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Tomado de: http://www.columbia.edu/cu/alumni/Magazine/Legacies/Morgan/ “There is no doubt that man, as an animal, inherits characteristics, good and evil, as do animals and plants”. Thomas Hunt Morgan (1866-1945) Zoologist Faculty 1904-28 Morgan's studies on inherited characteristics of the fruit fly laid the foundations of modern genetics and led to such advances as the deciphering of the human genome. His work earned him the 1933 Nobel Prize in Physiology or Medicine, making him the first native-born American to receive that honor. He also authored classic texts in genetics including Heredity and Sex (1913), The Physical Basis of Heredity (1919), Embryology and Genetics (1924), Evolution and Genetics (1925), The Theory of the Gene (1926), Experimental Embryology (1927), and The Scientific Basis of Evolution (1932). Morgan received his PhD in developmental biology from Johns Hopkins University in 1890 and taught at Bryn Mawr College before arriving at Columbia in 1904 to assume a newly established chair in experimental zoology. In 1910, he began his study of Drosophila melanogaster, the insect with which his name will always be associated. It was working with undergraduate students Calvin Bridges and Alfred Sturtevant, and in Schemerhorn Hall's "Fly Room" with graduate and postdoctoral scientists such as Hermann J. Mueller and George Beadle, that Morgan discovered the chromosomal basis for the inheritance of traits. He left Columbia in 1928 to serve as chair of the Biology Division at the California Institute of Technology THOMAS HUNT MORGAN AT COLUMBIA UNIVERSITY Genes, Chromosomes, and the Origins of Modern Biology Eric R Kandel The student of the humanities as well as the intelligent public looks at the history of human thought as a history of abstract ideas. . . . It is true that minds like those of Plato, Thomas Aquinas, Spinoza, Descartes, Hegel and Kant have exercised a strong influence upon the progress of thinking in all spheres, even upon the actual course of historical events. The scientist who looks beyond his specialized work is as fully aware of these historical facts as the humanist. But he is also aware that abstract thinking, remote from, and even antagonistic to the study of nature, leads easily into dogma, taboos and fettering of free thinking because it does not carry its own corrective, the recourse to factual evidence. The scientist, therefore, with all respect for the many facets of the human mind, is more impressed by the revolutions in thinking brought about by great factual discoveries, which by their very nature lead to generalizations which change at once the outlook of many, if not all, lines of thought. Such events are rare. In modern history three are most conspicuous: the explanation of the movements of the celestial bodies by Kepler, Copernicus and Newton; Galileo's experiments inaugurating the age of inductive science, and Darwin's establishment of the theory of evolution on the basis of an overwhelming body of facts. All of them at once evoked the wrath of the vested interests of the mind; all conquered within a generation or two all fields of intellectual endeavor and changed the basic aspects of practically every science, natural or humanistic. . . . . the rise and development of genetics to mature age is another instance of an allcomprising and all-affecting generalization based upon an overwhelming body of integrated facts, . . . [and] will rank in the history of science with such other great events as mentioned, . . . The basic tenets of genetics have already influenced decisively all parts of biology after what has been only a short span in the history of science; and further that beyond this, many other fields of science have fallen under the spell and we have every reason to believe that genetics is bound to remain in a pivotal position in the future. -Richard B. Goldschmidt, The Impact of Genetics Upon Science (1950) When future historians turn to examine the major intellectual accomplishments of the twentieth century, they will undoubtedly give a special place to the extraordinary achievements in biology, achievements that have revolutionized our understanding of life's processes and of disease. Important intimations of what was to happen in biology were already apparent in the second half of the nineteenth century. Darwin had delineated the evolution of animal species, Mendel had discovered some basic rules about inheritance, and Weissman, Roux, Driesch, de Vries, and other embryologists were beginning to decipher how an organism develops from a single cell. What was lacking at the end of the nineteenth century, however, was an overarching sense of how these bold advances were related to one another. The insight that unified these three fields- heredity, evolution, and development- and set biology on the course toward its current success came only at the beginning of the twentieth century. It derived from the discovery that the gene, localized to specific positions on the chromosome, was at once the unit of Mendelian heredity, the driving force for Darwinian evolution, and the control switch for development. This remarkable discovery can be traced directly to one person and to one institution: Thomas Hunt Morgan and Columbia University. Much as Darwin's insights into the evolution of animal species first gave coherence to nineteenth-century biology as a descriptive science, Morgan's findings about genes and their location on chromosomes helped transform biology into an experimental science. Even more important, Morgan's discoveries made it possible to address a series of questions regarding the function and structure of genes. What is their chemical nature? How do genes duplicate themselves? What goes wrong when genes mutate? How do genes provide the basis for understanding genetic disease? How do genes determine the properties of cells, the development of organisms, and the course of evolution? Answers to some of these questions came directly from Morgan and his students; while other advances were the work of scientists touched by his broader influence. In every case, the discoveries made by these pioneering researchers set the agenda for biology in the twentieth century. For example, George Beadle, who trained with Morgan and with Morgan's student Alfred Sturtevant '12C '14GSAS, joined Edward L. Tatum to examine how genes determine the properties of the cell. In addressing this problem, they discovered that genes control the synthesis of the cell's proteins, many of which are enzymes. Then Oswald T. Avery '04P&S, another graduate of Columbia, teamed with Maclyn McCarty and Colin MacLeod at the Rockefeller Institute for Medical Research to show that the transforming genetic material is made of DNA. Theodosius Dobzhansky '64HON, a postdoctoral fellow of Morgan's, related genetic mutations to evolutionary change. Hermann J. Muller '10C '11 '16GSAS, another Morgan student, discovered that Xirradiation dramatically increases the rate at which mutations occur, an advance that focused attention on the role of environmentally induced and inherited gene mutations in important diseases ranging from cancer to Huntington's disease and schizophrenia. Joshua Lederberg '44C, an academic grandchild of Morgan, discovered transduction -the ability of viruses to carry exogenous genes into a bacterial cell- the first step on the road to genetic engineering. James D. Watson and Francis Crick next showed that DNA has a double helical conformation, a chemical conformation that immediately led to an understanding of how DNA and genes are replicated. Edward B. Lewis, another academic grandchild of Morgan, used genetics to probe development and found that a special set of genes determines the organization of the body plan. Thus, biology at the beginning of the twenty-first century represents, in good part, the molecular realization of the ideas and way of thinking introduced at the beginning of the twentieth century by Thomas Hunt Morgan at Columbia University. Morgan and the Mechanisms of Mendelian Heredity Thomas Hunt Morgan was born in Kentucky in 1866 to a distinguished southern family whose members included Francis Scott Key. Morgan was trained as a developmental biologist, receiving his Ph.D. in 1890 from the Johns Hopkins University for work on the development of sea spiders, a specialized group of invertebrate animals, and in 1891 he accepted a teaching post at Bryn Mawr College. In 1904 Columbia University announced the establishment of a new chair in experimental zoology and offered it to Morgan. Arriving on campus, he came under the influence of his long-term friend and colleague, the zoology department's chairman, Edwin Wilson, one of the eminent cytologists of his time and a founder of the field of cell biology. Wilson convinced Morgan that the key to understanding development—how one cell, the egg, gives rise to the animal—is to understand heredity, since it provides the means by which the egg and the sperm carry the properties of individuals from one generation to another. Later findings proved Wilson correct, and we now know that the human genome consists of 46 chromosomes, arranged in 22 pairs of autosomes (not linked to sex), and one pair of sex chromosomes (two X chromosomes in females, one X and one Y chromosome in males). The 100,000 genes in our genome are arranged along the chromosomes in precise order, with each being uniquely identifiable by its location at a characteristic position (locus) on a specific chromosome. The two copies of a gene at corresponding loci on each pair of chromosomes are known as alleles. The modern concepts of heredity and the existence of alternative (allelic) forms of genes had been discovered in 1865 by Gregor Mendel, a teacher and monk of the Augustinian monastery in Brno, then part of the Austro-Hungarian empire. Mendel carried out breeding experiments with plants, especially garden peas, and identified hereditary traits in them. These traits, later called factors, were found by Mendel to account for such features as whether peas were wrinkled or smooth and for the differences between dominant and recessive alleles; he did not know, however, where these traits were located or what they were. Mendel's findings were published in the Proceedings of the Natural Science Society of Brno in 1866, only to be ignored until the turn of the century. His work was rediscovered in 1900, just before Morgan arrived at Columbia. In taking up his own inquiries, Morgan turned from Mendel's plants to the study of animals, but soon found that the rats and mice he was using reproduced so slowly as to be impractical for studying heredity. His search for a more suitable organism led him to Drosophila melanogaster, known as the fruit fly because it feeds on decaying fruit. Drosophila is small, about 3 mm long, and easy to raise in the laboratory -a thousand can be collected in a one-quart glass milk bottle. Moreover, it is fertile all year long and very prolific, producing a new generation every twelve days, or thirty generations per year. Not only are male and female offspring easy to distinguish, but embryonic development occurs outside the body, making it a simple matter to study the effects of mutations on development. Finally, Drosophila has only four pairs of chromosomes. Morgan began working seriously with Drosophila in 1907, with the intention of breeding many generations of flies, and perhaps producing one that looked different from the rest. In short, he hoped to find an occasional fly that had undergone a mutation, sudden change in body form, a phenomenon that had recently been discovered in plants by the Dutch biologist Hugo de Vries. But despite much effort and the breeding of successive generations, Morgan initially failed to detect a single mutation. "Two years work wasted," he lamented to one visitor to his laboratory. "I have been breeding those flies for all that time and I've got nothing out of it."(Harrison, R.G., "Embryology and Its Relations") Year of Discovery But Morgan persisted, and in April 1910 he suddenly had a breakthrough. In one of his bottles filled with Drosophila was a male fly with rather than the normal red eyes. Morgan realized the implications of this immediately; the birth of this single spontaneous mutant—this one male fly with white eyes—allowed him to begin addressing some key questions in heredity: How did this white eye color originate? What determines eye color? As the next step, Morgan bred this white-eyed (mutant) male to a red-eyed (wildtype) virgin sister and found that white-colored eyes are inherited in a special way. In the first generation of brother-sister mating, labeled F1, there were only red-eyed offsprings, suggesting that red eye color is dominant and that white eye color is recessive. To prove this idea Morgan carried out brother-sister matings with the next generation (F2) and found that the offspring followed the expected Mendelian ratio for a recessive trait: three red-eyed flies to every one white-eyed fly. With these experiments Morgan started a tradition, which continues to this day, whereby he named the gene "white" by the result of its mutation. But then came a surprise. He had expected there would be an equal number of males and females with white eyes, but it turned out that all the female flies had red eyes; only males had white eyes, and, even more, only some of them displayed the trait. Morgan realized that white eye color is not only recessive but is also linked in some way to sex. The subsequent appearance of two other spontaneous mutations (rudimentary wings and yellow body color) also linked to sex further suggested to Morgan that these three genes might be carried on the same chromosome and that this chromosome is the sex chromosome. By 1910, it was already known that chromosomes occur in pairs and that Drosophila had four pairs of chromosomes. Several decades earlier, these thread-shaped structures had been seen under a microscope to be located in the nucleus, but nobody knew their function. Morgan later was to describe them in the following terms: "The egg of every species of animal or plant carries a definite number of bodies called chromosomes. The sperm carries the same number. Consequently, when the sperm unites with the egg, the fertilized egg will contain the double number of chromosomes. For each chromosome contributed by the sperm there is a corresponding chromosome contributed by the egg, i.e., there are two chromosomes of each kind, which together constitute a pair." (Morgan, T.H. et al., The Mechanism of Mendelian Heredity) When Morgan turned to examining the fruit fly's chromosomes under the microscope, he immediately appreciated that not all four pairs of chromosomes were always identical. In particular, whereas female flies had two identical-looking X chromosomes, in the male the X chromosome was paired with a Y chromosome, which looks different and is never present in the female. Morgan deduced that a male must inherit the X chromosome from his mother and Y from his father, and he immediately spotted a correlation between these sex-linked chromosomes and the segregation of the factors determining eye color. When the mother was homozygous and had two copies of the gene for red eyes, the male offspring invariably had red eyes, even if the father had white eyes. But when the mother had white eyes, the male offspring did too, even if the father's eyes were red. In contrast, a female fly gets one X chromosome from each parent, and if one passed along an X chromosome with a gene for red eyes, the offspring had red eyes because the color is dominant over white. Only when both parents gave her an X chromosome with a gene for white eyes did she display the recessive trait. From these observations, Morgan concluded that the allele-producing eye color must lie on the X chromosome that governs sex. This provided the first correlation between a specific trait and a specific chromosome. Morgan's initial paper on fruit flies, entitled "Sex Limited Inheritance in Drosophila," was published in Science in July 1910. In this and in a subsequent paper published in Science in 1911, Morgan outlined his three major findings: (1) that genes must reside on chromosomes; (2) that each gene must reside on a particular chromosome; and (3) that the trait for eye color must reside on the sex chromosome, with the eye-color locus (or white gene) being missing on the Y chromosome and red being dominant on the X chromosome. These findings formed the heart of Morgan's most important idea: the chromosomal theory of heredity. He proposed that each chromosome contains a collection of small units called genes (a term he adopted from the Danish physiologist Wilhelm Johannsen who had lectured at Columbia in 1909), with different genes having specific locations along specific chromosomes. Once this idea formed in his mind, Morgan sensed that the experimental power of the fly would allow him to understand heredity. A focus on chromosomes and their morphology was not what Morgan had in mind when he started to work on flies. In fact, until he saw the white-eyed mutant and appreciated that its defect acted as if it were part of the X chromosome, he had been skeptical about Mendel's theory of heredity and Mendel's factors. Now that he had seen the possibility that these factors might have a physical reality as genes on chromosomes, Morgan began to view the Mendelian theory in a new light. A Legacy of Accomplishment As early as 1911, Morgan had redirected his research in an attempt to provide additional information about the chromosome theory of heredity, and before long he achieved another major conceptual breakthrough. Since chromosomes are contiguous assemblages of genes, those traits (mutations in some of the genes) mapping to one particular chromosome naturally tended to segregate together. But on occasion Morgan noted that these "linked" traits would separate, even while other traits on the same chromosome showed little or even no detectable linkage. From this evidence, Morgan inferred the process of chromosome recombination: he postulated that the two paired chromosomes could "exchange" or "crossover" between each other, and he further proposed that the frequency of recombination is a function of the distance between genes on the chromosome. The nearer two relevant genes lie on a chromosome, the greater their chance of being inherited together, while the farther away they are from each other, the more chance of their being separated by the process of crossing over. In short, Morgan suggested that the strength of linkage between genes depended on the distance between them on the chromosome. On the basis of these observations, Alfred Henry Sturtevant '12C '14GSAS, then an undergraduate at Columbia College, who was working with Morgan, recognized that the variations in the strength of linkage could be used as a means of mapping genes on chromosomes by determining their relative spatial distances apart. As Sturtevant himself later recalled: "I suddenly realized that the variations in the strength of linkage already attributed by Morgan to difference in the spatial separation of the gene offered the possibility of determining sequence in the linear dimensions of a chromosome. I went home and spent most of the night (to the neglect of my undergraduate homework) in producing the first chromosome map. . . ." (Sturtevant, A.H., Unpublished interview with G.E. Allen) The Morgan is now the unit of measurement of distances along all chromosomes in fly, mouse, and humans. A year after Morgan had spotted the white-eyed fly, Sturtevant drew up the first genetic map for the sex-linked genes. A sufficient number of mutations had by then been observed to allow him to express the strength of linkage in units of distance on a chromosome. In fact, the order and spacing that Sturtevant worked out in 1911 are essentially those found on modern maps of the Drosophila X chromosome. The profound insight that genes are aligned on the chromosome like beads on a string with specific distances between them eventually produced a conceptual basis for hunting for disease genes through linkage analysis and for mapping whole genomes, such as the human genome. All this was accomplished by a nineteen-year-old Columbia third-year undergraduate by simply skipping one night's homework! Morgan, who was not given to overstatement, later was to call the realization that genes could be precisely mapped in relation to one another on the chromosome as "one of the most amazing developments in the history of biology." (Shine, I. and Wrobel, S., Thomas Hunt Morgan: Pioneer of Genetics) By correlating breeding results with cytological observations of chromosomes under the microscope, Morgan's group rapidly transformed the abstract idea of Mendel's hypothetical factors into the physical reality of particular genes located at specific loci along the length of the chromosome. Initially their maps were quite abstract, since they were based only on the relative positions of genes to one another on the chromosome, as determined by linkage analysis -the sort of map now called a recombination map. But two decades later Calvin Bridges '12C '16GSAS succeeded in developing a second independent map -a physical one- showing the exact physical location of a gene on a chromosome. He accomplished this by exploiting an unanticipated advantage of Drosophila, which in its larval stages has chromosomes in its salivary glands that Theophilus Painter discovered to be multistranded and gigantic, much larger than the chromosomes of the other cells of the body. These giant chromosomes show a pattern of bands or stripes that divide each chromosome into physical subregions, and Bridges was ultimately able to recognize 1,024 invariant bands on the X chromosome. The development of physical maps proved especially valuable because they allowed a visual presentation of the sequence of genes on the chromosome -a sequence that can only be inferred from the abstract recombination map. By 1913 Sturtevant contributed yet another major breakthrough with his insight into the existence of different allelic forms, which he saw as alternative states (alleles) of the same gene at the same locus. Research on the white-eyed gene clearly revealed that a gene could mutate from one allele to another -from red to white. In some rare instances, a red allele was observed to mutate to a different allele, then to a third and eventually a fourth, with each new allele corresponding to a different eye color. But every time a gene gave rise to a new allele, the mutant form was perpetuated in the offspring and remained unchanged unless -again, in very rare cases- a new mutation occurred in one of the offspring. Thus, Morgan's group was able to show that alleles are remarkably stable! The low frequency of spontaneous mutation and the perpetuation of mutations that did occur indicated that genetic material is constant. The observation was soon confirmed in many other organisms, from Drosophila to man and from bacteria to yeast, offering proof both of inheritance and of the capacity for mutation to allow for evolutionary change in spite of the general constancy of genetic material. These seminal findings were summarized in 1915 by Morgan and his three Columbia students, Sturtevant, Bridges, and Hermann J. Muller, in The Mechanism of Mendelian Heredity, a book that proved to be of historic importance. To begin with, it set forth the physical basis for the new science of genetics. On top of that, the experimental discipline outlined in its pages provided the first experimental basis for a modern biology, transforming it from a descriptive science that relied heavily on morphology. Anatomy, the queen of the biological sciences from the time of the Renaissance to the beginning of the twentieth century, was now replaced by genetics as biology itself emerged as an exact, rigorous, quantitative experimental science that could exist on an equal footing with physics and chemistry. In recognition of his work on chromosomes, Morgan was awarded the Nobel Prize in Physiology or Medicine in 1933. He shared the prize money with Bridges and Sturtevant. The Nobel Prize recognized Morgan's two fundamental scientific contributions: the development of the chromosome theory of heredity, a theory of the gene that proved to be the driving biological concept of the twentieth century, and the creation of a new biology based on a rigorous experimental method. The Columbia Environment: The Fly Room Morgan also made a third contribution, a sociological one that helped introduce at Columbia and into American science as a whole a set of sweeping institutional changes. Until the start of the twentieth century, the leading American research universities -Harvard, Johns Hopkins, Columbia, and Chicago- had all been inspired by the model of the German research university, in which the Geheimrat, the great scientific leader, ordered the hierarchy of his subordinates. Morgan, however, based laboratory governance on democratic principles of merit rather than seniority. If one were to ask scientists around the world what is unique about America, they point to the university, and to this day foreign scientists are amazed that students working in a laboratory call professors by their first names. Morgan surrounded himself with a brilliant group of undergraduate and graduate students. Together they set up the Drosophila laboratory in Schermerhorn Hall, Room 613, known worldwide as the Fly Room. In retrospect, the Fly Room seems surprisingly small, measuring only 16 x 23 feet and containing eight desks. Yet, it housed a stream of Columbia students as well as foreign visitors and soon received wide recognition, not only for the remarkable quality and clarity of its science but also for the democratic nature of its social interaction. Morgan encouraged the free exchange of ideas in an atmosphere that was at once friendly, yet self-critical. The atmosphere in the Fly Room was described by Sturtevant, one of the youngest in the group. He wrote: "This group worked as a unit. Each carried on his own experiments, but each knew exactly what the others were doing, and each new result was freely discussed. There was little attention paid to priority or to the source of new ideas or new interpretations. What mattered was to get ahead with the work. There was much to be done; there were many new ideas to be tested, and many new experimental techniques to be developed. There can have been few times and places in scientific laboratories with such an atmosphere of excitement and with such a record of sustained enthusiasm. This was due in part to Morgan's own attitude, compounded with enthusiasm combined with a strong critical sense, generosity, open-mindedness, and a remarkable sense of humor." (Sturtevant, A.H., Thomas Hunt Morgan: Biographical Memoirs) Although this idyllic view was not shared by all,* the Fly Room nevertheless characterized science at its best and continues to provide a prototype for how research should be done, at Columbia and elsewhere. In terms of the work conducted there, the science that began at Columbia spread to laboratories all over the world as Morgan, the members of his group, and the scientists they trained helped to shape the course of biology during the decades that followed. Of the people who worked with Morgan directly or who worked with one of his students, five went on to win their own Nobel Prize: Muller, Beadle, Lederberg, and Lewis. Another student, Dobzhansky, went on to place evolution into a modern biological context. Impelled by their achievements, the center of influence in biology shifted from Europe to the United States, making the twentieth century an American Century in biology. At the same time, the open, critical, yet fully democratic and egalitarian atmosphere that was evident in the Fly Room soon came to characterize the distinctively American atmosphere of university research -an especially significant development as American graduate education increasingly became the model for graduate education throughout the world. I have benefited from the comments on this essay by Garland Allen, Norman Horowitz, Tom Jessell, Joshua Lederberg, E.B. Lewis, Robert Merton '85HON, Gary Struhl, Andrew Tomlinson, and Harriet Zuckerman '65GSAS. * As pointed out by Harriet Zuckerman, this view was not shared by Muller, who stood further away from the group than the rest and thought that his own contributions had not been fully recognized: see Zuckerman, 1977, pp. 141-143; see also Allen, 1978, pp. 201-208. BIBLIOGRAPHY Allen, G.E. (1978) Thomas Hunt Morgan: The Man and His Science. Princeton, NJ: Princeton University Press. Goldschmidt, R.B. (1950) "The Impact of Genetics Upon Science" in Genetics in the Twentieth Century, Essays on the Progress of Genetics in Its First Fifty Years (Ed. L.C. Dunn) pp. 1-23, New York, Macmillan. Harrison, R.G. (1937) "Embryology and Its Relations," Science 85:369-374. Jaffe, B. (1958) Men of Science in America: The Story of American Scientists Told Through the Lives and Achievements of Twenty Outstanding Men from Earliest Colonial Times to the Present Day. Rev. ed., 715 pp. Chapter 16. New York: Simon & Schuster. Judson, H.F. (1979) The Eighth Day of Creation: The Makers of the Revolution in Biology. New York: Simon & Schuster. Kohler, R. E. (1994) Lords of the Fly: Drosophila Genetics and the Experimental Life. Chicago: University of Chicago Press. Morgan, T.H. et al. (1915) The Mechanism of Mendelian Heredity. New York: Holt Rinehart & Winston. Reprinted. Johnson Reprint Corporation with an Introduction by Garland E. Allen, 1978. Morgan, T.H. (1934) Embryology and Genetics. New York: Columbia University Press. Morgan, T.H. (1938) The Theory of the Gene. New Haven: Yale University Press Shine, I., and Wrobel, S. (1976) Thomas Hunt Morgan: Pioneer of Genetics. Lexington: University of Kentucky Press. Sturtevant, A.H. (1959) Thomas Hunt Morgan: Biographical Memoirs. National Academy of Sciences 33:295. Sturtevant, A.H. (1965) Unpublished interview with G.E. Allen, Pasadena, Caltech Archives, pg. 28. Sturtevant, A.H. (1965) A History of Genetics. New York: Harper & Row. Watson, J.D. (1968) The Double Helix: A Personal Account of the Discovery of the Structure of DNA. New York: New American Library. Zuckerman, Harriet (1977) Scientific Elite: Nobel Laureates in the United States. New York: Free Press. Tomado de: http://www.nobelprize.org/nobel_prizes/medicine/laureates/1933/press.html Discurso de presentación del Premio Nobel a Thomas H. Morgan por F. Henschen, profesor del Royal Caroline Institute, el 10 de Diciembre de 1933. Award Ceremony Speech Presentation Speech by F. Henschen, member of the Staff of Professors of the Royal Caroline Institute, on December 10, 1933. Your Majesty, Your Royal Highnesses, Honourable Audience. As long as human beings have existed they will have observed children's resemblance to their parents, the resemblance or non-resemblance of brothers and sisters, and the appearance of characteristic qualities in certain families and races. They will also early have asked for an explanation of these circumstances, which has produced a kind of primitive theory of heredity chiefly on a speculative basis. This has been characteristic of the theories of heredity right up to our time, and as long as there existed no scientific analysis of the hereditary conditions, the mechanism of fertilization remained impenetrable mysticism. Old Greek medicine and science took much interest in these questions. In Hippocrates, the father of the healing art, you can find a theory of heredity that probably can be traced back to primitive ideas. According to Hippocrates, inherited qualities, in some way or other, must have been transmitted to the new individual from different parts of the organisms of the father and the mother. Similar ideas of the transmission of qualities from parents to children are to be found in other Greek scientists, and, modified, also in Aristotle, the greatest biologist of the olden times. Later on, this so-called transmission theory has been dominating. The only theory of heredity that has perhaps rivalled it, is the so-called preformation theory, an old scholastic idea that can be followed back to Augustine, the father of the Church. This theory maintained that, by the creation of the first woman, all following generations were also preformed in this first mother of ours. In modified form the preformation theory dominated the biology of the eighteenth century. Nevertheless, the transmission theory survived. Its last great representative was Darwin. He also seems to have understood heredity as a transmission of the personal qualities of the parents to the offspring through a kind of extract from the different organs of the body. This conception, however, that is thus deeply rooted in the biology of past times and that will still be adopted rather generally, is fundamentally false; it has been reserved to the genetic researches of our time to prove this. Modern hereditary researches are of a recent date, they are not yet seventy years old. Their founder is the Augustine monk Gregor Mendel, Professor at Brünn, who published (1866) his experiments on hybridization among plants, fundamental for this whole science. In the same year, in Kentucky, the man was born, who became Mendel's heir and founder of the school in heredity researches that has been called higher Mendelism, the winner of this year's Nobel Prize in Physiology or Medicine, Thomas Hunt Morgan. Mendel's observations are of revolutionizing importance. As a matter of fact they completely upset the older theories of heredity, although this was not at all appreciated by his contemporaries. Mendel's discoveries usually are stated in two heredity laws or better rules of heredity. The first of his rules, the cleaving rule, means that if two different hereditary dispositions or hereditary factors (genes) for a certain quality - for instance for size - are combined in one generation, they separate in the following generation. If, for instance, a constantly tall race is crossed with a constantly short race, the individuals of next generation become altogether medium-sized, or, if the factor «tall» is dominant, exclusively tall. In the following generation, however, a cleaving takes place, so that once more the size of the individuals becomes variable according to certain numerical proportions, then of four descendants: one tall, two medium-sized, and one short. The second of Mendel's rules, the rule of free combinations, means that, when new generations arise, the different hereditary factors can form new combinations independent of each other. If, for instance, a tall, red-flowered plant is crossed with a short, white-flowered one, the factors red and white can be inherited independent of the factors large and small. The second generation then, besides tall red-flowered and short white-flowered plants, produces short red-flowered and tall white-flowered ones. Mendel's immortal merit is his exact registration of the special qualities and consequent following of their appearance from generation to generation. In this way he discovered the relatively simple, recurrent, numerical proportions, which give us the key to a true understanding of the course of heredity. The experimental genetics of our century then has proved that, taken as a whole, these Mendel rules are applicable to all many-celled organisms, to mosses and flowering plants, to insects, mollusks, crabs, amphibia, birds, and mammals. Mendel's rules, however, met with the same fate as many other great discoveries that have been made before their time. Their significance was not understood, they fell into oblivion, and after pater Mendel had died in 1884, nobody mentioned them any more. Darwin apparently knew nothing about his great contemporary; otherwise he could have made use of Mendel's works for his own researches, and the rediscovery of Mendel's work was made only about 1900. By that time, however, the qualifications for the application and perfection of Mendel's theories were quite different from those of their first publication. The general biological attitude had changed, and, above all, the knowledge of the cell and the cell nucleus had made excellent progress. The mechanism of fertilization had been discovered by Hertwig in 1875, and in the eighteen-eighties Weismann had asserted the opinion that the nuclei of the sex cells must be the bearers of the hereditary qualities. The indirect or mitotic cell division and the chromosomes - the strange, threadlike, colourable structures that then appear - had been discovered by Schneider in 1873 already. Only several decades later, however, was the meaning of the remarkable cleaving, wandering, and fusion of these chromosomes during the different phases of the cell division and the fertilization understood. When, at last, Mendel's discoveries came to light, their significance was soon perceived. Behind Mendel's rules there must be some relatively simple, cellular mechanism for the exact distribution of the hereditary factors at the genesis of the new individual. This mechanism was found just in the proportion of chromosomes in the sex cells before and after the fertilization. The opinion that the chromosomes are the real bearers of heredity was first clearly pronounced by Sutton in 1903, and by Boveri in 1904. This opinion was enthusiastically received by the students of the cell. Only by this discovery organic life got the unity, the continuity that human thought demands and that is more real and more provable than the hypothetic common descent of Darwinism. The further development of the chromosome theory during the first decade of this century may here be skipped. However, the soil was well prepared when, in 1910, the American zoologist Thomas Hunt Morgan began his researches in heredity. These soon led him to the great discoveries regarding the functions of the chromosomes as the bearers of heredity that have now been rewarded with the Nobel Prize for Medicine in 1933. Morgan's greatness and the explanation of his astonishing success is partly to be found in the fact that, from the beginning, he has understood to join two important methods in hereditary research, the statistic-genetic method adopted by Mendel, and the microscopic method, and that he has always looked for an answer to the question: which microscopic processes in cells and chromosomes result in the phenomenons appearing at the crossings? Another cause for Morgan's success is no doubt to be found in the ingenious choice of object for his experiments. From the beginning Morgan chose the so-called banana-fly, Drosophila melanogaster, which has proved superior to all other genetic objects known so far. This animal can easily be kept alive in laboratories, it can well endure the experiments that must be made. It propagates all the year round without intervals. Thus a new generation can be had about every twelfth day or at least 30 generations a year. The female lays about 1,000 eggs, males and females can easily be distinguished from each other, and the number of chromosomes in this animal is only four. This fortunate choice made it possible to Morgan to overtake other prominent genetical scientists, who had begun earlier but employed plants or less suitable animals as experimental objects. Finally, few have like Morgan had the power of assembling around them a staff of very prominent pupils and co-operators, who have carried out his ideas with enthusiasm. This explains to a large extent the extraordinarily rapid development of his theories. His pupils Sturtevant, Muller, Bridges, and many others stand beside him with honour and have a substantial share in his success. With perfect justice we speak about the Morgan school, and it is often difficult to distinguish what is Morgan's work and what is that of his associates. But nobody has doubted that Morgan is the ingenious leader. As Mendelism can be summed up in Mendel's two rules, Morganism, at least to a certain extent, can be expressed in laws or rules. The Morgan school usually speaks of four rules, the combination rule, the rule of the limited number of the combination groups, the crossing-over rule, and the rule of the linear arrangement of the genes in the chromosomes. These rules complete the Mendel rules in an extraordinarily important way. They are all inextricably connected, and form together a close biological unity. It is true that Morgan's combination rule, according to which certain hereditary dispositions are more or less firmly combined, limits to a large degree Mendel's second rule that, at the formation of new hereditary substances, the genes may be freely combined. It is completed by the rule of the limited number of the combination groups, which has turned out to be corresponding to the number of chromosomes. On the other hand, the combination rule is confined by the strange phenomenon that Morgan calls crossing-over or the exchange of genes, which he imagines as a real exchange of parts between the chromosomes. This crossing-over theory has met with much resistance. During the last few years, however, it has got a firm support through direct microscopic observations. Also the theory of the linear arrangement of the hereditary factors seemed in the beginning a fantastic speculation, and the publication of Morgan's so-called genetic chromosome map, upon which the different hereditary factors are checked in the chromosomes like beads in a necklace, was greeted with justified scepticism. The fact was that Morgan had arrived at these sensational conclusions by statistic analysis of his Drosophila crossings and not by direct examination of the chromosomes, which, besides, is possible only in exceptional cases. But also on this point later researches have acknowledged him to be in the right, and nowadays also other genetic scientists admit that the theory of the localization of the hereditary factors within the chromosomes is not an abstract way of thinking but corresponds to a stereometric reality. The results of the Morgan school are daring, even fantastic, they are of a greatness that puts most other biological discoveries into the shade. Who could dream some ten years ago that science would be able to penetrate the problems of heredity in that way, and find the mechanism that lies behind the crossing results of plants and animals; that it would be possible to localize in these chromosomes, which are so small that they must be measured by the millesimal millimetre, hundreds of hereditary factors, which we must imagine as corresponding to infinitesimal corpuscular elements. And this localization Morgan had found in a statistic way! A German scientist has appropriately compared this to the astronomical calculation of celestial bodies still unseen but later on found by the tube - but he adds: Morgan's predictions exceed this by far, because they mean something principally new, something that has not been observed before. Morgan's researches chiefly occupy themselves with the family of Drosophila, and perhaps it may seem strange that his discoveries have been rewarded with the Nobel Prize for Medicine, which is to be bestowed on the man who «has done the greatest service to mankind» and «has made the most important discoveries in the field of physiology or medicine». To this may first be alleged that numerous later examinations of other genetic objects, of lower and higher plants and animals, have given evidence of the fact that, as a principle, Morgan's rules are applicable to all many-celled organisms. Further, comparative biological research has for a long time shown a far-extending fundamental correspondence between man and other beings. We can therefore consider it as a matter of course that also such an elementary function of the cell as the transmission of hereditary dispositions is similar, that, in other words, Nature uses the same mechanism with man as with other beings to preserve species, and that Mendel's and Morgan's rules thus are applicable also to man. Human hereditary researches have already made great use of Morgan's investigations. Without them modern human genetics and also human eugenics would be impractical - it may be that eugenics still chiefly remain a future goal. Mendel's and Morgan's discoveries are simply fundamental and decisive for the investigation and understanding of the hereditary diseases of man. And considering the present attitude of medicine and the dominating place of the constitutional researches, the role of the inner, hereditary factors as to health and disease appears in a still clearer light. For the general understanding of maladies, for prophylactic medicine, and for the treatment of diseases, hereditary research thus gains still greater importance. Mr. Steinhardt. The Caroline Institute regrets very much that Professor Morgan is not able to be here today in person. I beg Your Excellency, as the official representative of the United States of America, to accept the Nobel Prize for Professor Morgan. May I also ask Your Excellency, in forwarding the prize to him, to convey with it the admiring congratulations of our Institute. From Les Prix Nobel en 1933, Editor Carl Gustaf Santesson, [Nobel Foundation], Stockholm, 1934