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E Reports from the Breakout Session Groups A key component of the Workshop on Health and Medicine was the set of four breakout sessions that enabled individual input by workshop participants on the themes of the workshop: discovery, interfaces, challenges, and infrastructure. Each breakout session was guided by a facilitator and by the expertise of the individuals as well as the content of the plenary sessions. Each breakout group (color-coded blue, green, red, and yellow) was asked to address the same set of questions and provide answers to the questions, including prioritization of the voting to determine which topics the group concluded were most important. After every breakout session, each group reported the results of its discussion in ple- nary session. The committee has attempted in this report to integrate the information gath- ered in the breakout sessions and to use it as the bases of the information con- tained herein. When breakout groups reported votes for prioritizing their conclu- sions, the votes are shown parenthetically in this section. SESSION 1: DISCOVERY What major discoveries or advances related to health and medicine have been made in the chemical sciences during the last several decades? Blue Group Report Discovery and development of new pharmaceutical agents Protein-based drugs 46

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APPENDIX E Drug discovery Structure-guided drug design Antibiotics In silica chemistry Rapid roll out of AIDS therapeutics Drug delivery New anticancer drugs Effective methods for the synthesis of new pharmaceuticals Synthetic strategy Solid-phase synthesis Synthetic methods Catalysis in synthesis (organometallic) Chiral catalysts Enzymes and bioprocessing Catalytic antibodies Combinatorial and parallel chemistry Polymerase chain reaction (PCR) Medical diagnostics for prediction, detection, and distribution of disease Magnetic imaging Noninvasive imaging Contrast imaging Laser applications Biosensors Real-time analytical analysis Diagnostics Development of new molecular separations techniques for analysis, identification, and processing Separations technology Cellular signaling (9 votes) Green Group Report Understanding signal transduction Intracellular sensors of biomolecules (GFP) Molecular probes Post-translational chemistry and modification 47

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48 Molecular medicine (7 votes) Molecular mechanism of disease New drugs (stating) Structure-guided rational drug design Controlled release (large molecule delivery) Bio-engineered pharmaceutical agents Techniques and tools (7 votes) APPENDIX E In vivo imaging (MRI, PET) Mass spectrometry (MALDI, TOP) High-field and multidimensional NMR PCR Solving human genome (underlying technologies, DNA sequencing) Molecular modeling and dynamics Rapid and inexpensive diagnostics Bioprocessing (4 votes) Tissue engineering (artificial skin) Large-scale tissue culture Molecular and cell separation techniques Metabolic networks Modeling biological systems Synthetic methodologies (4 votes) Asymmetric synthesis Chemoenzymatic synthesis Templated synthesis Oligosaccharide chemistry Combinatorial methods (2 votes) Molecular synthesis High-throughput crystallization Protein engineering Nucleic acid engineering

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APPENDIX E Synthetic techniques (9 votes) Red Group Report Ability to synthesize and manufacture complex molecules Development of catalysts for chiral synthesis Solid-phase synthesis High-throughput synthesis and analysis Combinatorial chemistry Imaging modalities (6 votes) . Monitoring of single molecules Single molecule imaging Development of MRI Engineered proteins for fluorescent signaling Use of lasers in medicine, surgery, imaging Spectroscopy (6 votes) Advances in mass spectroscopy NMR Drug development (5 votes) Development of statins HIV therapy Computational chemistry (4 votes) Development of computer-aided experimentation Development of structure-based drug design Molecular amplification (4 votes) Recombinant DNA technology PCR Analytical tools (13 votes) NMR X-ray 49 Yellow Group Report

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so Mass spectrometry HPLC PCR DNA sequencing Micro array s Recombinant DNA SAMS Clinical diagnosis New therapies (11 votes) Natural products discovery Chemistry of enzyme active site Rational drug design Protease inhibitors Cardiovascular drugs Cancer therapies Chemistry of the cell (9 votes) RNA catalysis Signal transduction Natural product mechanisms Gases (e.g., O2, NO) Metal ions Noncovalent interactions Focus on function and structure Synthetic methods (7 votes) Selective chemical reactions Asymmetric synthesis and catalysis Synthesis on solid support Combinatorial chemistry Biomaterials (2 votes) Synthetic membranes Biocompatible materials Controlled drug release Tissue engineering, use of Plastics Disposable APPENDIX E

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APPENDIX E 51 SESSION 2: INTERFACES What are the major biomedical discoveries and challenges at the interfaces between chemistry and chemical engineering and other disciplines, including bi- ology, information science, materials science, and physics? Blue Group Report Material science (8 votes) Micro and nano fabrication Biofunctional"smart" materials Drug delivery systems Oral delivery Drug formulation Conductive polymers (nerve regeneration) Cell biology (7.5 votes) Homogeneous glycoprotein manufacturing Understanding cell surface New chemical types (natural products) Proteomics and metabolomics Genotype and phenotype correlations Understanding neural pathways Information science, computer science, and mathematics (6 votes) Cellular modeling Personalized medicine (genomics) Dynamic theory for multiscale modeling Proteomics and metabolomics Genotype and phenotype correlations Physics (4 votes) Imaging Single molecule studies Optical manipulation (tweezers) In vivo diagnostics

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52 Medicine (3 votes) Problem of drug resistance Agriculture (2.5 votes) Therapeutic proteins by transgenic plants and animals Improving agricultural production (feed the world) New chemical types (natural product discovery) Immunology (2 votes) New bioprocessing techniques (transgenics) New vaccines Green Group Report Cultural barriers at the interfaces (5 votes) Process versus discovery versus hypothesis-driven research Challenge: Chemists as part of a team Common standards for biological data Mechanism versus function or property Translational medicine (3 votes) Economic challenges (government reimbursement versus profit) Bioorganic synthesis-basic science versus clinicians Benefit: Clinicians can define the issue and point to technology needed APPENDIX E Chemists make things (1 vote) Natural products with unnatural function Manipulation of biomolecules Training students (1 vote) Challenge: Education of the other sciences about what chemistry does Undergraduate education Tension between broad and deep

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APPENDIX E Diagnostics (12 votes) . Red Group Report Early detection of cancer Personalized medicine Health sensors Near real-time diagnostics in a primary care setting Biosignatures Predictive mass spectometry Non-invasive sensor development Environmental and biohazard sensing Medical delivery and medical ethics Macromolecular complexes (8 votes) Small molecule control of macromolecular interactions Dynamic (time resolved) measurements at the molecular level Metal ion transport and bioaccumulation Computational and systems models (7 votes) 53 Computational chemistry and structure-based drug design Greater use of artificial intelligence and pattern recognition in diagnostics ganism) Better predictive models Systems level modeling through computation (e.g., molecular up to or- ImDroved drug formulation and delivery (5 votes) , c:, Implants and regenerative medicine (5 votes) Optimal development of cultural interfaces without loss of specialist training (4 votes) Ways to foster communication, collaboration, interdisciplinary research Yellow Group Report New instrumentation, miniaturization, and sensors (10 votes) Mechanical engineering Electrical engineering

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54 APPENDIX E Materials science Physics Computation: Structure-function modeling and bioinformatics (disconnect with language, storage, retrieval, standardization) (8 votes) Computer science Mathematics Modeling: Noncovalent interactions; Pharmacokinetic properties (6 votes) . Computer science Mathematics Pharmacology Physics Global molecular analysis: Metabolomics, proteomics (4 votes) Computer science Systems engineering Electrical engineering Single-cell analysis (3 votes) Mechanical engineering Electrical engineering Physics Single-molecule experimentation (3 votes) Mechanical engineering Electrical engineering Physics Agricultural science: Safe new crops, pest-resistance (2 votes) Veterinary medicine Entomology Botany Agronomy Environmental science Defining Protein Function (1 vote) Cell biology

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APPENDIX E Enzymology Cell differentiation (1 vote) Physics Biomaterials Electrical engineering Noninvasive imaging (1 ~rote) Physics E. . nglneenog Clinicians Nuclear science SESSION 3: CHALLENGES What are the biomedical challenges in the chemical sciences and engineer- Ing ~ New therapies (7 votes) Blue Group Report Viral therapies, known and unknown Cancer therapies Gene therapy Personalized medicine Genomic diagnostics Reactive sensors Exploitation of the human genome (6 votes) Connection of genomics with proteomics Protein folding Predictive protein and protein interaction "PCR" for proteins Interface systems biology with drug discovery (5 votes) Systems physiology Tools for handling complexity in biological systems Intelligent drug delivery, monitoring, and feedback 55

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56 Seamless electronic tissue interfaces Predictive ADMET (4 votes) Predictive biopharmaceutics Target selective delivery systems Target selective pharmaceuticals Green chemistry (3 votes) Selective transformations Regenerative medicine (3 votes) Engineering functional living tissue models In vivo tissue regeneration Development of universal or immune-tolerant cell sources Aging Understanding cognition (3 votes) Neurodegenerative diseases Depression, psychoses New mechanisms for pain control Green Group Report Controlled drug delivery to the site of action (5 votes) Pure air and water for the world (5 votes) In viva imaging of molecular events at 1-100 nm scale (4 votes) Develop effective antivirals (3 votes) APPENDIX E Robust, cheap, and reliable genetic testing for disease predisposition (3 votes) Molecular-level model of cell with predictive capability (3 votes) Early detection of disease (3 votes) Molecular machines for biomedical applications (2 votes)

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APPENDIX E Programmable cell-based synthesis of organic molecules (2 votes) Understand brain chemistry (e.g., consciousness) (1 vote) 57 Couple informatics with discovery-based R & D for molecular medicine (1 vote) Red Group Report Curing disease (10 votes) Host and microflora interactions: Relationship to chronic disease Curing viral diseases Prevention and cure of degenerative diseases Gene therapy: Making it work Smart nanoscale materials: Trigger delivery Functional cell surface modification Example: Drug targeting Higher understanding of noncovalent interactions (7 votes) 3D Macromolecular folding and assembly Understanding the Ribosome Understanding principles of protein folding Membrane-bound protein structure and mechanism Chemistry of life processes (6 votes) Whole cell model Synthetic cell Artificial life creation Understanding origin of life Using information from sequences of all organisms Harnessing the immune system (5 votes) Harnessing of immune system to provide next generation of therapies Immunologically reactive structures database Predict immunoreactivity Biocompatibility of materials

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58 Understanding brain processes (5 votes) Memory Learning Aging Outreach (4 votes) Resource allocation Chemical literacy for all Global accessibility to medicine Low cost, abundant Increased agricultural productivity Human surrogates for pharmaceutical testing (2 votes) Engineered tissue Computer modeling Understanding mechanism of differentiation and development Yellow Group Report Disease cures (12 votes) APPENDIX E Viral, universal antibiotic, cancer, aging (prior, AD) cancer, memory Regulation of body parts Genomics, proteomics, metabolomics (7 votes) Enhanced health, personalized medicine (prediction and prevention) Predict three dimensional structure from sequence Prediction of cellular function Chemical basis of: (5 votes) Thought and memory Addition Immune system Optimize chemical tools (4 votes) Ligands for every protein Ideal one-step, 100 percent synthesis

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APPENDIX E Livable environment (4 votes) Clean air, water, food Population balance (control) SESSION 4: INFRASTRUCTURE 59 What are the issues at the intersection of health and medicine and the chemi- cal sciences for which there are structural challenges and opportunities in teaching, research, equipment and instrumentation, facilities, and personnel ? Blue Group Report Need to evaluate funding model "One size does not fit all" Balance between single investigator and project grants Need more capital investment Better access to core facilities Education and training Need 21st century undergraduate curriculum Breadth and depth; need to assure talent pipeline (recruitment, diversity) How to deal with evolving department structures Need early lab experience Interdisciplinary culture needs to be supported Need to address ethical issues Regulatory issues for personalized medicine Better public perception of chemistry and better "marketing" Green/Red Group Report Working well Radioisotope facilities Entrepreneurship from investigation Students entering the workforce are high quality Some large scale facilities PNNL protein fragment database, CAMS (Livermore)

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60 Not working well Data mining: Management and sharing Academic core facilities support National and core facilities staffing Reward and mechanisms and collaborative research High-school outreach Needs APPENDIX E High-throughput screening facilities Nanofabrication facility Online exposure to the chemical literature for high-school and small-col- lege students National forums More crossdiscipline forums Increased input from industry and younger scientists . Education Graduate courses outside field of specialization Structure for a generalist Support for web-based courseware Possible Solutions Education Build laboratory rotation into Ph.D. Support for industrial and government internships Facilities Grant surcharge for facilities support Central repository of instrument parts Yellow Group Report Information exchange (7 votes) Realization of the need to collaborate Positive academia and industry interactions (spin offs) Intellectual property issues - Industry and university University and university (MTA) University, industry, and government Increase recognition of collaborations

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APPENDIX E Teaching (6 votes) Breadth and depth Emphasis of relevance of chemistry to human health Improved undergraduate chemical education Better laboratory course - Incorporate biochemistry in curriculum earlier Promote undergraduate research Continued increase in funding for science education Outreach (5 votes) Promotion of chemical science to the general public More involvement to improve K-12 science education Equipment and facilities (4 votes) More access to state of the art instrumentation Effective maintenance and access to shared facilities Remote access Hands-on access to large-scale facilities Research (1 vote) 61 Increase funding mechanisms to encourage discovery-based research to complement hypothesis-driven research Enhanced postdoctoral fellowships Independent of grants - Broader distribution to promote diversity Information and data (1 vote) Better search capabilities Needs to be standardized Quality control of information Needs to be standardized Pooling of information

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