 208–211; G. W. Corner, “on the Female Testes or Ovaries,” in Essays in Biology in Honor of H. M. Evans (Los Angeles, 1943), p. 686, cf. pp. 121–137; and The Hormones in Human Reproduction rev. ed, (Princeton, 1947).p. 281; C. E. Daniels, “De Graaf,” in Biographisches Lexikon der hervorragenden Aerzte aller Zeiten und Völker, II (Leipzig, 1885), 616; P. Delaunay, La vie médicale aux XVIe, XVIIe, XVIIIe siècles (Paris, 1935), p. 556; C. Dobell, Antony van Leeuwenhoek and His Little Animals (Amsterdam, 1932), p. 435; E. Gasking, Investigations Into Generation (Baltimore. 1967), p. 192: M. Klein, “Histoire et actualité de l’iconographie de l’ouvrage: De mulierum organis generationi inservientibus (1672) de R. de Graaf,” in Comptes rendus du 16e Congrès international d’histoire de la méecine, Mompellier, 1958, I (Brussels, 1959), 316- 320, also in Yperman (Brussels), 8 , fasc. 9 (1961), 3–7; and “Claude Bernard face au milieu scientifique de son époque,” in Philosophie et, méthodologie scientifiques de Claude Berard (Paris, 1967), p. 170, cf. pp. 97, 98; J. Lévy-Valensi, Les médecins et la médecine francaise au XVIIe siècle (Paris, 1933), p. 668; J. Needham, A History of Embryology, 2nd ed., rev. (Cambridge, 1959), p. 304; E. Nordenskjöld, Die Geschichte der Biologie (Jena, 1926), p. 648; A. Portal, Histoire de l’anatomie et de la chirurgie, III (Paris, 1770), 214–235; R. C. Punnett, “Ovists and Animalculists,” in American Naturalist,62 (1928), 481–507; A. Rey, De Sylvius á Régnier de Graaf (Bordeaux, 1930), p. 86, an M.D. diss.; J. Roger, Les sciences de la vie dans la pensée francaise de 18e siècle (Paris, 1963), p. 842; and A. Schierbeek, Jan Swammerdam 1637–1680, His Life and Works (Amsterdam, 1967), p. 202.

Marc Klein