Form Approved
SECTION i Budget Bureeu No, 68-RO

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mee

GROup
COUNCIL (Month, Year}

TO BE COMPLETED BY PRINCIPAL INVESTIGATOR (/tems 1 through 7 and 164}
1. TITLE OF PROPOSAL (Do not exceed 53 typewriter spaces)

DEPARTMENT OF
HEALTH, EDUCATION, AND WELFARE
PUBLIC HEALTH SERVICE

    
   
 
 

  

ORMERLY

 

GRANT APPLICATION

 

OATE RECEIVED

 

 

 

 

 

 

 

 

Resource Related Research - Computers and Chemistry (RR-00612 renewal)
2. PRINCIPAL INVESTIGATOR 3.DATES OF ENTIRE PROPOSED PROJECT PERIOD [This applicatic
2A. NAME (Last, First, Initial) / FROM THROUGH
Lederberg, Joshua 5/1/74 4/30/77
2B. TITLE OF POSITION 4, TOTAL DIR Re- Dine D
mus FOR PERIOD IN FOR FIRST 12-MONTH PERIC
Prof d :
ofessor and Chairman $1,639 ,456 $488,267
ty, State, Instructions) _

Department of Genetics

Stanford University Medical Center
Stanford, California 94305

Department of Genetics
Department of Chemistry, and
Department of Computer Science
Stanford University

 

Department of Genetics

 

 

 

 

 

3H. MAJOR SUBDIVISION (See Instructions)
School of Medicine
7. Hesserch Trvolving Humen Subjects (See Instructions} laventions (Renewal Applicants Only - See Instructions} 77
A.CINO 8.7) YES Approved: A. NO 8.(7] YES — Not previously reported
C. (3) YES — Pending Review Date C.CCJYES — Previously reported
TO BE COMPLETED BY RESPONSIBLE ADMINISTRATIVE AUTHORITY (ftems 8 through 13 and 168)
9. APPLICANT ORGANIZATION(G) (See Instructions} 7. ION (Check applicable item)
CIFEDERAL CJSTATE (CJ LOCAL [KJOTHER (Specify)
Stanford University Private, non-profitUniversity
sanford, California 94305 3 FICIAL iN ‘BUSINESS OFFICE WHO SHO D ALSO E
IRS No. 94-1156365 FFICIA ULD ALSO B
ARD iS MA
Congressional District No. 17 BOTIFIED IF AN AWARD dE

K. D. Creighton

Deputy Vice Pres. for Business and Finan:
Stanford University

Stanford, California 94305
7 AND TELEPHONE NUMB

18 NAME, TITLE, AND TELEPHONE NUMBER OF OFFICIALS) 1
SIGNING FOR APPLICANT ORGANIZATION(S) Telephone Number(415) 321-2 300. X2.
V
FOR INSTITUTIONAL GRANT PURPOSES (See instructions}

O1 School of Medicine

 

c/o Sponsored Projects Office 14, ENTITY NUMBER (Formerly PHS Account Number )
Tetephone Number {s) =2300___X2823 458210

16, CERTIFICATION ANO ACCEPTANCE, We, the undersigned, certify that the statements herein are true end complete to the best of our

knowledge end accept, as to any grant awarded, the obligation to comply with Public Health Service terms and Conditions in effect st the time of the
averd,

iSignetures required on ) — i , APR 26 ‘973

 

 

 

 

not

miM 396 (FORMERLY PHS 998
Rev. 1/73

 
——SECTION. 1.

DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE LEAVE BLANK
PUBLIC HEALTH SEAVICE PROJECT NUMBER

RESEARCH OBJECTIVES
NAME AND ADDRESS OF APPLICANT ORGANIZATION

 

 

 

 

Stanford University, Stanford, California 94305

SAME, SOCIAL SECURITY NUMBER, OFFICIAL TITLE, AND DEPARTMENT OF ALL mA PERSONNEL ENGAGED ON
PROJECT, BEGINNING WITH PRINCIPA ESTIGATOR OFESSIONAL

Lederberg, Joshua, Professor of Genetics, Department of Genetics
Djerassi, Carl, > Professor of Chemistry, Department of Chemistry
Feigenbaum, Edward, Professor of Computer Science, Dept. of Computer Sci
Buchanan, Bruce, ‘Research Computer Scientist, Dept. of Computer Scien
Duffield, Alan, » Research Associate, Department of Genetics ~
Pereira, Wilfred, Associate, Department of Genetics
Rindfleisch, Thomas Associate, Department of Genetics

Smith, Dennis Associate, De
7 ’ partment of Chemistry
_ Sridharan, Natesa, Associate, Department of Computer Science
A e,—-Den mer omistys

 

      
   
  
  
   
 
  
 
  
 
    

nme Pen

ove ry
TITLE OF PROJECT " — :

Resource Related Research - Computers and Chemistry
USE THiS SPACE TO ABSTRACT YOUR PROPOSED RESEARCH. OUTLINE OBJECTIVES AND METHODS. UNDERSCORE THE KEY WO
(NOT TO EXCEED 10) IN YOUA ABSTRACT.

 
 

         

 

The objectives of this research: program are the development of innovative
computer and biochemical, analysis techniques for application in medical research
and closely related aspects of investigative patient care. We will apply the unique
analytical capabilities of gas chromatograph /mass spectromet (GC/MS) and
Carbon(13) Nuclear Magnetic Resonance § ectromet (CMR) with the assistance of data
interpreting computer programs utilizing artificial intelligence techniques, to
investigate the chemical constituents of human body fluids in a variety of clinical
contexts, Specific subtasks of this program include; 1) the application of artificial
intelligence techniques to programs capable of interpreting mass spectra from basic
principles as well as extending mass spectral theory by analysis of solved spectrum
structure examples, 2) the extension of GC/MS data systems incorporating an increasing
level of automation and allowing the directed collection of specialized information,
3) the application of GC/MS techniques to analyze body fluids such as urine and
blood, and to relate detected metabolic abnormalities to clinically observable
disease states, and 4) the application of CMR techniques to assist in the determinatic

of chemical structure.

 

 

LEAVE BLANK

 

NIH 398 (FORMERLY PHS 398) PAGE 2
Rev. 1/73
The undersigned ayrees to accept responsibility for the
scientific and technical conduct of this project and for
provision of required progress reports if a gtant is awarded as
the result of this application.

      

-APR2610/3____ __- we, eA

Date Joshua Lederber

Principal Investigator
RESOURCE=RELATED RESEARCH: COMPUTERS AND CHEMISTRY

(RR-00612 - Renewal Application)

TABLE OF CONTENTS

Introduction eesoeootvoetweeeeeveeveeovneseeveeveevnene ov ease eooeoeveevmneeeeveevene ee ees P-1

Part A: Applications of Artificial Intelligence to
Mass Spectrometry oeeeseeooeseeeveeaesvseeveeeseeoeveeceee eevee enes oe eae P=5

Part BBCi): Mass Spectrometer Data System Development ........ Pri?

Part BCiI): Analysts of the Chemical Constituents of
Body Flulds @enpreeHeeeoveeseesee8seeseseeeeoeeewseseweeenheneeeeeneeees P-28

Part C: Extension of the Theory of Mass Spectrometry by
Computer @eeeenveeeeseeeeeseersreenseenoveeeteeoveeaeseeeseeeoetceeoaeeveeseteeeseenweeee P-39

Part D: Appltcattions of Carhon(13) Nuclear Magnetic

Resonance Spectrometry to Assist [In Chemical

Structure Determination ..cccccccscccsccesceececesese PUES
Sltgnificance ewpreeeeeeseseeveeeeeeveeteeewtensteseeseeenteenweeeeeweeseeseeoeneneeeoeesteesd @ PR?
Co? laborative Arrangements @eeeeoeausueee#eee9#8#Heesesee#etesenwreeoeoeeweeteeseeenvneseeeeree & D-~Rh
Facllittes Aval lable @eeoeeea2ns1seeesenteeneteeaeseeeeeeseeoeseeveeeeoeseensveeereeneteneownwte @ P-86
Human Subjects @eeeeoerneevnvwvensseeewvseeewpeoeaeneoueeteeoeoeeseeeesesvseeeesveespeseeveaeec ee P-&8

Budgets and Justification e@orevntetensvseeeveeneeeveee eevee eovonvne snes eeeeranene P-90

Blographles eseeeeeveeeeveeensvnsevrererevneeeveeveseeoeeeveevneoes een eeeaseenseeeevnevneveve P-117