Medicine of the Future—The Transformation from Reactive to Proactive (P4) Medicine Predictive, Personalized, Preventive and Participatory Lee Hood Institute for Systems Biology, Seattle

The Current Healthcare Debate The debate is centered on medicine of the past/present rather than medicine of the future Healthcare is a fundamental right of all citizens. When viewed in the context of medicine of the present--current health care is ineffective, costly and therefore impossible to extend to all citizens The healthcare debate today is about rationing and who will be left out or poorly served The key is to understand medicine of the near future (P4 medicine) and realize the transformation it will bring—an effectiveness and reduced cost—ultimately with the possibility of bringing adequate healthcare to all

The debate is centered on medicine of the past/present rather than medicine of the future

Healthcare is a fundamental right of all citizens. When viewed in the context of medicine of the present--current health care is ineffective, costly and therefore impossible to extend to all citizens

The healthcare debate today is about rationing and who will be left out or poorly served

The key is to understand medicine of the near future (P4 medicine) and realize the transformation it will bring—an effectiveness and reduced cost—ultimately with the possibility of bringing adequate healthcare to all

Contemporary Systems Biology is Predicated on Viewing Biology is an Informational Science

The digital information of the genome There are two types of Biological Information The environmental information that impinges upon and modifies the digital information.

The digital information of the genome

The environmental information that impinges upon and modifies the digital information.

Biological Structures that Handle Information Biological networks capture, transmit, process and pass on information Protein networks Gene regulatory networks MicroRNA networks Genetic networks Simple and complex molecular machines--execute biological functions

Biological networks capture, transmit, process and pass on information

Protein networks

Gene regulatory networks

MicroRNA networks

Genetic networks

Simple and complex molecular machines--execute biological functions

Most Sophisticated Integrated Biological Network Defined to Date

DNA mRNA Protein Protein interactions and biomodules Protein and gene networks Cells Phenotypes Organs Individuals Populations Ecologies Hierarchical or Multiscalar Levels of Biological Information

DNA

mRNA

Protein

Protein interactions and biomodules

Protein and gene networks

Cells

Phenotypes

Organs

Individuals

Populations

Ecologies

A Systems Approach to Prion Disease in Mice

Prion disease example: Prion Protein Exists in Two Forms Cellular PrP C PrP Genetic Mutations PrPSc Infections Spontaneous conversion Infectious PrP Sc

Global Transcriptome Analysis Uninfected brain Prion infected brain Inoculate w/ Prions Time-course array analysis: Mouse Genome array : 45,000 probe sets ~22,000 mouse genes. RNA from brain homogenate Prion strains : RML 301V Mouse strains: C57BL/6J FVB/N C r BL6.I FVB/ B4053 C57BL/6J-RML : 12 time points FVB/NCr-RML : 11 time points BL6.I-301V : 9 time points FVB/B4053-RML : 8 time points Almost 46 million Data points Carlson lab Inyoul Lee (Brianne Ogata, David Baxter) Bruz Marzolf (Microarray Facility)

Prion strains :

RML

301V

Mouse strains:

C57BL/6J

FVB/N C r

BL6.I

FVB/ B4053

C57BL/6J-RML : 12 time points

FVB/NCr-RML : 11 time points

BL6.I-301V : 9 time points

FVB/B4053-RML : 8 time points

Multiple groups: five inbred strains, two transgenic strains and one knockout strain Differentially Expressed Genes--DEGs--7400 to 333

Examples of Prion Subtractive Transcriptional Analyses Control vs disease-infected animals at 10 time points across disease progression in 8 mouse strains Subtract unique responses in 3 inbred strains Subtract responses from differing levels of prion proteins in transgenic/heterozygotic animals Subtract differences from infection with two different prion strains Subtract unique contributions for long and short period disease incubations Subtract differences arising in infected prion knockout animals (no disease)

Control vs disease-infected animals at 10 time points across disease progression in 8 mouse strains

Subtract unique responses in 3 inbred strains

Subtract responses from differing levels of prion proteins in transgenic/heterozygotic animals

Subtract differences from infection with two different prion strains

Subtract unique contributions for long and short period disease incubations

Subtract differences arising in infected prion knockout animals (no disease)

Neuropathological Features PrP accumulation Microglia / Astrocyte activation Synaptic Degeneration Normal Infected Nerve cell death

Integration of Different Types of Information Subtractive dynamic transcriptome analyses Network dynamics of relevant brain networks Dynamic histopathology of the brain Dynamic distribution of infectious prion particles in the brain Onset of clinical symptoms

Subtractive dynamic transcriptome analyses

Network dynamics of relevant brain networks

Dynamic histopathology of the brain

Dynamic distribution of infectious prion particles in the brain

Onset of clinical symptoms

PrP accumulation network

DEGs Encoding Known and Novel Prion Disease Phenotypes 231/333 DEGs encode known disease pathogenic networks 102/333 DEGs encode novel pathogenic networks--the dark genes of prion disease Androgenic steroid metabolism Iron metabolism Arachidonate/prostaglandin metabolism Three of the four prion-disease networks are seen in Alzheimer's disease--prion replication and accumulation is unique This study has interesting implications for thinking about drug targets for neurodegenerative diseases Implications for systems diagnostics

231/333 DEGs encode known disease pathogenic networks

102/333 DEGs encode novel pathogenic networks--the dark genes of prion disease

Androgenic steroid metabolism

Iron metabolism

Arachidonate/prostaglandin metabolism

Three of the four prion-disease networks are seen in Alzheimer's disease--prion replication and accumulation is unique

This study has interesting implications for thinking about drug targets for neurodegenerative diseases

Implications for systems diagnostics

A Systems Approach to Blood Diagnostics

Dynamics of a Prion Perturbed Network in Mice Nerve cell death

Organ-specific transcripts now identified for 50+ individual organs in mouse and humans. We have identified more than 200 brain-specific transcripts A Genomics Approach to the Identification of Organ-Specific Transcripts Organ-specific secreted protein mRNA tpm

Organ-specific transcripts now identified for 50+ individual organs in mouse and humans.

We have identified more than 200 brain-specific transcripts

Organ-Specific Blood Fingerprints Making Blood A Window Distinguishing Health and Disease Blood Vessel

Presymptomatic Diagnosis of Murine Prion Disease with Organ-Specific Protein in Blood Samples 15/45 brain-specific blood proteins enabled early detection Clinical Signs at 18 wk Presymptomatic Diagnosis at 10 wk

Organ-specific Protein Blood Fingerprints—Disease Diagnostics Early detection Disease stratification Disease progression Follow therapy

Early detection

Disease stratification

Disease progression

Follow therapy

Technologies Will Create New Patient Data Spaces to be Explored and Will Greatly Expand the Old Patient Data Spaces

What are the technologies that will transform systems or P4 medicine? High throughput DNA sequencing for individual human genome sequencing Targeted MRM mass spectrometry for discovery, validation and typing (initially) of blood fingerprints Microfluidic protein chip to measure blood organ-specific protein fingerprints and type millions of individuals New chemistry for protein-capture agents Single-cell analyses--deciphering the interplay of the digital genome and the environment In vivo and in vitro molecular imaging to assess disease distribution and follow therapy

High throughput DNA sequencing for individual human genome sequencing

Targeted MRM mass spectrometry for discovery, validation and typing (initially) of blood fingerprints

Microfluidic protein chip to measure blood organ-specific protein fingerprints and type millions of individuals

New chemistry for protein-capture agents

Single-cell analyses--deciphering the interplay of the digital genome and the environment

In vivo and in vitro molecular imaging to assess disease distribution and follow therapy

Genome Sequencing of Individuals

Study Families to Suppress Noise and Carry out Powerful New Genetic Analyses Unaffected parents Children with craniofacial malformation and lung disease Lynn Jorde and Michael Bamshad: family DNA—Sequencing by Complete Genomics, Inc

Advantages of Sequencing a Family Low error rate—1/10 5 340,000 new SNPs (4.2 million SNPs total) Recombinational maps of children’s genomes Inter-generational mutation rates Narrow down disease gene candidates for two diseases in children to three genes

Low error rate—1/10 5

340,000 new SNPs (4.2 million SNPs total)

Recombinational maps of children’s genomes

Inter-generational mutation rates

Narrow down disease gene candidates for two diseases in children to three genes

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 X 65 crossovers in (2) male meioses (left) 104 crossovers in (2) female meioses (right) Recominational Genome Map from Miller’s Syndrome Children 0 50 100 150 200 250 x x x Both children inherited the same allele from both parents Each child inherited a different allele from each parent Children inherited the same allele from dad, different alleles from mom Children inherited the same allele from mom, different alleles from dad

Microfluidic Protein Chip

DEAL for In vitro molecular diagnostics : Integrated nanotech/microfluidics platform Jim Heath, et al Organ 1 Organ 2 Tox response inflammation cells out 300 nanoliters of plasma Assay region Dynamic range--10 8 Sensitivity--high atmole 5 minute measurement

New Approach to Protein-Capture Agents

Antibody Displacement Technology Protein Catalyzed Capture Agents: triligands determined by repeated screening of target protein across synthetic bead-bound peptide libraries anchor peptide is selected on the first screen protein catalyzes the formation of second ligand to anchor ligand on second screen protein catalyzes the formation of the third ligand to the anchor and second ligand on third screen high affinity, stable and easily manufactured triligand capture agents confidential An example of a triligand PCC agent for bovine carbonic anhydrase II

Protein Catalyzed Capture Agents:

triligands determined by repeated screening of target protein across synthetic bead-bound peptide libraries

anchor peptide is selected on the first screen

protein catalyzes the formation of second ligand to anchor ligand on second screen

protein catalyzes the formation of the third ligand to the anchor and second ligand on third screen

high affinity, stable and easily manufactured triligand capture agents

Single-Cell Analyses

Multiplexed ELISA for secreted proteins Single Cell Analyses Adrian Ozinsky

Routine Analyses on Individual Patients with 10 years

Individual Patient High Throughput Assays of the Future Complete individual genome sequences —predictive health history—will be done sequencing families Sequence 1000 transcriptomes simultaneously in one DNA sequencing run from single cancer cells or single cells from biopsies--to stratify disease. 2500 blood organ-specific blood proteins —twice per year (50 proteins from 50 organs)—wellness assessment. Analyze 10,000 B cells and 10,000 T cells for the functional regions of their immune receptors—past and present immune responsiveness—follow vaccinations. Analyze individual stem (iPS) cells from each individual differentiated to relevant tissues to get important phenotypic information—molecular and imaging.

Complete individual genome sequences —predictive health history—will be done sequencing families

Sequence 1000 transcriptomes simultaneously in one DNA sequencing run from single cancer cells or single cells from biopsies--to stratify disease.

2500 blood organ-specific blood proteins —twice per year (50 proteins from 50 organs)—wellness assessment.

Analyze 10,000 B cells and 10,000 T cells for the functional regions of their immune receptors—past and present immune responsiveness—follow vaccinations.

Analyze individual stem (iPS) cells from each individual differentiated to relevant tissues to get important phenotypic information—molecular and imaging.

Organ-Specific Blood Protein Fingerprint Analyses Will Transform Biology and Medicine

Applications of Organ-Specific Blood Protein Fingerprints Disease diagnostics--early, stratification, progression, follow therapy Interactions of multiple organs in studying therapeutic responses, drug toxicity and biology Identification of disease-perturbed networks as a prelude to drug target identification Assessing the use of drugs in individuals--toxicity, response, dose, combinatorial therapies Wellness assessment--longitudinal data gathering – patient is their own control Do human biology from the blood--aging, development, physiological responses

Disease diagnostics--early, stratification, progression, follow therapy

Interactions of multiple organs in studying therapeutic responses, drug toxicity and biology

Identification of disease-perturbed networks as a prelude to drug target identification

Assessing the use of drugs in individuals--toxicity, response, dose, combinatorial therapies

Wellness assessment--longitudinal data gathering – patient is their own control

Do human biology from the blood--aging, development, physiological responses

Predictive, Personalized, Preventive and Participatory (P4) Medicine Driven by systems approaches to disease, new measurement (nanotechnology) and visualization technologies and powerful new computational tools, P4 medicine will emerge over the next 10-20 years

Driven by systems approaches to disease, new measurement (nanotechnology) and visualization technologies and powerful new computational tools, P4 medicine will emerge over the next 10-20 years

P4 Medicine Predictive : Probabilistic health history--DNA sequence Biannual multi-parameter blood protein measurements In vivo molecular imaging

Predictive :

Probabilistic health history--DNA sequence

Biannual multi-parameter blood protein measurements

In vivo molecular imaging

P4 Medicine Personalized : Unique individual human genetic variation mandates individual treatment Patient is his or her own control Billions of data points on each individual

Personalized :

Unique individual human genetic variation mandates individual treatment

Patient is his or her own control

Billions of data points on each individual

P4 Medicine Preventive : Design of therapeutic and preventive drugs via systems approaches Systems approaches to vaccines will transform prevention of infectious diseases Transition to wellness assessment

Preventive :

Design of therapeutic and preventive drugs

via systems approaches

Systems approaches to vaccines will transform prevention of infectious diseases

Transition to wellness assessment

P4 Medicine Participatory : Patient understands and participates in medical choices Patient increasing will make choices with doctor intervention

Participatory :

Patient understands and participates in medical choices

Patient increasing will make choices with doctor intervention

Will impact the health care system significantly: Pharmaceuticals Biotechnology Diagnostics IT for healthcare Healthcare industry Health insurance Medicine--diagnostics, therapy, prevention, wellness Nutrition Assessments of environmental toxicities Academia and medical schools P4 Medicine Will Transform the Health Care Industry Fundamentally new ideas need New organizational structures Healthcare System

Will impact the health care system significantly:

Pharmaceuticals

Biotechnology

Diagnostics

IT for healthcare

Healthcare industry

Health insurance

Medicine--diagnostics, therapy, prevention, wellness

Nutrition

Assessments of environmental toxicities

Academia and medical schools

Digitalization of Biology and Medicine Will Transform Medicine Analysis of single molecules, single cells and single individuals A revolution that will transform medicine even more than digitalization transformed information technologies and communications Digitization of medicine will lead to dramatically lower healthcare costs Single individual Single cell Single molecule

Analysis of single molecules, single cells and single individuals

A revolution that will transform medicine even more than digitalization transformed information technologies and communications

Digitization of medicine will lead to dramatically lower healthcare costs

Why the Digitalization of Medicine and P4 (Systems) Medicine Will Reduce Healthcare Costs Diagnosis will stratify disease and impediance match drugs Re-engineering disease-perturbed networks to normalicy with drugs—new and less expensive strategy for drug target discovery Survey wellness with 2500 blood organ-specific protein measurements biannually—global early detection Technologies exponentially increasing in the number of measurements they can make and decreasing in cost Other medical advances arising from mechanistic insights—stem cells, neurodegenerative, aging, vaccines, cancer etc.

Diagnosis will stratify disease and impediance match drugs

Re-engineering disease-perturbed networks to normalicy with drugs—new and less expensive strategy for drug target discovery

Survey wellness with 2500 blood organ-specific protein measurements biannually—global early detection

Technologies exponentially increasing in the number of measurements they can make and decreasing in cost

Other medical advances arising from mechanistic insights—stem cells, neurodegenerative, aging, vaccines, cancer etc.

Inventing the Future 20th Century Biomedicine 21st Century Biomedicine ISB Analyzing one gene and one small problem at a time Systems analysis of biology and medicine--e.g., predictive, preventive, personalized and participatory (P4) medicine Technology development Pioneer computational tools Transferring knowledge to society--joining academics and industry--changing K-12 science education--P4 medicine and society Strategic partnerships --for hard scientific problems--P4 medicine--industrial, academic, government, international

Analyzing one gene and one small problem at a time

Systems analysis of biology and medicine--e.g., predictive, preventive, personalized and participatory (P4) medicine

Technology development

Pioneer computational tools

Transferring knowledge to society--joining academics and industry--changing K-12 science education--P4 medicine and society

Strategic partnerships --for hard

scientific problems--P4 medicine--industrial, academic, government, international

ISB Strategic Partnerships to Hasten the Realization of P4 Medicine

Advantages of National and International Strategic Partnerships Take on challenging (big) problems in an integrated manner (P4 medicine) New approaches to raising significant funds to attack big problems Integrate the efforts of the best in the world Complementary technical and biological skills Medical expertise and accessibility to patients, patients samples and patient records Exchange of talented scientists, engineers, physicians and students

Take on challenging (big) problems in an integrated manner (P4 medicine)

New approaches to raising significant funds to attack big problems

Integrate the efforts of the best in the world

Complementary technical and biological skills

Medical expertise and accessibility to patients, patients samples and patient records

Exchange of talented scientists, engineers, physicians and students

ISB Strategic Partnerships for P4 Medicine P4 Medical Institute (P4MI)—integrating selected companies and academics around P4 demonstration projects Bring systems biology, P4 medicine and biotech industry to Luxembourg Bring systems medicine to a US medical school

P4 Medical Institute (P4MI)—integrating selected companies and academics around P4 demonstration projects

Bring systems biology, P4 medicine and biotech industry to Luxembourg

Bring systems medicine to a US medical school

ISB/Luxembourg Strategic Partnership Helping to creating a Center for System Biology similar to ISB Two collaborative research projects--$ 100 million over 5 years Helping establish biotech industry in Luxembourg—start ups and established companies--integrated personalized medicine company—Integrated Diagnostics

Helping to creating a Center for System Biology similar to ISB

Two collaborative research projects--$ 100 million over 5 years

Helping establish biotech industry in Luxembourg—start ups and established companies--integrated personalized medicine company—Integrated Diagnostics

Two Luxemboug Research Projects

ISB’s Approach to P4 Medicine: Genetics and Environment integration is key to future medicine Tissue, Blood protein And stem cell Read-out Predictive, Personalized Diagnostics Genome Environment Disease & Health Complex biological Networks Systems Genetics

Luxembourg Strategy Diseases of brain (neurodegenerative and cancer), liver (toxicity, hepatitis C, fibrosis, cancer) and lung (cancer, fibrosis, COPD) Use mouse models for each—signal/noise and dynamical networks Genomes, transcriptomes, miRNAomes, proteomes, and phenomices—analyze patient disease organs, blood and differentiated disease-relevant tissues from iPS cells (individual patient stems cells) Develop relevant technologies , e.g. single cell. Individual genome analyses, etc. Integrate data into predictive networks

Diseases of brain (neurodegenerative and cancer), liver (toxicity, hepatitis C, fibrosis, cancer) and lung (cancer, fibrosis, COPD)

Use mouse models for each—signal/noise and dynamical networks

Genomes, transcriptomes, miRNAomes, proteomes, and phenomices—analyze patient disease organs, blood and differentiated disease-relevant tissues from iPS cells (individual patient stems cells)

Develop relevant technologies , e.g. single cell. Individual genome analyses, etc.

Integrate data into predictive networks

A Second Strategic ISB Partnership—the P4 Medical Institute—ISB/OSU

The P4 Medicine Institute Slide Science & Technology Policy & Industry + P4 Medicine Institute A collaborative organization whose goal is to catalyze the personalized transformation of healthcare by: Accelerating translation of science to clinical practice Developing public-private industry collaboration Executing tangible & pragmatic demonstration projects Addressing technical, strategic, operational, policy, economic, & sociologic issues

Accelerating translation of science to clinical practice

Developing public-private industry collaboration

Executing tangible & pragmatic demonstration projects

Addressing technical, strategic, operational, policy, economic, & sociologic issues

P4MI Principles Scientific innovation based upon systems biology and emerging technologies will yield “killer app” insights and innovations that will enable industry disruption These technologic enablers will result in care that can be focused on health and wellness, the prediction and prevention of illness, individualized care for consumers of the future. This disruption will provide a path to improved outcomes at lower costs via more effective diagnosis, more precise therapies, and reduced costs to bring therapies to market. There exists current opportunities for insightful and visionary industry stakeholders to engage in business model redesign through participation in collaborative demonstration projects

Scientific innovation based upon systems biology and emerging technologies will yield “killer app” insights and innovations that will enable industry disruption

These technologic enablers will result in care that can be focused on health and wellness, the prediction and prevention of illness, individualized care for consumers of the future.

This disruption will provide a path to improved outcomes at lower costs via more effective diagnosis, more precise therapies, and reduced costs to bring therapies to market.

There exists current opportunities for insightful and visionary industry stakeholders to engage in business model redesign through participation in collaborative demonstration projects

Facilitating Opportunities Science & Technology Policy & Industry Reorient care delivery systems to leverage new care models, consumer engagement, wellness-focused care Redesign incentives & reimbursement models to facilitate P4 Medicine Develop collaborative mechanism for involvement of the many & diverse stakeholders needed for the emergence of P4 Medicine Address regulatory requirements, lega l protections, & policies needed to facilitate P4 Medicine Analyze sociologic, ethical, economic impacts associated with adoption of P4 Medicine Examine education requirements for medical workforce, industry, & consumers Develop methods to integrate genomic sequence data with diagnostic phenomic data Identify & characterize disease-specific biologic networks using systems approaches Identify & characterize organ-specific proteins, microRNA, other biomarker candidates Explore potential of novel technologies ( in vivo molecular imaging, iPS cells, single cell analysis) Develop secure storage databases to manage complex & dense molecular & phenomic data Enhance EHR technologies to leverage novel content derived from molecular investigation Establish information management & governance policies for personalized datasets

Reorient care delivery systems to leverage new care models, consumer engagement, wellness-focused care

Redesign incentives & reimbursement models to facilitate P4 Medicine

Develop collaborative mechanism for involvement of the many & diverse stakeholders needed for the emergence of P4 Medicine

Address regulatory requirements, lega l protections, & policies needed to facilitate P4 Medicine

Analyze sociologic, ethical, economic impacts associated with adoption of P4 Medicine

Examine education requirements for medical workforce, industry, & consumers

Develop methods to integrate genomic sequence data with diagnostic phenomic data

Identify & characterize disease-specific biologic networks using systems approaches

Identify & characterize organ-specific proteins, microRNA, other biomarker candidates

Explore potential of novel technologies ( in vivo molecular imaging, iPS cells, single cell analysis)

Develop secure storage databases to manage complex & dense molecular & phenomic data

Enhance EHR technologies to leverage novel content derived from molecular investigation

Establish information management & governance policies for personalized datasets

Impact of P4 Medicine to Industry & Society Transformative & disruptive potential of P4 Medicine extends to the entire healthcare industry Science & Pharma Health Systems & Payers Patients & Consumers Physicians & Education Diagnostics & HCIT Socioethical / Legal New dx tools that transform molecular data into content Electronic health records that leverage molecular data, correlate phenomic data, & provide true cognitive support Tech stack that integrates clinical, research, dx, & pt. generated data Rapid translation of science to clinical practice New drug discovery opportunities from systems biology Molecular blood ‘fingerprints’ to stratify disease & guide therapy selection Distribution of care locus – leveraging ‘medical home’ model Emphasis on wellness & prevention over illness Shift payer focus from volume to well-defined quality endpoints Preventive & predictive medicine yields new clinician thoughtflows Training must emphasize systems approach, HCIT support, risk & prediction, & personalization Privacy, security, consumer protection re: molecular data Consent for clinical & research use of molecular-level data Societal impacts of banked molecular data, biosamples Socioeconomic impact of P4 Medicine Personalization & Participation generate new consumer behaviors Consumer engagement technology requirements Consumer behaviors associated with biobanks & rapid scientific translation

New dx tools that transform molecular data into content

Electronic health records that leverage molecular data, correlate phenomic data, & provide true cognitive support

Tech stack that integrates clinical, research, dx, & pt. generated data

Rapid translation of science to clinical practice

New drug discovery opportunities from systems biology

Molecular blood ‘fingerprints’ to stratify disease & guide therapy selection

Distribution of care locus – leveraging ‘medical home’ model

Emphasis on wellness & prevention over illness

Shift payer focus from volume to well-defined quality endpoints

Preventive & predictive medicine yields new clinician thoughtflows

Training must emphasize systems approach, HCIT support, risk & prediction, & personalization

Privacy, security, consumer protection re: molecular data

Consent for clinical & research use of molecular-level data

Societal impacts of banked molecular data, biosamples

Socioeconomic impact of P4 Medicine

Personalization & Participation generate new consumer behaviors

Consumer engagement technology requirements

Consumer behaviors associated with biobanks & rapid scientific translation

P4 MI Core Competencies Translational Science Social Sciences & Ethics Policy & Regulation Technology Higher Education Commercial Analysis P4MI Charter Members Healthcare Delivery Legal Consumer Behavior

P4 MI Charter Members (ISB/OSU) Slide Healthcare Providers Patients & Consumers Payors & Employers Diagnostics & Biotech Medical Education Technology Vendors Pharma & PBMs Consumer Goods Regulators & Foundations 3-5 Charter Members drawn from groups above Establish governance & business model Collaborate on & commission projects of mutual interest Provide early direction & prioritization First rights to participate in projects of interest Benefit from commercial potential & IP of derivative solutions Science & Research

3-5 Charter Members drawn from groups above

Establish governance & business model

Collaborate on & commission projects of mutual interest

Provide early direction & prioritization

First rights to participate in projects of interest

Benefit from commercial potential & IP of derivative solutions

The Flattening of Many Worlds: Strategic Partnerships and the Globalization of Science The worlds of science, technology, health are flattening. Tremendous opportunities for national and international strategic partnerships in science, technology and education. Network of interacting complementary, institutions Training in systems biology and recruiting the best world talent Transferring and collaborating on new technologies and computational tools Strategic partnerships on systems approaches to biology and P4 medicine New patient populations New fundraising and commercialization opportunities

The worlds of science, technology, health are flattening.

Tremendous opportunities for national and international strategic partnerships in science, technology and education.

Network of interacting complementary, institutions

Training in systems biology and recruiting the best world talent

Transferring and collaborating on new technologies and computational tools

Strategic partnerships on systems approaches to biology and P4 medicine

New patient populations

New fundraising and commercialization opportunities

The Opportunities and Challenges of P4 Medicine Opportunities Explore mulii-billion dimensional data space leading to a deep understanding of disease mechanisms and hence effective and inexpensive new approaches to prediction, therapy ,prevention The potential to correlate 100s million of patient genotypes and phenotypes—and transform predictive medicine (diagnostics) Move rapidly towards a focus on wellness because of rapid responses to initial minor disease perturbations Challenges Data standaridized Universally accepted IT healthcare system to store, analyze, transmit, integrate and model data--no current system adequate Data available in an integrateable mode to analytic labs Biobanks for tissue and blood storage from individuals Ethics, social, legal, regulatory, economic issues resolved Deep research support for P4-oriented medicine to hasten its realization

Opportunities

Explore mulii-billion dimensional data space leading to a deep understanding of disease mechanisms and hence effective and inexpensive new approaches to prediction, therapy ,prevention

The potential to correlate 100s million of patient genotypes and phenotypes—and transform predictive medicine (diagnostics)

Move rapidly towards a focus on wellness because of rapid responses to initial minor disease perturbations

Challenges

Data standaridized

Universally accepted IT healthcare system to store, analyze, transmit, integrate and model data--no current system adequate

Data available in an integrateable mode to analytic labs

Biobanks for tissue and blood storage from individuals

Ethics, social, legal, regulatory, economic issues resolved

Deep research support for P4-oriented medicine to hasten its realization

The Conclusion The current debate on healthcare is centered on medicine of the past—and hence misses the enormous potential of medicine of the future (P4) for revolutionary change. Siloization with many different medical systems with different IT for healthcare, no data standardization, no effective biobanks for sample storage and no agreement on ethical, policy, societal, economic issues would be a disaster—integrative challenges Is the only the government in a position to handle the effective integrative challenges of P4 medicine?

The current debate on healthcare is centered on medicine of the past—and hence misses the enormous potential of medicine of the future (P4) for revolutionary change.

Siloization with many different medical systems with different IT for healthcare, no data standardization, no effective biobanks for sample storage and no agreement on ethical, policy, societal, economic issues would be a disaster—integrative challenges

Is the only the government in a position to handle the effective integrative challenges of P4 medicine?

The P4 Medical Institute Through the ISB/OSU Strategic Partnership Could Play a Key Role in Accelerating the Emergence of P4 Medicine

Acknowledgements Prion--Institute for Systems Biology Daehee Hwang Inyoul Lee Hyuntae Yoo Eugene Yi (proteomics core facility) Bruz Ma r zolf (Affymetrix core facility) Nanotechnology-- J Heath, Caltech Luxembourg projects-- David Galas, ISB P4 Medical Institute —Fred Lee, David Galas, Diane Isonaka Prion--McLaughlin Research Institute Great Falls, Montana Ranjit Giri Douglas Spicer Rajeev Kumar Rose Pitstick Rebecca Young George A. Carlson