* FE,f-LO'tiSiitP AP?i.ICATiON FORM CONFIDEM ;Of-fN.`SIMON GUGGENHEIM MEMORIAL FOUNDATION 551 FIFTH AVENUE*NE'M'~u.QKK 17-N&\- 1 \";' ice 1 *-I .- .j . . ..c..:r.- '\ APPLICATIONS and accompanying documents than October 15 of each year. In wha; field of leazzlice;, or of art, does your projd lie? Biology G~nci~ statement of project M~~ta.ki nn -in C . . .-___-__ -----I~-- ---T,.., . . . PERSONAL HISTORY: . . . .._.___ - _ ._ ----__ - ---_- -_ ___..- -- -.-.- __ _-____ _____- - Telephone TTn i VP? -xl&~ T 4 -&~cl. A permanent address~JL-.JJJth St ,J!kw~~k 35 N V -.._ Present 0ccupationAssoCiateX essornf -- ---.--.._. -- Place of birth_Br_ooklvn,L ~Datao~birdiZ~~~~ If not a native&m American citizen, date and place of natnrahtion. - ------ - Single, Married, Widowal, DivoUUd Name and addnse of wife or hu&adAU.zabeth J. Ry;rrq 501 14, 11~ _ ~JPW ~nrtc 25 Name azd address of neareat kin, if unmarried -_--__-- ___________ Ages of children, if any v--p ,-- . Have you any constitutional disorder or physical disability?-...--_- ____. -EL- -_- ~itt?tbisapplicationplea~saubmita errna~~~~Wp3ph. Please see attached sheet, 1. Give a axmmary of your education in the following form: Name of Institutio5 Academic: college Fordham Columbia university Columbia .-- Tech!licaI Profauional Mueicai hxtiatic ~ Sped Study __ Period of Study Degrees, Diplomas, (give data) certificate8 (gbe autu) --iw3-1974 1934-1937 A.B. 1937 - 1937-1941 A.M. 1939 -- -- Ph.D. 1941 ----- -- --------_ --------- -------~ - ---- 2. Give, a list of the scholar&pa or fellowships you have previously held or now hold, stating in each case the phms and perk& of tenure, the tidies pursued during your iwumbency, and amounts of&ertipm&: .National Research Council Fellowship in Zooloas. Stanford . * velmt of froEs eas and 3. State what foreign Ianguagea you have studied, and whether you are able to consult works on your s&j& in these: bguageee. Estimate your proficiency in reading, writing and qeaking each of wig-m? difficulty. -.-.-___ Francis 5. Ryan 2. 'Gf what learned, scientific or artistic societies are you a member? Phi Beta Kappa -Sigma Xi American Society of Zoologists American Society of Bacteriologists Botanical Society of America Genetics Society of America Society of Vertebrate Paleontology Marine Biological Laboratory Corporation, Woods Hole New York Academy of Sciences American Society of Naturalists Harvey Society . 1. Positions held (professional, teaching, scientific, administrative, business) : .Name of Institution or Org&tion Columbia University n . 11 I1 11 II 11 Title of Position Years of Tenure (Sk lb-4 Instructor 1942-19&1- Assistant Professor* 194-k-1946 11 n 1946-1948 Associate Professor- 19480 Comperution $2,800 4,000 5,500 6,600 ' . . 2, Of what learned, scientic or artistic societies are you a member?-- _--.-- 3. Submit a fuU account of tbe advanced work, research, or creative work you have already done, giving dates, subjects, and names of your principal teachers in these subjects. What are your present attainmenta in your proposed field of study? 4. Submit a list of youlr publications with exact titles, names of publishers, and dates and places of pUbIicSti05* (Please submit NO copies of each statement requested zmder items 3 d 4, above. Pkxzse do not submid copies of pub&x&ss or -cripts.) PLANS FOR WORK: Submit a statement giving detailed plans for the work you would pursue during your tenure of a Fellowship. This statement should include, &er u&u: a description of the project, including its character and scope, and the significance of its presumable contribution to knowledge, or to art; the present &ate of the project, time of commencement, progress to date, and expectation BS to oom= pletion; the place or places where the work would be carried on, and the authorities, if any, with whom it would be done; your expectation a8 to publication of the results of y0w.r work; and your ultimate purpose a6 a scholar or artist. This st&lenaent shdd be complete and carefuliy prepared. (Plee.se submit one more copy of IXANS FOR WORK than the number of your references.) If awarded a FeUowsh+- When would you wish to commence the study proposed?S.entember.L . . . %t is your estimate of its probable duration?..-U~&h~ filvq ng lprhti> ~-UP T shall be on sabbatical leave with a salary of $3,000. REFERENCES: Submit a list of names of persons from whom confidential information may be obtained concerning your abilities, especially in relation to the work you propose, and from whom expert opinion may be obtained as to the value and practicability of your proposed work. (All statements by references to the Foundation are held strictly confidential.) Name of Reference Position I Address I *J' G.W... Beadle Professor of Biolog si Biological Laboratories Executive Office of j California Institute of the Department J Technology. Pasadena, Calif. E.L. Tatum IProfessor of Biology Department of Biology d I Stanford University. Cal. K.W. Cooper 'Associate I Professor 1 Department of Biology of Biology Princeton University 1 I Princeton. N.J. Franz Schrader Department of Zoology 27 27 I period, state the facts regarding such applications:I&&z&-to appJ P to the Car- d of . Assoc.lated -ResearchW~f l?: .and-to-t.hP . Foundation as alternate possibilities. I-- --- --- - --~- -- -- --- . . If you apply elsewhere for any fellowship or scholarship after presenting this application, please notify the Foundation jmmediately. . SIGIUT~JRE- __Z------ --__ --- PLACE ANDDATE OFMAILING - - 1. 2. 3. 4. 5. 6. 7. SUGGRSTIGNS CONCERNING APPLICATIOfiS If convenient, please type application and additional material Use paper the size of this sheet, 8%" x ll', if possible, for writing all documents submitted. Every page or document submitted must bear the applicant's name plainly written. ' , Whenever tbe space provided in this form is not suitable for an applicant to present fully -the facts of his or her case, it is requested that they be stated in a separate document. Only one copy of the application form should be submitted to the Foundation by the applicant; the other may be retained by him for his own files. It is suggested that applications and accompanying documents be sent by registered mail, addressed to the John Simon Guggenheim Memorial Foundation, 551 Fifth Avenue, New York 17, N. Y. If you do not get a receipt for your application within a reasonable time, please notify the Foundation. ' i `.. . . 1 Francis J. Ryan 1940 1941 1941 1943 1943 1w 1944 1944 1945 1945 1945 1945 LIST OF PUBLICATIONS . - . Francis J. &Ryan and Ronald Grant. Tha ~thih~ for matu- ration and for ovulation of the frog's egg. pplys. 2001. 13:383-389. Francis 3. Ryan. The time-temperatW?@ relation of dif- ferent stages of development, Bi01, Bull. 81:432-440. Francis J. Ryan. Temperature change and the subsequent rate of development. 3. EXP. 2001. 88:2W+. Francis J. Ryan. Crossfng-over and second division segregation in fungi. Bull. Torrey Bot. Club. 70:605- 611. Francis 3. Ryan, F.W. Beadle and E.L. Tat-. The tube method of measuring the growth rate of Neurosnora. AID. J. Bot. 30:784-799. . -<.- Francis J. Ryan, E.L. Tatum and A.C. Giese. The.four- carbon respiratory system and growth of the mold Neuros- pora. J. Cell`and Comp. Physiol. 23: 83-94. Francis J, Ryan and Erwin Brand. A method for the determination of leucine in protein hydrolysates and in foodstuffs by,the use of a Neurospora mutant. Jour. Biol. Chem. 154:161-175. Robert Ballentine, Gwendolynn M. Tuck, Lillian K. Schneider and Francis J. Ryan. An unidentified growth factor for a gas gangrene Clostridium. Jour. Am. Chem. sot. 66:1990. Francis J. Ryan, Robert Ballentine, Lillian K. Scheider and Gwendolynn M. Tuck. Certain sulfonamide drugs and certain derivatives of ascorbic acid in ex erimental gas gangrene in wounded mice. Surgery 17: c- 7-53. Erwin Brand, Leo J. Saidel, William H. Goldwater, Beatrice Kassel and Francis J, Ryan. The empirical form- ula of beta-lactoglobulin. Jour. Am. Chem. Sot. 67:1524- 1532. Erwin Brand, Francis J. Ryan and Eugene M. Diskant. Leucine content of proteins and foodstuffs. Jour. Am, Chem. Sot. 67: 1532-1534. Francis J. Ryan R. Ballentine, E. Stolovy, M.E. Carson, and L.K. Schnel er. o ? The Biosynthesis of Pantothenic Acid. Jour. Am. Chem. Sot. 67~1857-1858. Francis J. Ryan 2 1946 Francis J. Ryan, Robert Ballentine Lillian K. Schneider, Edith Stolovy, Mary E. Corson and l!Xizabeth J. Ryan. The use of antibiotics, vitamin analogues and other compounds in experimental gas gangrene. Diseases 78:223-231, Jour. Inf. *J-946 Francis 3. Ryan and Joshua Lederberg. Reverse-mutation I and adaptation in leucineless Neurospora. Acad. Sci. 32~163-173. --- Proc. Nat. 1946 Francis J. Ryan. The application of Neurospora to bio- assay. Fed. Proc. 3~366-369. / '1946 *1946 1947 1947 '1947 '?948 +-I948 #1948 1948 1948 Francis J. Ryan, tine. Lillian K, Schneider and Robert Ballen- Mutations involving the requirement of uraoil in Clostridium. hoc. Rat. Acad. Sci. 32~261~271. Francis J. Ryan. tional mutants. Back-mutation and adaptation of nutri- 11:215-227. Cold Spring Harbor Symp. o$-Qutitit. Biol. Francis J. Ryan, tine. Lillian K. Schneider and Robert Ballen-' bition. The growth of Clostrid'um septicurn and its inhi- Jour. Bact. 53:t17- 3 ----eK ' Francis J. Ryan and Lillian K. Schneider. The relation of the bacterial production of ammonia gas to the growth of other organisms. J. Bact. $:209-2X1. Francis J. Ryan. of microorganisms. Genetics, biochemistry and Fhe growth Euclides. 77: 297-308. Francis J. Ryan. On the stability of nutritional mutants of bacteria. PNAS 34:425-435. Francis J. Ryan. The germination of conidia from bio- chemcial mutants of Neurospora. Am. J.. Bot. 35:497-503. Francis J. Ryan and Lillian K, Schneider. Consequences of mutation during the growth of biochemical mutants of Escherichia coli. I. The pattern of ada tation in his- tidineless cz?%res. J. Bact. 56:699-708. Francis J. Ryan, Laboratory Guide, Vertebrate Zoology and Evolution. A Kings Crown Press, Francis J. Ryan, Vertebrate Zoology and Evolution. A Lecture Guide. Kings Cro\m Press. * i Francis J. Ryan * 1948 ; 19%9 "1949 *1949 *I949 *1949 *1949 $1949 *1949. *194.9 3 T. C. Sheng and Francis J. Ryan. Mutations involving the production of conidia and the requirement for leucine in a mutant of 1Jeurospora. Genetics 33~221-227. Francis J. Ryan. Reverse mutation of biochemical mutants. Proc. 4th International Congresi; for Microbiology. Copenhagen, 1947:3!34, Francis J. Ryan, Zntcractfons during the gpotzth of mutating populations of bacteria. Proc; 6th Interna-` tional Congress for Experimental Cytology. Stockholm, 1947. Acta Physiol. Scandinavitia 18:220-224. -Francis J. Ryan and Lillian K. Schneider; Mutations during the growth of biochemical mutants of Escherichia 001~. Genetics 34:72+X. Francis J. Ryan and Lillian K. Schneider. The conse- quences of mutation during the giowth of biochemical mutants of Escherichia coli, histidine-independent II, The inhibition of in unshaken cultures, bacteria by histidinele>& bacteria J. Bact. 58:18~89~ Francis J. Ryan and Lillian K. Schneider. The conse- quences of biochemical mutants of Escherichia coli III. The inhibition of histidine-independent bacte;ia by histidineless bacteria in aerated cultures. J,sBact, 58 : 191-200. Francis J. Ryan and Lillian K. Schneider The conse- quences of mutatior; during the growth of*biochemical mutants of Bcherichia coli. IV. The mechanism of inhibition of histidine-independent bacteria by histi- dineless bacteria. 5. Bact. 58:201-213. Francis J. Ryan. isms. Adaptation and mutation in microorgan- Teaching Scientist, in press. David D. Perkins and Francis J. Ryan, MQtation in microorganisms, Ciencia y Investigation, fn press. Francis J. Ryan, Selected tiethods of Neurospora genetics. Methcds rin Medical Research, in press. I 1 . `, T Francis J. Ryan . PLAN FOR WORK My projbct is part of an attempt to understand the factors controlling growth by use of genetic techniques. We know that genes are in ultimate control of growth, but we bow little about what genes are like. We know that they control growth by enabling steps in biosynthesis, but we have only notions regarding the intimate details of this influence, We-know that genes are not perfectly stable, yet we do not have.adequate techniques to measure their instability. The- mutation of genes results in the formation of mutant nuclei, cells or organisms. These mutants, differing from their fel- lows, are, during growth, thrown into a competition, the out- come of which may or may not be satisfactory.` If satisfac- tory, the adjustment may be call!n adaptation, but we, do not know that all adaptations have this origin, That microorganisms have special advantages-for studies on the genetic control,of growth has been adequately demonstrated in recent years. Biochemical mutants have been obtained which are unable to carry out single steps zin bio- . synthesis due to mutations in single genes. These mutations, . . which we are studying in the red bread mold Neurospora and in bacteria, are frequently unstable, and we have been able to demonstrate that reverse-mutations occur. In Neurospora it has not yet been possible to measure the rate of back- mutation because of a surprising selection against the back- mutants. In Escherichia coli we have been able to satisfac- torily analyze the role oflection and have, with precision, calculated mutation rates by orthodox methods. The reliabil- ity of such methods has, however, become subject to question because of an inconsistency between the assumptions involved and the behavior of mutating populations of bacteria. This inconsistency resides in the notion that mutations are ran- dom and occur with a given chance per gene per unit time. Perhaps they do, in which event a hithertofore unrecognized disadvantage is associated with a newly arisen mutant. In either event, and I trust this year's researches will allow an answer, new methods must be used for the calculation of mutation rate. Once a reliable technique is developed, opportuni- ties not previously available exist for the study of factors controlling mutation rate. These include external variables such as radiation and temperature, internal variables such as genetic constitution, and finally, variables peculiarly asso- ciated with the mutating gene which may allow for directed mutation. It is by indirect methods such as these that clues can be secured about the nature of the gene and the physical chemistry of mutation. 1 Francis J. Ryan . 2 Knowledge of this character could be used directly in understanding the adaptive growth of microorganisms. The recent application of genetic techniques has shown that adap- tations to drug and bacteriophage resistance have their ori- gin in mutations. We have shown that mutations can also result in adaptations which dispense with growth factor ments. In addition, selection for or against the mutant require- plays a critical role in determining whether mutation is fol- lowed by adaptation, At the present time most geneticists feel that all inherited adaptations could be explained in terms of mutation and selection. On the other hand, micro- biologists have been reluctant to give up the feeling that adaptations are induced,by the environment. Perhaps this is - a healthy attitude, for there certainly are adaptations in Neurospora as well as in bacteria which are unorthodox either in the characteristics of the mutations which lead to them or in the nature of the ,selection involved. These unorthodoxies are under investigation. . -;*+ - Perhaps the outstanding laboratory in the world for work on the biochemical genetics of microorganisms is at the California Institute of Technology. I feel that I stem from ..- that school through my association with its members who were with me at Stanford. For this reason I have chosen to leave the United States and to work in the laboratories of Professor Andre Lwoff at the Pasteur Institute; Lwoff is one of the ,world's outstanding students of microbial nutrition and has recently undertaken studies on bacterial mutation. laboratories are Dr. Jaques Monod, In his desCultures.Bact&iennes:\ the author of"La Croissance of adaptive enzymes, who is active in the investigation and Drs. Raymond Latarajet and Elie Wollman, who are investigating the genetics and biochemistry of bacteriophage activity. In addition, closely associated with Lwoff is Professor Boris Ephrussi, who supervises a large laboratory devoted to the study of induced mutations in yeast. I furthermore believe that it would be to the advantage of my research to visit briefly other European laboratories. results Were I to spend a year with Professor Lwoff, the of my work would be published, as usual,in scientific journals.