THE ENGINES OF HIPPOCRATES Wiley Series on Technologies for the Pharmaceutical Industry Sean Ekins, Series Editor Editorial Advisory Board Dr Renee Arnold (ACT LLC, USA); Dr David D Christ (SNC Partners LLC, USA); Dr Michael J Curtis (Rayne Institute, St Thomas’ Hospital, UK); Dr James H Harwood (Pfizer, USA); Dr Dale Johnson (Emiliem, USA); Dr Mark Murcko, (Vertex, USA); Dr Peter W Swaan (University of Maryland, USA); Dr David Wild (Indiana University, USA); Prof William Welsh (Robert Wood Johnson Medical School University of Medicine & Dentistry of New Jersey, USA); Prof Tsuguchika Kaminuma (Tokyo Medical and Dental University, Japan); Dr Maggie A.Z Hupcey (PA Consulting, USA); Dr Ana Szarfman (FDA, USA) Computational Toxicology: Risk Assessment for Pharmaceutical and Environmental Chemicals Edited by Sean Ekins Pharmaceutical Applications of Raman Spectroscopy Edited by Slobodan Šašic ´ Pathway Analysis for Drug Discovery: Computational Infrastructure and Applications Edited by Anton Yuryev Drug Efficacy, Safety, and Biologics Discovery: Emerging Technologies and Tools Edited by Sean Ekins and Jinghai J Xu The Engines of Hippocrates: From the Dawn of Medicine to Medical and Pharmaceutical Informatics Barry Robson and O.K Baek THE ENGINES OF HIPPOCRATES From the Dawn of Medicine to Medical and Pharmaceutical Informatics BARRY ROBSON Director of Research and Professor of Biostatistics, Epidemiology, and Evidence Based Medicine, St Matthew’s University School of Medicine and Chief Scientific Officer, The Dirac Foundation O.K BAEK Senior Enterprise Solution Architect, Medical Informatics, Clinical Genomics, eScience and Emerging Industry Solutions A JOHN WILEY & SONS, INC., PUBLICATION The views expressed in this book are not necessarily those of IBM Corporation or any previous organization with which the authors have been or are associated Copyright © 2009 by John Wiley & Sons, Inc All right reserved Published by John Wiley & Sons, Inc., Hoboken, New Jersey Published simultaneously in Canada No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning, or otherwise, except as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate per-copy fee to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, (978) 750-8400, fax (978) 750-4470, or on the web at www.copyright.com Requests to the Publisher for permission should be addressed to the Permissions Department, John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, (201) 748-6011, fax (201) 748-6008, or online at http://www.wiley.com/go/permission Limited of Liability/Disclaimer of Warranty: While the publisher and author have used their best efforts in preparing this book, they make no representations or warranties with respect to the accuracy or completeness of the contents of this book and specifically disclaim any implied warranties of merchantability or fitness for a particular purpose No warranty may be created or extended by sales representatives or written sales materials The advice and strategies contained herein may not be suitable for your situation You should consult with a professional where appropriate Neither the publisher nor author shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages For general information on our other products and services or for technical support, please contact our Customer Care Department within the United States at (800) 762-2974, outside the United States at (317) 572-3993 or fax (317) 572-4002 Wiley also publishes its books in a variety of electronic formats Some content that appears in print may not be available in electronic formats For more information about Wiley products, visit out web site at www.wiley.com Library of Congress Cataloging-in-Publication Data Robson, Barry The engines of Hippocrates : from the dawn of medicine to medical and pharmaceutical informatics / Barry Robson, O.K Baek p ; cm.—(Wiley series on technologies for the pharmaceutical industry) Includes bibliographical references and index ISBN 978-0-470-28953-2 (cloth) Medical informatics I Baek, O K II Title III Series [DNLM: Medical Informatics Computing Health Services–trends Man-Machine Systems Medical Informatics Applications W 26.5 R667e 2009] R858.R615 2009 610.28—dc22 2008045094 Printed in the United States of America 10 To our parents and children, who share our DNA To our wives, who shared theirs with us To our nearly seven billion relatives, and the engines that are coming to protect us CONTENTS Preface ix About the Authors xi A Short Preview of Mankind, Medicine, Molecules, and Machines From Prehistory to Hippocrates 29 The Road to the New Medicine 73 The Imminent Challenge: Medicine as an Industry 125 The Next Decade: Personalized Medicine and the Digital Patient Record 177 Enforcing Your Rights: Medical Ethics, Consent, Privacy, and IT 225 Holistic Medicine and IT 259 Architecting It All Guardian Angels: Knowing Our Molecules, Drug and Vaccine Design, Medical Decision Support, Medical Vigilance and Defense 323 389 vii viii CONTENTS 10 What Next? At One with the Engines of Hippocrates 469 Glossary 515 Clinical Trial Terms 527 Notes, Bibliography, and Further Reading Guide 529 Index 577 PREFACE Information technology is poised on the brink of transforming healthcare IT is entwined with the continuing evolution of the molecular and physical sciences, and rather than dehumanizing us, IT has the potential to continually transform healthcare by the power of its information sharing and processing capabilities IT particularly has the power to restore good aspects of healthcare based on a personalized and holistic approach, which has been progressively lost, and increasingly so since the Industrial Revolution and the escalating patient-to-physician ratios of the last century This book is built on those premises to examine the task ahead, with emphasis on six key considerations required for a transformation that must realistically plan for construction on the historical foundations, opportunities, challenges, and controversies associated with medical advances First, there is the new awareness of human individuality as the diversity of the human genome that evolved over many thousands of years, responsible for the uniqueness of us all through our differing risks of developing diseases and differing responses to pharmaceutical drugs Second, there are our no less diverse cultural heritages, belief systems, concerns, and prejudices They are epitomized by the still significant split between Western medicine rooted in Hippocrates and Galen, and the enduringly popular systems of alternative, Eastern medicine, despite the long standing opportunities of the Arabic medicine to mediate between the two extremes Here, the broad definition of health by the World Health Organization encourages us to ponder the nature of, and strategy messages for, mental and spiritual well-being, including the strangely contrasting The views expressed in the book are those of the authors and not necessarily those of the IBM Corporation or any other previous employer of the authors ix x PREFACE and essentially impartial disciplines of Eastern Zen and Western existentialism Between these two opposites modern neurology and information technology are finding a common thread Third, there is a delicate balance between privacy and autonomy, or self-interest balanced against solidarity, and sharing and participating for the common good, which became a prominent and sometimes disturbing issue in the twentieth century Fourth, there is a pragmatic issue of timeliness of waves of new industry and economy, which is attributed largely to the rise of the Internet and may now be working to improve healthcare Fifth, coupled increasingly to that there is an issue of the healthcare and health insurance systems of today, the often entrenched and bureaucratic Towers of Babel beset by mountains of paper, high rate of medical error, and the challenge of the aging Baby Boomer population and internationally polarized between managed healthcare and socialistic philosophy Sixth, bringing us in closure with the first issue, there is not least the role and mode of practice of the pharmaceutical companies, currently caught in the early twenty-first century in transition between the revenue model of one blockbuster drug for everyone and the multiple personalized approaches that our differential genomics demands To tell that story with its many diverse aspects of broad human importance, the authors have sought to mix a journalistic and scientific style along with factual data and projected scenarios and use cases, along with short illustrative anecdotal snapshots It was considered to be a lost cause from the outset to render in exactly the same style a description of the coding principles of the US health provider billing system and the future impact of nanotechnology on human destiny in any event To maintain continuity so that the reader is not constantly flipping pages, we have sometimes allowed a degree of duplication with each portion to be complete in itself with the appropriate focus, and given references explicitly in situ, in the text Additionally, at the end of the book, we give sources, bibliography, and a guided further reading, the latter with reference to both broader topic source books and example original scientific papers Research papers are personal favorites due to the breadth of matters covered, but there should be enough information in the text for the reader to use the increasingly powerful Internet and find relevant material in seconds Barry Robson O.K Baek 584 eternalization (globalization in time) 129 ethics: as gut feeling 23 ethics: of autonomy 23, 127 ethics: of solidarity 23, 127 ethics:thermodynamics of 23, 24 Ethiopia 27 ethnicity 34 ethome 206, 111, 112 EU Data Protection Directive 190 EU Privacy Directive (privacy regulations) 145, 248, 250, 251, 337, 344 European Bioinformatics Institute 115 European Union Privacy Directive 190 euthanasia 229, 230 Eve (genetic) 27 evidence based medicine 137, 172, 199, 430, 469, 473–476 evolution 86 existentialism 284, 285 exoskeleton (human) 487 expanding universe 511 Expedia 118 expenditure: on healthcare 13, 302–308 experiential core 283 expert rules (for expert systems) 435 expert systems: certainty factor 432 expert systems: CF: see certainty factor expert systems: data mining 434–442 expert systems: empirical rules 435 expert systems: GLOBAL 433 expert systems: information theory 432 expert systems: MYCIN rules 432 expert systems: MYCIN 432 expert systems: non-reducibility of rules 439 expert systems: rule order 432 expert systems: rule types 432 expert systems: rules 431, 432 expert systems: syllogisms 442 expert systems: treatment of contrary information 432 Expression array 188 expression array 188, 206, 232 expression of DNA 99 Fano: Robert 368, 373 Fantastic Voyage (the book) 491, 503 INDEX Fantastic Voyage: Live Long Enough to Live Forever (the book) 508 fauvism: see favism fava beans 50 favism 50, 54 FDA Amendment Act 6, 147, 198, 238, 427 FDA CFR-21 (privacyregulations) 145 FDA: see Food and Drug Administration FDAAA: see FDA Amendment Act febrifuge 84 federalized data systesms 451 Federated data access 359 feeling atoms 494 Feigenbaum bottleneck 431 femtotechnology 512 Feng Sui 274, 288–289 fetch (double of a human) 481 Feynman: Richard P 491 FGENEH (the software) 97 fight or flight response 277 Finland 34 FIPPA (privacy regulations) 145 FIPPA 248, 249, 250 Firefox 115 first class protein 297 fiscal responsibilitis of HMO’s 139 FLASH (the software) 97 flu’: see influenza FNIH (the foundation) 148 folk medicine 259–277 Food and Drug Administration “international governance” 455–456 Food and Drug Administration: Amendment Act (2007) 6, 147–149, 198, 238, 427 Food and Drug Administration: general 6, 238, 454–456, 474 Food and Drug Administration: international connections 456, 457 Food and Drug Administration: international efforts 5–456 food: additives 296 food: poisoning (sub-clinical levels) 296 food: sensitivity to 296 forces of darkness 25 Foundation of the NIH 148 founder mutations 35, 65 Franciscans 79, 80 585 INDEX Frankenstein (the book) 134 Frankensteinn Unbound (the book) 486 free energy (of drug binding) 414 Freedom of Information and Protection of Privacy Act 248, 249, 250 freedom 287 Freud: Sigmund 263 Fukuyama: Francis 507 function surface (in drug design problem) 416 Furmark: Thomas 52 fusion of digital patient record with genomic information 196 future shock 8, Gaia hypothesis 510 Gaia: a New Look at Life on Earth (the book) 510 Galen 73, 74, 127 Galileo Galvani:Luigi 83 game (of the universe) 25 gamma waves 281 garlic 298 GATTACA (the movie) 22 GDP 13 Geisinger Health Systems 126 gemules (Darwin’s theory) of 86, 87 gene transfer 235, 41 Genera plantarum (the book) 82 General Electric 122, 177 General Practice Reserach Data Base 147 generic drugs 475 genetic constitution 197, 206 Genetic diagnosis 197 genetic diversity genetic expression 99, 206 genetic privacy 231 GenLang (the software) 97 Genographic project 27, 32 genome 109 genomic bomarkers 31 genomic drugs 102 genomic messaging system 246, 451 genomics 188, 196, 202, 252 genotype: see Chapter 206, 252 geomancy 274 George Ebers papyrus 51 Gerber: Christopher 495 Gerson: John 79 Gibbs: W Wait 499 gigabyte 12, 117 ginger 298 gingko 298 ginseng 81, 298 GJB2 (mutation) 35 GLOBAL (computer language) 433 global minimization 416 globalization 129 glucose-6-phosphate metabolism 405, 406, 407 glychorrhizic acid 52 Goethe (von): Johann W 100 Good Faith 289 good versus bad (Hippocratic view) 64 Google 118, 119 gout 53 GPRD (data base) 147 GRAIL (the software) 97 graphical interface 445 gray goo hypothesis 503, m505 Gray: Muir 473 Great Society Program 136 Greek Gate 45 Greek philosophers 44 Greek pragmatism 63 green field effect (on economy) 135 grid computing 452 Grossman: Jerome H 138, 139 Grossman: Terry 508 growth: of medical data 17 Gruber: Jonathan 125 guardianship (over health and conceptof) 38, 391–393 Gulliver’s Travels (the novel) 80 gun lobby 200 Guns Germs and Steel (the book) 76 Guyatt: Gordon 173 Hahnemann: Samuel 273 HAL-2000 computer 431 HALO 188 Hamilton: Edith 47 Han Dynasty 60 haplogroup: See Chapter 201 haplotype: See Chapter 201 586 Harvey: William 83 Hatch: Orrin (US Senator) 142 Hawking: Stephen HbS (mutation) 65, 67 healing knowledge 198 Health Emmergency Response System 479 health ID cards 302 health industry (bad state of) 133 Health information locator service (HILS) 190 Health information portability and accountability 189 health insurance (history of in US) 135, 136 Health Insurance Portability and Accountability Act 189, 208, 231, 233, 242, 243, 248, 249, 252, 253 health insurance: ethics and principles 304 Health Level Seven (HL7) 212, 450 Health Maintainance Organization 137–139 health: concept of 21 health: definition of 21 healthcare new hiring 126 healthcare: at the end of time 513 healthcare: business case for IT spending 142–144 healthcare: challenges 144–145 healthcare: cost cuts 305 healthcare: current state of (US) 133 healthcare: driver to state-run system 305 healthcare: e-Business 157–161 healthcare: economic predictions (difficulty of) 307 healthcare: expenditure 13, 302–308 healthcare: financial aspects 302–308 healthcare: function model 309–316 healthcare: future scenarios 316–320 healthcare: horizontal services 313 healthcare: insurance system barrier 302–308 healthcare: legacy systems 3, healthcare: national coalition 13 healthcare: networks/workflow 162, 310–312, 320, 397 healthcare: on-line 157 INDEX healthcare: origins of current state of 133–140 healthcare: process oriented 310 healthcare: services 313–316 healthcare: spending 133, 142–144, 303 healthcare: stakeholders 165, 166 healthcare: systems biology model 320–322 healthcare: vertical services 313 healthorbit (medical internet news) 18 healthy lifestyle 274 heart simulation 410, 411 heat (as in thermodynamics) 24, 512 Heinlein: Robert A 487 Helenes 46 Helsinki Declaration 233 hemaglobin gene 66 hematology 208 HER2 (mutation) 293 herbals 50 herbs Herceptin 151, 289 hERG (potassium channel) 410 heterogeneity and homogeneity of proteins 90 Heterogeneous archival life object 188 heterogenous data 324, 354–355, 356, 383, 451 heterozygous 35 hexokinase 407 HFE (mutation) 65 hierachic organization (of cells) 409 hierachic organization (of human body) 409, 410 hierarchal systems approach (hospitals) 312 hierarchic systems (linking levels) 411 hierogluphs 51 high density storage (for biochips) 485 high throughput screening 413 HIPAA (1) 145, 189, 208, 231, 233, 242, 243 HIPAA (2) 248, 249, 252, 253, 254, 258 Hippocrates 56, 57, 58 Hippocratic Oath 227, 228, 230, 231, 240, 242, 29, 68–71 history (as written) 260 Hittite 47, 48 587 INDEX HIV reporting regulations in California 459 HIV 201, 220, 39, 459 HL7 (the standatd) 175 HL7 CDA 202, 212 HL7 Clinical Data Architecture 212 HLA gene 200, 214, 424–426 HLA protein 214 HMO’s 306 HMO 137–139 Holcan okot 226 holistic healthcare: and patient-centric medicine 171 holistic healthcare: and personalized medicine 171 holistic healthcare: and systems biology 134, 320–322, 405 holistic healthcare: driver to state-run system 305 holistic healthcare: financial aspects 302–308 holistic healthcare: function model 309–316 holistic healthcare: general 259–264, 291–310 holistic healthcare: global challenge 322 holistic healthcare: insurance system barrier 302–308 holistic healthcare: networks/ workflow 310–312, 320, 397 holistic healthcare: process oriented 310 holistic medicine 295–277 Holmes: Oliver Wendell 269 holome 111 homeland security 140 homeobox genes 482 homeopathy 272, 273 homeostasis 75 Homidae 29 hominid Homo erectus 1, 30 Homo florensis 30 Homo heidelberggensis 30 Homo neanderthalensis 30 Homo sapiens 1, 29, 30 Homo species 1, 29, 30 homozygous 35 Honeywell Datamatic computer Hood: Leroy 320 Hooke: Robert 83 HOPE-People-to-People Health Foundation 198 hospices 76 hospitals (US): number of 13 host computers 114 HTML 114, 116, 159 http 115 Huang He: see Yellow River 43 human condition 282, 287 human experts 431 human genes: number of 14, 98 Human Genome Projects 93, 96, 97 human genome 196, 200 Human Rights Report on the United States 172 humaniaton (of coomputer systems) 394 humans: taxonomic classification 29, 30 Hume: David 83 humors 58, 79 Huxley: Aldous 22, 488 Hybels: Bill 488 hydrogen sulfide 275 hydrophobic effect 414 Hygeia (Greek) 43 Hymn to Ninkasi (The) 66 hyperlinks 116 hypertext markup language 211 hypertext transfer protocol: see http hypothesis testing 441 IA-64 architecture 159, 160 IBC 242 IBM Logo (written in atoms) 495 IC50 (pharmacology) 408 Ice Age 32 ice ages 471 IHE (the standard) 175 illusion: of reality 22, 284, 511 image data 437 imaging 15, 120, 121 Imhotep (Egyptian) 42 immortality 507, 508 Immortality: physics of 26 immune maturation 202 immune system 200 immunization: active 466 immunization: passive 466 Imperial College of London 178 588 implantable drug delivery system 479 IMR 177 IMS Disease analyzer 145 in silico screening 404 IND 237, 238 Independent Practice Association 137 India: Alai period 272 India: ancient medical principles 271, 272 India: ancient 270 India: traditional medicine 271 Indo-European 32, 46 Indus Valley 42 industrial strength products 127 industry (nature of) 127, 128 industry-academia conflict 128, 129 infectious disease 458, 459 infirmaries (medieval) 76–77 inflammation 261, 294 influenza 56 information based medicine 396 information content of human body 402 information limitations of capacity 509 information technology information theory 432 information-based medicine 177, 188 information-based personalized medicine 20, 470 informed consent 240, 242, 247, 250, 237 inheritance 63, 86 inhibition constant 407 inner power 269, 270, 271 Innovate America (the report) 132 innovation Institute for Systems Biology 320 Institutional Biosafety Committee (see IBC) 242 Institutional Review Board (see IRB) 236 insurance (history of in US) 135, 136 insurance: see health insurance integrated health environment (IHE) 175 integrated medical record 177 Intel 18, 159 intelligene (as knowledge) 397, 398 International Conference for Harmonization 456 INDEX Internet service providors 119 Internet 2, 113–121, 157–161 invasive chips 393 investigational new drug (see IND) 237 Iowa salmonella attack 466 IPA 137 IRB 236, 237, 239, 240, 254 Iri (Egyptian) 42 isotopes 402 IT (see information technology) IT spending (in healthcare) 141–142 Jaspers: Kark 285 Java applets 116 Jenner: Edward 38 Jericho Johnson: Lyndon (US President) 136 juggernaut molecules 506 Jung: Carl 275 junk DNA 40, 99 Jurassic Park (the novel) 22 Kahn: Jonathan 420, 476 Kaiser Company 135 Kaiser Foundation Health Plan 136 Kaiser Permamente 126 kapha energy 271 Kelly: Crosby 57 Kennedy: Edward (US Senator) 142 Kent: Steve 500 Kepler Kikuyu tribe 32 kinetic simulation 404, 406–408 Km (enzymology) 406 knowledge engineers 431 knowledge pyramid 437 Koan (Zen) 279 Koch: Robert 89 koukia: see fava beans Krass: Lawrence 511 Krateuas (Greek) 50 Krebs: Hans 165 Kreutzfeldt-Jacob disease 39, 55 Kumar-Smith-Stefanelli guideline-based model 310 Kuru 55 Kurzweil: Ray 507 kwashikor 36 589 INDEX L’Etaples: Lefevre 77 La Nausee (the novel) 285, 287 lactose intolerance 35 Lady Lovelace: see Byron laminar flow 484 Landauer: Rolf 403 language 33, 46 Lansky: David 302 Lascaux (cave paintings) 32 Laskey: David 12 LCT (mutation) 35 legacy healthcare systems 3, Leibnitz: Gottfried 80 Lem: Lanislov 22 Lemaitre: George 509 Leonardo da Vinci Lesk: Arthur M 106 Leucippus (Greek) 490 Levi-Straus: Claude 76 Levin: Ira 481 LHR 177 Li Shezan 59, 81 Li Yenwen 81 LibertyMedia 118 Library in Alexandria 472 licorice 261 Lieber: Charles 484 life energy 273–275 life force 273–275 life sciences Life span of clones 480 life: as expression of aperiodic crystal 25 life: cultural perspectives 290 life: eternal 509 life: in cities 42 life: in villages 42 life: quickening pace life: sanctity of 25 life: slowing of pace 26 life: spiritual: see Chapter ligand (drug binding) 404 ligand 197 limb regrowth 482 Limbo90 (the novel) 22, 488 limited data set 254, 255 limits: to growth of technology Lin: Shin 270 Lindlahr: Henry 274 Lindquist: Susan 497 Linnaeus: Carl 82, 86 Linux 159, 160 liquorish: see licorice Liu: Bin 18 Lloyd: Seth 403, 511 lock and key 404 logic: medieval studies 78, 79 long term view 132 longitudinal health record 177 Lovelock: James 510 Lower: Richard 83 Lull: Ramon 79 lumefantrine 52 Lunar Manufacturing Facility 502 lunasin 298 Luo Guanzhong 76 M122 (biomarker) 33 M130 (biomarker) 33 M168 (biomarker) 30, 32 M173 (biomarker) 32 M174 (biomarker) 33 M343 (biomarker) 30 M45 (biomarker) 30, 32 M89 (biomarker) 32 Mad Cow Disease 39, 55 magic bullet 89 Magna Grecia 54 magnetic resonance imaging (see MRI) 245 Mahuang (herb) 62 Makiowiack: Phillip 56 malaria 67 malnutrition 37, 38 mammoth 32 Manhattan Project 235 marasmus 36 Marco Polo 60, 62, 81 marijuana 476 Markle Foundation 12, 129, 268, 302 markup 116 Marshfield clinic 126 masochistic tendency 229 mass spectrometer 245 Master Person Identifier (see MPI) 256 materia medica 269 mathematical biology 131, 409 Mathematical Priniples of Natural Philosophy (The) (the book) 490 590 Mathematical Theory of Communication (A) (the book) 113 Matrix (the movie) 22, 394 Mayan Lacandon tribe 226 Mayo clinic 136 McMaster University EBM group 173 McMillan:Andrew 497 mechanical simulation 404 Medical and Healthcare products Regulatory Agency 147 medical errors 139, 140 medical ethics 227 medical event 178 medical imaging 15 medical informatics 168 Medicare 307, 308, 136, 141 medicine: origin of word 20 meditation 280, 281 megabyte 12, 117 Melski: John W 126 melting pot 34 memes 33, 276 MEMS 222 Mendel: Gregor 86 Merrell: Ronald T 129 Merrifield: Robert B 90 Mesirov: Jill 97 Mesoamerica 225 mesoscale dynamics 410 messaging systems 165, 450 meta-metadata 206 metabolic networks 407 metabolic processing of drugs 404 metabolism 407 metabolizing (of drugs) 298 metabolome 206 metabolomics 167 metaqualifier 209 methy mercaptan 275 methyicillin resistant staphylococcus aueus 309 metrics for assessing healthcare quality 133, 474, 476 MHRA (agency) 147 Michaelis-Menten kinetics 404 microarray chipsets 103 microbot 478 microe-electromechanical system 478 microelectromechanical system 222 INDEX microfluidic laboratory chips 413 microfluidics 197, 483 microlab 197, 202 microRNA 101 Microsoft Windows 159 Migrations: human 31 mimiviruses 41 Ming dynasty 81 Minoa 47 Minsky: Marvin 6, 9, 278, 392, 431 miracles 76 mircolabs 483 miRNA 1001 miror image bio-nanochemistry 500, 504 mirror-imaging molecular technology 500, 504–506 mistakes: in medical science 22 mitochondria: and somatic mutations 153, 292 mitochondria: DNA 27, 31 mitochondria: origin 45, 424 mitochondrial proteins 497 mizaj principle 272 molar concentrations 402, 404 mole 402, 404 Moore’s Law 494 Moore: Michael 133 moral character (in fiction) 488 morbidity 198 mortality 198 Mosaic 115 MPI 256 MPP (massively parallel processing) 18 MRI 197, 245, 10 mRNA 100 MRSA 309 Mulder: Gerrit 85 multicelluar life multilayer soft lithography 484 mutations: genetic 35, 65–67 mutations: in Darwin’s theory 86, 87 mutations: in HIV 294 mutations: mitochondrial 153 mutations: somatic 291 Mycenea 47 MYCIN (the software) 432 MYCIN rules 432 mysticism 266 INDEX nanobots 489, 501 nano-biotechnology 497 nanobioprocessors 492 nanobodies 499 nanobots: and cosmological scale computing 511 nanobots: and gray goo 504, 505–506 nanobots: chemical signalling 504 nanobots: D-proteins 500, 504–506 nanobots: on-board computers 504 nanobots: signal reception 504 nanobots: signal transmission 504 nanocomputers 504 nanoelectromechanical system 222 nanomaterials 494 nanomotors 492 nanoplumbing 494 nanorobotics 502 nanoscale films 493 nanosensors 502 Nanosystems 502 nanotechnology problems 504 nanotechnology 489–498, 501 nanotecnology: dissapointments 501 nanotubes as tiny radios 504 nanotubes 494 nanowires 498 NASA and nanotechnology 502 nasty medicine 276 National Coalition on healthcare 13 National Human Genome Research Institute 99 National institue of Clinical Excellence 475 National Institutes of Health—frequently mentioned eg 141, 148, 149, 492 National Research Act 235, 236 National Science Foundation 489 National Translational Cancer Research Network 293 Nature Cure 274 nausea (existentialism) 151, 285, 287 NCE: see new chemical entities ncRNA 101 Neanderthals 1, 30, 31 negative associations in analysis 438 negative photoresist 484 Nei Ching 60 Nelson: Ted 116 591 NEMS 222 nephrosis (congenital) 34 nervous breakdown 287 network infrastructure 397 neural nets 394 neural programs 282 neuropeptides 262, 264, 272, 281 neutraceuticals 297 new chemical entities 102 Newton’s laws 403 Newton: Isaac 5, 14, 490 Nguyen: Tan 51 NICE: see National institue of Clinical Excellence Nielsen: Peter 102 NIH: see National Institutes of Health Nirvana 281 non-reducibility of rules 439 nonconformism 284 nonrepudiation 221, 245, 246, 248, 249 normality (in health) 75 number: of atoms in human body 401, 402 number: of bits (information) in human body 402, 403 number: of bits (information) in living cell number: of bytes for storing/transmitting different data 117 number: of bytes per second 122 number: of diseases treated by acupuncture 62 number: of drug approvals and launches 51, 150 number: of drug approvals per year (US) 428 number: of drugs 51 number: of healthcare subscribers 136 number: of herbs used 51 number: of human genes 14, 97 number: of major world diseases 294 number: of medical errors 139 number: of new jobs in healthcare during recesssion 126 number: of people in prehistoric villages 471 number: of SNP’s (human genome) 108 number: of unfilled (US) nursing positions 393 592 number: of US hospitals 13 number: of US nurses 13 number: of US physicians 13 Nuremburg Code 233 nurses (US) (number of) 13 nutrigenomics 296, 167 nutrition 296–299 Oath: see Hippocratic Oath Obama: Barack (US President)— frequently mentioned see e.g Object Management Group 190 Observational Medical Outcomes Partnership 148, 149 obsidian blades 9, 493 Occam’s razor 49 Office of Research Integrity (see ORI) 240 Olympic games 44 Omega Man (the movie) 423 Omega Point 26 omes (the disciplines) 110, 111, 132, 166, 167, 404 OMG 190 OMOP (the consortium) 148, 149 on demand services 119 on-demand innovation system 164 on-line healthcare 157–161 oncology (and holistic medicine) 291 optical fiber 121 order: of a computational problem 14 order: of medical data 16, 17 organ regrowth 482 organ simulation 411 organelle 45 organic chemistry 88 organic compounds 88 Organon of the Art of Healing (the book) 274 ORI 240 Origin of Species (the book) 5, 86, 82 orphan drugs 51 Orwell: George 488 Osler: William 138 Out-of-Africa (diapsora) 30 outbreak response 460 outcome-driven health care 188 outcomes analysis 476 INDEX P-glycoprotein 201 pagan opinon of Hippocratic medicne 75, 77, 78 pairwise basis in anlysis 439 Panacea (Greek) 43 pandemic 463 Paracelsus 83 parallel processing 18 parasitic worms 38 Pare: Ambrose 83 Parks: Ronald 268, 290 passive immunization 466 Pasteur: Louis 6, 84 pasteurization patent rights patents 477 patient centric medicine 171 patient record 246, 252 patient: decision to become 263 patients 165 Patient’s Bill of Rights 206, 208, 225, 232 Patrick: John 119, 120 pattern discovery 435 Pauling: Linus C 93 payers 166 pellagra 36 pencillin 89 penicillin 52 Penrose: Roger 131 peptide nucleic acids 498 Pentium processor 18 Pepys: Samuel 83 periodic behavior 408 peripheral processing unit 395 Perl (computer language) 12 peroxisomes 506 Perseus (Greek) 486 Personal Genomics 232 personal health record 188 Personal Information Protection and Electronic Documents Act personal information 243, 245, 247, 250 Personal Life-time Health Plan (PLHP) 188 personalized medicine 20, 470 Peseshet (Egyptian) 42 pet fish puzzle logic in deduction 446 PET 197, peta 11 INDEX pharmaceutical chemistry 88 pharmaceutical industry expenditure 150 pharmaceutical market (global) 150, 151 pharmaceutical surveillance 198 pharmaceutical trials 228 pharmacogenomics: benefits 153–157 pharmacogenomics: definition 152 pharmacogenomics: economics 150, 151 pharmacogenomics: general 152–157, 197, 199, 202, 203, 238, 418 pharmacogenomics: origins—see Chapter pharmacogenomics: vaccines 420–426 pharmacogenomics: vigilence—see Chapter pharmacosurveillance 428, 474 pharmacovigilance: as driver in new healthcare system 426 pharmacovigilance: as extension of clinical trial 426 pharmacovigilance: concept 426 pharmacovigilance: early warnings for pharma industry 429 pharmacovigilance: economics 429, 430 pharmacovigilance: European Commission Initiative 457 pharmacovigilance: impact 430 pharmacovigilance: role of FDA 426 Phase IV trials 429 phenome 206, 111 phenomology 285 phenotype 206 PHI 231, 243, 251, 252, 253, 255, 256 Phillip the Good 77 philosophers (Greek) 44 PHIPA (privacy regulations) 145 PHR 188 phrmacoepidemiology 455 physician portal 446, 447 physicians: and evidence based medicine 474 physicians: as femtoengineers 513 physicians: as mediators 395 physicians: as stakeholders in healthcare 166 physicians: as too busy for computer keyboards 443 Physicians: best practice in communicable disease 459 593 Physicians: brain-to-brain contact 449 Physicians: clinical decision intelligence portals 445–448 Physicians: communication methods 449 physicians: errors by 139 physicians: in the “global village” 477 physicians: network infrastructure 391, 392, 397 physicians: number of (US) 13 physicians: paid in chickens 134 Physicians: personal wealth 449 physicians: pressure selling by 136 physicians: rural 396 physicians: urban 396 physicians: US social medicine phase 134 Physics of Immortality (the book) 26 physiome 111, 409 physiomics 166 Pioneer Institute for Public Health Policy Research 138 PIPEDA (privacy regulations) 145 PIPEDA 248, 249, 250 Pistorius: Oscar 487 pitta energy 271 PKI 246 placebo effect 52, 262, 264 placebo: general 52 placebogenic drugs 263 Planck’s constant 511 Planck: max 511 plants and stones (analogy to molecules and machines) pneumonic plague 459 poisonous plants 276 policy makers 166 polio 138 polydimethylsiloxane 484 polymer chain 201 polymorphism 197, 201, 418 population health concept 135 positive associations in analysis 438 Post-Genomic Era 102–104 post-genomic era 125 post-translational modification 93, 107 posttranslation modification 214 Powell: Enoch 120, 73 594 power (of humans) 489 PPO’s 306 PPU 395 practioners 165 praeter naturam 19, 75 predictive analysis 435 prepaid medical care 134 pressure selling (by physicians) 136 pressures (on healthcare system) 130–141 preventative medicine 196, 172 Prey (the novel) 22 Priessnitz: Vinconz 274 primary physician organization 178 primary prevention (epidemiology) 460 primordial atom 509, 510 Principia (The) 490 principles: see simples prions (in nanotechnology) 497 privacy compliance 243 privacy laws and regulations (list) 145 privacy laws 240 privacy 196 private fee-for-service 135 production-line science 130–132 prognosis 188 prostate cell genes 298 prosthetics 486 protease inhibitor 201 Protected Health Information (see PHI) 231, 243, 251, 252, 253 protection of privacy 244, 245, 247, 248 protein folding problem 95, 131, 513 protein modeling 197 protein nanobots 500, 504–506 protein polymorphism (and drug binding) 418 protein sequence 242 protein structure science 409 protein structure 197 protein 131, 177 proteome 110 proteomics 245, 252 protohuman protoplasm 86, 87 provenance provider induced demand 137 providers 166 Province of Alberta 188 INDEX Prozac 475 Psalms 63 pseudo-gout 53 psychogenomics 167 psychome 111 psychosocial effect 262 public key infrastructure (see PKI) 246 puerperal fever 53 Pulitzer Prize 228 putricine 275 PXR (receptor) 299 Pythagoras 50, 55 QT syndrome 411 quantitative structure activity relationships QSAR: see SAR quantum computing 18, 499 quantum mechanical calculations 91, 407, 412 quantum mechanics 131, 491, 492, 511 Quate: Calvin 495 quickening pace: of life 1, 26 Quin dynasty 60 quinine 50, 52 qunantum mechanics 91, 92, 403 qunatum mechanical calcultations 403 quwa’ principle 272 radiation (use of as health fad) 489 RAM 395 rate constants (enzymology) 407 rate law of kinetics 407 re-identification risk 254, 255, 256 Reagan-Udall Foundation 149 reagent 202 rebel (the) 286 Red Hat Linux 159 Regis: Ed 504 regularization 130–132 Reigimen (The) (the book) 58 relaxation 280, 281 REMi (a robot doctor) 392 remote monitoring 448 renaissence: European 1, repolarization (heart) 411 repurposing 426 request broker 164 resolution (of detection by biosnsors) 291 INDEX response to epidemics 460 Resurrection 26 retinal scans 291 retrovirus 202 review synopsis of the book and latest news 470 RFID chips 142, 393, 478, 485, 504 rickets 36 RNA: microRNA 101 RNA: mRNA 100 RNA: ncRNA 101 RNA: peptide backbone 102 RNA: rRNA 101 RNA: tRNA 101 roaming software 122 robot effect 283–285 robotization (of humans) 394 robots 278, 392, 501 Rodriguez: Raymond 298 Romance of the Three Kingdoms (the book) 75 Rosemary’s Baby (The) (the novel) 481 Rousseau: Jean-Jacques 83 RP-6 robot system 392 rRNA 201, 101 Rudoph II of Bohemia 79 ruh principle 272 rule order 432 rule types (for expert systems) 432 rules (for expert systems) 431, 432 Rutherford: Ernest 490 Sackett: David 173 salmonella 466 Salvarsan #606 (the drug) 90 Sangarm literature 272 Sanger: Frederick 90 SAR (struture activity relationships) 42 SARS 191, 423, 459 Sartre: Jean Paul 285 SCA (mutation) 66 scanning tunneling miscroscope 494 schistosomes 40 scholarships for medical school 134 Schroedinger: Erwin 25 Schwann: Theodor 86 Schweizer Erhard 495 science (end of?) 131 scientia (intellective power) 79 595 scientific mysteries 131 scientist’s dogma 132 Scopes monkey trial 87 Scott: Walter 81 scurvey 36 Sebastian 227 second class protein 297 Second Life (the software) 511 secondary prevention (epidemiology) 460 Section #905 (FDA Ammendement Act) secundum naturam 19, 75 Seife: Charles 24 selection: natural 86 selection: unnnatural 86, 87 selenium 298 self/non-self recognition 500 Selfish Gene (The) (the book) 34 Senate Health education Labor and Pensions Committee 142 senile decay 53 serological epidemiology 421 serum albumin 202 server computers 114 servers 114 service providor 163 services (healthcare) 313–316 seven principles (Indian medicine) 271 SGML (the software) 116 SGML 211 Shakespear shaman: see Chapter and Chapter 77, 133 Shang dysnasty 60 Shang Han Lun 60 Shannon: Claude 113 Shelley: Mary 134 Shen Nung 59 short term view 132 Shotliffe: Edward 168 sickle cell anemia 66, 107 SiCKO (the movie) 133 Siddha medicine 271 Siddha-Kapla medicine 271 silicon hydroxides simples 84, 89 simulation 15, 117, 404, 410, 411, 412 single nucleotide polymorphism 200 596 Sister Mary (a robot nurse) 392 Six Million Dollar Man (The) (the TV series) 486, 487, 493, 507 skatole 275 Skype 120 slave trade 44 slowing pace: of life 26 Smalley: Richard 493 smart matter 509 SNP 188, 196, 197, 200 SOAP (the software) 114 social healthcare: good aspects 308 social healthcare: under stress 308 social medicine (in US) 134 social medicine: see social healthcare Socrates 49 sodium channel 411 sodium flux 411 solidarity 23, 127, 290 soma 22 Song dynasty 82 sonic hedgehog (the protein) 107 soot 494 special Internets 121 Species plantarum (the book) 82 spending on IT 141–142 Spiderman (the comic/graphic novel) 487, 489 splicing 99 spooky action at a distance 510 stakeholders in healthcare 165, 166 standard generalized markup language 211 Starship Troopers (the book) 487 statutory requirement 190 steady state 408 stem cells 481, 482 stench (chemistry of) 275 stereoregular stuctures of macromolecules 93 stickiness of atoms 512 stomach ulcers 52 Stone: Edmund 84 Stonehenge storage from monitoring 451 strata: of population 12 stratified medicine 418, 419, 470 stress 277, 278 structural bioinformatics 197 INDEX structured data 437 strutucture activity relationships: see SAR stuttering (DNA) 99 stythe 53 Su Dongo 390, 401 Su Dungpo 390 substrate concentration (enzymology) 404 sugar metabolism 405, 406 sulforaphane 298, 299 Sumer (legacy in Greek medicine) 472 Sung period 61 superbug (MRSA) 309 superheroes 486 superoxide 391 superpowers 488 superstition 511 surgery (by local physicians) 136 surgery 74, 83, 84 surveillance industry 198 swunu (Egyptian) 42 Sydenham: Thomas 83, 84, 89 Sykes: Brian 32 syllogisms: in expert systems 442 syllogisms: in medieval logic 78 syllogistic logic in deduction 446 symbionts 423 Synge: Richard L M 90 synthesis and testing (decisions) 414 synthesis 88 syphilis 233, 90 systems biology model of healthcare 320–322 systems biology principles 169–171 systems biology 197, 238, 111, 112, 320, 322, 405, 409 T-epitopes 424 Talisman (The) (the novel) 81 Tamils 272 Taniguchi: Norio 490 tantric science 271 Taoism 401 taxonomic classification 29, 30 taxonomy: dogs 30 taxonomy: herbs 81 taxonomy: humans 29, 30 taxonomy: mammals 29, 30 INDEX taxonomy: medical data: see Chapter taxonomy: medieval knowledge 77 TBLASTX (the software) 97 telandic behavior 408 teleconsultation 450 telehealth 196, 448–451 telemedicine 129, 196 telemetric data 196 telomeres 481 terabytes 14, 12, 117 Terminal Man (The) (the novel) 22 terrorism 141 tertiary prevention (epidemiology) 460 text data 437 thalidomide 138 theoretical biology 409 theoretical chemistry 91, 92 therapeutai (Greek) 75 There’s Plenty of Room at the Bottom (Feyman’s lecture) 491, 501 thermodynamic solutions (in drug docking) 417 thermodynamics 23, 24, 403 theta waves 281 third world in space and time 129 Thirumular literature 272 Tholkappiam literature 272 Thompson: Joseph J 490 thousand dollar genome 108, 109 Time Machine (the novel) 22 timeliness of new healthcare 125 Tipler: Frank J 26, 27 Titricine 275 Toba catastrophe 471–472 Toffler: Alvin 125, 126 toixc plants 276 Tongjan gangmu (the book) 82 topology (in drug docking) 417 toxicity and herbal medicine 261 toxicology laboratory 237 toxicity 404 toxicogenomics 166 trade 31 tragedy of the commons (the economic principle) 127 Trajanus: Marucs U 127 trance 281 Trans-Euro Network-Home Care Management system study 449 597 transcriptome 109 translational research 130, 293, 473 treatment of contrary information 432 trematodes 40 tricks (in drug docking) 417 tRNA 201, 101 Troy 47 trucking role (of nanobots) 501 Truman: Harry (US President) 135 trusted custodian 220 tsunami 231 tuberculosis 138 turbulent flow 484 Turing: Alan Tuskegee Study 234 Tuskegee Syphilis Experiment 234 Tuskegee Syphilis Study 234 UDDI (the software) 114 UK Prescribing Support unit 147 Ulrich: Karl 126 Unani medicin 271 Unani Tibb doctrinne (India) 272 under-reporting adverse drug reactions 427 United States Homeland Securty Act 141 universal patient identifier 178 universe as engine of Hippocrates 509 universe: the game 25 Unix 160 unstructured data 437 urea (synthesis of) 85 URL 115, 116 US Department of Veterans Affairs 126 US Institute of Medicine 133 US Public Health Secutity and Bioterrorism (etc) Act 141 Ustad-ul-Atibba 272 UV (use of as health fad) 489 vaccination 38, 39 vaccines (bioengineered) 425, 426, 466 vaccines: attenuated 425 vaccines: killed 425 vaccines: peptide 425, 426, 466 vaccines: synthetic 425, 426 value propositions (for IT spending in healthcare) 143, 144 598 Vanilla Sky (the movie) 22 variance between data 438 vata energy 271 velvet VeriChips 485 Verne: Jules Versalius: Andreas 83 vertigo (existentialism) 285 Vicia Fab: see fava beans Victorian medicine 84 virtual screening 404 viruses (in nanotechnology) 498 vitality: see energy Vmax (enzymology) 406 Vogel: Frederich 152 volcanic ash and sulphuric acid (effects of) 471 Volcanic explosivity index 471 Volta: Allesandro G A von Hohenheim: Aureolus P T B 83 von Liebig: Justus von Mohl: Hugo 86 von Neumann: John 502 Voriconazole 150 Voth: gregory A 410 Voynich manuscript 79 Waterford Telemedicine Partners 161 Watson: James D 93 waves of industry 125 Web 2.0 (the Web software) 116 websites 114 Wedding: Danny 284 welfare medicine 305 well-being 178, 196 wellnet 188 Wells: Herbert G 6, 89, 487 Wells: Spencer 27, 46 Wennberg: John 137 Wesley: John 83 INDEX Whitehead Institute 97, 128 Who Are you When No One’s Looking? (the book) 489 WHO: see World health organization Wiktorowicz: Mary 456 William of Ockham 49 willow bark 84 Wilmut: Ian 480 wine (bad reactions) 296 Wired for Health Care Quality Act 142 witch-hazel 52 Wohler: Friederich 85 Wolfe: Bernard 22, 488 Woodcock: Janet 147 workflow manager 163 workflow 162, 310–312, 320, 397 World Health Organization 21, 399, 455, 456, 458, 463 world wide web 115, 116 wormwood 50, 52 wrong lock (drug binding) 404 WWW: see world wide web X-ray crystallography 93, 97 X509 (the standards) 246 Xia dynasty 60 XML (the software) 114, 116, 159 Y-chromosomal DNA 27, 46 Yahoo 118 Yellow River (civilizations) 43 yeti 30 Ying-Yang 61, 270, 289 Zen 279–282 Zhu Xi 82 zoonoses: see zoonotic diseases zoonotic diseases: list of 39, 40 zoonotic diseases: origins 39, 40 Zozer (Egyptian) 42 ... Robson and O.K Baek THE ENGINES OF HIPPOCRATES From the Dawn of Medicine to Medical and Pharmaceutical Informatics BARRY ROBSON Director of Research and Professor of Biostatistics, Epidemiology, and. .. from bone and antlers as well as stone Armed with their New Stone Age blade The Engines of Hippocrates: From the Dawn of Medicine to Medical and Pharmaceutical Informatics, by Barry Robson and O.K... Safety, and Biologics Discovery: Emerging Technologies and Tools Edited by Sean Ekins and Jinghai J Xu The Engines of Hippocrates: From the Dawn of Medicine to Medical and Pharmaceutical Informatics