PROPOSAL FORA GENETICS RESEARCH CENTER Submitted to the National Institute of General Medical Sciences June 1, 1973 School of Medicine Stanford University Form Approved SECTION | Budget Bureau No. 68-RO2¢69 DEPARTMENT OF LEAVE BLANK HEALTH, EDUCATION, AND WELFARE TYPE NUMBER PUBLIC HEALTH SERVICE GRANT APPLICATION REVIEW GROUP FORMEALY COUNCIL (Month, Year) DATE RECEIVED TO BE COMPLETED BY PRINCIPAL INVESTIGATOR (items 1 through 7 and 154) 1. TITLE OF PROPOSAL (Do not exceed 53 typewriter speces} Genetics Research Center 2, PRINCIPAL INVESTIGATOR 2A, NAME (Last, First, ‘ritial) Lederberg, Joshua \F ROM 3. DATES OF ENTIRE PROPOSED PROJECT PERIOD (This application) THROUGH 1/1/74 12/31/78 28. TITLE OF POSITION Professor and Chairman FCO MAILING ADDRESS (Street, City, State, Zip Code) Department of Genetics Stanford University School of Medicine Stanford, California 94305 321-1200 Ext. 5801 3G. DEPARTMENT, SERVICE, LABORATORY OR EQUIVALENT {See instructions) Depts. of Genetics and Pediatrics TH. MAJOR SUBDIVISION (See Instructions] N/A 4. TOTAL DIRECT COSTS RE- QUESTED FOR PERIOD IN ITEM 3 $2,659,305 5. DIRECT COSTS REQUESTED FOR FIRST 12-MONTH PERIOD $537,800 6. 'T See Instructions) Department of Genetics and Department of Pediatrics Stanford University School of Medicine Stanford, California 94304 9- Research Involving Human Subjects (See Znstructons) A.C) NO 8.7) YES Approved: _ C. Gd YES — Pending Review -29=73 Date TO BE COMPLETED BY RESPONSIBLE ADMINISTRATIVE AUTHORIT 4. Inventions (Aenewa! Applicants Only - See Instructors) A.CINO B.[_] YES — Not previously reported C. (CIVES — Previously reported Y {items 8 through 13 and 158) a APPLICANT ORGANIZATION(S! (See instructions) Stanford University Stanford, California 94305 IRS No. 94-1156365 Congressional District No. 17 16, NAME, TITLE, AND TELEPHONE NUMBER OF OFFICIALS) | SIGNING FOR APPLICANT ORGANIZATIONIS) Kathleen C. Butler Sponsored Projects Officer 41. TYPE O F ORGANIZATION (Check applicable itern) COFepeRAL C)stTate [LOCAL (3) OTHER (Specify! Private, non-profir NAME, TITLE, AODFESS, ANO TELEPHONE NUMEZA OF OFFICIAL IN BUSINESS OFFICE WHO SHOULD ALSO BE NOTIFIED IF AN AWARD IS MADE K.D. Creighton Deputy Vice President for Business & Finance Stanford University Stanford, California 94305 Telephone Number (415) 321-2300 _X2251 A222 /2=— i A AL COMPONENT TO RECEIVE CREDIT FOR INSTITUTIONAL GRANT PURPOSES (See instructions) O01 School of Medicine c/o Sponsored Projects Office 14, ENTITY NUNBER (Formerly PHS Account Number) 458210 Tetephone Number {s)__ (415) 321-2300__Ext. 2883 1& CERTIFICATION ANO ACCEPTANCE. We, the undersigned, certify knowledgs and accept, a3 to any grant ewerded, the obligation averd. that the stetements herein are true and compiete to the best of our to comply with Public Health Service terms and conditions in effect et the time of the SIGNATURES A. SIGNATURE OF PERSON NAMED IN ITEM 2A (Signetures required on oof ty Nn eTinee wh eg oy origina! copy only. Te. SIGNATU Use ink, “Per” signatures not ecceptzbie) 'S} OF PERSON(S. iden 7 ap ITEM 10 t - (See also page i) DATE MAY 39 1973 GATE 5/30/73 WIN 398 (FORMERLY PHS 398 SECTION 3 DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE LEAVE BLANK PUBLIC HEALTH SERVICE PROJECT NUMBER RESEARCH OBJECTIVES NAME ANO ADDRESS OF APPLICANT ORGANIZATION Stanford University, Stanford, California 94305 NAME, SOCIAL SECURITY NUMBER, OFFICIAL TITLE, AND DEPARTMENT OF ALL PROFESSIONAL PERSONNEL ENGAGED ON PROJECT, BEGINNING WITH PRINCIPAL INVESTIGATOR Joshua Lederberg, Professor and Chairman, Department of Genetics Howard Cann, Associate Professor of Pediatrics, Dept. of Pediatrics Norman Kretchmer, Professor of Pediatrics, Department of Pediatri Leonard Herzenberg, Professor of Genetics, Department of Genetics Luca Cavalli-Sforza, Professor of Genetics, Department of Genetics Luigi Luzzatti, Professor of {atrics and Community and Preventive Medicine, Department of Pediatrics Clifford R. Barnett, Associate Professor of Pediatrics, Professor of Anthropology, Department of Pediatrics (CONTINUED BELOW) TITLE OF PROJECT GENETICS RESEARCH CENTER USE THIS SPACE TO ABSTRACT YOUR PROPOSED RESEARCH, OUTLINE OBJECTIVES AND METHODS. UNOERSCORE THE KEY WORDS (NOT TO EXCEED 10) IN YOUR ABSTRACT. . A comprehensive program of basic and clinical research, uniting the efforts of the Department of Genetics attd Peadjatrics, will apply advances in analytical instrumentation to problems of genetic polymorphism and disease in man. Program areas include: Genetic errors of metabolism identified by computer-managed gas chromatography and mass spectrometry, applied to urine, blood and amniotic fluid; Detection of fetal cells in maternal circulation; Expression of genetic markers in fetal cells, linkage studies; antenatal diagnosis; Polymorphisms involving specific binding to plasma proteins; Psychological impact of genetic disease and counseling practices. * Kenneth Tsuboi, Sr. Scientist, Department of Pediatrics Alan Duffield, Research Associate, Department of Genetics Wilfried Pereira, Jr., Research Associate, Department of Genetics LEAVE BLANK PHS-398 PAGE 2 Rev. 3-70 The anijersigned agrees to accept responsibility for the scientific aud technical conduct of this project and for provision of required progress reports if a grant is awarded as the result of this application. Le MAY 30 973 Need ave To el fc \ Date Y Joshua Lederberg, ~~ Principal Investigator TABLE OF CONTENTS I. Introduction and Program Summary ....cceeecee eee es ene Comments on Organizatlon .iccccccvecvvecesssvsvce The Stanford Environment ...ccsoes Clinical Factilittes ceocccc ccc ccc cnc ccscccccccves Research Program Outline wccvnccccncvsscescccsces t1. Screening and Charactertzation of Inborn Errors of Metabolism by Gas Chromatography/Mass Spectrometry Analysts of Body Fluids (Drs. Lederberg, Kretchmer, Cann, and Nuffield) ..... 276.2 Budget and Explanation e@eeovovveeveseeeeaeeeeneseeeseeee ee eee tlt. Maternal Blood Stream - Arother Source of Fetal Tissue for Pre-Natal Diagnosis of Genetic 498 Disorders (Drs. Herzenberg and Cann) ouosesevreveceesere Budget and Explanation eoeveveoeveveevnenee oes eeseew eevee eoeeae ee @ {1V. Polymorphic Genetic Markers in Amniotic Fluid (Ors. Cann and Tsubol ) eseeoveveeevpeeevne eevee scoeoevneevnevnane eee ees Budget and Explanation eeseeeoeneeeeneeneneaeeaewaoaeaeee ee ee Vv. A Search for Genetic Polymorphtsms and Variances Of Specific Binding Proteins in Blood (Dr. Cavalli-Sforza) eeseveaevee even eevese ene seen oeveeee ene ee eee Budget and Explanation eeoeseveeoeveeoeoaneneveneanenesnaeansvseos eee ee Vi. The Impact of Genetic Counseling Practices on Family Decisions and Behavior (Ors. Barnett, Cann, and Luzzatti) eoeoeaeaevoee eee eevne ee ee Budget and Explanation oeeoeaesveosvseoeoseooe eevee e eee ane ese eee Vil. Overall Budgets esenvnaenvnesneveveeer eevee eeeevreeeaeevneweevee eve Program Director's Office Budget ...ccccececcsecs Aggregate Genetics Research Center Budget ....... VIET. Concluding Remarks (Dr. Lederberg) eeeeevneaeee P-17 P-78 P-85 p-97 P-190 P-119 P-122 P-139 P-133 P-145 | P-lh8 p-149 P-152 P-157 -3- TABLE OF CONTENTS (cont.) X. Professional Personne] eeeseee#ez#see#eteee»eeeeseeeveenreeeeeeeevs#ete¢e P-15690 Key Personnel and Backgrounds ...cccscccccccecseses Pr1El Relevant Research Support Summary for Departments of Genetics and Pediatrics .....cseeee. P-165 Individual Biographies eoeoeoeereovnesesneeereeeeeeseererve P-169