SECTION HM ~ PRIVILEGED COMMUNICATION PROGRAM DIRECTOR'S OFFICE DIRECT COSTS ONLY (Omit Cents) BUDGET ESTIMATES FOR ALL YEARS OF SUPPORT REQUESTED FROM PUBLIC HEALTH SERVICE ST PI js i ; DESCRIPTION GAME Ree. ADDITIONAL YEARS SUPPORT REQUESTED (This application only) TAILED BUOGET! | 2NO YEAR | 3RO YEAR | 4TH YEAR | STH YEAR | GTH YEAR | 7TH YEAR PERSONNEL COSTS 3,414 3,656 3,908 4,177 4,464 CONSULTANT COSTS (inctude fees, travel, etc.) - - - - - EQUIPMENT 7 - - - ~ SUPPLIES - - ~ - - OOMESTIC - - - - - TRAVEL FOREIGN _ - - ~ - PATIENT COSTS - - - - - ALTERATIONS AND - - - - - RENOVATIONS OTHER EXPENSES 5,000 5,300 5,700 6,000 6,400 TOTAL DIRECT COSTS 8,414 8,956 9,608 10,177 10,864 TOTAL FOR ENTIRE PROPOSED PROJECT PERIOD (Enter on Page 1, Item 4) ———$_——_» $ 48 > 019 page if needed.) Budget explanation attached REMARKS: Justify aif costs for the first year for which the need may not be obvious. For future years, justify equipment costs, as weil as any significant increases in any other category. Ifa recurring annual increase in personnel costs is requested, give percentage. (Use continuation PHS-398 Rev. 3-70 Pde 7 AGGREGATE BUDGET EXPLANATION The following budget is the aggregate of the five individual subprogras budgets and the Program Director's Office budget. Individual budget items such as personnel appearing in more than one budget and supply items like “chemicals, glassware, etc." have been combined to show only one such item each in this overall] budget. In considering the percentages of personnel time committed to this project, it should be noted that faculty personnel, as distinct from staff, also receive a portion of their salary from the institution. This institutional salary support assists in covering faculty efforts along research lines overlapping those in the present application. Therefore the faculty time percentages reflect contractual lower bounds on faculty commitment to this prograa. Salaries are uniformly increased at a rate of 6% per year to cover expected merit and cost 9f living increases. Staff benefits are applied based on the following University projections: 17%, 9/73~8/743 18.3%, 9/T4-8/753 19.3%, 9/75-8/76; 20.3%, 9/76-8/77; 21.3%, 9/77-8/783 22.3%, 9/78-8/79. Budget items other than “Equipment” and “Patient Costs" are in general increased by 6% per year to cover inflation, except in specific instances noted in the individual budgets. PRIVILEGED COMMUNICATION SECTION Il SUBSTITUTE THIS PAGE FOR DETAILED BUDGET PAGE GRANT NUMBER SUBSTITUTE PERIOO COVERED FROM THROUGH DETAILED BUDGET FOR FIRST 12-MONTH PERIOD 1/1/74 12/31/74 1. PERSONNEL (List aff personnel engaged on project) pb tas AMOUNT REQUESTED (Omit cents) NAME (Last, first, initial) TITLE OF POSITION %/HRS. | TOTAL Lederberg , J. Principal Investigator or 20 Program Director Cann, H. Assoc. Prof. of Pedg. 50 Kretchmer, N. Prof. of Peds. 10 ote Herzenberg, L. Prof. of Genetics 10 en aang : . ATE. PROGRAM. BUDGET Cavalli-Sforza, L. Prof. of Genetics 10 AGEREGATE. Barnett, C. Assoc. Prof. of Pedg. 20 ee Luzgzatti, L. Prof. of Peds. 10 Tsuboi, K. Senior Scientist 20 Duffield, A. Research Associate | 100 Pereira, W. Research Associate 100 Rindfleisch, T. Research Associate 20 Hulett, H. Research Associate 20 Open - Genetics Research Associate 100 Open - Pediatrics Research Associate 100 (continued) eenreennsmenececnemaemasscaas ie TOTAL + 345,600 2. CONSUL TANT COSTS (Include Fees and Travel) $ 3. EQUIPMENT (itemize) see attached s 126,200% 4. SUPPLIES see attached 35,700 s Srare a. vomestic 7 East Coast(3,500), 1 Mid-west (300), 1 West Coast(200 4,000 RAVEL (See Instructions) b. FOREIEN $ 6. PATIENT COSTS (Separate Inpatient and Outpatient) s Venepuncture (500) and genetic counseling (2,500) 3,000 7. ALTERATIONS AND RENOVATIONS Relocate equip., power, etc. for GC/MS data system s 1,800 8. OTHER EXPENSES (Itemize per instructions) see attached s 21,500 ». Subtotal — Items } thry § 0 ee | 5 537,800 10. TRAINEE EXPENSES (See Instructions) PREDOCTORAL No. Proposed s FOR a. STIPENDS | POSTDOCTORAL No. Proposed s OTHER (Specify) No. Proposed -{$ TRAINING DEPENDENCY ALLOWANCE s GRANTS TOTAL STIPEND EXPENSES ———nmene | S b. TUITION AND FEES s ONLY ce. TRAINEE TRAVEL (Describe) s 11, Subtotal — Trainee Expenses s 12, TOTAL DIRECT COST (Aad Subtotals, Itema 9 and 11, and enteron Page 2) $ 537, 800 Substitute Budget Page 5-72 P-1S3 GPO 630.753 For Forms PHS 398 and PHS 2499-3 continued 1. PERSONNEL Open Open — Pediatrics Veizades, N. Steed, E. Tucker, R. Wegman, A. Waters, R. Sakaguchi, S. Van West, B. Makk, G. Open - Pediatrics Summons, R. Open - Genetics Open - Genetics Pearson, D. Wyche, M. Boswell, M. Open - Genetics Open- - Genetics Open - Pediatrics Open - Pediatrics Open ~ Pediatrics Open Pediatrics Jamtgaard, R. Redse, R. Allen, M. Murray, R. Meyering, P. Open - Pediatrics Harlow, W. Cusumano, M. Open - Genetics TITLE Research Assoc.-Stat. Research Assoc. - Soc. Worker Research Engineer Research Engineer Computer Programmer Senior Res. Assist. Research Assist. Research Assist. Research Assist. Research Assist. Research Assist. Post.Doc. Fellow Grad. Res. Assist. Grad. Res. Assist. Electronics Tech. Lab. Tech. Lab. Tech. Engin. Tech. Research Tech. Interviewer Interviewer Statist. Clerk Data Coder Administrator Secretary—Prog.Dir. Secretary - IRL Secretary - Peds. Secretary - Gen. Typist Machinist Laboratory Diener Lab Glasswasher % TIME 20 50 33 33 75 10 100 50 100 100 50 100 50 50 40 100 100 50 100 50 25 50 65 15 30 25 50 10 100 10 50 25 Pte continued 3. EQUIPMENT 4 Column Gas Chromatograph $14 ,400* Mini-computer System & Inst. Interface 59,900* Amino Acid Analyzer 32 ,500%* Event Counter 2,700* Digital Voltmeter 900* Carbon Dioxide Incubator 2,500% Laminar Flow Hood — 1,000* Fluorescence Microscope 9,000* Eppendorf Microfuge 500% Buchler Power Supply 600% Constant Current Power Supply 1,000% Slab Gel Electrophoresis 300* Column Acrylamide Gel Electrophoresis 200% Destainer 200% Tape Recorder 500% Total Equipment $126,200* SUPPLIES Chemicals, glassware & lab. apparatus $18 ,000 GC Supplies (Columns, Phases, etc.) 1,100 Dry ice & liquid nitrogen 500 Data recording media (GC/MS, Calcomp, etc.) 1,800 Mini-computer supplies (start-up & continuing) 1,600 Mass spectrometer repair parts & supplies 2,300 Electronic parts & supplies 1,900 Amino acid analyzer supplies 2,000 Radioactive tracers 5,000 Expendable supplies (photo. plates, etc.) 1,500 Total Supplies $35,700 OTHER Visiting committee honoraria & expenses for annual symposium $5,000 Office supplies, telephone, repor. ,postage, publication costs, etc. 6,200 Mini-computer maintenance 6,000 Freight on capital equipment 500 Central computer usage & terminal rental 3,800 Total Other $21,500 Puss SECTION i! — PRIVILEGED COMMUNICATION AGGREGATE BUDGET DIRECT COSTS ONLY (Omit Cents) BUDGET ESTIMATES FOR ALL YEARS OF SUPPORT REQUESTED FROM PUBLIC HEALTH SERVICE DESCRIPTION gsteemoo | ADDITIONAL YEARS SUPPORT REQUESTED (This application only) TAILED BUDGET) | 2ND YEAR 3RD YEAR ATH YEAR STH YEAR 6TH YEAR 7TH YEAR tons $345,600 | 370,068 |431,528 | 461,243 | 492,966 CONSULTANT COSTS (include fees, travel, etc.) EQUIPMENT 126,200* | 23,000*] 18,100* | 5,300*| 6,000* SUPPLIES 35,700 37,700 | 42,400 44,800 47,700 DOMESTIC 4,000 4,700 4,900 4,900 5,400 TRAVEL FOREIGN 3,000 5,500 5,500 500 500 PATIENT COSTS ALTERATIONS ANO RENOVATIONS 1,800 OTHER EXPENSES 21,500 | 24,900 | 26,400 | 27,800 | 29,700 TOTAL DIRECT COSTS 537,800 | 465,868 |528,828 544 543 582 ,266 TOTAL FOR ENTIRE PROPOSED PROJECT PERIOD (Enter on Page 1, Item 4) ————» | $ 2,659,305 page if needed.) See individual subprojects for budget explanations REMARKS: Justify all costs for the first year for which the need may not be obvious. For future years, justify equipment costs, as well as any significant increases in any other category. If a recurring annual increase in personnel costs is requested, give percentage, (Use continuation PHS-398 Rey 2.70 SECTION VIII Concluding Remarks Dr. Lederberg P-1S7 Continuation page CONCLUDING REMARKS (Joshua Lederberg) The overt justification for the proposed Center is, of course, the collective value of the well-defined research projects that will make up its day to day work. However, its most important utility in the long run may be a new institutional arrangement that will generate now unforeseen lines of investigation. Molecular biology as a basic science has leaped far beyond its practical application to human problems. The more intimate intellectual association of gifted scientists and clinicians envisaged here, the development of an active interface among workers who spend much of their time still either in basic laboratory work or in the clinic, is the only possible way of advancing these applications. Speaking more personally, I can point to a number of anticipations from my own research career that might have been explored more aggressively had I then pressed them in an interdisciplinary context. My early work (with Tatum, Zinder and others) on genetic recombination and on viral transduction in bacteria was foreseen years ago as laying a groundwork for the development of a genetics of somatic cells and of means of importing reparative genetic information ("genetic engineering"). Subsequently, I tried to stress that the new molecular genetics would overtake other lines of concern about genetic impairment, and improvement, and that ethical issues would loom as large as technological opportun‘ties in public policy debates. While public reactions to these potentialities are in some respect overdrawn, geneticists obviously must inculcate and exhibit great sensitivity to the ethical issues of genetic intervention and how they are perceived by the public (1). Although much of my own laboratory research might go under the heading of genetic engineering of bacteria (2) I have been persuaded that prenatal diagnosis represents the most important practical avenue of genetic therapy or rather pre- emption of disease. For this reason, the application of automated technologies (growing in large measure out of NASA-supported work) is emphasized in this application. What is more difficult to foresee is the intensive development of the whole repertoire of tools of molecular genetics. Somatic cell genetics is well launched; but we will surely also have to learn how to use specific DNA replication, hybridization, transcription, and translation, i.e. the full range of gene action in vitro, to solve pressing diagnostic problems. Laboratory research shares a place with other interests. I can summarize these under the heading of a concern for the overall process of science, and its application for human benefit. These meta-scientific interests have been expressed in the public arena, as in efforts to enhance public understanding of science and provision for its support. More recently, I have been more involved in efforts to enhance the infrastructure of science, with work on new instrumentation coupled with feeble steps towards the use of computers for scientific "intelligence" (3). The Genetics Research Center is a plan to bring all of these themes to a focus ‘on an area most likely to advance genetic knowledge -- my fundamental scientific base -- and to generate tangible health benefits for the mutual advantage of both disciplines, and to satisfy the public's motives for continued investment in the health sciences. PHS-398 Page Rev. 2-69 GPO : 1969 © - 350-360 Pos DO NOT TYPE IN THIS SPACE-BINDING MARGIN Continuation page Bibliography 1. Lederberg, J.: in Challenging Biological Problems, Oxford U. Press, N.Y. 1972, p. 7 (J.A. Behnke, ed.) "Biological Innovation and Genetic Intervention". 2. Sgaramella, V.: Proc. Nat. Acad. Sci. 69:3389, 1972. "Enzymic Oligomerization of Bacteriophage P22 DNA and of Linear Simian Virus 40 DNA." 3. Lederberg, J.: in Biochemical Applications of Mass Spectrometry, John Wiley & Sons, N.Y. 1972, p. 193 (G.R. Waller, ed.) "Use of a Computer to Identify Unknown Compounds: The Automation of Scientific Inference." Res. 269 Page GPO : 1969 © - 350-360 P-lS9 SECTION IX Professional Personnel P-/66 KEY PERSONWEL AND BIOGRAPHICAL MATERIAL Joshua Lederberg, Ph.D. - Principal Investigator, Professor and Chairman, Department of Genetics. Professor Lederberg will serve as the Principal Investigator for the overall program, and for part 1, automated screening methods (SC/MS) for inborn errors of setabolism. In addition, Professor Lederberg maintains active research programs in genetic recombination in bacteria; mechanisms of DNA replication and reunion; interactions of environmental mutagens with DWA; and computer enaulation of human cognitive processes. Howard Cann, M.D. - Associate Program Director, Associate Professor of Pediatrics. Dr. Cann will assume responsibility for coordinating laboratory research with clinical applications within the program. This will involve screening of patients for their Suitability of participation in the relevant reseach projects, obtaining appropriate patients for projects, informing patients about the research projects and obtaining their consent for participation, insuring that proper evaluation, care and counseling are provided to patients and tamilies involved in these projects and planning for the application of the research findings to patient care. Dr. Cann will be directly involved with research projects on genetic markers in amniotic fluid, separation of fetal cells from the maternal circulation, the impact of genetic counseling on family decisions and screening and detection of inborn errors of metabolisa. Dr. Cann's research activities pertain to human polymorphisms and to somatic cell genetics and his clinical work involves him with hereditary illness and genetic counseling. He has set up and directs a laboratory for typing for various polymorphisas of erythrocyte antigens and enzymes and serum proteins. He has initiated an investigative program for applying somatic cell hybridization to prenatal diagnosis of hereditary disorders. LoL. Cavalli-Sforza, M.D. - Professor of Genetics The investigations of Professor Cavalli-Sforza have long contributed and continue to contribute important information on human popalation genetics. He has pioneered in applying demography to studies of population and genetic structure of man. Particularly pertinent to this program is his interest and work on variation agong populations in the frequency of inherited disorders and their determining genes. Professor Cavalli-Sforza also directs a laboratory program oriented toward the detection of specific binding proteins in P-/6f -2- blood. The detection of genetic polymorphisms of these proteins will be carried out by Professor Cavalli-Sforza as a research activity of this Genetics Center. Norman Kretchmer, M.D., Ph.D. - Professor of Pediatrics. Professor Kretchaer will participate in the research project dealing with screening and detection of inborn errors of metabolisa. He is well known for his research and clinical work in various inborn errors of metabolism. One of Professor Kretchrer's main research interests presently deals with lactase intolerance in man. His research program also involves the developmental biochemistry of the urea cycle and the pyvtimidine biosynthetic pathway in eukaryote cells and tissues. He has recently relinguished the chairmanship of the faculty committee for teaching the human biology curriculum at Stanford University. From 1959-1969 Professor Kretchmer was Chairman of the Department of Pediatrics. Leonard Herzenberg, Ph.D. - Professor of Genetics. Professor Herzenberg directs an active research program in immunogenetics with special emphasis on genetic and structural studies of souse immunoglobulins and on the mechanism and control of antibody synthesis. fhe development under his direction of instrumentation for separating cells by means of fluorescent sensing has provided potential methodology for separating fetal cells from the maternal bloodstream. Professor Herzenberg will participate in the project which will apply this methodology to antenatal diagnosis of genetic disorders. Clifforcd Barnett, Ph.D. - Professor of Anthropology and Associate Professor of Pediatrics. Professor Barnett has worked in medical anthropology for 10 years. His research activities have dealt with cultural and genetic aspects of congenital dislocation of the hips, fertility and birth spacing of partially acculturated Guatemalan Indians, and moth2r and infant interactions in reference to premature infants. He has designed and will direct the research project on the impact of genetic counseling on family decisions and behavior. Alan Duffield, Ph.D. - Research Associate in Genetics. Dr. Duffield is an organic chemist who has carried out fundamental studies in mass spectrometry of organic compounds. He is presently directing research involving the development of a multicogponent, automated system for analysis of biologic substances. He shall apply this system, which involves a gas liquid chromatograph, a mass spectrometer and computer Pr lOR -3- facilities to screening, detecting, and studying inborn metabolic errors in various body fluids and tissues. Kenneth Tsuboi, Ph.D. - Senior Scientist, Department of Pediatrics. Dr. TsuboL"s research interests have included the physiological chemistry and enzymology of erythrocyte intermediate metabolisn and more cecently, the biochemical genetics of various erythrocyte enzymes. He is also working on the enzymological characteristics of various primate cell culture lines. In this program he will participate in the project on linkage and prenatal diagnosis of inherited disorders. In particular, he will work in the detection of polymorphic enzyme markers in cultured amniotic fluid cells. Luigi Luzzatti, M.D. - Professor of Pediatrics. Professor Luzzatti is the director of the clinical cytogenetics laboratory and of the Birth Defects Clinics in the Department of Pediatrics. His clinical activities which are pertinent to this prograa, include coaprehensive care for patients (and their families) with birth defects, genetic counseling and screening amniotic fluid saaples {usually from women over 35 years of aye) for chromosomal abnormalities. He will participate in the project which investigates the impact of genetic counseling on family decisions. Herbert Schwartz, &.D. ~ Professor of Pediatrics. Professor Schwartz's research interests in hemoglobin synthesis, structures and function in health and disease, and their application to the prenatal detection of hereditary disorders involving hemoglobin, e.g. sickle cell anemia and thalassermia, will be incorporated into the program on exploring the maternal bloodstream for fetal cells. Dr. Schwartz will collaborate with Drs. Herzenberg and Cann in preliminary studies of fetal erythrocytes separated from maternal blood. Dr. Schwartz directs the hematology service of the Department of Pediatrics. Other members of the Department of Genetics who will not participate directly in this program but with whom we interact daily are Dr. Eric Shooter (Professor) and Dr. A.T. Ganesan (Associate Professor). Professor Shooter directs research into the structure and mechanism of action of the nerve growth factor protein. Dr. Ganesan is investigating the genetic control of chromosome replication in B. subtilis, the chemical basis of DNA replication, the mechanism of genetic recombination during DNA mediated transformation and the role of the nuclear membrane in chromosome replication in mammalian cells. Pree ~~ The clinical and research interests of Professor Irving Schulman, Chairman of the Department of Pediatrics, are devoted to various defects of coagulation, including inherited disorders. Other meabers of the Department of Pediatrics whose clinical and research activities relate to this program are Dr. Phillip Sunshine (Associate Professor of Pediatrics) and Dr. John Johnson (Assistant Professor of Pediatrics), Director and Associate Director of the Newborn and Premature Infant Nurseries, respectively. Dr. Sunshine and Dr. Johnson are toyether investigating the metabolic consequences of neonatal ornithine transcarbasylase deficiency ani detection of heterozygotes for the gene which determines this disorder. The research activities of Dr. Merton Bernfield, Associate Professor of Pediatrics, are designed to assess the norphogenetic behavior and cell surface properties of human cells and to utilize these assessments in studies of cells derived from individuals with birth defects. Dr. John Gribble, Assistant Professor of Pediatrics, is a pediatric hematologist whose research activities have dealt with in vitro biosynthesis of hemoglobin and biochemical and physiological aspects of pinniped hemoglobins. Dr. Gribble's clinical activities involve evaluation and treatment of patients with hereditary disorders of blood coayulation, including genetic counseling ot their families. The clinical and research activities of Dr. R.O. Christiansen (Assistant Professor of Pediatrics and Director of the Pediatric Metabolic and Endocrine Service) ani Dr. Judith Koehler (Assistant Professor of Pediatrics and Director of Pediatric Neurology) are quite relevant to the Genetics Center program. Even though the research activities of all of these individuals will not be supported by this grant, we are including bibliographic sketches on each of them because of their relevance to the overall Genetics Center prograa. Within one or two years after the activation of this program we anticipate the direct participation of one or more colleagues from the Department of Obstetrics and Gynecology. A search for chairman of this departaent is presently under way, and we expect that this individual will bring competence to Stanford in fetal physiology and fetal monitoring. We look forward to interacting in this program with our obstetrical colleagues in various projects pertaining to antenatal detection of yenetic disorders and selective abortion. P-1eYy aa ei tof Principal Investigator: Research Support Summary for Departments of Genetics and Pediatrics Relevant to Genetics Research Center . Program Director: Associate Program Director: Grant Title (unless otherwise noted) HOWARD CANN Associate Professor of Pediatrics Department of Pediatrics 1) LUCA CAVALLI-SFORZA Professor of Genetics Department of Genetics 1) 2) 3) NIH:HL-15008 AEC: AT-04-3-326 NIH:NS-10711 NIH: GM-20467 .ADAYAPALAM GANESAN woe Associate Professor of Department of Genetics 1) 2) NIH: GM50,199 NIH: GM14108 Pre-Natal Detection of Sickle Cell Anemta Mutation Rates and Mutational Loads in Man Genetic Study of Metabolism of Neural Transmitters Gene Diffusion, Natural Selection and Drift in Man Genetics Development Award-Research Career Program Chromosome Replication, Recombination and Cell Division DNA Synthesis and Genetic Recombination J. Lederberg H. Cann Current Year $ 38,717 32,000 65,000 47,587 21,433 34,902 Total Award Grant Term Budgeted 4% time $118,000 9/72-8/75 32,000 10/72-9/73 10% (Renewal pending) 207,000 9/72-8/75 20% 5/73-4/76 20% 147,351 Support recommended for 2 additional years ending 12/31/75, the amounts to be determined annually. 50% 211,996 6/72-5/77 LEONARD HERZENBERG Professor of Genetics Department of Genetics 1) NIH:GM-17367 Automated Cell Sorting - Clinical and Biological Uses 2) NIH:AI-08917 Genetics of Immunoglobins 3) NIH:CA-04681 Genetic Studies of Mammalian Cells 4) NIH:HD-01287 Fetal-Maternal Immunological Inter- actions JOHN D. JOHNSON Assistant Professor Department of Pediatrics 1) United Cerebral Developmental Aspects of Heme Palsy Protein Catabolism NORMAN KRETCHMER Professor of Pediatrics Department of Pediatrics 1) NIH:RR-00081 Clinical Research Center for Premature Infants 2) =NIH:HD-02147 Biochemical Studies of Development TMS 3) National Found. Growth and Differentiation of the CRBS-252 Placenta 4) NIH:HD-00047 Human Development and Pediatrics Train- ing Grant 5) NIH:HD-00391 Regulatim of Enzyme Action During Development 160,802 52,774 80,994 38,198 28,772 418,532 206,593 23,293 90,588 42,289 585,977 246 , 386 424,981 222,897 53,322 1,974,008 1,309,278 23,293 448,936 183,822 1/73-12/75 5/69-4/74 9/72-8/77 5/73-4/78 7/71-6/73 10/69-9/74 (Renewal pending) 6/66-5/74 (Renewal pending) 7/72-/6/74 7/70-6/74 9/68-8/73 (Renewal pending) 15% 20% 30% 10% 15% 152 10% 15% NORMAN KRETCHMER (continued) 5) NIH:CA14917 Pyrimidine Synthesis and Cellular 42,689 Proliferation in Colon 7) Educational Found. Epidemiology, Etiology, and 45,156 of America Physiology of Diarrhea in tne American Indian JOSHUA LEDERBERG Professor and Chairman Department of Genetics 1) NASA:NGR-05-020 Cytochemical Studies of Planetary 180,000 Micro-organisms 2) NIH:AI-05160 Genetics of Bacterila 60,000 3) NIH:RR-00612 Resource Related Research - Computers 194,408 and Chemistry (E. Feigenbaum, Principal Investigator; J. Lederberg and C. Djerassi, Co-Investigators) 4) NIH:RR-00785 Stanford University Medical 765,573 Experimental Computer Faciiity (SUMEX) -5) NIH:GMO0295 Training Grant in Genetics 143,964 GILDA LOEW Research Associate Department of Genetics 1) NSF:GB17980 Quantum Chemical Investigations 34,799 of Heme Proteins and Ferredoxins ‘Y 2) +NIH:DA00770 Quantum Chemicel Studtes of Opiate 57,557 Lu Narcotics 3,800,000 280,000 675,000 4,246,621 nod wa in ” cn ta a 34,799 134,239 6/73/5/76 7/73-6/75 (Renewal pending) 9/60-8/73 (Future support dubious) 9/68-8/73 (Renewal pending) 5/71-4/74 (Renewal pending) 8/73-7/78 (pending) 7/69-6/74 2/72-1/74 ‘Renewal pending) 9/73-8/76 (Pending) 20% 5% 112% 15% 02 20% 15% ERIC M. SHOOTER Professor of Genetics Department of Genetics 1) NIH:NS04270 Molecular Neurobiology - Proteins in the Nervous System 2) NSF:GB31982 Structure and Mechanism of Action of the Nerve Growth Factor KENNETH TSUBOL Senior Scientist Department of Pediatrics 1) NIH: Contract- Biochemical Parameters of Primate Div. of Biol. Cell Cultures Standards 89 -of 84,558 60,000 23,598 404,979 60,000 47,196 12/70-11/75 1/72-12/73 6/72-5/74 402% 20% SECTION Hl — PRIVILESED COMMUMICATION BIOGRAPHICAL SKETCH (Give the following information for all professional personnel listed on page 3, beginning with the Principal Investigator. Use continuation foges and fallow the same general format for each person} Prot. i, Letarhors Reredans-t abo Manat ne NAME Clifford R. Bamett TITLE Associate Professor of Pediatric’ Professor of Anthropology BIRTHDATE (*’o,, Day, ¥r) 8/17/29 PLACE OF BIRTH (City, State, Country) PRESENT NATIONALITY (/f non-U.S. citizen, SEX indicate kind of visa and expiration date) New York, New York U.S. Citizen ] Male C] Female EDUCATION (Begin with baccatsureate training and include postdoctoral) YEAR SCIENTIFIC Ss h INSTITUTION AND LOCATION DEGREE CONFERRED FIELD The City College, New York, New York B.S.S. 1950 Anthropology-Psycholos Cornell University, Ithaca, New York M.A. 1951 Anthropology Cornell University, Ithaca, New York Ph.D. 1960 Anthropology HONORS Executive Board, Society for Applied Anthropology 1967-70, Vice-President, 1971-72, President 1972-73, Past President 1973-74; Executive Board, Society for Medical Anthropology 1971-73; Chairman, Committee on Ethics, American Anthropological Association, 19271-74° Fellowshin reaci pient, Milbank Memorial Fimd MAJOR RESEARCH INTEREST Cultural Authropology --1971=722 [ro IN PROPOSED PROJECT Investigator RESEARCH SUPPORT (See instructions} Research Grant: Genetic Studies in the Lake Atitlan Basin, Guatemala, GM 15593; $14,130 for the current year; $300,000 for the six year period 1967 - 1973; National Institutes of Health. Howard M. Cann, M.D. - principal investigator. RESEARCH AND/OR PROFESSIONAL EXPERIENCE (Starting with present position, list training and experience relevant to area af project. List or most representative publications, Oo not exceed 3 pages fur each individual.) 1964- Associate to Full Professor, Anthropology; Associate Professor, Pediatrics, Stan. Un: 1964-1970 Assistant Director to Acting Director, Sciences, Stanford University. au dg Program in Medicine and the Behavioral 1962-1964 Research Associate to Associate Project Director, Navajo-Cornell Field Health Research Project, Dept. of Public Health, Cornell Univ. Medical College. 1961-1963 Resident Anthropologist, Navajo-Cornell Field Health Research Project at Many Farms, Arizona; Resident in Professional Practice, Russell Sage Foundation. 1955-1961 Senior Research Associate to Team Chairman, Foreign Areas Studies Division of Speciz! Operations Research Office of the American University, Washington, D.C. Publications (selected) ok “Untreated Congenital Hip Disease: A Study of the Epidemiology, Natural History and Social Aspects of the Disease in a Navajo Population". With D. Rabin, W. Arnold, R. Freiberger and G. Brooks. Supplement, American Journal of Public Health 55, 2. 1965. "Genetics of Diego Blood Groups in Guatemalan Indians: Use of Antiserums to Diego a and Diego > Antigens". With Howard M. ‘Cann and Betty Van West. Science, 162:1391, 1968. "Neonatal Separation: The Maternal Side of Interactional Deprivation". With P.H. Leiderman, R. Grobstein, M. Klaus. Pediatrics 45:197, 1970. (publications continued) RHS-398 Rev. 3-70 P-187 Prof. §. Letertcrs Cerarimes! of 7-- Publications (continued) "Child Spacing in a Highland Guatemala Community". With Jean Jackson and Howard M. Cann. In Culture and Population: A Collection of Current Studies, Polgar, (Ed.). Monograph 9, Carolina Population Center, Chapel Hill, 1971. pp. 139-148. “Health Care Experiment at Many Farms". With W. McDermott and K. Deuschle. Science 175:4017, January 7, 1972, pp. 23-31. "The Effects of Denial of Early Mother-Infant Interaction on Maternal Self-Confidence". With M. Seashore, A. Leifer and P. Leiderman. Child Development 43:1203, 1972. "Effects of Mother-Infant Separation on Maternal Attachment Behavior". With A. Leifer, P. Leiderman and J. Williams. In Press, Personality and Social Psychology. P-120 aan fv awk Ae ERE OT BIOGRAPHICAL SKETUH (Give the following information for a! professional personnet listed an peje 3, beginning with the Principat Invectigataz. Use continuation pages and follow the same general farmat for each person} NANE TITLE BIRTHDATE (to. Day, Yr} Merton R. Bernfield . Associate Professor April 9, 1938 PLACE OF BIRTH (City, State, Country) PRESENT NATIONALITY (ff non-U.S. citizen, SEX tod ee Hie kind of visa and expiration date) : Chicago, Illinois BoMale (CF) Femsta EDUCATION (Begin with baccalaureate training and include postdoctoral} _ INSTITUTION AND LOCATION DEGREE Peneisinen eto University of Illinois, Urbana, Illinois B.S. 1959 Medicine Graduate Division, University of Illinois, : Chicago, Illinois M.S. °1961 Biochemistry College of Medicine, Univ. of Illinois,Chil, M.D. 1961 HONORS ~ open Saye 4° Alpha Omega Alpha, 1959 Ross Award for Pediatric Research, 197: Borden Undergraduate Research. Award in Medicine C.V. Mosby Company Research Award MAJOR RESEARCH INTEREST - ROLE IN PROPOSED PROJECT Developmental Biochemistry Investigator - RESEATICH § Cy aT. fyctiuctians) ~ ee TH ESPs g et oS See Chet ea se and Oligoribunocleotide Synthesis, September 1, 1970 to August 30, 1975. Current year $26,816. Total $140, 381. NIH ED 06763 Extracellular Materials and Embryonic Organ Formation, Nay 1, 1972 = April 30, 1977. Current year $45,401. ‘Total $203, 648, National Foundation-March of Dimes R-~73-146 Morphogenetic Behavior of Human Cells July 1, 1973 - June 30, 1944. Total $40,000. RESEARCH ANO/OR PROFESSIONAL EXPERIENCE (Starting with present position, list training and experience relevant to ere of Rroseck Lats Or most representative publications, Do not exceed 3 poges for each individual. } ~~ 1970 - Associate Professor, Department of Pediatrics, Stanford University Scheal : . “Medicine; Stanford, California 1970 - Co-Director, Medical Scientist’ Training Program, Stanford University Schoa: . Medicine; Stanford, California. 1969-1970 Associate Director, Medical Scientist Training Program, Stanford Universit: School of Medicine; Stanford, Celifernia 1967 - Director, Birth Defects Research Center; Associate Director, Birth Defect Clinic, Department of Pediatrics, Stanford Un niversity School of Medicine; Stanford, California 1967-1970 Assistant Professor, Department of Pediatrics, Stanford University €cheol | ‘ Medicine; Stanford, California 1967-1967 Chief Resident, RevarEnent of Pediatrics, Stanford Medical Center, S 1965-1966 Research Invesi gator ational Institute of Child Health and Human De > with Dr. Clifford Crobetein, in the Department of Biology, University ar California, San Diego; La Jolla, California 1963-1965 Research Associate, National Neart Institute, with Dr. Marshall } Nirenbers: Bethesda, Maryland 1962-1963 Assistant Resident, Department cf Pediatrics, New York Hospital-Corre?l] >}. Center; New York, New York 1961~1952 Rotating Internship, Research and Education Hospitals, University of T1Li:. Chicago, Illinois P-171 Alis090 mr Nev. 3-70 51 Biographical, Sketch of Dr. Merton Bernfield Paxe Two, continuation of page one Publications Bernfield, M.R. and Nirenberg, M.W.: RNA Codewords and Protein Synthesis. Iv. The nucleotide sequences of multiple codewords for phenylaianine, serine, leucine, and proline. Science 147, 479-484, 1965. Bernfield, M.R. and Rottman, F.M.: Ribonuclease and Oligoribonucleotide Synthesis. III. Oligonucleotide synthesis with 5'-substituted uridine 2', 3'-cyclic phosphates, J. Biol. Chem. 242, 4134-4143, Maenpaa, P.H., and Bernfield, M.R.: Quantitative Variation in Serine Transfe: Ribonucleic Acid durirg Estrogen~Induced Phosphoprotein Synthesis in Rooster Liver. Biochemistry 8, 4926-4935, 1969. Bernfield, M.R.: Collagen Synthesis during Epitheliomesenchynal Inter- actions. Develop. Biol. 22, 213-231, 1970, Bernfield, M.R., and Wessells, N.K.: Intra- and Extracellular Control of Epithelial Morphogenesis. Develop. Biol. Supplement 4, 195-249, 1970. Bernfield, M.R., Banerjee, S.D., and Cohn, R.H.: Dependence of Salivary Epithelial Morphology and Branching Morphogenesis upon Acid Muco- polysaccharide-Protein (Proteoglycan) at the Epithelial Surface. J. Cell. Biol., 52, 674-689, 1972. 52 P-172, NAME Smal Howard M. Cann, M.D. ‘Associate Professor of Pediatrils March 31, 132: PLACE OF BIRTH (City, State, Country) PRESENT NATIONALITY (/f non-U.S. citizen, SEX indicate kind of visa and expiration date) Chicago, Illinois U.S. Citizen MK] mete C}Femets EDUCATION (823in with beccalaureste training and include postdoctoral) YEAR SCIENTIFIC INSTITUTION AND LOCATION DEGREE CONFERRED FIELD University of Colorado, Colorado B.A. 1950 Chemistry, Cum Laude , (General Studies) University of Colorado School of Medicine, M.D. "1954 . Colorado. _ HONORS 4971 - 1972 National Institutes of Health Special Research Fellowship, Genetics Laboratory, Department of Biochemistry, University of Oxford, England. 1966 - 1971 Scholar in Academia Medicine, The John and Mary R. Markie Foundation. f€ont inved-on-Page— 7 MAJOR RESEARCH INTEREST ROLE IN PROPOSED PROJECT SY™t™ Sf Human Somatic Cell Genetics ASSOCIATE INVESTIGATOR RESEARCH SUPPORT (See instructions) Research Grant: “Genetic Studies in the Lake Atitlan Basin, Guatemala, GM 15593; $28,260. for the current year; $300,000. for the six year period 1967 - 1973; 35% effort; National Institutes of Health. National Institutes of Health Special Research Fellowship for sabbatical leave at the University of Oxford (Professor Walter F. Bodmer), Genetic Control of Human Transsienciecic: Antigens, 1-FO3, HD51401-01; $12,371. for one year, September 1, 1971 - August 31, i972, 100% effort. RESEARCH AND/OR PROFESSIONAL EXPERIENCE (Szarting with present position, list training and experience rerevant to area OF Préjoca Lites or most representative publications, Do not exceed 3 pages for each ina. vidual.) September 1, 1971 - August 31, 1972 National Institutes of Health Special Research Fellowship, Genetics Laboratory, Department of Biochemistry, University of Oxford, England. 1970 - Associate Professor; Department -of Pediatrics, .Stanford University School of Medicine. 1964 - 1970 Assistant Professor of Pediatrics, Stanford University School of . Medicine 1963 - 1964 Instructor, Department of Pediatrics, Stanford University School cf ‘ Medicine. 1962 - 1963 National Science Foundation Senior Postdoctoral Fellow, institute of Genetics, University of Pavia, Pavia, Italy. 1960 - 1962 Postdoctoral Fellow, Department of Genetics, Stanford University . School of Medicine, Palo Alto, California. 1957 - 1960 United States Public Health Service, Washington, D.C., Director, National Clearinghouse for Poison Control Centers. Draft Classification: 4A. 1956 - 1957 Assistant Resident and Senior Resident in Pediatrics, Stanford University Hospital, San Francisco, California. 1955 - 1956 Assistant Resident in Pediatrics, University of Colorado Medical Center, Denver, Coloredo. : 1954 ~ 1955 Rotating Intern at San Francisco Hospital, University of California Service, San Francisco, California. RHS-398 Rev. 3-70 Page 17 Put?3 ‘Committees and Consultant 1968 - Committee on Drugs, American Academy of Pediatrics. 1965 - 1968 Genetic Consultant, Hereditary Defects Unit, California State Department of Public Health. 1965 - Genetic Consultant, Congenital Malformations Branch, Epidemiology Section, Dental Health Center, U.S. Public Health Service. Societies and Organizations American Academy of Pediatrics American Association of Poison Control Centers American Federation for Clinical Research American Public Health Association, Epidemiology Section American Society of Human Genetics Western Society for Pediatric Research Specialty Board Certification 1960 American Board of Pediatrics State and National Certification Diplomate of National Board of Medical Examiners Licensed to practice medicine in California and Colorado. BIBLIOGRAPHY» 1. Cann, H.M. and Herzenberg, L.A.: In Vitro Studies of Mammalian Somatic Cell Variation. I, Detection of H-2 Phenotype in Cultured Mouse Cell Lines, J. Exp. Med. 117:259, 1963. 2. Cann, H.M, and Herzenberg, L.A.: In Vitro Studies of Mammalian Somatic Cell Variation. II. Isoimmune Cytotoxicity With a Cultured Mouse Lymphoma and Selection of Resistant Variants.* J. Exp:-Med. ».1172267,. 1963... Dogteg ayn 3. - Berrai, I. and Cann, H.M.: Segregation Analysis of Juvenile Diabetes Mellitus, J. Med. Genet. 2:8, 1965. 4. Cann, H.M.: Computer Analysis in Human Genetics: "Segregation Analvsis and Demographic Genetics, Ann. New York Acad. Sci. 126:728, 1965. 5. Barrai, I., Cann, H.M., Cavalli-Sforza, L.L. and DeNicola, P.: The Effect of Parental Age on Rates of Mutation for Hemophilia and Evidence for Differing Mutation Rates for Hemophilia A and B, American J. Hum. Genet. 20:175, 1968. . 6. Cann, H.M. and Cavalli-Sforza, L.L.: Effects of Grandparental and Parental Age, Birth Order and Geographic Variation on the Sex Ratio of Liveborn and Stillborn Infants, American J, Hum. Genet., 20:381, 1968. 7. Cann, H.M.: Principles of Human Inheritance, in Human Genetics, Birth Defects, Original Article Series, The National Foundation, Vol. IV, November, 1958. Page 18 - P1747 FTus.cra. 1970 - 379-535 are UN FRCS or ACe-UINOING CAARGIN CPI NOT 10. 11. 12. 13. 14. BIBLIOGRAPHY (Continued) Cann, H.M., Van West, B., and Barnett, C.R.: Genetics of Diego Blood Grouns in. Guatemalan Indians: Use of Antiserums to Dia and Dib Antigens, Science, 162: 1391, 1968. Greenstein, R.M., Harris, D.J., Luzzatti, L.L. and Cann, H.M.: Cytogenetic Analysis of a Boy with the XXXY Syndrome: Origin of the X-Chromosomes, Pediatrics, 45:677, 1970. Dungy, C.I., Aptekar, R.G. and Cann, H.M.: Herediatry Hydrometrocol,os with Polydactyly in Infancy. Pediatrics, 47:138, 1971. Barnett, C.R., Jackson, J. and Cann, H.M. Childspacing in a Highland Guatemala Community, in Culture and Population: A Collection of Curren Studies, Polgar, S. (ed.), Carolina Population Center, Univ. North ceretina, Chapel Hill, 1971. Watson, W. and Cann, H.M.: Genetic Counseling in Dermatology. Pediat. Clin. N. America 18:757, 1971. Watson, W., Cann, H.M., Farber, E, and Nall, L.: The Genetics of Psoriasis. Arch. Dermatol., In Press. Bodmer, W.F., Bodmer, J.G., Coukell, A., -Cann, H.M. and Van West, B.: Some Further Data on the Joint Segregation of HL-A and Haptoglobin. Ann. Hum. Genet. (London), In Press. Book Review Carter, C.0.: Human Heredity, Cytogenetics 2:55, 1963. HONORS (Continued from Page 17) 1964 1963 1962 Society for Pediatric Research - 1968 Research Career Development Award, National Institutes of Health, U.S. Public Health Service ; - 1963 National Science Foundation Senior Postdoctoral Fellowship. P-175 Poge 19 Stussce tae st