SUMEX STANFORD UNIVERSITY MEDICAL EXPERIMENTAL COMPUTER RESOURCE RR-00785 COMPETING RENEWAL APPLICATION Submitted to BIOMEDICAL RESEARCH TECHNOLOGY PROGRAM NATIONAL INSTITUTES OF HEALTH June 1, 1985 STANFORD UNIVERSITY SCHOOL OF MEDICINE Edward H. Shortliffe, Principal Investigator Edward A. Feigenbaum, Co-Principal Investigator DEPARTMENT OF HEALTH AND HUMAN SERVICES PUBLIC HEALTH SERVICE GRANT APPLICATION FOLLOW INSTRUCTIONS CAREFULLY Form aooroved OMB Ain. 0925-0001 LEAVE BLANK TYPE ACTIVITY NUMBER REVIEW GROUP FORMERLY COUNCIL/BOARD (Montn, year) |DATE RECEIVED 1. TITLE OF APPLICATION (Oo nor exceed 56 typewriter spaces! SU Medical Experimental Computer Resource (SUMEX) 2. RESPONSE TO SPECIFIC PROGRAM ANNOUNCEMENT CINO LJ YES (/f “YES,” state AFA number and/or announcement title) 3. PRINCIPAL INVESTIGATOR/PROGRAM DIRECTOR 3a. NAME (Last, first, middie) Shortliffe, Edward H. 3c. POSITION TITLE Associate Professor of Medicine OCIAL SECURITY NUMBER 3d. MAILING AODRESS (Svreer, city, state, 21 Stanford University School of Medicine Room TB-105 3e. DEPARTMENT, SERVICE, LABORATORY OR EQUIVALENT Department of Medicine Stanford, CA 94305 3f. MAJOR SUBDIVISION 39g. TELEPHONE (Area code, number and extension School of Medicine (415) 497-6979 4. HUMAN SUBJECTS 5. RECOMBINANT DNA J Exemotion # fino ClyYes j OR [no Oves OJ Form HHS 596 enclosed 6. DATES OF ENTIRE PROPOSED PROJECT PERIOD From: 8/1/86 Through: 7/31/91 DIRECT COSTS REQUESTED FOR ENTIRE PROPOSED 7. OIRECT COSTS REQUESTED]3. FOR FIRST 12-MONTH 8UD- GET PERIOD {from page 4) PROJECT PERIOD (from page 5) s 1,370,257 $s 6,963,247 9. PERFORMANCE SITES (Organizations and addresses} Stanford University School of Medicine Stanford, CA 94305 10. INVENTIONS (Compering continuation application onty! Previousiy reported £1 No OR Not previously resorted 11. APPLICANT ORGANIZATION (Name, address, and congressional district) O ves Stanford University c/o Sponsored Projects Office Encina Hall, Room 40 Stanford, CA 94305 Congressional District No. 1l 12. TYPE OF ORGANIZATION Ol Public. Specity (1 Feaeras state CT Local Private Nonprofit O For Profit (Generat) C For Protit (Smal! Business) 13. ENTITY IDENTIFICATION NUMBER IRS No. 94-1156365 14. ORGANIZATIONAL COMPONENT TO RECEIVE CREDIT FOR BIOMEDICAL RESEARCH SUPPORT GRANT Code ol Description OFFICIAL IN BUSINESS OFFICE TO BE NOTIFIED IF AN AWARD IS MADE (Name, title, address and telephone number.) Patricia Byers, Contract Officer Sponsored Projects Office Encina Hall, Room 40 Stanford, CA 94305 (415) 497-2883 18, 16. OFFICIAL SIGNING FOR APPLICANT ORGANIZATION (Name, title, address and telephone number} PATRICIA CYERS SENIOR CONTRACT OFFICER Sponsored Projects Office Encina Hall, Room 40 Stanford, CA 94305 (415) 497-2883 17. PRINCIPAL INVESTIGATOR/PROGRAM DIRECTOR ASSURANCE: SIGNATURE OF PERSON NAMED IN 3a {in ink. “Per’’ sign Pb rand WV. / S/AY (SS SIGNATURE OF PERSON NAMED IN/16 1 agree to accept responsibility for the scientufic conduct of the project and to provide the required progress reports if a grant (s awarded as a re- sult of this application, Willful provision of false information 1s a criminal offense (U.S. Code, Title 18, Section 1001). . CERTIFICATION AND ACCEPTANCE: | certify that the statements here- MRE in are true and complete to the best of my knowiedge, and accept the ob- fia ink. “Per"’ signature not accepraole! ligation to comply with Public Health Service terms and conditions if 3 QFant is awarded as the resuit of this application. A wilfully false certiti- cation is a criminal offense (U.S. Code, Tite 18, Section 1001). . a : aoe Qa SF r s fe | ts PHS 398 (Rev. 5/82) ; | E. H. Shortliffe ~ ct De - Pei. E. Shortliffe Principal Investigator Medicine & Computer Science E. Feigenbaum Co-Principal Investigator Computer Science T. Rindfleisch Director of Resource Medicine & Computer Science C. Jacobs ONCOCIN Investigator Medicine L. Fagan AIM Liaison Medicine W. Yeager Systems Programmer/Assistant Medicine Resource Director B. Buchanan Professor of Research - Computer Science Computer Science B. Hayes~Roth : Senior Research Associate Computer Science H. Brown , Senior Research Associate * | Computer Science P. Nii | Research Associate Computer Science | | | AASTRACT OF RESEARCH PLAN: State the appiicatian’s lOM AAI Obie tives und specie aims, Maki ceference Uo te egitim re cectaess of the Dronect aneb thuseripe comeiwssry the methodology tor uchieving Preset uoais. Avoid summarne oF Gast deca mpi snimanty ryeb g 1st Veo tt oerson. 7 “eet S “eunt £9 serve a$ 2 succinct and accurate descripbun ci ine pioposed Wark wren sepgraiea irom the aosmeaiecn, DO NGT EXCEED THE SPACE PROVIDED. Stanford University is developing and operating a national shared computing ‘resource (SUMEX-AIM), in partnership with the NIH Biomedical Research Technology .Program, to explore applications of computer science research in artificial intelligence _(AI) to health research. There are three main objectives of the resource: 1) to .develop and provide the computing resources and human assistance needed by scientists working on a broad range of biomedical applications of AI; 2) to demonstrate that it is feasible to provide resqurces and assistance to a national community of researchers, integrating distributed and centralized computing technology with local and national computer communication networks; and 3) to develop the community of scientists inter- ested in working on AI in Medicine (AIM), promoting its growth and vigor through ,@lectronic communications. Besides the economic advantages of resource sharing made possible by electronic communications, we believe that a new style of science is emerging from communications-enhanced settings, ; AI research is aimed at understanding the principles of computer-based symbolic knowledge representation, reasoning, and problem-solving processes and applying these to increase the computer's effectiveness as a tool in knowledge-intensive fields like ‘medicine and biology. Our research work is driven by real-world scientific applica- ‘tions, chosen because of their relevance to current important biomedical problems and _because they expose key underlying AI research issues. Current application areas include programs for differential diagnosis, cancer chemotherapy protocol management, protein structure inference, and drug interaction advice. Resource core research goals include basic research in areas such as blackboard problem-solving architectures and knowledge acquisition; methodologies for clinical decision-making advisors; and the development of network-based Lisp workstation computing environments. Additional resource users will be selected within available resource capacity with the help of an AIM Executive Committee and Advisory Group on the basis of reviews of the proposed research. Selection criteria will include general scientific interest and merit, relevance to the resource AI mission, and the community orientation of the | collaborator. . i 2 ee | Collaborative Project Abstracts Table of Contents 1. Budget, Biographies, and Environment 1.1. Total Resource Budget 1.1.1. Budget for First 12-Month Period 1.1.2. Budget for Entire 5-Year Project Period 1.2. 2060 Operations Budget 1.2.1. Budget for First 12-Month Period 1.2.2. Budget for Entire 5-Year Project Period 1.3. Budget Explanation and Justification 1.3.1. Total Resource Budget 1.3.2. 2060 Operations Budget 1.4. Biographical Sketches 1.5. Current and Pending Support 1.6. Resources and Environment 2. Resource Plan 2.1. Introduction and Background 2.1.1. Principal Investigators’ Executive Summary 2.1.2. Objectives 2.1.2.1. Resource Goals and Definitions 2.1.2.2. Specific Aims 2.1.2.3, Resource Scope 2.1.2.4. Significance to Biomedicine 2.1.3. Background 2.1.4. Resource Progress 2.1.4.1. Summary of Prior Goals 2.1.4.2. Progress Highlights 2.1.4.3. Resource Equipment Details 2.1.4.4. Core System Development 2.1.4.5. Core AI Research 2.1.4.6. Dissemination Activities 2.1.4.7. Training Activities 2.1.4.8. Resource Community Management 2.2. Planned Resource Activities 2.2.1. Core Research and Development 2.2.1.1. ONCOCIN-Related Core Research 2.2.1.2, Basic Research in AI 2.2.1.3. Resource Hardware and Core System Development 2.2.2. Collaborative Research 2.2.3. Service 2.2.4, Training 2.2.5. Dissemination 2.3. Resource Organizational Structure 2.3.1. Organizational Structure Privileged Communication i WO CON” BN Fe pee 109 115 118 118 120 133 162 178 178 178 178 179 179 E. H. Shortliffe Collaborative Project Abstracts 2.3.2. Resource Staff Responsibilities 180 2.3.3. Resource Operating Procedure 181 2.3.3.1. New Project Recruiting 181 2.3.3.2. Stanford Community Building 181 2.3.3.3. Existing Project Reviews 182 2.3.3.4. Resource Allocation Policies 182 2.3.4. Support of Service and Collaborative Projects 183 2.3.5. Resource Advisory Committee 184 3. Impact of Current Biomedical Problems 185 4. Institutional Development 187 5. Future Plans 189 6. Collaborative and User Projects 191 6.1. Stanford Projects 193 6.1.1. GUIDON/NEOMYCIN Project 194 6.1.2. MOLGEN Project 202 6.1.3. ONCOCIN Project 209 6.1.4. PROTEAN Project 220 6.1.5. RADIX Project 225 6.2. National AIM Projects 233 6.2.1. CADUCEUS Project 234 6.2.2. CLIPR - Hierarchical Models of Human Cognition 240 6.2.3. MENTOR Project 245 6.2.4. SOLVER Project 249 6.3. Stanford Pilot Projects 258 6.3.1. CAMDA Project 259 6.3.2. REFEREE Project 267 6.4. National AIM Pilot Projects 273 6.4.1. PATHFINDER Project 274 6.4.2, RXDX Project 279 Appendix A. Stanford Knowledge Systems Laboratory 285 Appendix B. Resource Operations and Usage Data 293 Appendix C. AIM Management Committee Membership 307 Appendix D. Collaborative Project Abstracts 311 E. H. Shortliffe ii Privileged Communication Collaborative Project Abstracts List of Figures Figure 1: SUMEX-AIM DEC 2060 Configuration 83 Figure 2: SUMEX-AIM DEC 2020 Configuration 84 Figure 3: SUMEX-AIM Shared DEC VAX 11/780 Configuration 85 Figure 4: SUMEX-AIM File Server Configuration 86 Figure S$: SUMEX-AIM EtherNet Configuration 94 Figure 6: Sample Chemotherapy Protocol Hierarchy 121 Figure 7; Sample ONCOCIN Rule, Translated to English from Internal 122 Format Figure 8: Components of the Meta-OPAL System 126 Figure 9: Levels of BBl's Control Blackboard with Examples from 137 PROTEAN Figure 10: An Example PROTEAN Heuristic at the Focus Level 138 Figure 11: Example of Preliminary BB1 Explanation 139 Figure 12: The components of a Learning System. 145 Figure 13: Summary of Rules of Generalization and Specialization by 148 Fu [19] Figure 14: Total CPU Time Consumed by Month 294 Figure 15: Monthly CPU Usage by Community 296 Figure 16: Monthly Terminal Connect Time by Community 297 Figure 17: Cumulative CPU Usage Histogram by Project and Community 299 Figure 18: TYMNET Terminal Connect Time 306 Figure 19; ARPANET Terminal Connect Time 306 Privileged Communication iii E. H. Shortliffe