OR. KEOERBERG- RESOURCE-RELATED RESEARCH COMPUTERS AND CHEMISTRY (RR-00612 RENEWAL APPLICATION) Submitted to the BIOTECHNOLOGY RESOURCES BRANCH OF THE NATIONAL INSTITUTES OF HEALTH December, 1973 School of Medicine Stanford University CAI, COON meena an ne eed ecg Teer oe or ane ror ener d Form Approved SECTION | Budget Bureau No, 68-RO249 DEPARTMENT OF LEAVE BLANK HEALTH, EDUCATION, AND WELFARE TYPE IPR PUBLIC HEALTH SERVICE OGRAM NUMBER |REVIEW GROUP [FORMERLY GRANT APPLICATION COUNCIL (Month, Year) DATE RECEIVED To BE COMPLETED BY PRINCIPAL INVESTIGATOR (/tems 1 through 7 and 15A) 4. TITLE OF PROPOSAL (Do not exceed 53 typewriter spaces} Resource Related Research - Computers and Chemistry (RR-00612 renewal) 2. PRINCIPAL INVESTIGATOR 2A. NAME (Last, First, Initial} Djerassi, Carl 2B. TITLE OF POSITION Professor of Chemistry 13. DATES OF ENTIRE PROPOSED PROJECT PERIOD (This application) FROM THROUGH 5/1/74 4/31/79 4. TOTAL DIRECT COSTS RE. [6. DIRECT COSTS REQUESTED QUESTED FOR PERIOD IN FOR FIRST 12-MONTH PERIOD 2G. MAILING ADDRESS (Street, City, state, Zip Code) Department of Chemistry Stanford University Stanford, California 94305 3%. OEGREE Ph.D. 2F. TELE. Area LEPHONE DATA | 415 321-2300, Ext. 2783 ITEM 3 $1,350,795.00 $276,197.00 &. PERFORMANCE SITES) (See Instructions) Department of Genetics, Department of Chemistry, and Department of Computer Science Stanford University 2G. DEPARTMENT, SERVICE, LABORATORY OR EQUIVALENT (See instructions) : Department of Chemistry 3H. MAJOR SUBDIVISION (See Instructions) School of Humanities and Sciences 7. Research involving Human Subjects (See /nstructions) ACONO B.E3 YES Approved: C.£) YES — Pending Review Date & Inventions (henews/ Applicants Only - See Instructions} A.EINO B.(_] YES — Not previousiy reported Cc. CJYES — Previously reportea TO BE COMPLETED BY RESPONSISLE ADMINISTRATIVE AUTHORITY (items 8 through 13 and 158) 9. APPLICANT ORGANIZATION (S} (See instructions] Stanford University Stanford, California 94305 IRS No. 94-1156365 Congressional District No. 17 10. NAME, TITLE, AND TELEPHONE NUMBER OF OFFICIALS) r SIGNING FOR APPLICANT ORGANIZATION(S} c/o Sponsored Projects Office Telephone Number (s) (415) 321-2300, X2883 Tt. TYPE OF ORGANIZATION [Check appiicable item) COFeEpeRAL (Clistate CJ LOCAL EX OTHER (Specify) Private, non-profit University 12. NAME, TITLE, ADDRESS, ANC TELEPHONE NUMBER OF OFFICIAL IN BUSINESS OFFICE WHO SHOULD ALSO BE NOTIFIED IF AN AWARD IS MADE K. D. Creighton Deputy Vice Pres. for Business & Financ: Stanford University Stanford, California 94305 Telephone Number (415) 321-2300 ,X2551 GZNTZATIONAL COMPONENT 10 RECEIVE CREOIT FOR INSTITUTIONAL GRANT PURPOSES (See /astructions) 20 School of Humanities and Sciences ENTITY NUMBER (Formerly PHS Account Number) 458210 14. 16 CERTIFICATION AND ACCEPTANCE. We, the undersigned, certify that the statements herein are true and complete to the best of our knowledge and accept, as to any grant awarded, the obligstion to comply with Public Health Service terms and conditions in effect at the time of the averd, SIGNATURES A. SIGNATURE OF PERSON NAMED IN ITEM 2A DATE (Signatures required.on ; Original copy only. TB. SIGNATURE) OF PERSONS? NAMED IN ITEM 10 DATE Use ink, “Per” signatures B. SIGNATURE(S) OF PERSON(S) not acceptable) WIM 398 (FOREERLY PHS 398 Rev. 1/73 SECTION 1 DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE LEAVE BLANK PUBLIG HEALTH SERVICE PROJECT NUMBER RESEARCH OBJECTIVES NAME AND ADDRESS OF APPLICANT ORGANIZATION Stanford University Stanford, California 94305 II oe en eee NAME, SOCIAL SECURITY NUMBER, OFFICIAL TITLE, ANO DEPARTMENT OF ALL PROFESSIONAL PERSONNEL ENGAGED ON PROJECT. BEGINNIN INVESTIGATOR Carl Djera ber Professor of Chemistry, Department of Chemistry; Joshua Professor of Genetics, Department of Genetics; Edward Feigenbauz of Computer Science, Department of Computer Science; Bruce > esearch Computer Scientist, Department of Computer Science; Alan Duffie » Research Associate, Department of Genetics; Dennis Smith, e Tec sociate, Department of Computer Science: Harold Bro > be supplied Associate, Department of Computer Science; Geoff Dromey, SS# applied at a later date, Department of Computer Science. “TITLE OF PROJECT Resource-Related Research -- Computer and Chemistry USE THIS SPACE TO ABSTRACT YOUR PROPOSED RESEARCH, OUTLINE OBJECTIVES ANO METHODS. UNDERSCORE THE KEY WORT (NOT TO EXCEED 10) IN YOUR ABSTRACT. The -bjectives 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 chromatography/mass spectrometry (GC/MS) 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 (AI) 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 to provide stand-alone capabilities for collecting low and high resclution mass spectral and metastable ion data, 3) the application of GC/MS and AI techniques to analysis of biomolecular structure elucidation problems of a large number of collaborators, and 4) the extension of artificial intelligence techniques to an interactive system for computer assisted structure elucidation based on a variety of data. LEAVE BLANK NIH 398 (FORMERLY PHS 398) PAGE 2 Rev. 1/73 ; a a —— 1 SECTION IH — PRIVILEGED COMMUNICATION M THROUGH DETAILED BUDGET FOR FIRST 12-MONTH PERIOD 4/31/75 AMOUNT REQUESTED (Omit cents) FRINGE BENEFITS 5/1/74 DESCRIPTION (itemize) TIME OR EFFORT *%/HRS, PERSONNEL SALARY TOTAL TITLE OF POSITION PRINCIPAL INVESTIGATOR LISTE) SEPARATELY ON ATTACHED CONSULTANT COSTS EQUIPMENT ui nt Purchase (First Year Items Onl Displa ermina PDP 11/20 Upgrade nt Maintenance: -1 ul Part et GO 00 SUPPLIES upplie oO Liquid Nitrogen DOMESTIC TRAVEL FOREIGN PATIENT COSTS (See instructions} RATIONS AND RENOVATIONS OTHER EXPENSES (/temize) Publications, telephone, office supplies, postage 4,000 Computer Terminal Lease (4) 5,400. Computer Usage - 370/158 (First Year Item Only) 5,060 TOTAL DIRECT COST (Enter on Page 1, Item 5) pe 276.197 DATE OF DHEW AGREEMENT: INDIRECT % S&W* [WAIVED COST 47 exN'TD 2%. 1 (2 UNDER NEGOTIATION wiTH: . Cc - J 9 (See Instructions]. ———1L_.% Une — “IF THIS IS A SPECIAL RATE (e.g off-site], SO INDICATE, NUH 398 (FORMERLY PHS 398) PAGE 3 Rev. 1/73 ‘ PRINCIPAL INVESTIGATORS: C. Djerassi J. Lederberg E. Feigenbaum RESEARCH ASSOCIATES: B. Buchanan (1) A. Duffield D. Smith N. .Sridharan H. Brown G. Dromey PROGRAMMERS: W. White R. Tucker SENIOR RESEARCH ASSISTANT: A. Wegmann ELECTRONICS ENGINEER: N. Veizades GLASS BLOWER/MACHINEST: E. Steed RESEARCH ASSISTANTS: L. Masinter M. Stefik To Be Appointed SECRETARIAL SUPPORT: K. Wharton TOTAL: (1)Dr. Buchanan's salary charges do not begin until 9/1/74 at which time DETAILED SALARY DATA NIH GRANT #RR-00612 5/1/74-4/31/75 to Effort 10 10 10 30 25 100 100 100 100 100 100 100 60 25 100 100 100 100 Fringe Salary Benefits Total -O- -0- -0- -0- -0- -0- 2,910 514 3,424 7,000 1,237 8,237 6,195 1,094 7,289 16,200 2,862 19,062 16,050 2,835 18,885 16,200 -2,862 19,062 15,500 2,738 18,238 14,400 2,545 16,945 14,100 2,491 16,591 15,000 2,650 17,650 11,670 2,062 13,732 4,410 779 5,189 5,070 895 5,965 4,915 868 5,783 4,915 868 5,783 9,400 1,662 11,062 $163,935 $28,962 $192,897 his NIH Research Career Development Award expires. SECTION || — PRIVILEGED COMMUNICATION DIRECT COSTS ONLY (Omit Cents) BUDGET ESTIMATES FOR ALL YEARS OF SUPPORT REQUESTED FROM PUBLIC HEALTH SERVICE DESCRIPTION iGavene | ADDITIONAL YEARS SUPPORT REQUESTED (This application only) TAILED B 2ND YEAR 3RD YEAR 4TH YEAR STH YEAR BRERA 7TH YEAR TOTAL PERSONNEL COSTS 192,897 | 210,611 | 225,129 | 240,630 [257,383 [1,126,650 CONSULTANT COSTS (include fees, travel, etc.) -0- -0- -0- -0- -o- -0- EQUIPMENT 58,100 | 11,770 | 12,947 | 14,241 | 15,665 | 112,723 . SUPPLIES 9,600 6,920 | 7,612 8,370 | 9,207 41,709 DOMESTIC TRAVEL 1,200 1,320 | 1,452 1,597 | 1,757 7,326 FOREIGN -0- -0- -0- -0- -0- -0- PATIENT COSTS -0- -0- -0- -0- -0- -0- ALTERATIONS AND RENOVATIONS -0- -0- -0- -0- -0- -0- OTHER EXPENSES 14,400 } 10,340 | 11,374 | 12,511 | 13,762 62,387 TOTAL DIRECT COSTS 276,197 | 240,961 | 258,514 | 277,349 | 297,774 {1,350,795 TOTAL FOR ENTIRE PROPOSED PROJECT PERIOD (Enter on Page 1, [tem 4) ————_——» $ 1,350,795 page if needed.) See following pages for budget justification. REMARKS: Justify ail 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 “NER 398 (FORMERLY PHS 39¢) Rev. 1/73 ee er ree ane ape Rudgqet Justification Tha availability of existing equipment - including the mass spectrometer and SUMFX computer - avoids the need for reguesting funas for major laboratory itens and sabstantial computing costs. Thus, the major expense in the resulting hudget is for personnel. We feel that the personnel listed here are necessary to carry out the researzth, as justified helow. Pecurring costs are about £227,000 per year. First year expenditures are higher to provide the instrumentation necessary for mass spectrometry service in the first year. #e are regiesting funds for five years to coincide with the funding of the AIM-SUMBY resource, to which we hopa to make significant constributions. This badqet overlaps slightly with the buiget for the Genetics Pasearch Canter (J. Lederberg, Principal Investigator). Dr. Alan Duffieldats 25% salary budgeted here is covered hy the other budget {vhere 100% of his salary is budgeted). 10% of Ms. Annemarie #eamann's salary is covered there (with 109% of her salary huaqeated here). These are the only overlapping items. We have no 9fficial notification of Genetics Tenter funding; if the present proposal is successful, the Genetics Center budget will be adjusted accordingly. tn the five-year budget, salaries are increased by 6% per year and staff benefits are computed at 17% for the period 5/74-8/74, 18% For the period 9/74-8/75, and are increased 1% per year thereaftar, based on current University projections. Other budget catejories are increased by 19% per year to account for inflation. Parsonnal: RBRICE GS. 33 CHANAN Dr. Bruce Buchanan holds an NIH Research Career Development Award to work on applications of artificial intelligence to health-related problems, inclujiing theory formation by computer. Tis work on those aspects of this grant is thus consistent with the Davelonment Award. Half-time support is requested after the tkici year of the Development Award (starting September, 1974) to tover tha sontingency that the award will not be extended to the Full five years. These funds will he returned if the Award is extended, DENNIS H. SMITH Pr. Dennis H. Smith has been a memher of the DENDRAL project since July, 1971. He has been responsible for the MS and its computer suppoct, and has been involved in the application of the AI programs to structural studies of hiomedically important zompounas, primarily steroids. These responsibilities will tontinune ia the future, with particular emohasis on providing the mass spectrometer/Al program link to the use®r community and its Bass spectrometry and general structure elucidation needs, and in oroviding the necessary chemical knowledge and input for development of the computer programs and user interfaces for the proposed computer assisted structur® elacidation effort. ALAN OUFFIELD Jr. Alan Doffield is the senior scientist in charge of the mass spactrometry facilities of the GRC. Because of his expertise in the analysis of mass spectra from various fractions of human body fluids, ho will provide the link between the structure elucidation technianes of this proposal and other scientists with similar problems. The GC/HRMS facilities are also expected to provide service to the Genetics Center for hiqh resolution analysis of zompourds isolated from body fluids. VATESA SRIDHARAN Dr. Sridharan will he responsible for developing interface routines that allow new researchers to make use of the structure alucidation programs. We expect these routines to accept infornatioa about a research problem, in semi-formal terms, and translate it into a format the program can use. They should be sonplete enough so that indiviiual researchers do not need to know about the inner workings of the programs. In addition, he will sontinue to help Dr. Brown and Mr. Masinter with development of the cveclic generator program. (Within a few days of this writing, Dr. Sridharan has decided to take a leave of absence. During his absence we will recruit another Research Associate to perform his Inti2s.} HAROLD RROWN Nr, Hacold Brown's knowledge of graph theory and combinatorial mathematics is essential to the development of the cyclic structure yenerator. Many problems with development and imolamentation of this program have required sophisticated, new mathematical solutions worked out by Dr. Brown. For example, qganerating the dictionary of cyclic graphs and assembling substructices involve problems in graph theory that Dr. Brown is surrantly working on. Or. 3rown has submitted a proposal to the NSF to cover his salary for this research. If that grant is awarded, funds requested here for his salary will not be needed. P. GEOFF DROMEY Dr. 3eoff Dromey is a chemist with strong conputer science interests who has been associated with the project since Soptamber, 1973. He has become familiar with many aspects of the NENOR’L performance programs and will be expected to help outside researchers use those programs. Yn adjition, he will he jeveloping new programs, such as the program for molecular ion Jetermination from mass spectra. WILLTAM C. WHITE Mr, Willian White provides high-level programming support for the theory formation programs, including helping to devise new programs in response to new research problems as well as implamenting them. He wrote almost all of the LISP code for the INTSIM program, for example, and is currently responsible for the AULEGEN program, MO, ANNEMAPTE WEGMANN “s, Annemarie Wegmann is the Senior Research Assistant in charge af the GC/HRMS system. She was formerly head of Hewlett-Packard's Palo Alto gas chromatography applications laboratory and has been cresponsibla for the operation of the GC/MS system since the Yelivory to our laboratory of the MAT-711 (November, 1971). Her technical ability is absolutely essential to the continued gperation and development of the mass spectrometry facility. INSTRIMEN®T SUPPORT PERSONN EL oO tessears, Yaizades and Steed will assist part time in maintaining the GC/ES system. Mr. Veizades is an Flectronics Engineer who is responsible for the electronic and mechanical systems as well as proviling the necessary voltage read-out and control development for the metastable analysis data system. Mr. Steed is a Research "nzineer rasponsible for the system glasswork and vacuum system mai nkenanca. x RORFRT THCKER “Mr. Pobert Tucker implements and maintains the computer programs for data acquisition and reduction of MS data. This includes translating existing PL/ACME into FORTRAN and PDP-11 assembly langiayze. In addition, he will be responsible for improving these proqrams for repetitive HRMS scans, implementing the multiplet resolution algorithm and the software necessary for semi-automated tallaction of metastable ion data. PRY M, MASTNTER Larcy Masinter, Research Assistant, will continue to work with - Lederberg and Brown on the developmert of the cyclic ucture generator. His LISP expertise has been an invaluable ource for every member of the research team. Yuwie es aan = sy D “AO We ¢ MARK STEREPIK Mr. Mark Stefik, Research Assistant, combines two years of axzerience on the ACME/™S data acquisition system with a long-tern commitment to computer science. He has developed interactive library search capabilities for the mass spectrometer and will continue to improve them. His knowledge of the data acyuisition conpuater programs will he very valuable in assisting initial translation of those programs into FORTRAN (from PL/ACME code) for tha axtendead PNP-11/20 systen. RESPFARIH ASSISTANT - unnamed wo have interviewed two prospective Research Assistants, hoth of whom have broad chemical experience and strong conputer science interests. We request funds to hire one of them to provide additional links between computer science technigues and structure alucidation problems. SECRETARIAL SUPPORT Qna Cull-time secretary is necessary for the secretarial support af this number of scientists. Ms. Kathleen Wharton is now with the Computer Science group. POUTPMENT DNRCHASEs t= discussad in the text (Section III.A), in the first year we olan t9 augment our existing PDP-11/720 computer (4k memory) to allow its %peration as a stand-alone data system. We plan to ada 16k of memory ($3,900), a floating print arithmetic unit ($7,500), in industry compatible tape drive ($9,900), a disk drive (10,500), a low soveed communications interface ($1,000), and a bootstrap loader and clock ($1,209). These devices together with state sales tax total to £34,000. The prices quoted are representations »f the most cost-effective suppliers of the respective devices we rave heen able to locat2. We will continue to review the market haforea implementation to maximize technical and cost performance. As stated above, we plan to provide interface proyrams to provide the communication link between the users and the programs. The universal language of molecular structure is diagranmatic representation of the structures, drawn usually in two dimensions (oc as two-dimensioral representations of three dimensional information). Therefore, we feel that a graphics terminal such as the DET GT-40 is necessary for effective sharing of the programs among Stanford users. The GT-40 terminal is a good choice for nerforniaq this structural display task, for a number of reasons. Programs are available for input and output of structural information which can be modified to run on a GT-40 (e.g., we have just implemented on an experimental basis routines made available to us by R. Feldman, NIN); Sophisticated structural display provarams have been written especially for a GT-40 which we would hope to noint; and the ATM-SUMFX resource will specifically support one GT-40 for use by the SUMEX staff. This terminal will be physically located in the MS laboratory since all of the users will interact with that laboratory. FQOUTPMENT MATNTSNANCE: Maintenanc2? is budgeted for the proposed stand-alone PDP-11/20 system under DEC contract base? on current prices. Also included +3 a hudget for maintenance of the MAT-711 system. This estimate is based on our experience with parts replacements to date. We will provide the necessary maintenance manpower (see personnel justification) because Varian cannot provide adequate service. SUPPLIFS: Supplies are budgeted in various categories based on our operating ayparience to date. Flectronics supplies include parts necessary for maintaining our electronics and test equipment (#1,000) as well as parts in the first year for the metastable ion data system (3,200). These comprise several D/A and A/D converters for 3ccalerating voltage, ESA voltage, and magnetic field control as well as parts to upgrade the Hall probe mass marker. GC supplies jnclude carrier gases, columns, phases, syringes, septa, etc., for SC/MS operation. The liquid nitrogen is required for cold trap yperation on the MAT-711. Chemicals, glassware, etc., include the various organic chemicals, glassware, apparatus, glass tubing, atc., needed to support the GC/MS laboratory operation. Data recording media include special nv sensitive recoriing paper for the MAT-711, paper for GC and instrumentation recorder, and salcomp paver and pens for ion currennt and spectrum plotting. “iri-computer supplies include paper, magnetic tape, ribbons, spare disk cartridges, etc., for data system operation. TPAVELS The travel budget covers estimated neels (2 east coast and 2 west soast) trips for attending related professional meetings and Literfactiag potential program users nationally. Pomestic travel is budgeted for two Fast Coast trips and two California trips per year among all personnel. No foreign travel is budgeted. ITHER: The “otharc” budget includes operating telephone, office supplies, postaqe, re2production, etc., support necessary for this project basel on our previous experienzte. The "computer usage" allocation provides a continued limited usage of the 370/158 computer during the angqmentation of the PDP-11/20 systam. This cost does not apnear in later years. Terminal rental covers four terminals to he distributed among the ™S laboratory, the lTomputer Science Dept., and J. Lederberg's lahcratory. BIOGRAPHICAL SKETCHES /O SECTION II —- PRIVILEGED COMMUNICATION Principal Investigator: Carl Djerassi BIOGRAPHICAL SKETCH ; (Give the following information for all professional personnel listed on page 3, beginning with the Principal Investigator. Use Continuation pages and follow the same genera’ format for each person. } NAME TITLE BIRTHDATE (Mo., Day, Yr.) Carl DJERASSI Professor of Chemistry October 29, 1923 PLACE OF BIRTH (City, State, Country) PRESENT NATIONALITY (ff non-U.S. citizen, SEX indicate kind of visa and expiration date) Vienna, Austria U.S.A. Male (] Femate EDUCATION (Begin with baccalaureate training and include postdoctoral) YEAR SCIENTIFIC INSTITUTION AN TI N AND LOCATION DEGREE CONFEARED FIEID Kenyon College A.B. (summa 1942 Chemistry, Biology cum laude) University of Wisconsin Ph.D. 1945 Organic chemistry, Biochemistry (minor) HONORS Hon, D.Sc., Natl. Univ. of Mexico (1953), Kenyon College (1958), Worcester Polytechnic Institute (1972); Hon. Prof., Fed. Univ. Rio de Janeiro (1969). Member U.S. National Academy of Sciences, American Academy of Arts and Sciences, foreign member, Royal Swedish Academy of Sciences, German Academy of Natural Scientists (leopoldina), Brazilian Academy _of Sciences, (cont, below) MAJOR RESEARCH INTEREST Niqt, prod. chemist ROLE IN PROPOSED PROJECT (steroids, alkaloids, terpenoids, antibiotics) and _ ; chem. applications of physical methods (mass Principal Investigator _spec,, optical rotatory aispersion, circular RESEARCH SUPPORT (See instructions) dichroism). Current Total % Time Grant Title Period Year Budgeted Effort NIH AM 04257 Mass Spectrometry in 10/1/70 to $52,306 $316,016 10% Organic and Biochemistry 9/30/75 NIH GM AM Marine Chemistry with 1/1/73 to $75,650 578,180 18% 06840-15 special emphasis on steroids 12/31/77 NSF Pending Grant Application #P3P3689, Magnetic Circular Dichroism in Organic Molecules, in the amount of $27,640. RESEARCH AND/OR PROFESSIONAL EXPERIENCE (Starting with present position, list training and experience refevant to area of project. List all or most representative publications. Do not exceed 3 pages for each individual.) Academic Experience: Professor of Chemistry, Stanford University, 1959~present. Associate Professor (1952-1954) and Professor (1954-1959), Wayne State University. Industrial Research Experience: Ciba Pharmaceutical Co., summit, N.J.: Research Chemist, 1942-1943 and 1945-1949, Syntex Corporation: Associate Director of Chemical Research (Mexico City) 1949-1952, Research Vice President (Mexico City) 1957-1960; (Palo Alto, California) 1960-1968, ; President, Syntex Research 1968-paesemt, Zoecon Corporation (Palo Alito), President, 1968-preesat. Editorial Boards: 1972, (Current) Journal of the American Chemical Society, Steroids, Tetrahedron, Organic Moss Spectrometry. (continued on next page) Honors (cont.) Mexican Academy for Scientific Investigation. Hon. Fellow of Phi Lambda Upsilon. Amer. Academy of Pharmaceutical Sciences, British Chemical Society and Mexican Chemical Society, Phi Beta Kappa. Numerous hon. lectureships including 1964 Centenary Lecturer (The British Chemical Society) and 1969 Annual Chemistry Lecturer, Royal Swedish Academy of Engineering. American Chemical Society Award in Pure Chemistry (1958), Baekeland Medal (1959); Fritzsche Award (1960).’ Intra-Science Research Foundation Award (1969),’ Freedman Patent Award of American Institute of Chemists (1971). Foreign Member, Royal Swedish Academy of Sciences (1972). D.Sc. (hon.), Worcester Poiytechnic Institute (1972). Scheele-Lecturer, Pharmaceutical Society of Sweden (1972); American Chemica! RHS-398 Society's Award for Creafive Invention (19/73), National Medat cr serence (7/5). Rev. 3-70 age U.S, SOVERNMENT PRINTING OFFICE : 1971 O - 481-796 Hf ‘ ; DO NOT TYPE IN THIS SPACE-BINDING MARGIN BIOGRAPHICAL SKETCH (C. Djerassi) Continuation page = Principal Investigator:Cart Djerassi RESEARCH AND/OR PROFESSIONAL EXPERIENCE (cont.) Miscellaneous: {Chairman of the AAAS Gordon Research Conferences on Steroids and Natural Products (1952-1954); Member of American Pugwash Committee (1968 to present); Chairman of Latin America Science Board of National Academy of Sciences (1966-1968); Chairman of National Academy's Board on Science and Technology for International Development. - PUBLICATIONS Author or co-author of six books and approximately 800 publications dealing with natural products (notably steriods, terpenoids, alkaloids and antibiotics), medicinal chemistry (primarily antihistamines, oral contraceptives and anti-inflammatory agents) and applications of physical methods (mass spectrometry, optical rotatory dispersion, magnetic circular dichroism) to organic and biochemical problems. PHS -398 Page Rev, 2-69 GPO : 1969 © - 350-360 fer TITLE BIRTHOATE (Ata, Gay, £4) Rahs rofessor and Executive Head, LEDERBERG, JOSHUA Department of Genetics 5-23-25 PLACE OF BIRTH (City, State, Counvy) PRESENT NATIONALITY (/f non-US estizen, SEX : Indicate kind of visa and expiration data) Montedair. New Jersey U.S.A. TA Male (i Feralas EDUCATION (Begin with baccalsureate training und include postdactorai)} ~ YEAQ SCIENTIFIC INSTITUTION ANO LOCATION DEGREE oan | eee Columbia College, New York B.A. 1944 College of Physicians & Surgeons, : Columbia University, New York (1944-46) Yale University Ph.D. 194? Microbioglozy HONORS 1957 =- National Academy of Sciences 1958 - Nobel Prize in Medicine MAJOR RESEARCH INTEREST ROLE IN PROPOSED PROJECT Molecular Genetics; Artificial Intelligencg PRINCIPAL INVESTIGATOR RESEARCH SUPPORT (See sasxrucaons) SEE ATTACHMENTS: RESEARCH ANDO/ORA PROFESSIONAL EXPERIENCE (Starting with present positon, list {raining end expenence relevant to area of prcjech hist alt or most representanve publications Do notexceed 3 pages for each individual) 1961- 1957-1959 1957 1950 1947-1959 | 1946-1947 1945-1946 Stanforc University _,Director, Kennedy Laboratories for Molecular Medicine oo... 0002 eee ce ten “Eggo Professor, Genetics and Biology, and Executive Head, Department of Genetics, Stanford University - University of Wisconsin Chairman, Department of Medical Genetics Melbourne University, Australia Fullbright Visiting Professor of Bacterlolcgy University of California, Berkeley Visiting Professor of Bacteriology University of Wisconsin Professor of Genetics Yale University. Research Fellow of the Jane Coffin, Childs Fund for. Medical Research Columbia University. Research Assistant in Zoology Professional Activities: e NIMH: National Menral’ Health Advisory Council 1967- 1961-1962 President (Kennedy)'s Panel on Mental Retardation 1960- NASA Committees: Lunar and Planetary Missions Board 1958-"_ National Academy of Sciences: Committees on Space Biology . 1950-. President's Science Advisory Committee panels: National Institutes of Health, National Science Foundation study sections (genetics) RHS-398 - Rev. 3-70 Grant Number 1) NASA:NGR-05-020-004 2) NIH:AI-05160 3) NIH:GM 4) NIH:RR-00785 5) NIPX. Computer Lab- alth Care Réegoukce Progran @ N1HW:GM00295 h/ RESEARCH SUPPORT SUMMARY FOR JOSHUA LEDERBERG Grant Title Cytochemical Studies of Planetary Micro-organisms Genetics of Bacteria Genetics Research Center Stanford University Medical Experimental Computer Facility (SUMEX) Successor to #3 Lagge Scale~Qcreening o dy Fluids for tabolic Nhigns of DiseaSe.with Comput @x managed Chromatogra and Mass ‘Spectrometr Training Grant in Genetics Current Year $150,000 60,000 547,035 571,567 a 121,172 N Total Award $3,950,000 280,000 2,609,383 2,769,262 908, 238 321,163 12/7/73 Grant Term Budgeted % Time 9/60-8/74 4% (Future support dubious) 9/68-8/73 15% (Renewal Pending) 9/73-8/78 10% (Pending) 10/73-7/78 202% 9/73<8/78 vs (Pend > Program Funds impounded) 7/1/73-6/30/77 15% SELECTED LIST OF PUBLICATIONS Lederberg, J., 1959 A View of Genetics Les Prix Nobel en 1958: 170-89. Buchs, A., A. B. Delfino, A. M. Duffield, C. Djerassi, B. G. Buchanan, E. A. Feigenbaum, and J. Lederberg, 1970. Applications of Artificial Intelligence for Chemical Inference. VI. Approach to a general method of interpreting low resolution Mass spectra with a computer. Helvitia Chimica Acta 53 (6): 1394-1417. Feigenbaum, E. A., B. G. Buchanan, J. Lederberg, 1971 On generality and problem solving: a case study using the DENDRAL program in Machine Intelligence 6, (B. Meltzer and D. Michie, eds.), Edinburgh University Press, P. 165-190. Reynolds, W. E., V. A. Bacon, J. C. Bridges, T. C. Coburn, B. Halpern, J. Lederberg, E. C. Levinthal, E. Steed, R. B. Tucker, 1970 A Computer Operated Mass Spectrometer System. Analytical Chem. 42:1122-1129, September 1970. Lederberg, J. "Use of Computer to Identify Unknown Compounds: The Automation of Scientific Inference" in Biochemical Applications of Mass Spectrometry (G. R. Waller, ed.). John Wiley & Sons, New York (in press). 1S SECTION Il — PRIVILEGED COMMUNICATION BIOGRAPHICAL SKETCH (Give the following information for all professional personnel listed on page 3, beginning with the Principal Investigator. Use continuation pages and follow the same general format for each person} NAME TITLE . BIRTHDATE (Mo,, Day, Yr.) Principal Investigator, Feigenbaum, Edward A. © DENDRAL Project 1+20-36 PLACE OF BIRTH (City, State, Cauntry) PRESENT NATIONALITY (/f non-US citizen, SEX indicate kind of visa and expiration date) Weehawken, New Jerse U.S. Citi | > y Citizen 7 Male (1 Female EDUCATION (Begin with baccalaureate training and include postdoctoral) . YEAR SCIENTIFIC INSTITUTION AND LOCATION DEGREE CONFERRED FIELD Carnegie Institute of Technology Pittsburgh, Pennsylvania B.S. 1956 Electrical Engineering Ph.D. 1959 Benavioral Sciences. .HONORS and memberships: American Psychological Association; Association for Computing Machinery (Member of the National Council 1966-68); American Association for the Advancement of Seience, SIGBIO Chairman, 11/73-present. MAJOR RESEARCH INTEREST : ROLE iN PROPOSED PROJECT Artificial Incelligence , Principal Investigator RESEARCH SUPPORT (See instructions) RESEARCH AND/OR PROFESSIONAL EXPERIENCE (Starting with present position, list training and experience relevant to area of projece List al’ or most representative publications, Do not exceed 3 pages for each individual.) 1965~ Stanford University, Computer Science Department Faculty 1965-1968 Stanford University, Director, Computation Center 1963 Summer Research Training Institute in Computer Simulation of Cognitive Processes (National Science Foundation) 1962 Carnegie Corporation. Summer Research Training Institute in Heuristic Programming. Faculty member. 1960-1964 University of California, Berkeley Research-Center for Research in Management Science, 1960-1964 Research-Center for Human Learning, 1961-1964 Assistant and Associate Professor, School of Business Administration, 1960-64 1957-1960 The RAND Corporation, Santa Monica, California 1956 - IBM Seientific Computing Center, New York Selected Publications: "Applications of Artificial Intelligence for Chemical Inference I. The Number artt of Possible Organic Compounds. Acyclic Structures Containing C, H, O andi, J. Am. Chem. Soc., 91, 2973 (1969). (Co-Author). "Applications of Artificial Intelligence for Chemical Inference II. Interprevation of Low Resolution Mass Spectra of Ketones", J. Am. Chem. Soc., 91, 2977 (1969). (Co~Author). . . RHS-398 Rev. 3-70 ; . /, b Publications of Edward Feigenbaum "Applications of Artificial Intelligence for Chemical Inference III. Aliphatic Ethers Diagnosed by their Low Resolution Mass Spectra and Nuclear Magnetic Resonance", J. Am. Chem. Soc., 91, 7440 (1969). (Co-Author). "Heuristic DENDRAL: A Program for Generating Explanatory Hypotheses in Organic Chemistry", in Machine Intelligence 4, Edinburgh University Press, 1969. (Co-Author). — “Toward an Understanding of Information Processes of Scientific Inference in the Context of Organic Chemistry", in Machine Intelligence 5, sdinburgnh University Press, 1970. (Co-Author). "A Heuristic Program for Solving a Scientific Inference Problem: Summary of Motivation and Implementation", Stanford Artificial Intelligence Project Memo No. 104, November 1969. (Co-Author). “Applications of Artificial Intelligence For Chemical Inference IV. Sa urated Amines Diagnosed by Their Low Resolution Mass Spectra and Nuclear i Resonance Spectra", Journal of the american Chemical Society, 92, 6 (Co-Author). "Applications of Artificial Intelligence for Chemical Inference V. An Approach to the Computer Generation of Cyclic Structures. Differentiation Between All the Possible Isomeric Ketones of Composition C6H100", Organic Mass Spectrometry, 4, 493 (1970). (Co-Author). "Applications of Artificial Intelligence for Chemical Inference VI. Approach to a General Method of Interpreting Low Resolution Mass Spectra with a Computer", Chem. Acta Helvetica, 53, 1394 (1970). (Co-Author). "On Generality and Problem Solving: A Case Study Using the DENDRAL P " in Machine Intelligence 6, Edinburgh University Press (1971). (Co-Au "A Heuristic Programming Study of Theory Formation in Science”, 3 of the Second International Joint Conference on Artificial Intel Imperial College, London (September 1971). (Co-Author). n” ae 4 -_ roceedings r nee, ~~ v + ra Be a "Applications of Artificial Intelligence for Chemical Inference VIII. An Approach to the Computer Interpretation of the High Resolution Mass Specvra of Complex Molecules. Structure Elucidation of Estrogenic Steroids", Journal of the American Chemical Society, 94, 5962-5971 (1972). (Co-Author). "Heuristic Theory Formation: Data Interpretation and Rute Formation", in Mechine Intelligence 7, Edinburgh University Press (1972). (Co-Author). "Applications of Artificial Intelligence for Chemical Inference X. Intsum A Data Interpretation Program as Applied to the Collected Mass Spectra of Estrogenic Steroids", Tetrahedron, 29, 3117 (1973). (co-author). /7 SECTION It - PRIVILEGED COMMUN. ION BIOGRAPHICAL SKETCH {Give the following information for all professional personnel listed an page 3, beginning with the Principal Investigator. Use continuation pages and follow the same general format for each person. ] NAME TITLE BIRTHDATE (to., Day, Yr) Buchanan, Bruce G. Research Computer Scientist 7-77-40 PLACE OF BIRTH (City, State, Country) PRESENT NATIONALITY {/f non-US citizen, SEX indicate kind of visa and expiration date) St. Louis, Missouri U.S.Citizen . 44) Mate (1 Female EDUCATION (Begin with baccalaureate training and include postdoctoral} YEAR SCIENTIFIC INSTITUTION AND LOCATION DEGREE CONFERRED FIELO Ohio Wesleyan University B.A. 1961 | Methematics Michigan State University M.A., Ph.D. | 1966 Philosophy ‘HONORS Recipient of National Institutes of Health Career Development Award (1971-21976) MAJOR RESEARCH INTEREST ROLE iN PROPOSED PROJECT Artificial Intelligence Associate Investigator RESEARCH SUPPORT (See instructions) NIH Research Career Development Award, GM-29662 elf RESEARCH AND/OR PROFESSIONAL EXPERIENCE (Starting with present position, list training and experience relevant to area ofproject List or most representative publications, Do not exceed 3 pages for each individual.) 1972-present Research Computer Scientist, Stanford University 1966-1971 Research Associate, Stanford Artificial.Intelligence Project Publications: "On the Design of Inductive Systems: Some Philosophical Problems". British Journal for the Philosophy of Science 20 (1969), 311-323. (Co-Author). "Applications of Artificial Intelligence for Chemical Inference II. Interpretation of Low Resolution Mass Spectra of Ketones". Journal of the American Chemical Society, 91, 2977-2981 (1969). (CorAuthor). "Applications of Artificial Intelligence for Chemical Inference I. The Nurber of Possible Organic Compounds: Acyclic Structures Containing C, H, O and N". Journal of the American Chemical Society, 91, 2973-2976 (1969). (Co-Author). “Applications of Artificial Intelligence for Chemical Inference III. Aliphatic Ethers Diagnosed by Their Low Resolution Mess Spectra and NMR Data". Journal of the American Chemical Society, 91, 7440-45 (1969). (Co-Author). “Heuristic DENDRAL: A Program for Generating Explanatory Hypotheses in Organic . Chemistry". Machine Intelligence.4, Edinburgh University Press:(1969). (Co-Author). RHS-398 Rev. 3-70 1S Publications of Bruce Buchanan: "Toward an Understanding of Information Processes of Scientific Inference in the Context of Organic Chemistry". Machine Intelligence 5, Edinburgh University Press (1969). (Co-Author). "On Generality and Problem Solving: A Case Study Using the DENDRAL Progren". _ Machine Intelligence 6, Edinburgh University Press (1969). (Co-Author). "Some Speculation About Artificial Intelligence and Legal Reasoning". Stanford Law Review, Vol. 23, No. 1, November 1970. (Co-Author). - “Applications of Artificial Intelligence for Chemical Inference VI. Approach to a General Method of Interpreting Low Resolution Mass Spectra with a Computer”. Chemica Acta Helvetica, 53, 1394 (1970). (Co-Author). "An Application of Artificial Intelligence to the Interpretation of Mass Spectra". Mass Spectrometry Techniques and Appliances (1970). "Applications of Artificial Intelligence for Chemical Inference IV. Saturated Amines Diagnosed by Their Low Resolution Mass Spectra and Nuclear Magnetic Rescnarce Spectra". Journal of the American Chemical Society, 93, 6831 (1970). (Co-Author). "The Heuristic DENDRAL Program for Explaining Empiricel Data". Proceedings of IFIP Congress 1971, Ljubljana, Yugoslavia. (Co-Author). "A Heuristic Programming Study of Theory Formation in Science". Proceedings of Second International Joint Conference on Artificial Intelligence, Imperial College, London (1971). (Co-Author). “Applications of Artificial Intelligence for Chemical Inference VIII. An Approach to the Computer Interpretation of the High Resolution Mass Spectra of Complex Molecules. Structure Elucidation of Estrogenic Steroids". Journal of the American Chemical Society, 1972. (Co-Author). "Heuristic Theory Formation: Data Interpretation and Rule Formation". Machine Intelligence 7, Edinburgh University Press (1972). (Co-Author). "Review of Hubert Dreyfus' 'What Computers Can't Do: A Critique of Artificial Reason'", Computing Reviews (January, 1973). "Applications of Artificial Intelligence for Chemical Inference IX. Analysis o Mixtures Without Prior Separation as Illustrated for Estrogens". Submitted to Journal of the American Chemical Society. (Co-Author). o a. tne "Applications of Artificial Intelligence for Chemical Inference X. Intsum A Data Interpretation Program as Applied to the Collected Mass Spectra of Estrogenic Steroids". Tetrahedron, 29, 3117 (1973). (co-author) "Rule Formation on Non-Homogeneous Classes of Objects". In proceedings of the Third International Joint Conference on Artificial Intelligence (Stanford. 1973). (co-author). "Current Status of the Heuristic DENDRAL Program for Applying Artificial Intelligence to the Interpretation of Mass Spectra". DENDRAL Project Memo, August 1973 /? Biographical Sketch of Bruce G. Buchanan Memberships: Association for Computing Machinery (ACM) Philosophy of Science Association American Association for Advancement of Science (AAAS) 20 SS St ey Lg et 2 ri eee Use continuation cops and foilow ine sa general format for each person} NAME Alan M, DUFFIELD TITLE . BLATHOAT Research Associate Decen PLACE OF BIATH (City, State, Country) Perth, Western Australia PRESENT NATIONALITY [/f non-US citizen, SEX indicate kind of visa and expiration date} Australian, Permanent resident Tomircrant Vien (2 Male [7 Femaia EQUCATION (devia with Daccatauregte waning and include postdoctoral) . INSTITUTION AND LOCATION DEGREE YEAS SCIENTIEIC CONFERRED FIELO University of Western Australia B. Sc(lst Class , F . Hons) 1958 Organic Chemistry ~ University of Western Australia Ph.D. 1962 Organic Chemsitry | HONORS 1 MAJOR RESEARCH INTEREST ‘Applications of mass spectrometry to Biology and Biomedical Problems ROL? IN PROPOSED PROJECT Organic Chemist/mass spectroscopist RESEARCH SUPPORT (See instrucdons) N/A : 4 i Of Most representatve publications Oo not exceed 3 cages for each individual.j settee ee fins 18 Rev, 3-79 1970 1969 1965 1963 1962 69 63 An Application of Artificial Int Mass Spectrometry, ©. New York, 1971, po, 121-178 By B. G S3uchancn, A. M. Du Bn a ee ae rT ee tt te “ Research Associate, Department of Genetics, Stanford University School of Medicine - Eead of the Mass Spectrometry Laboratory, Chemistry Department Stanford University . Research Associate, Department of Chemistry, Stanford University Postdoctoral Fellow, Department of Chemistry, Stanford University RESEARCH ANO/OR PROFESSIONAL EXPERIENCE (Starting with present position, fist training and experience reievant £0 area of pra,eC& List ail Postdoctoral Fellow, Department of Biochemistry, Stanford University School of Medicine. . 7 PUBLICATIONS SINCE 1971 alligence to the Interpretation of Mass Spectra. B.W.G. Milne, Ede, John Wiley and Sons, ffield and A. V. Robertson Ly 10, ll, 12, Mass Spectrometry in Structural and Stereochemical Problems. CCIV. Spectra of Hydantoins.II. Electron Impact Induced Fragmentation of some Substituted Hydantoins. Org. Mass Spectr., 5, 551 (1971) By R. A. Corral, 0. 0. Orazi, A. M. Duffield and C. Djerassi Electron Impact Induced Hydrogen Scrambling in Cyclohexanol and Isomeric Methylcyclohexanols. | ~ Org. Mass Spectr., 5, 383 (1971) , sO By R. H. Shapiro, S. P. Levine and A. M. Duffield .. Derivatives of 2-Biphenylcarboxylic Acid. Rev. Roumain. Chem., 16, 1095 (1971) By A. T. Balaban and A. M. Duffield Alkaloide aus Evonymus europaea L. Helv. Chim. Acta, 54, 2144 (1971) By A. Kldsek, T. Reichstein, A. M. Duffield and F. Santavy Studies on Indian Medicinal Plarts. XXVIII. Sesquiterpene Lactones of Enhyura Fluctuans Lour. Structures of Enhydrin, Fluctuanin and Fluctuadin. Tetrahedron, 28, 2285 (1972). By E. Ali, P. P. Ghosh Dastidar, S. C. Pakrashi, L. J. Durham and A. M. Duffield The Electron Impact Promoted Fragmentation of Aurone Epoxides. Org. Mass Spectr., 6, 199 (1972) By B. A. Brady, W. I. O'Sullivan and A. M. Duffield The Determination of Cyclohexylamine in Aqueous Solutions of Sodium Cyclamate by Electron Capture Gas Chromatography. Anal. Letters, 4, 301 (1971) By M. D. Soloman, W. E. Pereira and A. M. Duffield Computer Recognition of Metastable Ions. Nineteenth Annual Conference on Mass Spectrometry, Atianta, 1971, p. 63 - . By A. M. Duffield, W. E. Reynolds, D. A. Anderson, R. A. Stillman, Jr. . and cC. E. Carroll Spectrometrie de Masse. VI. Fragmentation de Dimethyl-2,2-dioxolanes-1,¢- Insatures. Org. Mass Spectr., 5, 1409 (1971) By J. Kossanyi, J. Chuche and A. M. Duffield Chlorpromazine Metabolism in Sheep. II. In vitro Metabclism and Preparation of 3H-7-Hydroxychlorpromazine. ~~ Journees D'Agressologie, 12 , 333 (1971) By L. G. Brooks, M. A. Holmes, I. S. Forrest, V. A. Bacon, A. M. Duffield and M. D. Solomon Mass Spectrometry in Structural and Stereochemical Problems. CCXVII. ’ Electron Impact Promoted Fragmentation of O-Methyl Oximes of Some a,8-Unsaturated Ketones and Methyl Substituted Cyclchexanones. Canadian J. Chem., 50, 2776 (1972) By Y. M. Sheikh, R. J. Liedtke, A. M. Duffield and C. Djerassi As M. Publications 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. Thermal Fragmentation of Quinoline and Tsoquinoline N-Oxides in the Ion Source of a Mass Spectrometer. Acta Chem. Scand., 26, 2423 (1972). By A. M. Duffield and 0. Buchardt _ ‘Applications of Artificial Intelligence for Chemical Inference. VII. An Approach to the Computer Interpretation of the High Resolution Mass Spectra of Complex Molecules. Structure Elucidation of Estrogenic Steroids. J. Amer. Chem. Soc., 94, 5962 (1972) By D. H. Smith, B. G. Buchanan, R. S. Englemore, A. M. Duffield, A. Yeo, E. A. Feigenbaum, J. Lederberg and C. Djerassi Mass Spectrometry in Structural and Stereochemical Problems. CCXIX. Identification of a Unidirectional Quadruple Hydrogen Transfer Process in 7-Phenyl-hept-3-en-2-one O-Methyl Oxime Ether. Org. Mass Spectr., 6,1271 (1972). By R. J. Liedtke, Y. M. Sheikh, A. M. Duffield and C. Djerassi An Automated Gas Chromatographic Analysis of Phenylalanine in Serum. Clinical Biochem., 5, 166 (1972) | . By E. Steed, W. Pereira, B. Halpern, M. D. Solemon and A. M. Duffield Pyrrolizidine Alkaloids. XIX. Structure of the Alkaloid Erucifoline. Coll, Czech. Chem. Commun., (1972) . By P. Sedmera, A. Kiasek:s A. M, Duffield and F, Santavy. Mass Spectrometry in Structural and Stereochemical Problems. CCXXII, Delineation of Competing Fraementation Pathways of Complex Molecules from a Study of Metastable Ion Transitions of Deuteratec Derivatives. Org. Mass Spectr., 7, (1973) -By D. H. Smith, A. M, Duffield and C. Djerassi Chlorination Studies I. The Reaction of Aqueous Hypochlorous Acid with Cytosine. Biochem. Biophys. Res. Commun., 48, 880 (1972) By W. Patton, V. Bacon, A. M. Duffieid, B. Halpern, Y. Hoyano, W. Pereira and J. Lederberg A Study of the Electron Impact Fragmentation of Promazine Sulphoxide and Promazine using Specifically Deuterated Analogues. Austral. J. Chem., 26, (1973). By M. D. Solomon, R. Summons, W. Pereira and A. M. Duffield Spectrometric de Masse. VIII. Elimination d'eau Induite par Impact Electronique dans le Tetrhydro-1,2,3,4-naphtalenediol-1,2. Org. Mass. Spectrom., 7 (1973). By P. Perros, J. P. Morizui, J. Kossanyi and A. M. Duffield The Determination of Phenylalanine in Serum by Mass Fragmentography Clinical Biochem., submitted for publication (1973). By W. E. Pereira, V. A. Bacon, Y. Hoyano, R. Summons and A. M. Duffield xT SECTION If — PRIVILEGED COMMUNICATION BIOGRAPHICAL SKETCH (Give the following information for all professional personnel listed on page 3, beginning with the Principal Investigator. Use continuation pages and follow the same general format for each person.) NAME TITLE BIRTHDATE (Mo,, Day, Yr) Dennis H. Smith Research Associate 11/12/42 PLACE OF BIRTH (City, State, Country) PRESENT NATIONALITY (/f non-U,S. citizen, SEX indicate kind of visa and expiration date) New York USA X5 mate “Cleemate EDUCATION (Begin with baccalaureate training and include postdoctoral} YEAR SCIENTIFIC INSTITUTION AND LOCATION DEGREE CONEERRED FIELD Massachusetts Inst. of Technology Cambridge, Mass. S.B. 1964 Chemistry University of California, Berkeley Berkeley, California Ph.D. 1967 Chemistry HONORS Alfred P. Sloan Foundation Scholarship NASA Predoctoral Traineeship Phi Lambda Upsilon, Sigma Xi MAJOR RESEARCH INTEREST ROLE IN PROPOSED PROJECT ~ Spectromet and A.I. in Chemist : Mass Sp ty ry Research Associate RESEARCH SUPPORT (See instructions) N/A RESEARCH AND/OR PROFESSIONAL EXPERIENCE (Starting with present position, fist training and experience reievant to area of projecé List ait or most representative publications, Do not exceed 3 pages for each individual.) 1971-Present Research Associate, Stanford University, Stanford,Ca. 1970-1971 Visiting Scientist, University of Bristol, Bristol, England 1967-1970 Assistant Research Chemist, University of Calif.at Berkeley, Berkeley, Ca. 1965-1967 NASA Pre-Poctoral Traineeship, University of Calif.at Berkeley,Berkeley, Ca. Publications: See attached list. RHS398 : Rev. 3-70 oo uf 6. 10. PUBLICATIONS: D. H. SMITH H. G. Langer, R. $. Gohlke and D. H. Smith, "Mass Spectrometric Differential Thermal Analysis," Anal. Chem., 37, 433 (1965). S. M. Kupchan, J. M. Cassady, J. E. Kelsey, H. K. Schnoes, D. H. Smith and A. L. Burlingame, "Structural Elucidation and High Resolution Mass Spectrometry of Gaillardin, a New Cytotoxic Sesquiterpene Lactone," J. Amer. Chem. Soc., 88, 5292 (1966). D. H. Smith, Ph.D. Thesis, "High Resolution Mass Spectrometry: Techniques and Applications to Molecular Structure Problems," Dept. of Chemistry, University of California, Berkeley, Califomia (1967). H. K. Schnoes, D. H. Smith, A. L. Burlingame, P. W. Jeffs and W. D&pke, "Mass Spectra of Amaryllidaceae Alkaloids: The Lycorenine Series," Tetrahedron, 24, 2825 (1968). A. L. Burlingame, D. H. Smith and R. W. Olsen, "High Resolution Mass Spectrometry in Molecular Structure Studies, XIV. Real-time Data Acquisition, Processing and Display of High Resolution Mass Spectral Data," Anal. Chem., 40, 13 (1968). A. L. Burlingame and D. H. Smith, "High Resolution Mass Spectrometry in Molecular Structure Studies Il. Automated Heteroatomic Plotting as an Aid to the Presentation and Interpretation of High Resolution Mass Spectral Data," Tetrahedron, 24, 5749 (1968). W. J. Richter, B. R. Simoneit, D. H. Smith ond A. L. Burlingame, "Detection and Identification of Oxocarboxylic and Dicarboxylic Acids in Complex Mixtures by Reductive Silylation and Computer-Aided Analysis of High Resolution Mass Spectral Data," Anal. Chem., 41, 1392 (1969). The Lunar Sample Preliminary Examination Team, "Preliminary Examination of Lunar Samples from Apollo 11," Science, 165, 1211 (1969). S. M. Kupchan, W. K. Anderson, P. Bollinger, R. W. Doskotch, R. M. Smith, J. A. Saenz Renauld, H. K. Schnoes, A. L. Burlingame and D. H. Smith, "Tumor Inhibitors, XXXIX. Active Principles of Acnistus arboresceis. Isolation and Structural and Spectral Studies of Withaferin A and Withacnistin," J. Org. Chem., 34, 3858 (1969). A. L. Burlingame, D. H. Smith, T. O. Merren and R. W. Olsen, "Real- time High Resolution Mass Spectrometry," in Computers in Analytical Chemistry (Vol. 4 in Progress in Analytical Chemistry series), C. Hh. Ov and J. Norris, Eds., Plenum Press, New York, 1970, pp. 17-38. ao