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THEOPHILUS SHICKEL PAINTER August 22, October 5, l 969 BY BENTLEY GLASS IN T H E S T E ~ ~ A R D A Y S O F Drosophila genetics during the 1920s and 1930s, only two principal centers of such re- search existed in the United States. The California Institute of Technology attracted Thomas Hunt Morgan from Colum- bia University in 1929, and he brought with him his two stu- dents, Alfred H. Sturtevant and Calvin B. Bridges, who a decade earlier had contributed to the establishment of the chromosome theory of heredity. The CalTech group also in- cluded Theoclosius Dobzhansky, lack Schultz, and a constel- lation of notable visiting fellows, present for a year or two, such as George Beadle and Curt Stern. During the same period a second stellar group formed at the University of Texas in Austin. H. I. Muller, one of the original trio of Morgan's graduate students, tract created a great stir in genetics with his 1927 discovery that X-rays will induce mutations at frequencies hundreds, even thousands, of times higher than rates of spontaneous mutation. A gen- erous grant from the Rockefeller Foundation macle it pos- sible for Muller, joined by I. T. Patterson ant! T. S. Painter of the Department of Zoology at Austin, to establish a cytoge- netical program for exploiting the new discovery. Graduate students were recruiter! and given fellowships, the earliest of which went to C. P. Oliver, Wilson S. Stone, and the writer of 309
310 BIOGRAPHICAL MEMOIRS this memoir. Muller soon found that X-rays produce chro- mosomal breaks and rearrangements in addition to gene mu- tations, Oliver worker! out the relation of point mutations to radiation dosage, Painter collaborates! with Muller in analyz- ing chromosomal rearrangements, and Patterson explored an exciting new field mosaic types of mutation produced by X-rays. Bursts of exciting new findings made the rivalry with CalTech as hectic as a close basketball game, ant! Painter was a central figure in all of it. EARLY LIFE AND EDUCATION T. S. Painter was born in Salem, Virginia, the son of Franklin V. N. Painter ant! Laura T. Shicke! Painter. T. S.'s father was an esteemed educator, a professor of modern lan- guages and English literature at Roanoke College. Both par- ents were very religious, and their son was brought up in an atmosphere of culture and religious faith that marked him deeply. His midclle name was that of his mother's family; his given name reflects his parents' Christian orientation. As a boy, T. S. was sickly and obtained most of his elementary ant} secondary education by home tutoring. He entered Roanoke College in 1904 anc! graduated with a B.A. degree in 1908. The college was a small one and clid not provide a diversity of scientific courses. Painter was attracted to chemistry ant! physics but had no opportunity to acquaint himself with biol- ogy. Having received a scholarship in chemistry, he entered Yale University as a graduate student in 1908. Here he met Professor L. L. Woodruff of the Biology Department and asker! to be permitted to sit in a corner of the laboratory anal look at objects under a microscope, which he hac! never had an opportunity to use before. Professor L. L. Woodruff as- signec! Painter a microscope and proviclec! him with a hay
THEOPHILUS SHICKEL PAINTER 311 infusion full of active bacteria, protozoans, and algae. Painter was fascinates! and soon decided that he wanted to change his field from chemistry to biology. He receiver! an M.A. degree in 1909 and a Ph.D. in 1913, uncler the direction of the fames! authority on spiders Alex- ancier Petrunkevitch. Painter learned the techniques of cy- tology as practicer] at that time ant! for his thesis explored the process of spermatogenesis in a species of spicier. His first scientific publication (1913, I) was a paper on dimorphism in males of the jumping spider, Maevia vittata. His second (1914,1) was his thesis research. Painter then went to Europe for a year of postdoctoral study, partly in the laboratory of Theodor Boveri, in Wurzburg, ant! partly at the famed Marine Zoological Station at Naples. At that time Boveri was among the foremost cy- tologists in the world. More than a clecacle earlier he had established, in studies of the fertilization and development of Ascaris eggs, that each chromosome controls development in- clividually. Chromosomes, furthermorealthough they seem to disappear after the close of each mitotic cell divi- sionhave a persistent continuity and reappear in the next mitosis in the same place they occupier! before their disap- pearance. Most surprisingly, they continue to bear whatever aberrant distinctions they might previously have acquired by accident. Boveri was a stout supporter of the chromosome theory of heredity which he had enunciates! inclependently of W. S. Sutton, a student of E. B. Wilson at Columbia. Later, when ~ was taking a graduate course with Painter at Austin, it was a matter of astonishment to me that ~ never heard him reminisce about those exciting times or make any reference to Boveri or to what he learned from him. The experience at Naples, with its marvels of marine life for a cytologist to explore, seemed to affect Painter more. His next publications (lealt with problems of the forces involved
312 BIOGRAPHICAL MEMOIRS in the cleavage of the fertilized egg into a multiplicity of cells by means of repeated mitotic cell divisions. Back in the Uniter} States from a war-torn Europe, Painter received an appointment as an instructor in zoology at Yale for two years. He was also asked to teach marine invertebrate zoology at the Woods Hole Laboratory in the summers of 1914 and 1915. There he met two persons who were to be exceedingly important in his life. The first, Mary Anna Thomas, was a young student in his course who woulc! later become his devoted wife. The second, John Thomas Patter- son, was the young head of the Zoology Department at the University of Texas in Austin. Patterson offered Painter the academic post that brought him to the institution where he would spend the remainder of his life. In his Biographical Memoir of I. T. Patterson (1965,1), Painter told of the warm and friendly way in which the two first met while playing baseball with other teachers and researchers at Woods Hole. Painter's research at this period greatly resembled the type of experimentation on developing invertebrate embryos favored by E. B. Wilson and E. G. Conklin. He first studied the effects of carbon dioxicle on the developing eggs of As- caris, the material for which hac} been obtained at Wurzburg. His next study also took its origin from work begun in Eu- rope, this time at Naples, where Painter had discoverer! spiral asters in developing eggs of sea urchins and become curious about their participation in the process of embryonic cleav- age. He investigates! the occurrence of monaster eggs, the light they threw on cell mechanics during division, and the influence of narcotics on cell division. Painter demonstrates! that eggs may divide in the absence of asters, that a factor clerived from the nucleus is requires! for division, and that the asters presumably play a regulatory role in the distribu- tion of the nuclear factor. In May 1916, Painter enlisted in the National Guarc! at
THEOPHIEUS SHICKEE PAINTER 313 New Haven ant! became a sergeant of the Headquarters Company of the Tenth Regiment of Fielc! Artillery. Dis- chargec! in September 1916, he married Anna Thomas on December 19, 1917. Their children two boys and two girls and, eventually, their grandchilclren made a warm, closely knit family. With the advent of World War ~ in 19 ~ 7, Painter was com- missioned a first lieutenant of the U.S. Army Signal Corps and was sent to Toronto's Imperial Flying School to find out what measures were needed! to establish a ground! school of aviation in Austin. After the school was established, he served as a member of its academic board and was promoted in 1918 to captain in the U.S. Army Air Service. In April 1919 he retiree] as a captain of the Reserve Corps. Though Painter went to Austin in 1916 as an adjunct pro- fessor of zoology, military service interrupted his research for several years, and he was not promoter! to associate professor until 1921. Four years later, in 1925, he was appointed full professor with membership in the graduate faculty. Painter was a man of broad interests and cheerful dispo- sition. He often visited his students in the laboratory to exchange ideas, giving them encouragement as well as di- rection. He taught undergraduate courses in aciclition to graduate cytology, and for many years- a popular premedical course in comparative anatomy. He played tennis and golf ant! lover! swimming, fishing, and crabbing. He was also an inveterate hunter, liking nothing more than to take down his rifle to hunt deer or antelope. He was a fine gar- clener, ant! his flower displays were a marvel to all visitors. He particularly enjoyed hybridizing irises to produce new patterns of remarkable color. He was an expert with tools and macle furniture for his home. In later years he turner! to jeweIry-making and again cleveloped great skill at produc- ing objects that reflected his fine taste. He took a strong part
314 BIOGRAPHICAL MEMOIRS in his church's activities and in various clubs. In many ways the antithesis of the stereotypical Texan, he was both re- served and self-controlled. CHROMOSOME CYTOLOGY AND SEX CHROMOSOMES Back at the University of Texas after his military service, Painter resumed his cytological studies of spermatogenesis in a common small lizard, Anolis caroZinensas. But he quickly turned to a new problem: the number of mammalian chro- mosomes and their morphology, with particular emphasis on the nature of sex determination. In the zoology laboratories of the Department, embryol- ogist Car} G. Hartmann was engaged in studying the repro- cluction of the opossum. "There was 'possum meat all over the lab," Painter remarked, a fine opportunity for him to switch from spillers, marine organisms, and lizards to the enticing field of mammalian cytology. Almost nothing was known about mammalian chromo- somes at the time, although it was supposed that mammals must have sex chromosomes corresponding to those of in- sects and that an XXffemale)-XY(rnale) distinction would ex- ist. It proved quite easy, in fact, to find the sex chromosomes of the opossum, for they were the smallest pair of chromo- somes in the cell, and during spermatogenesis they always lay in the center of a ring of the other, larger chromosomes clur- ing the metaphase of mitosis. In those days all tissues used for cytological examination were successively fixed, embed- ded in paraffin, sectioned, and stained. It was of prime im- portance to get the tissues fresh from dissection into the fix- ing fluicI. Painter invented a sort of multiblaclec} knife by mounting a number of safety razor blades in parallel, close together, which he used to cut up the spermatogenic tubules of the testis immediately after the organ was excised. Painter demonstrated that the male opossum's sex is de-
THEOPHILUS SHICKEL PAINTER 315 terminec! by a tiny Y-chromosome in place of one of the fe- male's larger X-chromosomes. He shower! that in meiosis of the male's spermatocytes prior to formation of spermatozoa, the X and Y chromosomes pair and then segregate, so that each male reproductive cell carries either an X- or a Y- chromosome, but not both. As in insects, then, if all egg cells carry a single X-chromosome anct if fertilization by the two sorts of spermatozoa is random, the X-bearing sperm would produce female offspring; the Y-bearing sperm wouIcl pro- duce males. Having thus shown that sex determination in a marsupial mammal corresponds to the process already known from in- vertebrates, Painter set his sights on placental, or eutherian, mammals, and- through a fortunate circumstance was able to obtain fresh human testicular tissue. One of his for- mer premedical students was practicing medicine in a state mental institution in Austin where, "for therapeutic reasons," Painter wrote. "they occasionalIv castrated male individuals." Painter's former student made it possible for him to obtain and preserve, "within thirty seconds or less after the blood supply was cut oh, a human testis" (197l,1~. We students in the Austin laboratory speculated widely that such tissue was also obtained from criminals executed at the nearby Hunts- ville prison, but this was probably just idle gossip. Painter himself never confirmed such a source. Painter's first work on human chromosomes, therefore, preceded his study of primates, though their order of pub- lication was reversed. A year before he publisher! his fuller account of human spermatogenesis and human sex chro- mosomes (1923,1), a short announcement on the sex chro- mosomes of"the monkey" appeared in Science. To solve the enigma of sex determination in humans, Painter turned to two species of monkey the New WorIc} Brown Cebus and the OIct WorIc3 Rhesus (Rhesus macacus). As
316 BIOGRAPHICAL MEMOIRS he pointed out in this pioneering work (1924,3), it was highly desirable and perhaps necessary to establish four matters for each species examined: (~) the morphology of the diploid chromosome complex and the chromosome number of the male; (2) the haploid number revealed in the second sper- matocytes; (3) the morphology and behavior of the sex chro- mosomes (X and Y) during meiosis; and (4) the morphology and chromosome number of the female complex. Cross- checks among these observations should bar all possibility of error, even though many species of mammals including the primates Painter was investigating" have many more and much smaller chromosomes in their karyotypes than do opossums or the insect species in which the chromosomal determination of sex was first established. (A "karyotype" is the term used to designate the entire group of chromosomes characteristic of a cell of a particular species. This conic! be a diploicl cell with two complete sets of chromosomes or, more frequently, the chromosome complement of a haploic! cell with a single set of chromosomes one of each distinctive kind characterizing the species.) Painter's demonstration of the X-Y type of sex determi- nation in these mammals ant! in the human species was com- pelling. His drawings of the larger X-chromosome and the much smaller Y-chromosome, connected to each other by a thin strand while segregating in the first prophase of meiosis, left no doubt. The number of chromosomes was less certain. Some hu- man cells seemed! to show a count of forty-eight chromo- somes in the cliploic! primary spermatocyte, others only forty- six. Previous investigators of human chromosome number also varied in their counts, though most settled for forty- eight. Painter himself took the evidence of his "best cell" and reported the number as forty-eight, confirming an error that
THEOPHIEUS SHICKEE PAINTER 317 would be perpetuated in dozens of textbooks (including one of my own) until a new set of techniques for counting chro- mosomes was introducer! in the mid-1950s. In 1956, using new stains (such as acetocarmine and Feulgen's stain specific for DNA) and soft somatic tissues (especially embryonic tis- sues) that could be smeared; using coIchicine to halt clividing cells in metaphase and hence greatly increase the number of such cells observable; and using hypotonic salt solutions to spread the chromosomes of dividing cells apart to eliminate their clumping into uncountable masses, I. H. Tjio and A. Levan made a definitive determination that the human dip- loid chromosome number is forty-six, i.e., twenty-three pairs of homologous chromosomes in human ctiploid cells. Painter experienced deep chagrin over this error in what had long been regarded as a primary discovery for which he was known ant} universally cited. Yetgiven the source of his material and the procedures available to him in the early 1920s he may not have been entirely wrong. Indivicluals with mental disorders are not prime material for cletermin- ing normal chromosome number and morphology, for they sometimes have forty-seven, forty-eight, or even more chro- mosomes ant} exhibit more frequently than normal persons transIocations and deletions of chromosomes that would ap- pear to alter their number. Recently T. C. Hsu, a well-known cytogeneticist, reexam- ined some of the original preparations on which Painter based his erroneous chromosome count and found that the chromosomes were so badly clumped and cut into segments by the microtome knife, it was a marvel Painter was able to find any cells at all that seemed to give a clear chromosome count. Given that human chromosomes are exceedingly small, that the dyes used in the 1920s darkly stained other matter in addition to chromosomes, ant! that microtome slices rarely proclucecl whole, undamaged cells for examina-
318 BIOGRAPHICAL MEMOIRS tion, Painter's error was wholly natural and forgivable. In any case, it in no way diminishes the importance of his discovery of the XX-XY mechanism for determining sex in mammals (inclucling humans), a significant contribution to science. Painter subsequently examined and recorded the chro- mosome number of the horse (probably 60; XX-XY sex cle- termination), the bat Nyctinomous mexicanus (2 N = 48), the Eu- ropean hedgehog (2 N = 48), the armadillo (2 N = 60), the rabbit (2 N = 44), and the dog (2 N prob. 521. Additional marsupials examined included besides the opossum (2 N = 22) Phascolarctus (2 N = 16), Sarcophilus (2 N = 14), Das- yurus (2 N = 14), and the kangaroo Macropus (2 N = 12~. Painter identified an XY pair of sex chromosomes in all of these marsupial and placental mammals except the hedge- hog, armadillo, ant! clog species he did not investigate ex- tensively enough to judge- though an XY male type was not exclucled in them either. In summary, Painter shower! that marsupial mammals in general have a lower chromosome number than placental mammals; that all, or almost all, placentals (including hu- mans) have a high chromosome number ranging from forty- four to sixty; ant! that all of them have, or probably have, an XX-XY type of sex determination depending upon a partic- ular pair of sex chromosomes in which the Y-chromosome (carried by the male) is far smaller in size than the X- chromosome. If these studies placed Painter in the first rank of cyto- geneticists, the focus of his next research project established him firmly in the forefront of classical genetics. One of Painter's students, E. K. Cox, tract determined that the chro- mosome number of the common house mouse, Mus musculus, is forty. Yet W. H. Gates reported that a Japanese waltzing mouse found in the F! offspring of a cross between normal (dominant) ant! Japanese waltzer (recessive) parents seemed
THEOPHIEUS SHICKEE PAINTER 319 to owe its phenotype to the loss of the chromosome carrying the normal dominant allele. Carefully examining descendants of this mouse, Painter found that all of them hac! the full complement of forty dip- loid chromosomes. He also determined that the males carrier! a typical XY chromosome pair and concluded, therefore, that the original mouse found to be exceptional by Gates could not have sufferer! the nondisjunctional loss of an entire chro- mosome the one carrying the normal allele of the waltzing gene. He hypothesized instead that there tract been a deletion of the part of that chromosome that normally carries the allele in question a hypothesis he subsequently verified by observing that these mice carried two heteromorphic pairs of chromosomes, the sex chromosome pair, plus another pair in which one homologue was very much smaller than its part- ner. Painter's study of the Japanese waltzing mouse appears to have been the first cytological identification of a deletion producing a specific genetic effect (1927,1~. DROSOPHILA CYTOGENETICS "One day," Painter wrote, " ... ~ found tH. J.] Muller clown on the floor with a pipette trying to recover some ova- ries which he had spilled from a dish. As skillful as he was in genetic analysis, he clidn't have great skill in handling such small material. So ~ suggested to him ~ think ~ caught him just at the right time 'Why don't you let me study those ovaries ant! tell you where the oogonial chromosomes have actually been broken?' Again, it was a case of being in the right place at the right time! Muller furnished me with fe- male Drosophila carrying a transIocation and by examining oogonial metaphases ~ would determine how much of an ex- change had taken place." (197l,l, pp. 34-35.) So began a collaboration that eventually led to grouncl- breaking, parallel investigations of genetic and cytological
320 BIOGRAPHICAL MEMOIRS variations inclucec! by the action of X-rays on genes and chro- mosomes ant] to Painter ant! Muller's paper on the parallel cytology and genetics of induced transIocations and cleletions in Drosophila a genetics classic (1929,14. Though transIocations investigated -My and [~-~) clid not at that time reveal the fact that all transIocations are ac- tually reciprocal exchanges, they did show that the size of the cytological piece taken from one chromosome and attached to another did not correspond precisely in size to the portion of the genetic map that was transIocated. The importance of this observation was greatly enhanced by the finding that- in the case of deletions of a coherent portion of the genetic map of the X-chromosome the cytological loss was much greater than would be expected from the ratio of the lost portion to the total genetic length of the chromosome. This finding led, furthermore, to the discovery that there is a large portion of "heterochromatin" at the base of the X- chromosome a segment that appears to carry few, if any, genes. Most of the cleletions excised a considerable part of this heterochromatin. The two authors went on to find a case of a new linkage- group establishecl by the transIocation of a fragment carrying certain genes to an independent spincile fiber attachment. Only much later was it learner! that this case represented! a transIocation of a portion of an autosome to the basal portion of a Chromosome IV thathaving lost most of the regular fourth chromosome genes conic! freely undergo nondis- junction, eventually to become a new pair of chromosomes. Painter published a cytological "map" of the X-chromosome that reflected! this discovery, ant! Muller reported on their joint studies at the Sixth International Congress of Genetics in 1932. What is generally regarded as Painter's most notable dis- covery in cytogenetics occurrect in 1932, while the writer of
THEOPHILUS SHICKEL PAINTER 321 this memoir was still a graduate student in his Department. Quite independently, but simultaneously with E. Heitz and Hans Bauer in SwitzerIancI, Painter identifier! the strange- looking tangled balls of thick strands to be seen in the nuclei of the salivary glands of all Diptera (first describer! by E. G. Balbiani in ISSI) as being closely paired homologous chro- mosomes. Aider! by the wealth of established genetical infor- mation then available on Drosophila melanogaster, he then car- ried the genetic analysis considerably further than his cocliscoverers in Europe. Painter also introcluced a new cytological method! for making salivary glanc! preparations, mentioned casually in his first paper announcing the new kind of chromosomes (1933,2~. It was an application of the acetocarmine smear methocl, long used by cytologists who worked on maize chro- mosomes. Painter adapted the method] to the fruitfly. He simply (dissected out the salivary glancls from a third instar Drosophila larva in a drop of physiological saline solution, transferred! the glancts to a strop of acetocarmine stain, placed a coverglass over them, ant! uncier the dissecting micro- scopepressed with the point of a dissecting needle on each nucleus within the glancI. When an appropriate amount of pressure was exerted, the nuclear membrane burst and the releaser! chromosomes took up the stain in their numerous crossbands. Painter saw that there were six strancis, one short ant! five long. Each strand} remained attached at one end to a mass identified as a "chromocenter," the fused heterochromatin of each chromosome. Painter identified each chromosome by using Drosophila stocks that had a cleletion of a portion of one chromosome that wouIcl enable that particular chromo- some to be picket! out. One strand was iclentified as the X- chromosome; two as the respective left and right arms of Chromosome Il; and two as the left and right arms of Chro-
322 BIOGRAPHICAL MEMOIRS mosome III. The short strand, by process of elimination, was Chromosome IV. Painter recognized, again from the study of the giant Drosophila chromosomes in individuals that were heterozygous for a deletion, that each strand consists of two closely-pairecI, homologous chromosomes. By using a variety of genetically known stocks containing cleletions of short portions of the sequence of genes in the X-chromosome (the supply of which was expertly furnished to Painter by Wilson S. Stone), Painter quickly made a cyto- logical salivary chromosome map of the X-chromosome of D. melanogaster. The cytological sequence of genes was in the same order as the known genetic map of X-chromosome loci baser! on crossover frequencies, but the distances between genetic loci ctid not correspond exactly to the cytological map. While certain regions were expander! somewhat, others were contracted. In general, however, the agreement was very goof! better than for the agreement between crossover link- age maps and the cytological map derived from ordinary so- matic or germ cells that did not develop giant chromosomes. In a second paper publisher! in 1934, Painter continued his analysis of giant salivary gland chromosomes in stocks carrying deletions, inversions, or transIocations. When one chromosome of a homologous pair carried a cleletion, the longer mate formed a loop or buckle at the region, so that the exact points of breakage of the deletion could be cleter- mined at the level of incliviclual crossbands. In the case of a heterozygous inversion, a large loop was former! with the two homologues passing around the loop in opposer! directions, so that every band could still fins! ant! pair precisely with its mate in the other chromosome. In transIocations a cross- shaped figure wouIc! result, for at the point of the exchanger! strands, the chromosomes wouIcl switch partners. From these studies it became apparent that all transIoca- tions are in fact mutual or reciprocal exchanges, even
THEOPHILUS SHICKEE PAINTER 323 though the fragment from one chromosome may be large and that from the other very small. It also became estab- lishecI, as Muller and others hac} previously conjectured, that the reattachments of fragments of broken chromosomes take place only between two broken ends, as though they were in some way "sticky," or as we wouIct now say, through the re- union of broken chemical bonds. These studies showed conclusively, as the genetic studies hac! intimated, that the attraction between homologous chro- mosomes is point by point, locus by locus, band by banal, and not a synapsis caused in some vague way by chromosomes as entire units. From the standpoint of physics and chemistry, this conclusion is one of the most interesting findings of cy- togenetics. At this stage of his career, honors came rapidly to T. S. Painter. Yale University conferred on him the honorary de- gree of D.Sc. in 1936. He was awarder! the Daniel Giraud Elliot Mecial of the National Academy of Sciences in 1933 and was elected! a member of the Academy in that same year. He was elected! a member of the American Philosophical So- ciety in 1939. Painter was greatly interested in the nature and function of the heterochromatin. From the comparison of salivary chromosomes with those of regular somatic cells or cells of the germ line, he conclucled that about three-eighths of the X-chromosome of Drosophila is missing in the salivary gland chromosomes, and that the Y-chromosome of the male is missing almost entirely, although in the usual somatic cells the Y-chromosomeunlike the Y of a mammal is very large, almost as large as the X-chromosome. The apparent disappearance in the salivary gland cells of the heterochro- matin must, he thought, be related in some way to difference in function. The salivary glance cells clid not seem to carry the usual kind of genes that become evident from their mutation.
324 BIOGRAPHICAL MEMOIRS Musing over this problem, he was led away from the detailed task of chromosome mapping, which he willingly left to Cal- vin Bridges' sharp eyes and unending appreciation of (retail. Painter resolved to seek out the functions of different kinds of genetic material, especially the heterochromatin. How, he wonclerecI, does the alterec! nature of chromosomes in particular organs, such as salivary glands, relate to spe- cializect cellular function? Except for a joint paper with Wilson Stone on the relation of chromosome fusion to speciation in the Drosophiliciae ~ ~ 935,3), and two papers ~ ~ 935,2 and 4) one written jointly with I. T. Patterson on the salivary glanc! chromosome map of Chromosome Ill, Painter concentrated on this new clirec- tion until his research was interrupted in 1944. With his student Allen Driven, he examined the course of clevelopment of the salivary gland nucleus in the fly Simulium virgatum in order to see just how the giant paired salivary gland chromosomes arose and what their structure might be in comparison with simpler, single-strancled chro- matids of more ordinary cells. With another student, Eliza- beth Reindorp, he traced the development of endomitosis in the nurse cells of the Drosophila ovary, a process that gives rise to multistrandecl chromosomes that do not aggregate and consolidate into giant chromosomes of the salivary gland type. He studied the synthesis of cleavage chromosomes and clemonstrated that the rapid series of cleavage divisions, in- volving the synthesis of great numbers of new chromosomes from the original new sets in the zygote, or fertilized egg, would be impossible were it not for the abundant feeding of amino acids and nucleotides derived from previously synthe- sizec3 proteins and nucleic acids in the nurse cells into the oocyte during its period of maturation. Cases of cytoplasmic or matroclinous inheritance might also be explained by the
THEOPHIEUS SHICKEE PAINTER 325 accumulation of such materials in the cytoplasm of the egg cell. Painter summarized this work at a CoIc} Spring Harbor Symposium in ~ 940 ~ ~ 94 ~ ,2~. With A. N. Taylor he continued working on nucleic acic! storage in the toad's egg, while with J. J. Biesele he examined the alterations in the nature of chromosomes in cancerous cells of the mouse, where much en(lomitosis and polyploidy were found. Painter even undertook to assay the relation of cell growth in the pollen grains of a flowering plant, Rhoeo discolor, to the amounts of nucleic acid they possessed an investigation he initiates] prior to Avery, MacLeod, and McCarty's clemonstra- tion that, in pneumococcus transformations of genetic type, it is the nucleic acid, not protein, that acts as the genetic ma- terial. In light of this research, Painter also seems to have suspected] that nucleic acid was the material responsible for the hereditary transmission of characters. UNIVERSITY ADMINISTRATION In 1944 T. S. Painter's professional life changed abruptly: he became a university administrator. The president of the University of Texas at that time had defended the academic freedom of two faculty members who had engaged in liberal political activities ancl spoken at meetings of labor organiza- tions. The Regents of the University forcer! the president to resign and looker! hastily for a caretaker who coup be ex- pected to refrain from political action and at the same time wouIc} be of high academic reputation. A committee of three members of the faculty met with the Regents in order to make suggestions for a resolution of the ctifficulties, and Painter was one of the three. According to the minutes of the Special Committee of the Faculty that was delegated the task of preparing a memorial resolution following Painter's cleath,
326 BIOGRAPHICAL MEMOIRS the committee of which Painter was a member met with the Regents ant! then retired for the night. After Dr. Painter was asleep, he was called and asked to return to the meeting. He was told that the president had been dismissed. The Board of Regents asked Dr. Painter to become the acting president. He faced a dilemma. His research program was at a critical stage. He received many pro and con opinions from the faculty and other friends of the University. Finally he decided to accept the temporary appointment because that seemed to be the best way to keep faculty control over the destiny of the University of Texas. He and the Regents asked the faculty to form a com- mittee to suggest nominees for permanent president. When no satisfactory nominee was named, the Board of Regents appointed Dr. Painter to be president so that he could have full authority to carry out the needs of the University. The appointment was accepted with the stipulation that the term would last only until a satisfactory president could be found. Twice Dr. Painter wanted to resign from the presidency but each time he was persuaded to continue in the position. In 1952, his resignation was ac- cepted and he returned to his duties as a teacher. Without a cloubt Painter served his university effectively cluring a most trying period. He played the role of conserv- ative in the best sense. Although some members of the faculty protested when he accepted the change from acting presi- clent to president, because they felt that this was a repudia- tion of his promise not to accept an over for the full presi- dency, it may have been the only reasonable solution at the time to an irreconcilable conflict between the state repre- sented by the Board of Regents and the governorand the faculty of the University. Today, after clecacles have passed, the entire academic community can be grateful for Painter's skill at mediation and compromise. He retained the respect of all. RETURN TO SCIENCE Perhaps no challenge to a scientist who has absented him- self for some years is as great as that of returning to an active program of scientific investigation. The exponential advance
THEOPHILUS SHICKEL PAINTER 327 of science necessarily implies that during a lapse of even two or three years from the laboratory, fundamental changes in understanding will have occurred to such an extent that the returneci scientist's erase of current knowledge and mastery ~ ~ 1 of available techniques are outmocled. So it was with Painter, but his determination was indom- itable. His colleagues testify that he spent more time in the library reacting current periodicals and books than did any graduate student. He also asked to be reassigned to the teach- ing of cell biology to untlergracluates anti cytology to grad- uate students, and thus addled to his burden all the reviewing and relearning required for teaching. As the Memorial Res- olution prepared by his fellow faculty members records, he was successful: He developed a good knowledge of modern cellular molecular biology. Often he noticed that a researcher's data could be used to answer in part some classical biological problem, although the author had not mentioned that possibility. The interpretations were too narrow in coverage. As a consequence, Dr. Painter decided to teach his students the recent, chemi- cally-oriented discoveries and to make certain that they had a broader basic training in biology so that they could understand the biological implica- tions of the discoveries. To Dr. Painter, a narrow channel of research may find answers for one small field of interest, but it will not serve the purpose of biology unless it has some major impact upon a basic biological problem. One can verify his concern with the broader implications by glancing at eleven scientific papers written by Painter be- tween 1955 and 1969. They seem to follow naturally from the earlier work on the salivary chromosomes of dipterans ant! the endomitosis in the nurse cells of the ovary. But they all probe the greater question of how it is that the hereditary materials passer! down from one generation to another in the course of reproduction are converted into a multiplicity of end products in (different tissues. Working with J. J. Biesele again and with the advantage of electron microscopyPainter was able to show how the
328 BIOGRAPHICAL MEMOIRS precursors needed for the secretion of royal jelly (the only food consumed by the queen bee) are produced in the honey- bee in special gland cells of young worker bees. Producing as many as 1000 eggs a day, the queen bee requires a consid- erable supply of both proteins and DNA, which is supplied by the royal jelly. When workers feed heavily on bee bread, their gland cells develop and produce the royal jelly. According to George E. Palade, Keith Porter, and others, royal jelly gland cells in the young worker bees produce the proteins by means of an extensively developed endoplasmic reticulum. Painter and Biesele searched for the origin of this cellular structure of endoplasmic tubules that apparently de- rive from outpockets of the nuclear membrane of the cell as the gland cell undergoes endomitosis. As this process enters a stage comparable to the prophase of ordinary mitosis, the numerous nuclei in the gland cell fragment and a myriad of ribosome-like bodies pass out through nuclear pores to be- come the polyribosomes attached to the walls of the endo- plasmic tubules. This process clearly shows how an ovum be- comes enriched with protein and nucleotides. In his final paper, Painter advised vouna researchers from · - . AS own experience: J (J "I get the impression that young people [today] master some sophisticated technique such as labeling cellular structures with radioactive isotopes fol- lowed by autoradiography, DNA and RNA hybridization, ultracentrifu- gation in gradients and all the rest and then look around to see how they can use their acquired skills! From my experience I think you should first select and define some broad biological problems, select a suitable material upon which to work and use any available techniques for the solution of your problem. The most important thing is for you to have a biological and not a test tube approach." (1971,1) How well his own research exemplifies! that ability to identify the problem, find the right material, and develop the neces- sary techniques!
THEOPHIEUS SHICKEE PAINTER 329 Although research always stool! foremost in his heart, Painter found time and energy for many other activities. He served on the University of Texas Premedical, Predental, ant! Library committees. He frequently attencled the meetings of scientific societies and, in adclition to serving on other com- mittees of the American Philosophical Society, was a member of its Council from 1965 to 1967. He server! for six years on the Council of the National Academy of Sciences ant! six more on its Finance Committee. He was a member of the American Society of Zoologists, the Genetics Society of America, the Association of American Anatomists, the Amer- ican Society of Naturalists, and the Societa Italiana di Biolo- gia Sperimentale. He was a member of the Boy Scouts of America Commit- tee (1935-40), an advisor to the Dental Research Council (1949-52), and advisor on research to the American Cancer Society. He server! on the Commission on Colleges and Uni- versities of the Southern Association and was its chairman for three years; the Southern Regional Education Board; the National Committee on Accreditation; and the Board of the Institute of Nuclear Studies at Oak Ridge. He was a National Lecturer for Sigma Xi in 1936-37. Locally, he was a member of the Rotary Club, Town and Gown, and the English Speak- ing Union. He was electect to the Hall of Fame for Famous Ameri- cans, server! as president of the American Society of Zoolo- gists in 1940, ant! received the first M. D. Anderson Award for Scientific Creativity and Teaching from the M. D. Ander- son Hospital and Tumor Institute in 1969. Perhaps what he regarded most highly among his honors was his elevation to the rank of distinguishes! professor of the University of Texas in 1939. It was characteristic of him that he died as he had lived- suddenly, on his return home to Fort Stockton, Texas, from
330 BIOGRAPHICAL MEMOIRS a hunting trip, in his eighty-first year and as active as ever. Two papers- "The Origin of the Nucleic Acid Bases Found in the Royal Jelly of the Honeybee" (1969,1) and "Chromo- somes and Genes Viewed from a Perspective of Fifty Years" ~197 I, I) appeared posthumously. THE AUTHOR OF THIS MEMOIR iS deeply indebted to the Univer- sity of Texas Faculty Committee that prepared the Memorial Min- ute on T. S. Painter that is quoted above. Members of this Com- mittee were C. P. Oliver, chairman; I. I. Biesele; and R. P. Wagner. I would also like to acknowledge with deep gratitude the receipt of various documents, both published and unpublished, from Mrs. T. S. Painter. Without access to them there would have been seri- ous gaps in the account, especially in respect to T. S. Painter's ad- . . . ministrative career.
THEOPHILUS SHICKEL PAINTER 331 SELECTED BIBLIOGRAPHY 1913 On the dimorphism of the males of Maevia vittata, a jumping spi- der. Zool. Jahrb. Abt. Syst. Oekol. Geogr. Tiere, 35:625-35. 1914 Spermatogenesis in spiders. I. Zool. tahrb. Abt. Anat. Ontog. Tiere, 38:509-76. The effect of carbon dioxide on the eggs of Ascaris. Proc. Soc. Exp. Biol. Med., 11 :62-64. 1915 An experimental study in cleavage. I. Exp. Zool., 18:299-323. The effects of carbon dioxide on the eggs of Ascaris. l. Exp. Zool., 19:355-85. 1916 Some phases of cell mechanics. Anat. Rec., 10:232-33. Contributions to the study of cell mechanics. I. Spiral asters. I. Exp. Zool., 20:509-27. 1917 A wing mutation in Piophila casei. Am. Nat., 51:306-8. 1918 Contributions to the study of cell mechanics. II. Monaster eggs and narcotized eggs. J. Exp. Zool., 24:445-97. 1919 The spermatogenesis of Anolis carolinensis. Anat. Rec., 17: 328-29. 1921 Studies in reptilian spermatogenesis. I. The spermatogenesis of lizards. J. Exp. Zool., 34:281-327. The Y-chromosome in mammals. Science, 503-4.
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THEOPHILUS SHICKEL PAINTER 333 1927 The chromosome constitution of Gates' "non-disjunction" (v-o) mice. Genetics, 12:379-92. 1928 A comparison of the chromosomes of the rat and mouse with ref- erence to the question of chromosome homology in mammals. Genetics, 13: 180-89. The chromosome constitution of the Little and Bagg abnormal- eyed mice. Am. Nat., 62:284-86. Cell size and body size in rabbits. l. Exp. Zool., 50:441-53. 1929 With H. J. Muller. Parallel cytology and genetics of induced trans- locations and deletions in Drosophila. J. Hered., 20:287-98. With H. J. Muller. The cytological expression of changes in gene alignment produced by X-rays in Drosophila. Am. Nat., 63: 193-200. 1930 Recent work on human chromosomes. }. Hered., 21:61-64. Translocations, deletions, and breakage in Drosophila melanogaster. Anat. Rec., 47:392. 1931 With I. T. Patterson. A mottled-eyed Drosophila. Science, 73:530- 31. A cytological map of the X-chromosome of Drosophila melanogaster. Science, 73:647-48. (Also in: Anat. Rec., 51: 111.) 1932 With H. J. Muller. A cytological map of the X-chromosome of Dro- sophila. Proc. 6th Int. Congr. Genetics (Ithaca), 2:147-48. With H. I. Muller. The differentiation of the sex chromosomes of Drosophila into genetically active and inert regions. Z. Indukt. Abstamm. Vererbungsl., 62:316 - 65.
334 BIOGRAPHICAL MEMOIRS 1933 A method for the qualitative analysis of the chromosomes of Dro- sophila melanogaster. Anat. Rec., 57 (Suppl.~:90. A new method for the study of chromosome rearrangements and the plotting of chromosome maps. Science, 78:585-86. 1934 A new method for the study of chromosome aberrations and the plotting of chromosome maps in Drosophila melanogaster. Genet- ics, 19:175-88. The morphology of the X-chromosome in salivary glands of Dro- sophila melanogaster and a new type of chromosome map for this element. Genetics, 19:448-69. A new type of cytological map of the X-chromosome in Drosophila melanogaster. Am. Nat., 68:75-76. (Also in: Genetics Soc. Am., 2:45-46.) Salivary chromosomes and the attack on the gene. I. Hered., 25:464-76. 1935 Salivary gland chromosomes in Drosophila melanogaster. Am. Nat. 69:74. The morphology of the third chromosome in the salivary gland of Drosophila melanogaster and a new cytological map of this ele- ment. Genetics, 20:301-26. With Wilson S. Stone. Chromosome fusion and speciation in Dro- sophilae. Genet., 20:327-41. With I. T. Patterson. Localization of gene loci in the third chro- mosome of Drosophila melanogaster. Rec. Genetics Soc. Am., 4:76. (Also in: Am. Nat., 70:59.) Some recent advances in our knowledge of chromosomes. Advances inModernBiology, 2:216-23. Moscow: State Biological and Med- ical Press. 1937 Eds. T. S. Painter and I. B. Gatenby. Bolles Lee's The Microtomist's Vade-Mecum, 10th ed. Philadelphia: P. Blakiston's Son & Co. With Allen B. Griffen. The origin and structure of the salivary
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336 BIOGRAPHICAL MEMOIRS Cell growth and nucleic acids in the pollen of Rhoeo discolor. Bot. Gaz., 105:58-68. The effects of alkali and urea on different types of chromosomes. Anat. Rec., 87:462. 1944 A cytologist looks forward. Tex. Rep. Biol. Med., 2:206-22. The effects of urea and alkali on chromosomes and the interpre- tative value of the dissolution images produced. }. Exp. Zool., 96:53-76. 1945 Chromatin diminution. Trans. Conn. Acad. Arts Sci., 36:443-48. Nuclear phenomena associated with secretion in certain gland cells with special reference to the origin of the cytoplasmic nucleic acid. J. Exp. Zool., 100:523-47. 1953 Some cytological aspects of the nucleic acid problem. Tex. Rep. Biol. Med., 11: 709-14. 1954 Regional cooperation in education. Proc. Am. Philos. Soc.,93:266- 69. 1955 Do nuclei of living cells contain more DNA than is revealed by the Feulgen stain? Tex. Rep. Biol. Med., 13:659-66. 1958 The selection and recruitment of graduate students "First, you must catch your hare." Grad. J., 1:41-50. 1959 The elimination of DNA from some cells. Proc. Natl. Acad. Sci. USA, 45: 897-902. Some values of endomitosis. In: Biological Contributions. Ed. Mar- shall Wheeler. University of Texas, 5914:235-40.
THEOPHILUS SHICKEL PAINTER 337 1964 Fundamental chromosome structure. Proc. Natl. Acad. Sci. USA, 51: 1282-85. With I. I. Biesele and R. W. Riess. Fine structure of the honey bee's royal jelly gland. Tex. J. Sci., 16:478. 1965 John Thomas Patterson (November 3, 1878-December 4, 19601. In: Biographical Memoirs, vol. 38, pp. 223-62. New York: Co- lumbia University for the National Academy of Sciences. 1966 With I. J. Biesele. The fine structure of the hypopharyngeal gland cell of the honey bee during development and secretion. Proc. Natl. Acad. Sci. USA, 55:1414-19. With J. J. Biesele. A study of the royal jelly gland cells of the honey bee as revealed by electron microscopy. In: Studies in Genetics. III. Morgan Centennial Issue, ed. Marshall R. Wheeler. Univ. Tex. Publ., 6615:475 -99. The role of the E-chromosomes in Cecidomyiidae. Proc. Natl. Acad. Sci. USA, 56:853-55. With J. J. Biesele. Endomitosis and polyribosome formation. Proc. Natl. Acad. Sci. USA, 56: 1920-25. (Also in: Science, 154:426.) 1969 The origin of the nucleic acid bases found in the royal jelly of the honey bee. Proc. Natl. Acad. Sci. USA, 64:64-66. 1971 Chromosomes and genes viewed from a perspective of fifty years of research. L. J. Stadler Memorial Symp., 1:33-42.
