New Fields of Research Defined by Open Science Visionaries

The purpose of an open-science non-profit research startup like DIYgenomics is research innovation.

The value is in being able to propose a unique and visionary research agenda of questions that are forward-looking and not the focus or interest of the institutional research industry.

Research innovation falls into two tiers:

First is preventive medicine questions, ‘medicine that matters to me’ (e.g.; small groups or individuals), and non-pathologies.

More importantly, the second tier is defining completely new fields of research such as athletic performance genomics, social intelligence genomics, cognitive performance genomics, and DIYneuroscience, and making progress on widespread philosophical and societal problems such as the destigmatization of physical and mental health issues, and the reduction of discrimination as a broad social problem.

DIY open-science, crowdsourced health social networks, and community biohacking labs are the early-stage startup/venture capital arm of the expanding preventive medicine ecosystem of health services, and are able to surface projects of interest that can then be pursued at the institutional level as relevant.

Future of Life Sciences: Top 10 List

The next wave of the biotechnology revolution is underway and promises to reshape the world in ways even more transformative than the agricultural, industrial, and information revolutions that preceded it.

It is not unimaginable that at some point, all biological processes, human and otherwise, could be understood and managed directly.

Here is a top ten list of key areas of contemporary advance in life sciences:

1. Synthetic Biology and Biotechnology 
2. Regenerative Medicine and 3D Printing 
3. Genomics, “Omics,” and Preventive Medicine 
4. Neuroscience 
5. Nanotechnology 
6. Big Health Data and Information Visualization 
7. Quantified Self (QS), Wearable Computing, and the Internet-of-Things (IOT) 
8. DIYscience, Citizen Science, Participatory Health, and Collective Intelligence 
9. Aging, Rejuvenation, Health Extension, and Robotics 
10. Space 

More information: Slideshare talk from the Max Planck Institute

DIY Philosophy: Crowd Models to Democratize Participatory Thinking

The model for computing and info tech exploded with the PC and the Internet – democratizing the field across all strata and making it accessible to any interested individual. The worldwide technology and startup industry has boomed and proliferated as a result. DIY science is doing the same for crowdsourced labor, quantified self-tracking, biology hacking, and the shift to the 21st century health paradigm of preventive medicine. The field of philosophy is ripe for similar democratization – some tip-offs are that it is one of the few remaining areas comprised primarily of white males, and where memorization is still important.

Philosophy Improves Sophistication of Modern Thinking 
Philosophy is the sport of thinking – one of its great benefits is its broad applicability beyond the dusty academic discipline to one’s own personal thinking and lifestyle. A key contemporary use of philosophy is in helping to provide a deeper and more sophisticated means of understanding our fast-paced technologized modern world and our place therein. Many people are interested in philosophy but few have the affordance or interest for full-time involvement which has seemed to have been required given the notorious density and inaccessibility of philosophical works.

Crowd Models Facilitating Philosophy Accessibility 
Crowd models (analogous to the PC revolution) are starting to change the former inaccessibility of philosophy. Philosophy courses and reading groups are popping up at free public universities (the Public School, the University of the Commons), podcasts are acquiring significant listenership, and online communities and publications have growing participatory audiences (e.g.; e-Flux, Plasticities Sciences Arts).

FQXi for Philosophy
While there are some research institutes supporting philosophy like the University of London's Institute of Philosophy, one next step in creating the more overt sensibility of the DIY philosopher as the analog to the DIY scientist and software hacker would be to have Philosophy Research Institutes that specifically promote DIY philosopher participation through essay contests, conferences, and other acknowledgement and community-building activities – an FQXi (e.g.; a research institute encouraging speculative innovation in physics and cosmology) for philosophy is needed.

Venter's Deep Linkage: Microbiome, Synbio, Genomics, and Computing

As usual, Craig Venter’s remarks on April 16, 2013 at UC Berkeley did not disappoint - they were inspirational, informative, and demonstrative of progress. Of note is the multidisciplinarity amongst different branches of his labs’ work, for example using synthetic DNA to perform genomic error correction in stem cell operations, genome transplantation between yeast and bacterial species, and linking microbiome activities to pathology and synthetic biology/biofuel synthesis. Some key points were:

• Microbiome – YASP (yet another sequencing problem) – While the human genome is currently thought to contain about 42,000 genes, the microbiome has 10 million genes across diverse phyla, taxa, and species 
• Biofuel – to obtain engineered algae with the desired phenotype that would be a viable alternative to oil, 300 parameters must be engineered 
• Gene function – even in the minimal genome for Mycoplasma genitalium, there are 50 genes whose function is unknown 
• New gene discovery – so far in general scientific discovery, 80 million genes have been found, 95% from ocean water sampling; again in these ‘design components for the future,’ function is unknown 
• ‘Digital phenotype’ is needed for health advance and big health data stream integration – an extended EMR with standardized transmittable digital data for all manner of phenotypic data, both phenotype 1.0 (e.g.; health history, prescriptions, lab results, etc.) and phenotype 2.0 (e.g.; digital omics profiles like proteomics and metabolomics).

Memory and empathy studies launch on crowdsourced health platform!

Two new health studies organized by DIYgenomics and collaborators have recently launched on the crowdsourcing platform Genomera. One is a memory study: Dopamine Genes and Rapid Reality Adaptation in Thinking and the other is an empathy study: Social Intelligence Genomics & Empathy-Building.

The Genomera platform boasts over 700 community members who are interested in participating in studies. While several of the approximately 30 listed studies investigate genetics as a related component of health, it is not necessary to have data from 23andMe or other consumer genomics services to join the health collaboration community and participate in studies. There are already 40 participants in the memory study and almost 20 in the empathy study.

The objective of the memory study is to see if genetic variants related to dopamine processing in the brain impact the processing of memories. The study is being conducted in conjunction with leading researchers at the Center of Cognitive Neurorehabilitation in Geneva Switzerland. The participation requirements are to complete an online Memory Filtering Task which takes approximately 40 minutes and a short Demographic Survey.

The objective of the empathy study is to confirm and extend research linking genetic profile and social intelligence, specifically whether individuals with certain genetic profiles may have a greater natural capacity for optimism and empathy, extraversion, and altruism. The participation requirement is to complete two short standardized online surveys for empathy quotient and other personality attributes. In addition, there is an optionally available Personal Virtual Coach app for empathy-building, a sort of SIRI 2.0 for mental performance optimization.

Key challenge of our era: health and preventive medicine

Delivering health care and keeping populations healthy is a key problem of the current era. Health expenditures currently comprise 17% of U.S. GDP and are growing; simultaneously health in the U.S. is in decline, with a new CDC report estimating that by 2030, 42% of American adults will be obese, compared to 34% today and 11% will be severely obese, compared to 6% today.

The Realization of Preventive Medicine
A key part of addressing health challenges is the realization of preventive medicine. Preventive medicine and health maintenance consist of identifying and managing conditions in the 80% of their life cycle before they become clinical, ideally avoiding clinical onset. Workable models for the execution of preventive medicine need to be developed. By definition, a broader ecosystem than the traditional medical establishment will be participating in all steps of the value chain ranging from health research to clinical delivery. More flexible regulatory models are needed that preserve the core ethical principles of the traditional models, but are geared towards the internet era and an expanded notion of health and health maintenance with a larger ecosystem of service providers and participants. The payments ecosystem needs to adapt in parallel, allowing for a wider range of payment mechanisms including out-of-pocket payments, H.S.A. dollars, patient advocacy group funding, and traditional (and increasingly diminishing) insurance payments.

Blood Tests 2.0 advances with dried blood spot testing

Moving into an era of preventive medicine and health self-hacking, blood tests 2.0 is an obvious area for expected innovation, moving whole classes of blood tests from $100+ lab-administered arm draws to fingerstick tests conducted at home. One of the most promising techniques for realizing blood tests 2.0 is dried blood spot (DBS) testing. From a biochemistry perspective, the volume of blood taken in a serum draw is not required for many tests; a few drops would be adequate for many tests. Some exciting recent progress in dried blood spot testing was announced with NanoInk’s protein biomarker detection platform, based on dip pen nanolithography, which was used to identify and quantitate four clinically-relevant cytokines. The technology cannot detect everything, but could possibly be used to identify hundreds of proteins, and pave the way for low-cost home blood marker monitoring.

Home-administered fingerstick tests are already available for several markers, although the cost is not necessarily cheaper and a health care professional may still need to be involved. Blood spots from a fingerstick are placed on filter paper to dry and then sent to a lab for analysis. Tests are available for vitamin D, hormone levels (including estradiol, progesterone, testosterone, and cortisol), cardiometabolic markers (including insulin, high sensitivity C-reactive protein, total, HDL and LDL cholesterol, hemoglobin A1c, and triglycerides) from ZRT Labs. Theoretically, dozens of blood tests could be re-invented as fingerstick tests that are self-administered and interpreted in easy diagnostic readers or mobile-phone attached sensors.

Sage Commons Congress drives participatory medicine

The second Sage Commons Congress was held in San Francisco CA April 15-16, 2011. Conceptually an ‘open science,’ ‘data 2.0,’ ‘health 2.0,’ and ‘medicine 2.0’ event, the main purpose was for a variety of working groups to collaborate and outline goals for future work. The open science focal points for the group were data (aggregation, packaging, access, and usability) and public engagement. Of particular note was the launch of a new journal, Open Network Biology, which aims to facilitate experiment reproducibility through improved access to underlying data. The event is summarized here, and conference videos and presentations are available here.

The congress was an example of the growing activity in alternatives to the traditional conduct of health research and medicine, and important as an ongoing collaborative effort between many open health science initiatives. Alternative efforts could become a key partner in traditional health care delivery, particularly in realizing preventive medicine through measurement and intervention while conditions are still pre-clinical. Boutique physicians, health social networks, quantified self health tracking, patient-controlled health records, and patient-organized clinical trials could be important features in the near-term health landscape.

Citizen science genomics

A group of interested citizen scientists came together to explore how they could make their 23andMe personal genomic data actionable. A small (n=7) non-statistically significant pilot study was conducted looking at polymorphisms (e.g.; typos) in SNPs in the MTHFR gene and their connection to Vitamin B deficiency and high (undesirable) homocysteine levels. Four out of seven participants, though healthy, had high baseline homocysteine levels. For five of the study participants, a regular drugstore multivitamin worked best for reducing homocysteine levels. Overall, homocysteine levels were reduced 19%, commensurate with 23% reductions achieved in traditional clinical trials.

This is an important example for two reasons: the preventive medicine model and the crowdsourced research model.

1. This study illustrates one approach to the challenge of preventive medicine. Prospective tracking of genomic data + phenotypic data + interventions could help to establish baseline measures of wellness in large populations, shift health management responsibility to individuals, and potentially prevent or delay the clinical onset of conditions.
   
2. This study shows the value of crowdsourcing citizen scientists for research studies as they increasingly have access to their health information, may be willing to contribute their data to various studies, and have the interest and motivation to investigate conditions of personal relevance.

Paper: Citizen Science Genomics as a Model for Crowdsourced Preventive Medicine Research, December 23, 2010

Citizen scientists innovate research model

It is clear that quantified self-tracking, preventive medicine, and community-based research conducted by citizen scientists could be a huge new industry. The coming era of very large data sets and continuously collected information with algorithmic tools for signal-to-noise interpretation could significantly shift how the baseline measures of health are defined and managed. Citizen science is re-innovating the model for conducting science at every level.

In the traditional research model (Figure 1), there is a principal investigator at an institution, conducting research on subjects, under the purview of an Institutional Review Board, supported by grant funding and publishing results in journals.

Figure 1. Traditional Science Research Model

(source: DIYgenomics - an open platform for citizen science research)

The citizen science model (Figure 2) is different as there is no distinction between investigator and subject, everyone is an investigator and participant; therefore the analog to the IRB is different, perhaps there are citizen ethicists, or a list of FAQs. Funding could come from patient advocacy groups, innovative research foundations, social venture capital, and crowd-sourcing; and research results could be self-published on the web.

Figure 2. Citizen Science Research Model
(source: DIYgenomics - an open platform for citizen science research)

Health 2.0 business models

Health 2.0 is about re-envisioning every aspect of health and health care. New business models are starting to develop to support this innovation ecology. First, accompanying the new paradigm of community research (peer cohort studies à la Patients Like Me (lithium) and DIYgenomics (MTHFR mutation/Vitamin B-12 deficiency), could be social venture finance, corporate sponsorship from supplement companies and other remedy vendors, crowdsourced finance (i.e.; Kickstarter), and philanthropist contributions. Second, the traditional venture capital model is already being applied to health 2.o startup companies, including through organizations such as the Health 2.0 Accelerator. Third, whole new industries may sprout from the nascent efforts of health advisors and wellness coaches. The health advisor is the analog to the financial advisor or mortgage broker, able to integrate a client's health data streams, needs, and interests with available offerings, across a spectrum of economic models: insurance reimbursable, HSA dollars, and direct out-of-pocket spending.

Individuals to drive personalized medicine era

The Personalized Medicine World Congress held January 19-20, 2010 in Mountain View, CA was one of the first business conferences devoted to personalized medicine. There is a lot of excitement about personalized medicine and genomics given some recent announcements regarding whole human genome sequencing. First, Complete Genomics reported the costs of consumables (required chemical reagents), dropping to $4,400, and even $1,500 (Supporting Online Material page 27) per genome. Illumina similarly announced dramatic price drops, an estimated all-in cost of $10,000 per whole human genome with the new HiSeq 2000 machine. Illumina currently charges individuals $48,000 for whole human genome sequencing. The HiSeq 2000 is priced at $690,000 per machine and BGI (formerly the Beijing Genome Institute) has ordered 128.

Complete Genomics’ CEO Cliff Reid made an interesting point that despite genomic sequencing having been progressing at 10x improvements per year since 2006, theoretical limits are starting to be reached and the industry will probably return to regular Moore’s Law progress curves (18 month performance doublings). While third-generation sequencers such as Complete Genomics (using a short-read sequencing-by-probe-ligation technology) and Pacific Biosciences (using a single-molecule real-time sequencing by synthesis technology) may start to reach limits, fourth-generation sequencers using other technologies such as nanopores (e.g., Oxford Nanopore Technologies), and electron microscope imaging (e.g., Halcyon Molecular, ZS Genetics), may be able to keep the sequencing industry progressing at faster-than-Moore’s-Law rates.

The most hopeful comments came from Esther Dyson and Leroy Hood. Esther Dyson, pointing out the still heavy focus on health institutions rather than consumer-empowerment for transformation to the personalized medicine era said that she felt like she was “representing the PC world at a mainframe convention.” Directly paralleling the current medical system, she also noted that when Gutenberg arrived with the printing press, the priests said ‘there’s no reason people need to read the bible themselves, we can read it for them.’ However, as shown in Figure 1, personalized medicine is about wellness, not disease, and while there are certainly overlaps with the current domain of physicians, there may be minimal encroachment due to automated tools and new health ecosystem participants such as wellness advisors.

Figure 1. Wellness becomes the domain and responsibility of the individual

Leroy Hood set forth a detailed plan for the future of medicine, P4 Medicine: medicine that is predictive, personalized, preventive, and participatory. Looking for the fingerprints of health vs. disease, he envisions a future where billions of data points are investigated per individual. There could be at least four relevant data sets. One data set is the whole human genome sequence. Another could be a biannual wellness screen for 2,500 blood-based organ-specific proteins indicating possible precursors to disease. A third data set could be an immune system screen of the 10,000 B cells and 10,000 T cells, looking at the functional regions of immune receptors, and past and preset immune responsiveness. A fourth data set, in the instance of cancer, could be taking a single cancer call and sequencing 1,000 transcriptomes simultaneously to understand how cancer is expressed in particular individuals. These data sets could help to realize medicine as an information science and address the specificity of disease and wellness in individuals.

Preventive Medicine and Docs vs. Genomics

Despite NIH Director Francis Collins’ strong support of personalized genomics (he claims he lost 15 pounds after finding out through direct-to-consumer genetic testing that he is at higher risk for Type 2 Diabetes) and noting that the only way to successfully transition to the genomic era is with a skilled professional work force, doctors are taciturn about embracing genomics, and rarely try it even when it is made available to them and their patients for free (less than 5% uptake in a recent example with El Camino Hospital and DNA Direct making genomic testing available to 1000 physicians).

Top 10 reasons doctors will probably not be the ones implementing genomic data in patient care, in rank order. Physicians...

1. think they have to be the domain experts of any health area they direct for patients and are too constrained, unwilling or unable to be a genomics domain expert
2. do not see the clinical utility of genomics
3. have the attitude that genomics is optional, not required
4. have a precedent for non-adoption of preventive medicine tools as evidenced by slow uptake of molecular diagnostics
5. driven by liability, malpractice fears
6. self-direct per insurance non-reimbursability
7. believe genomics overconsumes scarce medical resources
8. are already cost, time, new knowledge acquisition constrained
9. are resistant to change and enjoy autonomy in directing their own practices
10. do not have specific tools for implementing genomics in their practices

Number one reason physicians would adopt genomics:

1. if their peers did

Physicians are intelligent and could easily adopt genomics
In reality the way that genomics adoption unfolds in the traditional health care system could be straightforward. Once regulated, physicians would have no choice but to adopt. Whole human genomes would be on file in patient Electronic Medical Records (EMR) and genomics tests could be a few more items on the standard blood test menu where primary care physicians interpret results within quantified ranges. Even though physicians are spending on average only 12 minutes with each patient per year in the US, they are required to spend 100-200 hours per year on Continuing Medical Education, and being quite intelligent, could easily master the basics of delivering genomic medicine.

Best quotes from the September 2009 National Coalition for Professional Education in Genetics (NCHPEG) meeting:

• “Not only is genomic data useless, educating physicians about genomic data is useless”
• “Learning about genomics might be useful to my practice, so would speaking Spanish, but I’m not going to do it”

Solution: new care provider tier for Preventive Medicine

The disincentives to physician adoption of genomic medicine are really part of the bigger issue of how societies are going to shift to preventive medicine in general.

The traditional health care model of physicians and insurance companies is probably not going to deliver preventive health, a new tier of care providers, entrepreneurs, is.

Figure 1. Future Health

Image: MS Futures Group, Oct. 2009

A model for the future of health care is presented in Figure 1. The patient is at the center, increasingly taking responsibility for managing their own health. Easy-to-use tools, both devices and web-based software, could provide the first shell of actionable health information to individuals. Over time (decades), there is no reason that the primary care provider could not be superseded by automated health monitoring tools.

New Era Preventive Care Specialists: the Health Advisor
The next preventive medicine shell is the new tier of health care providers. When consumers say “I have my genomic data, now what?” traditional doctors say, “I have no idea what to do with that” or “That is not clinically useful,” but the New Era Preventive Care Specialists do not. They show what to do with personalized data by using genome-in-the-cloud browser tools to make genomic data intelligible and actionable. They incorporate genomic data, together with family history and current phenotype and biomarker data into an overall care plan (when is Keas finally going to launch? what about Omicia?), with a systemic approach (when will Entelos license their virtual patient technology to consumer-pointing applications?).

The Health Advisor (analagous to the Financial Advisor) could be one of the fastest growing new job areas. The business model may be traditionally trained experts in general medicine, genomics, nutrition and sports medicine coming together in private clinics to work in the new paradigm of exploding volumes of digitized health data (both health metrics collected daily and genomic, transcriptomic, etc. data) together with EMRs. One first service could be EMR assembly where patients own and control the data. Other services could include all manner of personalized health plan creation and monitoring. Anti-aging treatments would be another logical area for inclusion.

Health Savings Account (HSA) Dollars
Accustomed to the third-party pay model, consumers may object to paying for medical services (although they do shell out several billions of dollars per year for weight-loss products) but instead of paying directly out-of-pocket, it is quite possible that preventive care services could be purchased with pre-tax HSA dollars, as more than half of U.S. large-company plans may be offering as an insurance option. This marketing point that should not be lost on the new era of preventive health providers.