Perspectives

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

A DIAMONDIN A DESERT

first met LEWISJ. STADLERin 1936, in the spring did not have this shortcoming but therewere technical I of my senior year as anundergraduate at the difficulties to which I will refer in more detail later. University of Missouri in Columbia. I was told by a Although I was unaware of it at thetime, the spring faculty member in the Department of Chemistry that of 1936 saw the beginnings of the flowering of ge- he had recommended me toSTADLER to fill a vacancy netics at the University of Missouri. ERNESTR. SEARS as a technical assistant. After a brief interview, I was andJosEPH G. O’MARA came to theUniversity to join offered and accepted the job.I later became his grad- STADLER, GEORGEF. SPRAGUEand LUTHERSMITH. uate student. BARBARAMCCLINTOCK came in the fall of 1936 to a STADLERwas in mid-career when I joined his group. position in the Department of Botany. FREDM. UBER His principal goal in research was to identify the arrived at about the same time to a position in the material basis of the gene. To this end he devoted Department of Physics. His research, in collaboration himself to the study of mutations, those induced by with STADLER,was concerned with the genetic effects X-rays and ultraviolet light and those which arose of ultraviolet light. I was aware that LEWISSTADLER spontaneously. I was hired to help develop filters that must have had an important hand in these appoint- would screen out successive bands of ultraviolet light ments. The effect of his influence was obvious and it for the ultimate purpose of seeing which bands in- was also obvious that he was the acknowledged leader duced gene mutations, so that a profile of frequency of the group. His leadership was subtle since he held of mutations as a function of wavelength could be no official position that entitled him to assume such a obtained. Many substances of biological significance role. The group was not departmentalized; there was had known absorption spectra and it was his hope that no formal organization. I think he was recognized for the genic material could be identified by finding the his intellectual force and thatthis was the basis for his relationship between mutations and the wavelengths preeminence. He was easy-going, imperturbable and, that were effective in producing them. above all, brilliant. STADLER’Sinvestigation of gene mutation induced STADLERwas becoming more and moreinvolved in by X-rays, published in 1928, was a historical land- the use of ultraviolet light for the induction of chro- mark in plant genetics. H. J. MULLERearlier (1927) mosomal effects. The sunlamp that he was using was had published a more complete account of similar soon replaced by aquartz monochromator, which results with Drosophila. The two men arrived at their permitted him to treat pollen grains with individual results independently but MULLERwas favored in the wavelengths of ultraviolet light, thereby disposing of choice of material, Drosophila having a generation the need for filters. The lines of the ultraviolet spec- time of about 12 days whereas, at that time, only one trum could also be measured for the energy of emis- crop of corn (or barley,used by STADLERfor his early sion. The two sperm nuclei of each pollen grain are experiments) could be grown each year. Many of his eccentrically disposed, with a layer of starch and the contemporariesthought that STADLER should have outer layer of the pollen grain between the nuclei and shared the Nobel Prize that was awarded to MULLER the radiation. The loss of energy due toabsorption or in 1946. STADLERhimself extolled the achievements scattering by the overlying materials varied with the of MULLERin his posthumous article in Science (1 954). wavelength and was a significant factor in evaluating Drosophila was excellent experimental material for the radiation’s effects. Since the spherical pollen X-ray studies but was inadequatefor studies with grains assumed all possible orientations with respect ultraviolet light because the tissues overlying the testes to the sperm nuclei, correction had to be made for were relatively opaque to thewavelengths that proved the amount of overlying material as a functionof the to be effective in causing genetic effects. Corn pollen position of the sperm nuclei. Infact, it could be

Genetics 119 739-741 (August, 1988) 740 H. Roman

reasonably assumed that when the nuclei were farthest lacked anthocyanin; if the S element was lacking, the from the radiation source, that is, when the overlying seed was devoid of anthocyanin. Both P and S could material was maximal, most of the ultraviolet radia- mutate independently, but there was an interaction tion failed to reach the nuclei, the greatest loss occur- between them revealed by their rates of mutation, ring at the shorterwavelengths. each ofwhich fluctuated underthe influence of When these corrections were applied-the distri- changes in theother element. Thus the P and S bution of sperm nuclei by a formula devised by SE- elements were not only related, but the composition WALL WRIGHTand theloss of energy due to thepollen of one element or array of elements affected the rate grain contents above thenuclei, measured experimen- of mutation of the other. By one criterion-the fact tally byUBER-an experimental curve was obtained thatthe one couldmutate independently of the relating the effectiveness of the various wavelengths other-the two elements appeared to be separable as in inducing chromosomal effects (STADLERand UBER two genes; by the other criterion-the interdepend- 1942). The curve could be construed as denotingthat ence of the two elements-the R locus appeared to the absorbing material responsible forthe genetic house a single gene (STADLER1954; STADLERand effects was DNA. This remarkable achievementtakes EMMERLING 1956).The slight but constant variation on a new significance when one understands that the in phenotype of the many alleles testedindicated results were published decades in advance of the dis- furtherthat these might be the elusive truegene covery of the structure of DNA (WATSONand CRICK mutations of evolutionary significance. This was the 1953) and the interpretation that DNA was the ge- state of his investigations at the time of his death as a netic material. Small wonder that STADLERdid not consequence of Hodgkin’s disease on May 12, 1954, jump to this conclusion and in fact turned his attention at the ageof 58. to other ways of getting clues to the structure of the The quality of the group thathe had assembled, or gene. DNA was then regarded not as an informational was influential in assembling, is indicated by the hon- polymer but as a molecule too simple in structure to ors that were awarded to membersof the group, either account for gene replicationor theeffects of the gene. before or afterhis death. STADLERhimself was elected In a series of persuasive papers, STADLERpointed to the National Academy of Sciences, the American out thatradiation-induced mutations could not be Academy of Arts and Sciences and the Philosophical assumed to be true gene mutations, that is, those of Society. MCCLINTOCK,SPRAGUE, and SEARSwere also consequence in the evolutionary process. True muta- elected to theNational Academy of Sciences. SPRAGUE tionscould not be easily distinguished fromother (1978), MCCLINTOCK(1981) and SEARS (1986) each genetic effects induced by radiation, such as chromo- shared the Wolf Prize. In addition, MCCLINTOCKwas somal aberrations, including small deletions and po- awarded the Nobel Prize in 1983 in recognition of sition effects. Thus their frequency could not be de- her discovery of what are now known as transposable termined precisely, but a very low upper limit could elements. be set. I am reminded at this juncture of a conversation I STADLERnext turnedto spontaneous mutation, that had with MAX DELBRUCKon the occasion of his first is, mutation whose origin was unknown but which, in visit to the United States, in 1937. I asked him why his estimation, offered a greater possibility of estab- he had chosen to come to the University of Missouri, lishing criteria for the true gene mutation. He chose which was out of the way in his extensive itinerary. the R locus for this purpose because this locus was He replied that one had to come to Columbia if one sufficiently variable in the different strains of corn was interested in the nature of the gene, no matter if that were under cultivation, because it had a mutation it were out of the way. “It’s a diamondin a desert.” rate that was not so rare as to be unmanageable, and What more can be added to describe this remarka- because it had well defined phenotypes. The R locus ble man? He was a master of experimental design. His affected anthocyanin pigmentation in various parts of lectures and writings were noted for their clarity and the plant and in the seed. lucidity. He was always approachable. He was a gentle After an extensive series of experiments with dif- man, quiet but sure of himself. I never knew him to ferentstrains of maize, collected from presumably be angry with his colleagues or tospeak ill of anyone. independent sources, STADLER concluded that theR He and his wife CORNELIA werecordial hosts and it locus consisted of two sets of elements, those that was a great pleasure to be a guest in their home. A affected pigmentation in the plant (P)and those that memoir published for the National Academy of Sci- affected pigmentation of the seed (S). The number of encesprovides information about STADLER’Sback- such elements could not be ascertained but each had ground andfamily life, and brings together aspects of enough homology to the other so that the two could the scientist and the private man in a way that gives a be separatedby unequal crossing over. If P was absent, more complete portrait of an extraordinary person under the appropriate genetic background, the plant (RHOADES1957). Perspectives 74 1

I am indebted to my wife CARYLfor her help in recalling events RHOADES,M. M., 1957 Lewis JohnStadler 1896-1954. Biogr. of some 50 years ago and her expert editing of the manuscript. Mem. Natl. Acad. Sci. 30 329-347. Thanks are also due to E. R. SEARS,who made valuable comments STADLER, L.J., 1928 Mutations in barley induced by X-rays and in its preparation. radium. Science 68: 186-187. HERSCHELROMAN STADLER,L. J., 1954 The gene. Science 120: 81 1-819. Department of Genetics STADLER,L. J., and M. M. EMMERLING,1956 Relation of unequal University of Washington crossing over to the interdependence of R’ elements (P)and Seattle, Washington, 98 195 (S). Genetics 41: 124-137. STADLER,L. J., and F. M. UBER,1942 Genetic effects of ultraviolet radiation in maize. IV. Comparison of monochromatic LITERATURECITED radiations. Genetics 27: 84-1 18. MULLER,H. J., 1927 Artificial transmutation of the gene. Science WATSON,J. D., and F. H. C. CRICK,1953 Genetic implications of 46: 84-87. the structure of deoxyribonucleic acid. Nature 171: 737-738.