Future of Health: Overview of Participant-driven Research and Medicine

Future of Health: Overview of Participant-driven Research and Medicine Melanie Swan FounderDIYgenomics+1-415-505-4426@DIYgenomicswww.DIYgenomics.orgm@melanieswan.com 37th health seminar "Patient-driven research and medicine" November 10, 2011, Lausanne Switzerland Slides: http://slideshare.net/LaBlogga

About Melanie Swan • Founder DIYgenomics, futurist and applied genomics expert • Current projects: MelanieSwan.com • Education: MBA Finance, Wharton; BA French/Economics, Georgetown Univ • Work experience: Fidelity, JP Morgan, iPass, RHK/Ovum, Arthur Andersen • Sample publications: • Swan M. Meeting Report: American Aging Association 40(th) Annual Meeting, Raleigh, North Carolina, June 3-6, 2011. Rejuvenation Res. 2011, Aug;14(4):449-55. • Swan, M., Hathaway, K., Hogg, C., McCauley, R., Vollrath, A. Citizen science genomics as a model for crowdsourced preventive medicine research. J Participat Med. 2010, Dec 23; 2:e20. • Swan, M. Multigenic Condition Risk Assessment in Direct-to-Consumer Genomic Services. Genet. Med.2010, May;12(5):279-88. • Swan, M. Translational antiaging research. Rejuvenation Res.2010, Feb;13(1):115-7. • Swan, M. Engineering Life into Technology: the Application of Complexity Theory to a Potential Phase Transition of Intelligence. Symmetry2010, 2, 150:183. • Swan, M. Emerging patient-driven health care models: an examination of health social networks, consumer personalized medicine and quantified self-tracking. Int. J. Environ. Res. Public Health2009, 2, 492-525. Source: http://melanieswan.com/publications.htm

Top 10 list of participative health initiatives Automated self-tracking devices Microbiomics Personal health records Image credit: http://www.dreamstime.com Crowdsourced health studies Social media Blood tests 2.0 Smartphone health apps Health advisor Whole human genome sequencing Health social networks Personalized genomics 2010 2015 2020+ 2

Agenda • Introduction: context for participative health • Participant-driven health initiatives • Social media, smartphone health apps, PHRs • Personalized genomics • Crowdsourced studies • Next-generation participative health • Future medicine conclusion Image credit: Natasha Vita-More, Primo Posthuman 3

Information transmission eras Analog Digital Life code ? 2100+ 17,300 years ago 1455&1950-2000 2000-2100 Painting, scrolls Press, Transistor DNA ?

Biology is an information technology DNA sequencing: 10x/yr improvement I love you 01001001001000000110110001101111011101100110010100100000011110010110111101110101 I hate you 01001001001000000110100001100001011101000110010100100000011110010110111101110101 Image credit: http://pubs.acs.org/cen/_img/87/i50/8750cover2_law.gif

Biology is theinformation technology Organ regeneration (urethra) Algal biofuel Image credit: Anthony Atala lab Image credit: http://www.rexresearch.com Artificial cell booted to life Whole organ decellularization and recellularization (heart) DNA nanotechnology latch box for drug delivery Image credit: J. Craig Venter Institute Image credit: Thomas Matthiesen Image credit: Aarhus University

Rising worldwide health care costs Source: http://www.kff.org/insurance/snapshot/OECD042111.cfm

Woeful state of global public health systems • Rising health care costs • Aging populations worldwide • Anticipated physician shortages • Cost per new drug: $1.5 billion • New drug apps: 23 in 2011 vs. 45 in 1996 • Biotechnology investment reticence1 • Upcoming period of care rationing? Image credit: http://www.boomertownsquare.com 1Source: http://www.innovationnewsdaily.com/medical-innovation-pharmaceutical-drugs-2090

Citizen science definition • Performing scientific investigation without professional training in the field Image credit: http://www.southernfriedscience.com Institutional science research Citizen science health and biology Citizen science: 200+ organizations1 1http://scienceforcitizens.net/finder

Citizen science health – why now? • Tools • Plummeting cost of genome sequencing • Availability of consumer blood tests • Online bioinformatics tools • Education and support • Local DIYbio labs, online forums Image credits: http://www.biocurious.org Image credit: http://diybionyc.blogspot.com

Participative health definition • Health 2.0, Medicine 2.0, eHealth, participative health (2008) • “Use of a specific set of Web [2.0] tools (blogs, Podcasts, tagging, search, wikis, [health social networks], etc.) by actors in health care including doctors, patients, and scientists, using principles of…in order to personalize health care, collaborate, and promote health education” 1 • Society for Participatory Medicine (2010) • “Participatory Medicine is a movement in which networked patients shift from being mere passengers to responsible drivers of their health, and in which providers encourage and value them as full partners”2 1Source: http://en.wikipedia.org/wiki/Medicine_2.0#cite_note-jmir.org-3 2Source: http://e-patients.net/archives/2010/04/a-patient-centric-definition-of-participatory-medicine.html

Participative health activities Image credit: Getty Images

Health 2.0 social media • Web 2.0 in the health context • Blogs, twitter, facebook, wikis, search, google+, video Image credit: http://www.siliconangle.com

Social media increases health literacy • Consumer response to social media • 27% of US internet users track health data online, 18% seek others with similar health concerns1 • 67% of Europeans trust social media information2 • European physician response to social media • 30% physicians are members of social networks2 • 2/3+ interested in joining social networks2 • 41% believe social media will play an increasingly important role in shaping their patient management and treatment3 Image credit: http://ramialsindi.wordpress.com 1Source:http://www.pewinternet.org/Reports/2011/Social-Life-of-Health-Info.aspx 2Source: http://www.mmm-online.com/europe-edges-us-in-social-media-for-health-info-says-study/article/166461/ 3Source: http://www.worldofhealthit.org/sessionhandouts/documents/PS34-1-DeniseSilber.pdf

Social media health tech: Physician consultation and review Image credit: http://www.webicina.com Image credit: http://www.americanwell.com Image credit: http://www.3gdoctor.com

Smartphone as personal doctor • Mobile is the platform • US: more cell phones (328 m) than people (315 m)1 • Smartphone users • One billion+ by 20132 • 81% physicians using smartphones 20123 • Explosive growth in application (app) downloads • 5 billion in 2010 versus 300 million in 20094 • Health-related apps: 7,0004 • Intimate continuous interaction platform • Phone loss noticed within 5 minutes vs. 1 hour for wallet loss Image credit: http://www.psfk.com 1Kang C. Number of cell phones exceeds US population. Washington Post. October 11, 2011. 2Dufau S. Smart phone, smart science: how the use of smartphones can revolutionize research in cognitive science. PLoS One. 2011. 3Kiser K. 25 ways to use your smartphone. Physicians share their favorite uses and apps. Minn Med. 2011. 4Boulos MN. How smartphones are changing the face of mobile and participatory healthcare. Biomed Eng Online. 2011.

Smartphone health apps • Consumer uses • Education, information, and self-tracking • Physician uses • Access patient information, contact colleagues, information look-up (billing codes, drug formularies, reference material) • Health app focal areas • Nutrition, exercise, diabetes, obesity • Mental health and behavioral change • Scaled up research projects • Thousands recruited in months1 Image credit: http://www.mobihealthnews.com Image credit: tehgaygeek.blogspot.com 1Dufau S. Smart phone, smart science: how the use of smartphones can revolutionize research in cognitive science. PLoS One. 2011.

PHRs (personal health records) • Patient-administered medical records • Traditional: blood type, family history, Rx data • Health 2.0: genome profiles, self-tracking data • Link with traditional medicine • Cost savings, real-time information access, error reduction, improved communication for individuals & health systems • PHR use is growing • 11% PHR use in 2011, +3% from 2008 (Deloitte) • Aetna 1.5 million users (Sep 2011) • Improved health outcomes • PHR users 68% better at following up on recommended care • Empowers health self-management, more active role Image credit: http://mymedsphr.com

Health social networks Image credit: http://glennamoe.com • Definition • Online health interest communities where members may… • …share demographic and condition-related information • …track treatments, symptoms, and outcomes • …find other similar patients for condition benchmarking • …join collaborative health studies • Physician-focused • Sermo (global), BlogFMC (France+), Good Doctor’s Forum (China), DoctorsNet (UK) • Consumer/patient-focused

Health social networks and collaboration Health social networks Health collaboration communities (global & local) Source: Extended from Swan, M. Emerging patient-driven health care models: an examination of health social networks, consumer personalized medicine and quantified self-tracking. Int. J. Environ. Res. Public Health 2009, 2, 492-525.

Global perspective: culture matters • US: early adopter • UK: public health initiatives • Europe • Regulation, DIY culture, informed, initiative-taking • France (early-adopter, self-responsibility taking)1, Germany (+environment, light footprint, institutional mistrust), Denmark (self-tinkering, self-informed), Italy/Spain (institutional context) • Middle East / South Korea / Singapore • Rapid early adopters, financial resources, less-democratic political regimes • Latin America / Asia / Africa (BRIC) • Straight to health 2.0/genomic medicine; regional leaders in key industries (e.g.; genomic sequencing and interpretation) Image credit: http://www.worldofstock.com 1French National Reference Center for Health Care and Autonomy

Personalized genomics definition • Using genetic sequencing profiles of individuals in health and wellness decisions • Consumer cost = $99 • International availability, 100,000+ subscribers Allele, variant, SNP (single nucleotide polymorphism); “typo” in red; normal in green Example: rs1801133 AGAA, AG, GG Example: rs7412 CTCC, CT, TT Image credit: http://123RF.com

Numerous useful applications of genomics • Established • Ancestry • Carrier status • Identity (paternity, forensics) • Maturing • Health condition risk1 • Pharmaceutical response2 • Novel • Athletic performance capability • OTC product response • Environment/toxin processing • Farther future • Predictive wellness profiling: aging, cancer, immune response Image credit: http://bit.ly/fovpJc 1Source: Swan M. Multigenic condition risk assessment in direct-to-consumer genomic services. Genet Med. 2010 May;12(5):279-88. 2Source: http://www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm083378.htm

1,000,000 SNPs scanned and mapped to 214 conditions Direct-to-consumer genomics: 23andMe Source: http://www.23andme.com; open source genomes http://www.snpedia.com/index.php/Genomes

23andMe colorectal cancer marker Source: http://www.23andme.com

Pathway Genomics drug response Source: http://www.pathway.com

Consumer genomics comparison scorecard • Which service to buy? *Physician prescription required 1Conditions, genes, variants, underlying research references, and methodology white paper(s) available on public website

T T T T T T T C C Open-source mobile apps (5,000+ downloads) • Health condition, drug response, athletic performance capability • Private 23andMe data upload • Android • iPhone “genomics” 4,000+ downloads “genomics” 1,000+ downloads Android development: Michael Kolb, Lawrence S. Wong, Laura Klemme, Melanie Swan iOS development: Ted Odet, Greg Smith, Laura Klemme, Melanie Swan

DIY genotyping kits: Cofactor Bio • Markets: • Research: one-off genotyping • Classroom education • How it works • Select SNPs of interest • Order kit ($20/kit (minimum 4)) • Go through DNA collection, extraction, PCR amplification steps • Send results to lab for sequencing • Check online for results 1Source: http://cofactorbio.com/education

Example: what to do with your data • Check if you have the risk allele for the BDNF gene • Determine related SNP/rsID#, rs6265 (neuroplasticity) • Search genomic data for rs6265 genotype (e.g., CC) • Determine the risk allele (which letter?) (e.g.; G1) • Current genomics search resources • PharmGKB, dbSNP, GWAS catalog, SNPedia Source: http://www.wired.com/wiredscience/2009/10/genetically-bad-driving 1Ribeiro, L. et. Al., The brain-derived neurotrophic factor rs6265 (Val66Met) polymorphism and depression in Mexican-Americans. Cellular, Molecular and Developmental Neuroscience. May 8, 2007.

Finding your BDNF data, variant rs6265 • Consumer genomic services genotype 1 million variants but only map a few up to the annotation browser

Athletic performance Source: http://www.genome.duke.edu/education/seminars/journal-club/documents/Assael_2009.pdf

Athletic performance Image credit: http://www.istockphoto.com V = number of variants; % = ratio of favorable polymorphisms to total alleles for a sample individual; S = number of studies Source: Swan, M. Applied genomics: personalized interpretation of athletic performance GWAS. 2011 . Submitted.

Lung cancer risk and drug response • Risk and drug response for specific cancers Image credit: http://www.xianet.net Source: Swan, M. Review of cancer risk prediction in direct-to-consumer genomic services. (poster) Canary Foundation Early Detection Symposium, May 25-27, 2010, Stanford University, Stanford CA.

Predictive wellness profiling: cancer Image credit: http://utmb.edu • Proto-oncogene/tumor suppressor gene polymorphisms TP53: cell cycle arrest, PTEN: cell cycle progression modulator, MYC: cell cycle regulator Source: DIYgenomics

Wellness profiling: immune system • Immune system genomic wellness profiling • Immune response: T-cell activation • CTLA4, CD226, CD86, IL3 Image credit: http://www.iayork.com CTLA4: T-cell inhibition; IL3: growth-promoting cytokine Source: DIYgenomics

Product and environment genomic profiling • OTC product response, efficacy, and side effects • Skin (anti-wrinkle,1 antioxidant, anti-itching creams, personalized mosquito repellent) • Hair (hair loss treatments) • Esophagus (reflux, bile acid response treatments) • Teeth (periodontitis remedies) • Sleep (insomnia treatments) • Environmental exposure: toxin processing • Benzene • Quinone oxidoreductase • PAHs metabolism • Arylarene metabolism • Mercury and lead exposure • Liver and kidney health (general) Image credit: http://sciencephoto.com Source: DIYgenomics 1 P&G, Kaczvinsky JR et al, Skin Therapy Lett, 2011

Microbiomics Skin microbiome ecosystem distribution • 10x human cells (2 kg, +4°C), 150x genetic repertoire • 15-20 body sites • Skin, eyes, mouth, nose, lungs, GI tract, genitals • Activities: ferment food, produce vitamins, prevent pathogen growth • Influences disease, drug response, nutrient pathways • Compositional and functional analysis Image credit: Grice EA et al, Nat Rev Microbiol, 2011, Figure 3

GI microbiome project: my.microbes.eu • EMBL Heidelberg, 1451 € • Enterotype affiliation1 • Bacteroides (biotin synthesis) • Prevotella (thiamine synthesis) • Ruminococcus (folate synthesis) • Novel promicrobial and antimicrobial treatments • Stimulatory • Inhibitory Science for everyone Enterotype affiliation analysis Image credits: my.microbes.eu 1Source: Arumugam M et al. Enterotypes of the human gut microbiome. Nature. 2011 May 12;473(7346):174-80.

Genome politics and regulation • Our world is not Gattaca • Issues: human cloning, sex selection, genetic privacy, non-discrimination • UN Convention on Human Rights and Biomedicine 1997 (Ch IV Human Genome) • U.S. Genetic Information Nondiscrimination Act (GINA) 2008 • Biocitizenry, health as a basic human right Image credit: http://www.sonypictures.com Image credit: http://sciencephoto.com

Direct-to-consumer genomics trade-offs

Crowdsourced health studies DIYgenomics MTHFR Vitamin B deficiency study1 • Definition: • Research studies that derive participants and data from a large group of people through an open call • Researcher-organized • PatientsLikeMe • 23andMe • Participant-organized • Quantified Self • Genomera • DIYgenomics 1. Genotype profiles 2. Homocysteine levels umol/l Blood Test # C + LMF Baseline Centrum LMF Baseline 1Source: Swan, M., Hathaway, K., Hogg, C., McCauley, R., Vollrath, A. Citizen science genomics as a model for crowdsourced preventive medicine research. J Participat Med. 2010 Dec 23; 2:e20. Results are not statistically significant and intended as a pilot demonstration

PatientsLikeMe studies • Patient-organized ALS lithium study • 2008: 348 initial patients, 149 (2 mos), 78 (12 mos) • No effect found: patient self-experimentation, observational study (149 cases/447 controls) & traditional randomized studies • ALS (amyotrophic lateral sclerosis) • Handedness connection between limb physical activity and disease onset in arms but not legs • Additional items for condition sensitivity measurement scale (motor skills, emotion, mobility) • Low participation in ALS studies due to lack of invitation, enrollment cost concerns & confusion • Comparative research: pathological gambling tendencies (ALS 3%, Parkinson’s disease 13%) Source: Swan, M. Review of Crowdsourced Health Research Studies. 2011. Submitted.

PatientsLikeMe: drug-related studies • Off-label use for amitriptyline (depression) and modafinil (wakefullness-promoting; narcolepsy and sleep apnea) • 40% ALS amitriptyline users unwanted excess saliva reduced • 36% MS and PD modafinil users reported decreased fatigue • Quantifying medication adherence • 36% participation rate from MS community • 16-51% (by treatment) missed one dose in the last 28 days • Patient sentiment per PLM forum discussion • Positive outlook for MS drug Tysabri (natalizumab) despite being linked to 3 cases of progressive multifocal leukoencephalopathy (PML) in 2008 Image credit: http://wdfyfe.wordpress.com Source: Swan, M. Review of Crowdsourced Health Research Studies. 2011. Submitted.

PatientsLikeMe: user experience • Health social network participation (19% response) • Positive reaction, comfort in sharing health data • Uses: learn about symptoms, understand treatments and side effects, make decisions about treatments • Peer benefits of condition benchmarking relative to others • Next steps for improving health social networks • Interpreting unstructured information, managing churning community populations, self-reported data challenges • Examine health social network participation and link to real-world outcomes • Identify and create new tools to further empower health self-management, for example to facilitate patient-organized studies Source: Swan, M. Review of Crowdsourced Health Research Studies. 2011. Submitted.

Future of Health: Overview of Participant-driven Research and Medicine