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Harrison, Ross Granville

Harrison, Ross Granville

(b. Germantown, Pennsylvania, 13 January 1870; d. New Haven, Connecticut, 30 September 1959)

biology.

Harrison, who was to become one of the pioneers of experimental embryology, was the only son of Samuel Harrison and Catherine Barrington Diggs. Samuel Harrison was a grandson of William Harrison, who came to Philadelphia from England in 1798 under contract to the Bank of the United States to design bank notes; William’s son, Ross’s grandfather, was an engraver and cartographer. Samuel Harrison, Ross’s father, was a mechanical engineer; he spent ten years in Russia designing rolling stock for the firm of Joseph Harrison (not related) of Philadelphia, who was under contract to the czar to build the railroad from St. Petersburg to Moscow.

Ross Harrison’s education began in Germantown and was continued in Baltimore, Maryland, where his family moved during his boyhood. He entered the Johns Hopkins University in 1889; his work was sponsored by William Keith Brooks, and he received the Ph.D. degree in zoology in 1894. His doctoral dissertation was a morphological study of the development of the unpaired and paired fins of bony fishes.

During the academic year 1892–1893 Harrison studied at the university in Bonn, beginning his work on the fins of fishes under Moritz Nussbaum. He made other trips to Bonn in 1895–1896, 1898, and 1899. He received the M.D. degree in the latter year but never practiced medicine. Harrison had an excellent ear and mind for languages and spoke German as fluently as English; during the early years of his career he wrote a number of his major publications in German.

Harrison married Ida Lange at Altona, Germany, in 1896. They had five children: Richard, a cartographer; Elizabeth, a pediatrician; Dorothea, a landscape architect; Eleanor, who married Rufus Putney, Jr. (Putney later became a professor of English); and Ross, a successful businessman.

Harrison’s first teaching position was at Bryn Mawr College, where during the academic year 1894–1895 he was lecturer on morphology as a substitute for Thomas Hunt Morgan, who was on a year’s leave of absence. After a year’s study at Bonn (1895–1896) he returned to the Johns Hopkins University in 1896 as instructor in anatomy in the medical school. He was promoted to associate in 1897 and to associate professor in 1899. In 1907 Harrison became the first Bronson professor of comparative anatomy at Yale, where he remained for the rest of his life. He was promoted to Sterling professor of biology in 1927 and became professor emeritus in 1938. From 1907 to 1938 he was head of the department of zoology.

Harrison’s most important single scientific contribution was the innovation of the technique of tissue culture. It was he who first adapted the hanging drop method to the study of embryonic tissues in order to demonstrate the outgrowth of the developing nerve fiber; the first reports of these experiments, carried out from 1905 to 1907 at the Johns Hopkins Medical School, were published in 1907. At the time of these experiments there were three theories as to the mode of origin of the developing nerve fiber: (1) the cell-chain theory, which held that the nerve fiber is formed in situ by the cells that form the nerve sheath; (2) the plasmoderm theory, which claimed, that the fiber is formed in situ by preformed protoplasmic bridges, under the influence of functional activity; and (3) the outgrowth theory, which maintained that the fiber is the product of the nerve cell itself. The outgrowth theory was then the most generally accepted, according to Harrison; but the main supporting evidence for it at that time was descriptive.

Harrison saw that the hypothesis could be confirmed experimentally if the nerve cell could be grown outside of the body, in the absence of sheath cells and protoplasmic bridges. Accordingly he removed portions of the nerve tube from frog embryos at stages before the fibers had formed, then studied their cellular development in hanging drops of frog lymph removed from the lymph heart and allowed to clot. In this way he could directly observe with a microscope the formation of the fiber by the nerve cell, and his observations firmly established the validity of the outgrowth theory. A contribution of vital significance not only to neurology but also to theoretical embryology, this was a final step in establishing that the cell is the primary developmental unit of the multicellular organism. “The reference of developmental processes to the cell,” wrote Harrison in 1937, “was the most important step ever taken in embryology” (“Embryology and Its Relations,” p. 372). His own confirmation of the nerve outgrowth theory played an important part in the analysis of developmental phenomena at the cellular level.

A number of investigators, including Julius Arnold, Gustav Born, Leo Loeb, and Gottlieb Haberlandt, had been attempting for a decade or more before the publication of Harrison’s results to grow tissues or cells in isolation in vitro or in vivo. Their attempts had not been as successful as Harrison’s, and it was unquestionably Harrison’s experiments involving the observation of living tissues in hanging drop preparations that gave impetus to the further use of tissue and cell culture and that established it as a technique adaptable to the solution of a wide variety of problems in biology and medicine. Yet its importance in oncology, virology, genetics, and other related fields is still equaled by its importance in embryology itself. Sixty years after its first introduction into embryology laboratories, observation of the activities of cells in culture is one of the most popular pursuits of developmental biologists.

Another of Harrison’s early contributions that was of great importance to the development of experimental embryology was his adoption of Born’s method of embryonic grafting. In 1896 Born described the results of experiments in which he had successfully joined separated living parts of amphibian larvae. Harrison began similar experiments in 1897 in order to study the growth and regeneration of the tail of the frog larva. Born had shown that it was possible to perform fusion experiments using parts of embryos from different taxonomic families; in 1903 Harrison reported the results of experiments in which he grafted the head of the frog larva of one species to the body of a larva of a species of a different color, at the stage before the lateral line sense organ was complete. By taking advantage of the different natural pigments in the two species, he was able to observe that the sense organ developed by means of the posterior migration of the rudiment from the head into the trunk and tail. By solving a particular problem in which Harrison was interested, these experiments also served to demonstrate brilliantly the possibilities of interspecific (heteroplastic) grafting as an embryological technique. Hans Spemann, who received the 1935 Nobel Prize for physiology or medicine for his contributions to experimental embryology, acknowledged in 1936 the importance of Harrison’s method of heteroplastic grafting for the experiments that led to his own theories of embryonic induction. Questions of great theoretical import to embryology had been raised by Wilhelm Roux and Hans Driesch, but the methods used by these pioneer investigators were extremely crude in comparison with Harrison’s. Harrison and his students in America shared with Spemann and his students in Germany the honors for both the intellectual and the technical advances that brought the science of experimental embryology to full maturity.

During his lifetime Harrison and his students studied experimentally, principally in amphibian embryos, aspects of the development of a number of structures. Particularly noteworthy were studies on the relationships between the nervous system and the musculature. Harrison showed in 1904 that the amphibian limb could develop in the absence of the nerve supply. By means of heteroplastic grafting, he also attacked some hitherto highly elusive problems concerned with the control of growth in embryos, attaining results that could be expressed with great quantitative precision at a time when quantitative study of embryological phenomena was barely beginning. Transplanting the limb bud of a fast-growing tiger salamander larva to the flank of a slower-growing spotted salamander (1924), he showed that the limb maintained its own rate of growth; thus he could obtain a larva or adult bearing a limb far greater in size than that typical of the species. Later (1929), by performing heteroplastic transplants of the optic rudiment between the spotted and the tiger salamander, at a stage before the development of the optic nerve, he demonstrated that the size of the midbrain roof, where the optic nerve terminates in amphibians, is regulated by the size of the retina, specifically, by the number of fibers in the optic nerve, which grows into the brain from the retina. He also performed experiments (1929) on the correlative development of parts of the eye itself; by heteroplastic grafting he showed that reciprocal interactions between rudiments of the optic cup and the lens are involved in the regulation of the size of both of these components of the eye.

Another very original and significant group of experiments demonstrated the varied nature of the contributions to the embryo of the neural crest. Harrison, by a particularly ingenious set of heteroplastic transplantation experiments, proved that this structure, commonly thought to have been ectodermal in origin and significance, forms the cartilage of the gill skeleton in amphibians. One of his students, Graham DuShane, working under Harrison’s guidance, demonstrated experimentally that the pigment-bearing cells of the amphibian are formed by the neural crest and not from the mesoderm, as had previously been generally believed. These results were far-reaching in their implications with respect to the old theories of germ-layer specificity, which had to be abandoned as a result of these and other data from experimental embryology.

But even more significant and original than these experiments were a series of studies on the development of the amphibian limb and its asymmetry. The vertebrate organism is bilaterally symmetrical, a number of the organs on the left side of the body, including the limbs, being mirror images of those on the right. The limb of the spotted salamander forms from a simple disk of mesoderm covered by ectoderm, and Harrison investigated the manner in which the disk becomes a right or a left limb. Harrison first demonstrated (1918) that the limb-forming potentialities of the disk are located in its mesoderm and then that the disk is, in the terminology of his day (adopted from Hans Driesch), a harmonious equipotential system. That is, any part of the rudiment, provided that it contains mesoderm, can form any part of the limb; a half-disk can form a whole limb. Next (1921) he devised an extensive series of experiments in which he grafted the disk in either normal or inverted position onto the same side of the body from which the disk had been taken, or onto the opposite side of the body; the disk can form a normal limb under any of these conditions. From the fact that a noninverted disk grafted on the opposite side of the body from which it was taken develops a limb of reversed symmetry (that is, a left limb develops on the right side, or vice versa), white an inverted disk grafted onto the opposite side develops a limb with its symmetry conforming to the side onto which it is implanted (that is, a left limb develops on the left side or a right limb on the right side), Harrison concluded that at the tail bud stage of the larvae, on which the experiments were performed, the anteroposterior axis of the limb is already determined, but not the mediolateral (transverse) or the dorsoventral. It was later shown by Harrison and his students that each of the three axes is determined in turn; for the limb, no stage has been found at which the anteroposterior axis is not determined.

Harrison later performed comparable experiments with the rudiment of the inner ear of the spotted salamander. Only preliminary reports of these experiments were published (1936, 1945), but their results demonstrated that during the development of this organ there is a stage at which none of the three axes is determined; each of the three is determined in its turn. Harrison believed that the progressive determination of the three axes must rest on some change in the orientation of the ultrastructural particles constituting the organ rudiment, and in collaboration with W. T. Astbury and K. M. Rudall he attempted in 1940 to look for evidence of such orientation by X-ray diffraction; the results were inconclusive because of the inapplicability of the method to the study of living and preserved tissues. The question as to the basis of the development of asymmetry thus remains where Harrison left it, but it is one of fundamental import and of considerable interest to molecular biology. When the answer to it is determined by methods not accessible to Harrison in his day, it will still be remembered that it was as a result of his transplantation experiments that the question could be shown to be amenable at all to experimental investigation. Harrison was interested in the intimate structure of protoplasm at least as early as 1897, and through nearly half a century of thought and experimentation he brought its investigation out of the realms of speculation and into the instrument rooms of modern molecular biology.

As an individual as well as a scientist Harrison was known for his dispassionate temperament and his calm judiciousness, and he held many important administrative offices besides the chairmanship of his department at Yale. He was an officer or member of advisory or administrative boards of many scientific and academic institutions and societies and of a number of government agencies. He was a trustee of the Marine Biological Laboratory at Woods Hole, Massachusetts, from 1908, and a member of the board of the Bermuda Biological Laboratory from 1925; he was a member and trustee of the Woods Hole Oceanographic Institution from 1930 to 1959, and his vision and foresight did much to advance oceanography to its present position among modern sciences. Harrison‘s most far-reaching administrative contribution was as chairman of the National Research Council during the critical years 1938–1946. He was one of the founders of the Journal of Experimental Zoology and was its managing editor from its beginning in 1903 until 1946. He received many honors, among them honorary degrees from Johns Hopkins, Yale, the universities of Chicago, Cincinnati, Michigan, and Dublin, Harvard, Columbia, Freiburg, Budapest, and Tübingen. He was elected to the National Academy of Sciences in 1913 and to the American Philosophical Society in the same year, and became a corresponding or honorary member of many foreign academies and societies, including the Royal Society and the French Academy of Sciences. He received a number of medals, among them the Archduke Rainer Medal of the Zoological-Botanical Association of Vienna in 1914, the John Scott Medal and Premium of the City of Philadelphia in 1925, the John J. Carty Medal of the National Academy of Sciences in 1947, and the Antonio Feltrinelli International Prize awarded by the Accademia Nazionale dei Lincei in 1956.

Harrison was exceptionally modest and objective; honors were to him less important than the establishment and maintenance of high standards of scientific endeavor. The greatest honor he would have wished would be to be remembered not only as the demonstrator of the outgrowth of the nerve fiber by a new and crucial experimental method but also as an investigator who by his intellectual acumen and technical imaginativeness contributed heavily to the origins and successful development of the important science of experimental embryology, which formed such an important bridge between the old morphology of the nineteenth century and the new molecular biology of the twentieth.

BIBLIOGRAPHY

I. Original Works. A complete bibliography of Harrison’s publications is included in the memoir by Nicholas (see below). His major articles include the following: “Ueber die Entwicklung der nicht knorpelig vorgebildeten Skelettheile in den Flossen der Teleostier,” in Archiv für mikroskopische Anatomie, 42 (1893), 248–278; “Die Entwicklung der unpaaren und paarigen Flossen der Teleostier,” in Archiv für mikroskopische Anatomie und Ertwicklungsgeschichte, 46 (1895), 500–578; “The Growth and Regeneration of the Tail of the Frog Larva. Studied With the Aid of Born’s Method of Grafting,” in Archiv für Entwicklungesmechanik der Organismen, 7 (1898), 430–485; “Ueber die Histogenese des peripheren Nervensystem bei Salmo salar,” in Archiv für mikroskopische Anatomie und Entwicklungsgeschichte, 57 (1901), 354–444; “Experimentelle Untersuchungen über die Entwicklung der Sinnesorgane der Seitenlinie bei den Amphibien,” ibid., 63 (1903), 35–149; “An Experimental Study of the Relation of the Nervous System to the Developing Musculature in the Embryo of the Frog,” in American Journal of Anatomy, 3 (1904), 197–220; “Experiments in Transplanting Limbs and Their Bearing Upon the Problems of the Development of Nerves,” in Journal of Experimental Zoology, 4 (1907), 239–281; “Observations on the Living Developing Nerve Fiber,” in Anatomical Record, 1 (1907), 116–118, and in Proceedings of the Society for Experimental Biology and Medicine, 4 (1907), 140–143; “Embryonic Transplantation and Development of the Nervous System,” in Anatomical Record, 2 (1908), 385–410, and in Harvey Lectures for 1907–1908 (1909), pp. 199–222; “The Development of Peripheral Nerve Fibers in Altered Surroundings,” in Archiv für Entwicklungsmechanik der Organismen, 30 , pt. 2 (1910), 15–33; “The Outgrowth of the Nerve Fiber as a Mode of Protoplasmic Movement,” in Journal of Experimental Zoology, 9 (1910), 787–846; “The Stereotropism of Embryonic Cells,” in Science, 34 (1911), 279–281; “The Cultivation of Tissues in Extraneous Media as a Method of Morphogenetic Study,” in Anatomical Record, 6 (1912), 181–193; “The Reaction of Embryonic Cells to Solid Structures,” in Journal of Experimental Zoology, 17 (1914), 521–544; “Experiments on the Development of the Fore Limb of Amblystoma, a Self-Differentiating Equipotential System,” ibid., 25 (1918), 413–461; “On Relations of Symmetry in Transplanted Limbs,” ibid, 32 (1921), 1–136; “Experiments on the Development of Gills in the Amphibian Embryo,” in Biological Bulletin. Marine Biological Laboratory, Woods Hole, Mass., 41 (1921), 156–170; “Some Unexpected Results of the Heteroplastic Transplantation of Limbs,” in Proceedings of the National Academy of Sciences of the United States of America, 10 (1924), 69–74; “Neuroblast Versus Sheath Cell in the Development of Peripheral Nerves,” in Journal of Comparative Neurolology, 37 (1924), 123–205; “The Development of the Balancer in Amblystoma, Studied by the Method of Transplantation in Relation to the Connective-Tissue Problem,” in Journal of Experimental Zoology, 41 (1925), 349–427; “The Effect of Reversing the Medio-Lateral or Transverse Axis of the Forelimb Bud in the Salamander Embryo (Amblystoma punctatum Linn.),” in Archiv für Entwicklungsmechanik der Organismen, 106 (1925), 469–502; “On the Status and Significance of Tissue Culture,” in Archiv für Zellforschung, 6 (1928), 4–27; “Correlation in the Development and Growth of the Eye Studied by Means of Heteroplastic Transplantation,” in Archiv für Enwicklungsmechanik der Organismen, 120 (1929), 1–55; “Esperimenti d’innesto sul cestello brachiale di ‘Clavelina lepadiformis’ (Müller),” in Atti dell’ Accademia nazionale dei Lincei. Rendiconti, Classe di scienze fisiche, mathematiche e naturali, 6th ser., 11 (1930), 139–146, written with Pasquale Pasquini; “Some Difficulties of the Determination Problem,” in AmericanNaturalist, 67 (1933), 306–321; “Hetroplastic Grafting in Embryology,” in Harvey Lectures for 1933–1834 (1935), pp. 116–157; “On the Origin and Development of the Nervous System Studied by the Methods of Experimental Embryology (The Croonian Lecture),” in Proceedings of the Royal Society, 118B (1935), 155–196; “Relations of Symmetry in the Developing Ear of Amblystoma punctatum,” in Proceedings of the National Academy of Sciences of the United States of America, 22 (1936), 238–247; Embryology and Its Relations,” in Science, 85 (1937), 369–374; “Die Neuralleiste,” in Anatomischer Anzeiger, supp. 85 (1938), 3–30; “An Attempt at an X-Ray Analysis of Embryonic Processes,” in Journal of Experimental Zoology, 85 (1940), 339–363, written with W. T. Astbury and K. M. Rudall; “Relations of Symmetry in the Developing Embryo,” in Transactions of the Connecticut Academy of Arts and Sciences, 36 (1945), 277–330; and “Wound Healing and Reconstitution of the Central Nervous System of the Amphibian Embryo After Removal of Parts of the Neural Plate,” in Journal of Experimental Zoology, 106 (1947), 27–84.

Harrison’s unpublished records and documents have been deposited in the archives of the Yale University Library, New Haven, Connecticut.

II. Secondary Literature. Selected biographical notices and memoirs are M. Abercrombie, “Ross Granville Harrison 1870–1959,” in Biographical Memoirs of Fellows of the Royal Society, 7 (1961), 111–126; A. M. Dalcq, “Notice biographique sur M. le Professeur R. G. Harrison,” in Bulletin de l’Académie r. de médecine de Belgique, 6th ser., 24 (1959), 768–774; P.-P. Grassé, “Notice nécrologique sur Ross Granville Harrison,” in Comptes rendus hebdomadaires des séances de l’Acàdemie des sciences, 250 (1960), 2622–2623; J. S. Nicholas, “Ross Granville Harrison,” in Anatomical Record, 137 (1960), 160–162; “Ross Granville Harrison, Experimental Embryologist,” in Science, 131 (1960), 1319; “Ross Granville Harrison 1870–1959,” in Yale Journal of Biology and Medicine, 32 (1960), 407–412; “Ross Granville Harrison 1870–1959,” in Yearbook, American Philosophical Society (1961), 114–120; and Ross Granville Harrison 1870–1959,” in Biographical Memoirs. National Academy of Sciences, 35 (1961), 132–162; J. M. Oppenheimer, “Ross Granville Harrison,” in H. Freund and A. Berg, eds., Geschichte der Mikroskopie. Leben und Werk grosser Forscher, II (Frankfurt, 1965), 117–126; and “Ross Harrison’s Contributions to Experimental Embroyology,” in Bulletin of the History of Medicine, 40 (1967), 525–543, repr. in J. M. Oppenheimer, Essays in the History of Embryology and Biology (Cambridge, Mass., 1967), pp. 92–116; and P. Pasquini, “Ross Granville Harrison,” in Acta embryologiae et morphologiae experimentalist, 3 (1960), 119–130.

Jane M. Oppenheimer

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Harrison, Ross Granville

Ross Granville Harrison, 1870–1959, American biologist and anatomist, b. Germantown, Pa., Ph.D. Johns Hopkins, 1894. He went to Yale as professor of comparative anatomy in 1907 and held various honorary positions there until his death. He is known for his work on nerve development in the embryo and on nerve regeneration as well as for his discovery of a method of tissue culture that permits study of isolated living cells in a controlled environment.

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"Harrison, Ross Granville." The Columbia Encyclopedia, 6th ed.. . Retrieved August 24, 2017 from Encyclopedia.com: http://www.encyclopedia.com/reference/encyclopedias-almanacs-transcripts-and-maps/harrison-ross-granville