Perspectives

Anecdotal, Historical and Critical Commentaries on Genetics Edited by James F. Crow and William F. Dove

Harvard, Agriculture, and the Bussey Institution

J. A. Weir

Division of Biology, University of Kansas, Lawrence, Kansas 66045

The genes are units useful in concise descriptions of the From a movement led by the physicist WALLACESABINE, phenomena of heredity. Their placeof residence is the chro- a GraduateSchool of Applied Science was organized in mosomes. Their behavior brings about the observed facts of 1906 to replace the undergraduate Lawrence Scientific genetics. For the rest, whatwe know about them is merely an interpretation of crossover frequency. In terms of geometry, School. As part of the reorganization in 1908, “Bussey” chemistry, physics, or mechanicswe can give them no descrip became a graduateschool for advanced instruction and tionwhatever. E. M. EAST (1926) research in scientific problems that relate and contrib Ute to practical agriculture and horticulture-this just at the time when the claims ofgenetics could no longer be ENETICS had its first influence in agriculture and ignored. In recommendingto President ELIOTthat W. E. G first achieved independent status in agricultural CASTLE’S work be transferred from Cambridge to the colleges. The main training ground was the Bussey In- Bussey Institution, Dean SABINEwrote, “The University stitution of Harvard University. has Professor Castle to start with; to lose him will be to By his will of 1835, BENJAMINBUSSEY left his extensive lose the best man in the country in genetics.” So instead farm (now the Arnold Arboretum) toHarvard to be held of going to Wisconsin or Yale, CASTLE moved hisanimals forever as a Seminary for “instruction in practical agri- to Forest Hills, soon LO be joined by the noted plant culture, in useful and ornamental gardening,in botany, geneticist EDWARDMURRAY EAST from the Connecticut and in such other branches of natural science, as may Agricultural Experiment Station. CASTLEand EASThave tend to promote a knowledge of practical agriculture, been thesubjects of recent Perspectives (SNELLand REED and the various arts subservient thereto and connected 1993; NELSON1993); see also the biographies by WRIGHT therewith.” The government of the University is also“to (1963) and JONES (1944). cause courses of lectures to be delivered there . . . and WILLIAMMORTON WHEELER, an erudite scholar who also to furnish gratuitous aid . . . to such meritorious rated artistry in taxonomy above all hisother powers, left persons as may resort there for instruction.” Texas in1908 to join the Bussey as Professor of Economic The bequest did not become available until 1861, and Entomology. He was appointed dean in 1915 when the the school did not open until 1871, following the con- Bussey was separated from the other schools of applied struction of a suitable building. The initial appoint- sciences, but in 1929 he resigned in favorof the more con- ments included, as instructor of farming, BUSSE~S genial atmosphere of the Museum of Comparative Zool- grandson-in-law, THOMASMOTLEY, who came with the ogy. IRVINGW. BAILEY, who came to the Bussey from the farm; FRANCIS STORER, brother-in-lawHarvard’s of Presi- defunct School of Forestry, acted as secretary. Between dent ELIOT,as professor of agricultural chemistry and 1912 and 1939, 44 doctorates in genetics were awarded. dean; andFRANCIS PARKMAN, famous the historian, as pro- Animal genetics had its roots in liberal arts, not ag- fessor of horticulture. riculture, with Johns Hopkins University as the early The resourcesfor the school were seriously de- leader. E. B. WILSON,the cytologist (Ph.D. 1881), T. H. pleted when a number of Bussey estate rental prop- MORGAN(Ph.D. 1890), E. G. CONKLIN(Ph.D. 1891), and erties were destroyed in theGreat Boston Fire of R. G. HARRISON (Ph.D. 1894), ostensibly students of the November 9-10, 1872. The meager income was aug- morphologist W. K. BROOKS,came under the influence mented by growing vegetables, cutting firewood, and of the physiologist H. NEWELLMARTIN and, except for CON- boarding horses. The school never did come up to WN, hrthered their studies inEurope. (MORGAN,who re- Harvard undergraduate standards,which were not all tained his interest in embryology,was the only one to be- that high, at best. come a member of the Genetics Societyof America.)

Genetics 136: 1227-1231 (April, 1994) 1228 J. A. Weir

At Harvard, C. B. DAVENPORT(Ph.D. 1892) and W. E. breeder, whereas H. C.MCPHEE (EAST’S student) became CASTLE(Ph.D. 1895) were students of EDWARDL. MARK, Chief of the Animal Husbandry Division of the U.S. Bu- whose doctorate in 1876 from the University of Leipzig reau of Animal Industry. P. W. GREGORYwent to Davis, was under RUDOLPHLEUCKART, an early proponent of the where he investigated the genetics of cattle, including need to combine morphology and physiology. Their the- size inheritance,and alsoworked with rats. EDWARD ses, based on morphological studies, were published in LIVESAYbecame professor of animal husbandry at West the Bulletin of the Museum of Comparative Zoology. Virginia. NELSON WATER^ went on to a career in poultry Both DAVENPORTand CASTLEhad farmbackgrounds and research. Four of CASTLE’S23 doctoral candidates spent later worked with laboratory and farm animals. DAVEN- their entire careers after graduation working with eco- PORT, with a B.S. degree in civil engineering, brought nomic species; four others were so engaged over a pe- quantitative methods to biology but turnedhis attention riod of years. EAST’Sstudent, W. R. SINGLETON,studied to eugenics and administration. CASTLE, whoassisted coat color inheritance in horses in collaboration with DAVENPORTas a student and succeeded him at Harvard CASTLE.The first generation of geneticists were able to when DAVENPORTdeparted in 1899, had little interest in pursue problems in pure and/or applied research. eugenics and nonein administration, but they remained CASTLE’Sown favorite specieswas the rat. He hadcome close friends, and DAVENPORT,through control of Car- to distrust the conceptof gametic purity on finding that negie funds, provided assistance to CASTLEat the Bussey. the Mendelizing guinea pig characters, polydactylism, Both men were interested in heredity even before 1900, long hair, and rough coat were not exactIy the same so their grasp of Mendelism, after its rediscovery in 1900, when extracted from crosses. To test his hypothesis, he was not immediate because they carried a considerable undertook aselection experiment with hooded rats and baggage of seemingly conflicting evidence. by 1914 had rearedand studied the color pattern of over After the rediscovery of MENDEL’Slaws, there ensued 25,000 rats. With great persistence he defended his hy- lively debate about the extentto which the laws applied pothesis in the face of mounting criticism-some rather to animals, including man.Naturally it was the conspicu- heated. EMERSONand EAST’Sclassic paperon maize, ous characters that attracted attention at first, but, as the showing that quantitative charactersare inherited in Men- inheritance of more and morecharacters was shown to delian fashion,appeared in 1913,a year beforethe comple- behave according to simple Mendelism or oneof its eas- tion of CASTLE and PHILLIPS’monograph (1914).The con- ily understood modifications, attention shifted to the cept was debated in Bussey seminars, with CASTLE and EAST materials in their own right-on one hand,as sources for holding opposing views. CASTLE was not convinced until he new problems; on the other, as a new approach to the performed the critical experiments suggested by WRIGHT. solution of old problems, such as the limits of selection His retraction appeared in the American Naturalist in 1919 or the consequences of inbreeding. (CASTLE 1919).In L. C. DuNN’swords, “Castlecured himself From 1901 to 1905, CASTLE,with the cooperation of of disbelief inthe integrity of the gene the hard way-by 15 four students in successive years, followedthe effects of years of arduous experimentation.” inbreeding in Drosophila melanogasterthrough 59 gen- It is noteworthy that bothCASTLE and EASTconsidered erations of brother-sister mating. After the move to the it the function of the professor to provide space, mate- Bussey, no one used Drosophila for thesis research, but rials, encouragement, and little else, with course work in it became the favorite material for Harvard undergradu- diverse areas only suffkient to broaden the students’ ate teaching in Cambridge, so the graduate students perspective. CASTLE’Sfirst graduate students, JOHN A. were familiar with its usefulness. They kept abreast of DETLEFSEN,who axrived in 1908 and worked with guinea developments and some, notably E. C. MACDOWELL,L. C. pigs, and EDWNCARLETON MACDOWELL,who arriveda year DUNN,and S. C. REED, later used Drosophila for research. later and worked with rabbits, receivedtheir doctorates in Although he emphasized the importance of labora- 1912. They did not share CASTLE’S skepticism concerning tory animals in the study of inheritance, CASTLE retained the multiple-factor theory, and MACDOWELL’Sthesis, pub- an interest in farm animals. Between 1940 and 1961 lished as a monograph (1914),carried a prefatory note (after retiring to Berkeley) he published 17 papers on by CASTLE:‘Wile not entirely sharing his views, I have coat colors in horses, and while at the Bussey he pub- tried not to bias his judgment either for or against the lished on inheritance in sheep and dairy cattle and on multiple-factor hypothesis which he adoptsin this paper. various aspects of animal breeding. But to avoid misunderstanding, I wish to say that in my After graduation, a number of CASTLE’Sstudents and own opinion the theory of the purity of the gametes has two of EAST’Sworked with economic animals. JOHN not been established.” CASTLEwas aware that the top DETLEFSENworked with rats, mice, and cattle at Illinois. signer of the thesis is not the only or even the chief source SEWALLWRIGHT went to the Bureau of Animal Industry, of guidance. He himself had been influenced more by while L. C. DUNNwent to the Connecticut Agricultural C. B. D.4WNPORT than by his professor, E. L. MARK. Experiment Station at Storrs, where he worked with The only students to use rats exclusively for doctoral poultry. TAGEELLINGER from Denmark became a plant thesis research were H. W. FELDMANon sterility and 1229 fertility, GREGORYPINCUS on cytological studies, and breeding with emphasis on maize. (His doctoral re- LIVESAYon hybrid vigor, whileDUNN andW. L. WACHTER search was on the potato.) In1905 EASTjoined the Con- worked on linkage in rats and mice. CLYDEKEELER’S thesis necticut Agricultural Experiment Station where he re- was on rodless retina in mice, but hepublished 18 papers mained until the call to Harvard in 1909. between 1940 and 1949 on rats. LAURENCE SNYDERpub- Relations between EAST and his student, R. A. EMERSON lished on the effects of X-rayson rats while at theBussey, (S.D. 1913),were unusual in that EMERSON,6 years older but his doctoral thesis was on blood groups in man, and than EAST, was already an established investigator at the he remained a humangeneticist. With great persistence University of Nebraska.The two remained close friends himself and toleranceon the partof others, CASTLE con- and collaborators. tinued to collect and study mutants in the rat,even after Although EMERSONwas the first to earn the doctorate moving to California in 1936. degree in plant genetics at the Bussey, he was not EAST’S Rabbits and guinea pigs were natural choices at the first graduate student. That distinction goes to H. K. turn of the century because both species thrive under HAYES, whojoined theConnecticut Station as assistantto ordinary laboratory conditions. CASTLE assembled and EASTon July I, 1909. EASThad already accepted the offer studied a number of traits before the Bussey was reor- from Harvard but remained at the Connecticut Station ganized, but about theonly ones to stick mainly to one until the fall. Withthe Harvard master’s degree in 1911, species were SEWALLWRIGHT with guinea pigs and PAUL HAYESdid notsubmit his doctoral thesis until 1921,using SAWNwith rabbits. C. C. LITTLE,founder of The Jackson data on wheat and corn from the University of Minne- Laboratory, was the first graduate student to work with sota, the institution he joined in 1915. mice, but eventually most of CASTLE’Sstudents adopted As successor to HAYES, DONALDJONES (S.D. 1918) was the mouse, as did WRIGHT’S.W. H. GATES’ thesiswas on the sole geneticist at the ConnecticutStation from 1915 theJapanese waltzing mouse, later shown by T. S. until 1921, when PAULMANGLESDORF came as his assis- PAINTERto involve a chromosome deletion.In the 1930s, tant. With materials left behind by EASTand HAYES,prior SHELDONREED worked on harelip, FRANKCLARK on hy- experience in practical horticulture, and friendly rela- drocephalics, siderocyte anemia and brachyury, SUMNER tions with EAST and E. H. JENKINS, JONES was in a par- BURHOEon waved coat, and LLOYDLAW on size inherit- ticularly favorable position. With an undiminished pas- ance. It became increasingly evident that the mouse sion for gardening and plant breeding, JONES became would serve asa model for humandiseases. At Columbia involved in theoretical genetics-the theory of heterosis, University DUNNpicked up work on themouse where he cytoplasmic male sterility, fertility-restoring genes, so- had left off as a student (having published on black- matic segregation, and sex differentiation-but he is best and-tan in 1916, on yellow in 1919, and on sable and known as the inventor of the doublecross method of corn white spotting in 1920). He brought the much debated breeding and as co-author with EAST of Inbreeding and Out- role of modifjmg genesto a satisfactory state by his thor- breeding(EAS~and JONES 1919).For further information on ough analysis of“subthreshold alleles”that modify spot- EAST, EMERSON,and JONES, see NELSON (1993). ting. He early perceived that thet-complex was uniquely Before mechanization, the horse was theunit of fitted for intensive study of gene action, while the dis- power, animal husbandry was in the driver’s seat, and covery oft mutants in feral populations led to studies in vocational subjects prevailed. Consequently, eventhough population genetics and distorted segregation ratios. he majored in chemistryand physics, R. A. BRINK’Sdegree Even though their attendance at the Bussey Institu- from the Ontario Agncultural Collegewas not accepted by tion was separated by 10 years,the careers of DUNN(S.D. Cornel1 University.So he went to Illinois, wherehe became 1920) and GEORGED. SNELL(S.D. 1930) were strikingly a botanist, obtained a master’s degree, and was recom- similar. Both became interested in genetics under the mended to the Bussey by DETLEFSEN. influence of JOHN H. GEROULDat Dartmouth College; At the time, EAST’Sexperimental work was confined both had experience with mice before attending the almost exclusively to studies on self sterility in tobacco. Bussey, and their dissertations involved linkage in ro- J. B. PARK(S.D. 1916), andEDCARANDERSON (S.D. 1922) dents; both later came to concentrate on a very small before BRINKand E. R. SEARS (S.D.1936) after, worked segment of a mouse chromosome, and in the process on different aspects of the problem.BRINK’S assignment each developed stocks that are highly prized. In 1980, was the physiology ofpollen. That thematching of prob- GEORGESNELL, age ’7’7, shared the Nobel Prize in Physi- lem and studentwas not aperfunctory matter is evident ology or Medicine for his work on histocompatibility from EASTto SEARS(June 14,193’7):“I am sorry that, with genes. Similarities between the HLA system in humans the amount of work you have gone through, there are and the major histocompatibility complex in mice have so manynegative results. . . You begin to see how reinforced the fundamental nature of SNELL’Spainstak- difficult it is to set out problems for graduate students ing efforts over many years. where the problem is worth while and results can be E. M. EAST was trained as a chemist, but as assistantto more or less guaranteed inside of three years.” The the- C. G. HOPKINSat Illinois he became interested in plant sis problem was by no means an end in itself, and most 1230 J. A. Weir

Bussey students pursued quitedifferent lines ofresearch Staking out for himself the much neglected classifi- in later life. BRINK’Sdistinguished career at Wisconsin, cation of weeds and cultivated plants, ANDERSON made with contributions to plant breeding andtheoretical ge- contributions to methodology, theory, and teaching netics, is described by OWENand NELSON(1986). methods. Impressed by the rarity of hybrids under natu- KARL SAX (S.D. 1922) and PAULMANGLESDORF (S.D. ral conditions in contrast to thesurvival of hybrid swarms 1925) channeled their research to conform to Harvard in “hybridized habitats,” he emphasized the role of in- directions. On appointment in 1928 as Associate Pro- trogressive hybridization in plant evolution. His closest fessor of Plant Cytology at the Arnold Arboretum, SAX friend; G. L. STEBBINS, with similarinterests, was never abandoned work with wheat, dividing his efforts be- connected directly with the Russey, although KARL SAX tween horticultureand comparativechromosomal was on his thesis committee. studies. Later he turned his attention to radiation cy- At the Sixth International Congress of Genetics held tology, a line followed by a number of his graduate in Ithaca, New York,in 1932, there were 399participants students.In 1940, when MANGLESDORFreturned to from the United States, including CASTLE,EAST, and 32 Harvard, hemade the transitionfrom practical of their students (Figure 1). T. H. MORGAN,from Cal breeding to study of the ancestry of corn, an inter- Tech, was president of the Congress, but formerBussey est he acquired at Texas A and M. student C. C. LITTLE waschairman and general secretary, RALPH SINGLETON(S.D. 1936), like SAX,received his L. C. DUNNwas secretary of the council, E. M. EASTwas BSc. and M.Sc. from Washington State College and was chairman of the program committee, and D. F.JONES was steered to theBussey by E. F. GAINES. Hisdoctoral thesis chairman of the publications committee. Because the was on tetraploid hybrids in tobacco. As senior ge- conference was held at Cornell, with R. A. EMERSONas neticist (1948-1955) atthe Brookhaven National chairman of the local committee, theselection cf Bussey Laboratory, he studied induced mutations ingrowing men is not surprising, but it is significant that this carried plants laid out in concentric circles around a central over to the organization of the Genetics Society of cobalt-60 source. America later in the same year. E. R. SEARSand HAROLD SMITH(Ph.D. 1936) were Upthrough 1931 genetics was affiliatedwith the among the last of the Bussey students. 0. D. BEASLEY‘S American Society of Zoologistsand the Botanical Society Ph.D. was awarded in 1939.) SMITHended up as Profes- of America. Becausea numberof geneticists were mem- sor of Plant Genetics at Cornell, while SEARSspent bers of neither Society, it was decided in 1931 to reor- his entire career after graduation at the University of ganize the Joint Genetics Sections as an independent Missouri. Pickingup where SAXleft off, SEARSlaunched society. A cordial invitation was tendered to “geneticists a research program in wheat cytogenetics that re- interested in agriculture” toapply for membership. R. A. mained at the cutting edge throughout his lifetime. BRINKwas chosen to organize symposia of interest to He developed thecomplete series of wheat aneu- agriculturists, but “GeneticistsInterested in Agriculture” ploids, nullisomic through tetrasomic, for all 21 chro- was discontinued as a separate group. The first seven mosomes. Also, combining a number of techniques, presidents of the Society had Bussey connections: including X-irradiation, he was able to transfer disease Year President Location resistance to wheat from a wild relative. 1932 L. C. DCNN Co!umbiaUniversity EDGARANDERSON’S career was unlike that of any other 1933 R. A. EMERSON Cornell University Bussey graduate student.Shy, precocious, introspective, 1934SEWALL WRIGHT Universityof Chicago independent, disliked by Bussey classmates, but afavor- 1935 D. F. JONES Connecticut Agricultural ite of EAsT’s-whom he admired but with reservations- Experiment Station ANDERSON was fitted to break new ground in a field es 1936 P. W. WHITING UniversityofPennsylvania chewed by other students from agricultural colleges. 1937 E. M. EAST Harvard University Since the secrets of inheritance had come from artifi- 1938 L. J. STADLERUniversity of Missouri cially cultivated forms, it is not surprising that geneticists were unsympathetic to themethodologies of taxonomy. (WHITINGwas a research worker at the Bussey in 1927, ANDERSON used genetics as a tool rather than an endin STADLER in 1925-1926.) itself and was primarily a naturalist. Of graduate school At the Seventh International Congress held in London, he said, “My thesis [the genetic behavior of cross sterility Cambridge,and Edinburgh in 1939, the Busseywas again well in Nicotiana] was not particularly interesting: the topic represented. In additionto nine holders of theBus~ey doc- was largely a question of whatwas available. I don’t think torate, the program included presentationsby 12 Bussey vis it did me any harm and it did give me an insight into iting scientists, most of whom had spent 1 or 2years there. a certain field” (ROE 1952, 98). p. After graduation, ANDER- To declare financial exigency as the reason for closing SON spent his entire professional career attached to the an institution is like sayingthe candidatelost because he Missouri Botanical Garden in St. Louis (1922-1931 and didn’t get enoughvotes. The tide in the affairs of men 1935 on) and the Arnold Arboretum (1931-1935). began in earnest in 1924, the year that Harvard failed to 1231

FIcmKI;. 1.-A group picture of attendees at the 1932 International Congress of Genetics at Cornell University who had been associated with the Bussey Institute. Its influence is apparent. Front row: KmI. SAX,L. C. DUNN,P. w. WHITING, c. c. LITTl.E, 0.E. WHITE,Mrs. W. E. CASTLE, Mrs. KARL SAX,E. M. EAST, N. F. WATEKS,F. H. CLARK, D. W. DAVIS,R. A. EMEKWN.Second row: G. G. PINCUS, E. c. MACDOWI-I.,R. B. (hLDSCHMIDT, w. E. CAvI.E, H. w. FELDMAN,L. H. SmER, H. c. MCPHEE,G. L. SIATE, E. F. GAINFS, R. A. BRINK,E. N. WENTWORTH.Third row: A. MARSHAK,J. BEN HILI.,HAIG DERMEN,L. J. STADLER,P. C. MANGELWOW, S. C. REED, EDGAR fb4DERSON.J. B. PARK, G. D. sNEl.l., J. I. &.NI)AI.I., D. F. JONFS. Back row: M. R. IRWIN, w. R SINGLETON, s. H. YARNEI.1.. H. P. RILEY, T. w. WHlTAKER, L. c. STRONG,WlL.I.IAM GATFS,P. W. GKEC;ORY, C. R. BURNHAM,P. B. SAWIN, R c. Ronn. respond to the Rockefeller Foundation’s willingness to LITERATURE CITED invest up to $20,000,000 as an endowment fora broadly Ckr1.E. W. E, 1919 Piebald rats and selection, a correction. Am. Nat. conceived program of fundamental biological research. 53: 370-375. Although the Bussey lingered on until 1936, the final CA.STI.E,W. E., and J. C. PHILLIPS, 1914 Piebald rats and selection. Publication No. 195, Paper No. 21. Carnegie Institutionof paroxysm occurred in September 1929 when, by a vote Washington, Washington, D.C. of 10 to 9, theBoard of Overseers turned down the Har- EA.-, E. M., 1926 The concept of the gene. Proc. Int. Congr. Plant vard Corporation’s decision to appoint RAYMOND PFARL Sci. 1: 889-895. FA.ST, E. M.,and D. F. JONFS, 1919 Inhrppdingnnd Ozctbr~rding.J. B. as dean of the Bussey Institution. Lippincott, Philadelphia. Joining the University of California in 1936 as re- EMERSON,R. A,, and E. M. EAST, 1913 The inheritance ofquantitative search associate in mammalian genetics, CA.STLE became characters in maize. Bull. Nebraska Agric. Exp. Sta. 2 1-120. JONFS, D. F., 1944 Edward Murray East (1879-1%8). Biogr. Mem. the first recipient of the Kimber Genetics Award of the Natl. Acad. Sci. 23: 217-242. National Academy ofSciences in 1955 and continued to MAcDowEI.I., E. C., 1914 Size inheritance in rahbits. Publication No. work almost up to his death in 1962. 195, Paper No. 22. Carnegie Institution of Washington, Wash- ington, D.C. On April20, 1937, WILLIAMMORTON WHEELER col- Nmwx, 0.E., 1993 A notable triumvirate of maize geneticists. lapsed on theHarvard Square subway and died within a Genetics 135 937-941. few minutes. On November 8,1938, RALPH W. WETMORE OW.N,R. D.,and 0.E. NELSON, 1986 Row. ALEXANDERBRINK, 1897- 1984. Genetics 112: 1-10. spent the eveningwith EASTin the hospital where EAST’S ROE, A., 1952 Thp Mnking of n SriPnlist. Dodd, Mead & Co., operation was scheduled for the following morning. New York. Recalling events of his career in genetics and grasping SNEI.1.. G. D., and S. REED, 1993 WIr.1.mM ERNF-STCASTLE, pioneer mammalian geneticist. Genetics 133 751-753. WETMORE’Shand in both of his, EAST said, “Tomorrow WRIGHT,S., 1963 Wll.l.lnw ERNE.STG\sn.E, 1867-1962. Genetics 48: it will be all over.” It was. 1-5.