Broader Perspective

Ubiquitous information technology fields

2009-11-08T10:36:00.001-08:00

The broadest thematic point in futurist Ray Kurzweil’s opening keynote at Singularity University on November 6, 2009 was that once any area becomes an information technology, it starts conforming to the exponential curves of Moore’s Law progress that have defined the computing and communications industries since 1900 or earlier.

Health is well on its way to becoming an information science with genomic sequencing and synthesizing, bioinformatics and continuous automated biomarker capture. Energy is starting to be an information science with the smart grid, essentially an electron routing network allowing on-demand ingress and egress of diverse flows. Many other fields could behave in the networking and packet-routing metaphor, directing fungible quantized resources to where they are needed and requested like people in driverless cars, neurons in a brain, clean air and water molecules, disease management and health care delivery. Since demand varies, market principles could be used for unobtrusive resource allocation in automatic markets that meet and transact per digitally-inferred demand profiles and pre-specified permissions.

All science is in some phase of becoming or has already become an information science in the sense of using computational models, simulation and informatics.

With computation and communication becoming increasingly embedded in every manufactured object, it is obvious that many more if not all fields could become information technologies.

Intelligence, for example, is becoming an information science. With the exponential growth of computing, it is likely that at some future point, machine intelligence could surpass that of humans. One path forward is to reengineer life into technology that can keep pace with technological advances. There are already three dimensions of progress towards this goal: understanding the existing examples of the brain through neuroscience, simulating and building de novo intelligence in software and robotic forms and integrating human and machine capabilities with brain-computer interfaces, creating the biomolecular interface of integrating organic and inorganic material.

Social sciences
The question arises about how seemingly subjective and nuanced fields like politics could become information sciences. In the short term this is already happening with citizen journalism and collective organization through social networking (examples: flashmob protests and Twitter Iran election feedback). In the longer term, it is imaginable that political artificial intelligences, pleasantly absent the agency problem and special interests of human politicians, could start to perform low level political tasks and over time be used to a much larger degree in policy formation, public resource allocation and administration of nation state affairs.

Synthetic biology enables green petroleum

2009-11-01T06:25:00.000-08:00

The good news about the number of worldwide vehicles, approximately 1 billion at present and expected to double in the next few decades, is the number of fossil fuel alternatives feverishly underway, many of which have established pilot projects and are expected to launch in selected commercial markets in 2011.

Synbio enables green petroleum

The current killer app of synthetic biology, the programming and engineering of biology, is green petroleum.

Several companies are developing improved versions of fossil fuels which can be easily substituted into the existing worldwide fuel infrastructure for autos, planes, etc. at approximately the same cost of fossil fuels (oil is presently $80 per barrel). Pilot plants are underway and commercial introduction is expected in 2011. Sapphire Energy and Synthetic Genomics are working with algal fuel, ramping the highly efficient natural process of algae creating petroleum through photosynthesis.

Other companies such as Amyris Biotechnologies are using synthetic biology to generate ethanol, and LS9 is synthesizing carbohydrates into petroleum with designer microbes. In the farther future, late-generation biofuels are contentious but already being envisioned by companies like Craig Venter’s Synthetic Genomics, employing carbon dioxide (CO2) as a feedstock for bacteria to convert into methane using molecular hydrogen as the energy source.

Green petroleum vs. electric vehicles
There may be less of a competition between transportation fuel alternatives and more of a market suitability analysis governing which choices arise in which areas. Large markets like the U.S. are already showing signs of both, or all, alternatives arising. Markets and countries with other parameters such as smaller size, increased government involvement and more stringent emissions regulations my make a strategic commitment towards certain choices, for example an interesting train and EV-sharing program announced in Denmark.

International electric vehicle leader Better Place notes that the ‘Goldilocks’ markets for greenfield electric vehicle networks are countries that are not too big to risk the introduction of such a disruptive solution and not too small such that economies of scale would not work. The poster child market for the company is Israel, with has networks of charging stations already installed in Tel Aviv and plans to build another 100 in Jerusalem for the mass availability of electric cars in 2011.

Role of B.S. in Advanced Society

2009-10-25T07:14:00.000-07:00

B.S. is a deeper philosophical topic than it might seem at first glance. Two interesting books contemplate the matter: B.S. and Philosophy (2006) and On B.S. (2005).

What is the role of B.S. in advanced society? Since it exists, it must have some role, possibly related to conflict reduction and social lubrication. A second reason for B.S. could be the complex values hierarchies in which individuals and societies operate. Social pressure and belongingness may trump truth as values. When someone is asked a question, the presupposition is that he or she may be able to answer and the inclination of the person asked is to try to respond even if a misrepresentation, e.g.; B.S., occurs.

These authors and others agree that B.S. has proliferated from the past to the present. Given that, what could be said about the future, is B.S. likely to increase or decrease? In the short term it will probably continue to increase but could then be reduced in the longer term with the advent of more advanced technology.

Personalized hypertargeted B.S.
On one hand, technology is increasing the detectibility of B.S., suggesting that B.S. could go down in the future. On the other hand, information is continuing to explode, providing more potential venues for B.S., suggesting that B.S. could go up in the future. B.S. is like spam or commercials, growing, but simultaneously control mechanisms are also growing to mediate interactions. Although B.S. could be more insidious, less detectible and even desirable when it is highly personalized and hypertargeted such as marketing is starting to be now.

Politicians replaced by Artificial Intelligences
Considering fields ranging from science, with a zero-low tolerance for B.S., to politics, with a high tolerance for B.S., it is possible in the future that it would be desirable to replace people in high-B.S. professions with Artificial Intelligences. This would solve the agency problem and special interests control overnight. Policy debates could be resolved by running a million different permutations via virtual simulation varying every parameter of a given policy change such that overall utility is maximized.

Affinity Capital

2009-10-18T09:03:00.000-07:00

A key concept in the 2.0 Economy is affinity capital. Deeper levels of information about every economic transaction are starting to be available such that individuals, businesses and communities can be very specific in directing and democratizing their capital. In many cases, products can be chosen that are organic, recyclable, fair trade, made from sustainable materials and made by companies with fair labor practices or whatever affinities or attributes the buyer cares about.

Affinity-directed capital can influence both cash inflows and outflows. Affinity inflows are the money earned. Earners can now be more selective by checking Corporate Social Responsibility reports if thinking of working for large companies, by being entrepreneurs and contractors, finding projects on website marketplaces like TopCoder (software programming), oDesk (professional services) and 99 designs (graphic design) or by having clients seek them directly through their web activities and content. A taxonomy of affinity capital marketplace links is available here.

Affinity capital influences capital outflows too: investing, donating and purchasing. In investing, socially-responsible investing (SRI) mutual funds have been available for several years, and now peer-to-peer lending and social venture capital platforms allow investors to direct capital into these asset classes too. Philanthropy is merging with investing in cases like Kiva where investors find a lower or blended financial return is acceptable when social outcomes can also be achieved. The SocialCapitalMarkets conference has continued to draw several hundred worldwide social entrepreneurs to talk about how to bring social change with economic transactions at their annual September conference in San Francisco. The organization also sponsors The Hub, twelve worldwide physical spaces for social capital markets collaboration.

Affinity purchasing, voting with dollars based on product attributes, is another way of democratizing capital as consumers and businesses check websites like ClimateCooler, the Fair Trade Federation and others to see how socially and environmentally friendly products are before buying or purchasing directly from green product websites like GreenHome or other affinity-based marketplaces.

Socially-responsible and environmentally-friendly are some of the biggest affinity attributes but the key point is that deep attribute knowledge means that capital can be directed granularly to ANY affinity attribute.

FutureThink: the Mindset of the Future

2009-10-11T09:26:00.000-07:00

To think strategically about the future, it is necessary to realize that the mindset of today may be outdated for appropriately contemplating the future. The inadequacy of current human minds is sometimes given as a possible reason that humans may not be able to understand the full physics of the universe (multiple dimensions, multiple universes) or design artificial general intelligence.

One technique to improve the current mindset is to try deriving future intellectual norms from historically trending principles.

There are other examples of this concept. Successful athletes do not move to where the ball is now but where it is going to be. Ray Kurzweil exhorts not to invent a future object based on today’s technology, but rather where the technology will be in the future.

Three key principles and one meta-principle are discussed below.

1. Increase in humaneness: The first historical principle that can be identified is an increase in humaneness. Over time, there are new tiers of behavior that are deemed inhumane and become unacceptable. For example, slavery was acceptable in past eras but is not now, many societies have moved away from capital punishment and diminished discrimination is ongoing. Some contemporary issues are the rights of homosexuals, and noise and light pollution. In the future, it could be seen as inhumane to keep people waiting, or bored, or under-actualized, or without personalized-temperature control, or exposed to air pollution or disease toxins emitted by others.

Medicine and dentistry are obvious fields of increased humaneness. Today state-of-the-art treatment from 100 years ago seems primitive and barbaric. When seen from the lens of the future, it is easy to contemplate a time where people would be shocked to be operated on with a knife; we are already starting to see this now as da Vinci robotic surgery is 90% less invasive than traditional methods.

2. Increase in choices: A second historical principle is an increase in choices. For example, in music, with the advent of records, industry insiders were afraid that people would stop listening to the radio, however there was a boom in both as they reinforced each other and expanded music-listening as a category. If a new concept provides value, it helps to refine, stratify and expand the whole market. Contemporary examples are TiVo, YouTube and free e-books spurring traditional sales.

3. Decrease in limitations: The third idea is related to the second, not just are there more choices but there are new choices. For example, population growth may be a problem if only certain areas of the Earth can be inhabited and if resources are constrained, but FutureTech may open up living in places that were formerly uninhabitable (for example, the Seasteading Institute is investigating the feasibility of water-based settlements). Resources could become more abundant such as is happening now with solar and wind energy and the possibility of repurposing of cellulosic plant waste for fuel or food with synthetic biology. A significantly higher population could be supportable on Earth. Today’s constraints will not be tomorrow’s constraints.

Meta-principle: Abundance
These three principles, increase in humaneness, increase in choices and decrease in limitations are all aspects of the overarching principle of abundance. With abundance, there is more in every dimension, not a world of either/or scarcity. For example, a classic futurist thought experiment is whether someone would forsake their embodied form by uploading their mind to a computer. This is a perfect example of the fallacy of applying current thinking, e.g.; today’s resource scarcity mindset, to future scenarios. A future seems much more likely where many options would be possible. People may have many digital backup copies of their mind files, possibly multiple copies engaging in different activities, as well as one or more embodied forms, rather than an either/or choice of identity representation. An increase in options in existing and new possibility spaces, physical, intellectual, emotional and philosophical, is the hallmark of abundance thinking about future scenarios.

Preventive Medicine and Docs vs. Genomics

2009-10-04T07:06:00.002-07:00

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...

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
do not see the clinical utility of genomics
have the attitude that genomics is optional, not required
have a precedent for non-adoption of preventive medicine tools as evidenced by slow uptake of molecular diagnostics
driven by liability, malpractice fears
self-direct per insurance non-reimbursability
believe genomics overconsumes scarce medical resources
are already cost, time, new knowledge acquisition constrained
are resistant to change and enjoy autonomy in directing their own practices
do not have specific tools for implementing genomics in their practices

Number one reason physicians would adopt genomics:

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.

Status of Stem Cell Research

2009-09-27T07:31:00.000-07:00

The World Stem Cell Summit in Baltimore MD held September 21-23, 2009 attracted several hundred professionals to discuss contemporary science, industry and societal perspectives on stem cells. Attendance was high, but down from last year and, similar to cancer meetings, a key theme several keynote speakers acknowledged was

the overall lack of truly meaningful progress in stem cell research in the last twenty years.

Science Focus: Safe Stem Cell Generation
The science tracks featured current research in different stem cell areas including the production of safe hESC (human embryonic stem cells) and iPS (induced pluripotent stem cells) for use in regenerative medicine, the research and therapeutic use of mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) and reports from specific sub-fields: cancer stem cells, cardiovascular stem cells and neural stem cells. Overall, the work presented was incremental and in many cases, confirming what has been known already, such as a growing confirmation that cancer stem cells are probably responsible for triggering the resurgence of cancer but cannot at present be distinguished from other cells at the time of tumor removal.

Contract Research Demand: Cell Therapies and Recombinant Proteins
One stem cell area experiencing growth is contract research organizations, the outsourcing tool of choice for research labs and pharmaceutical companies in the production of biological materials. For large contract research manufacturing such as Basel, Switzerland-based Lonza, the biggest demand area is in cell therapies. Cell therapies denote the introduction of any type of new cell into other tissue for therapeutic purposes, but in the current case generally means any variety of stem cell-based therapies. Other large contract research manufacturing organizations such as Morrisville, NC-based Diosynth (owned by Schering Plough) lead in biologics (antibodies, protein production) production, an important area for nextgen biotech where synthetic biology could have a big impact.

For smaller contract research manufacturing organizations producing test compounds (e.g.; 1 liter for $10,000) and scaling to Phase I and II clinical trial quantities such as Baltimore MD-based Paragon Bioservices, the biggest demand is for recombinant proteins. Recombinant proteins are created by inserting recombinant DNA into a plasmid of rapidly reproducing bacteria and can take many useful forms such as antibodies, antigens, hormones and enzymes.

Venture capital hot topics: zinc fingers, RT PCR, tech transfer
Zinc fingers (small protein domains that bind DNA, RNA, proteins and small molecules) have been surfacing in a variety of cutting-edge biotech innovations. In July 2009, St. Louis, MO-based biotechnology chemical producer Sigma-Aldrich (SIAL) announced the creation of the first genetically modified mammals using zinc finger nuclease (ZFN) technology to execute modifications such as taking away the tail of the zebrafish. A second example of recent landmark research involving zinc fingers is that of Carlos Barbas at Scripps who uses zinc finger proteins to reprogram serine recombinases as a more specific alternative to the homologous recombination method of genome modification. In addition, the Barbas lab has a useful web-based zinc finger protein design tool available for public use, Zinc Finger Tools.

Real-time PCR offerings continue to expand and flourish with declining prices as startup newcomer Helixis announced a $10,000 real-time PCR solution at the conference.

Bethesda, MD-based Toucan Capital, a leading investor in stem cells and regenerative medicine discussed their sixteen interesting portfolio companies such as San Diego CA-based VetStem who is conducting joint and tendon stem cell therapies for race horses.

Johns Hopkins has one of the country’s leading technology transfer programs, licensing a growing number of technologies each year (nearly 100 in the last fiscal year), and has a searchable, though not extremely user-friendly, website.

Personalized genomics inflection point

2009-09-20T07:27:00.000-07:00

One of the world’s fastest accelerating technologies is that of genomic sequencing. The first whole human genome (6 billion base pairs) was sequenced at a cost of $3b and was completed in 2003. The current cost is $20,000 for researchers (Complete Genomics) and $48,000 for consumers (with Illumina’s EveryGenome program). Leading third-generation sequencing company Pacific Biosciences affirmed at the Cold Springs Harbor Laboratory Personal Genomes meeting September 14-17, 2009 that the company has 12 prototype instruments in operation and continues to be on track for ~$100 (“the cost of a nice dinner”) whole human genome sequencing to be commercially available in the second half of 2010. NimbleGen indicated that they may have a $2,000 exome sequencer available in 2010.

In a challenging venture capital climate, Pacific Biosciences was able to close an additional $68m round in financing on August 12, 2009. Leading commercial sequencer Complete Genomics was also notable in closing a $45m D round on August 24, 2009. The company has sequenced 14 whole human genomes to date, and hopes to sequence exponentially more, 10,000, in 2010 at a minimum cost of $5,000 per genome.

Viability of DTC genomics sector
Where the genomics technology sector has rosy prognostications, the direct-to-consumer personalized genomics market has volatility. Events in the last several months have led to questions of the sector’s viability with upheavals at the three leading companies, 23andme (“Avey Leaves 23andMe to Start Alzheimer's Research Foundation Using DTC Genomics Firm's Platform"), deCODEme (“deCODE close to broke” – Augusty 11, 2009) and Navigenics (“Navigenics Names Jonathan Lord, MD to Serve as President and Chief Executive Officer” April 7, 2009). Absent innovation, DTC genomics companies are a “window business” in the sense that the window for their current offerings may only be open for a short time with the advent of whole human genome sequencing and standardized public multi-SNP condition interpretation tools.

Figure 1. Direct-to-Consumer Genomics Offerings: ongoing price declines (Chart PDF)

As depicted in Figure 1, there are three types of Direct-to-Consumer (DTC) genomics offerings currently available directly to individuals: one-off SNP (single nucleotide polymorphism) tests for specific conditions and paternity tests, multi-SNP risk assessment tests mapping several SNPs to dozens of disease conditions and whole human genome sequencing assessing hundreds of disease risks. The five companies offering multi-SNP risk assessments are: 23andme ($399 for 111 conditions), deCODEme (42 conditions for $985), Navigenics (28 conditions for $999), Gene Essence (84 conditions for $1,195) and Pathway Genomics (77 conditions for $249). 23andme, deCODEme and Navigenics are the most transparent, disclosing the specific SNPs, research references and risk assessment methodologies for their tests, Gene Essence discloses SNPs and Pathway Genomics does not disclose anything. A detailed condition and SNP analysis is here.

Slow DTC genomics adoption
DTC genomics has had slow adoption so far for several reasons, first, there has been very little marketing, few consumers know of the availability and value proposition of DTC genomics services. Second, since automated tools are not yet available, many people are not interested in preventively managing their health, and may still perceive it to be in the responsibility and domain of health care professionals. Third, the conventional but incorrect view is that genetic information is already known (from family history), negative and deterministic. Fourth, as initially pointed out by ExperimentalMan David Ewing Duncan, there are conflicting interpretations from DTC services for the same conditions such as heart attack. This is because the scientific community has little knowledge and agreement yet regarding multi-SNP conditions. DTC companies are looking at different SNPs, assigning different quantitative risk values and employing differing estimates of overall population averages which all contribute to heterogeneous interpretations of risk for the same condition.

VC guide to anti-aging biotechnology investing

2009-09-13T04:43:00.000-07:00

Several promising startup companies focused on the nascent but obviously significant and growing anti-aging biotechnology space were present or discussed with interest at the recent SENS4 (Strategies for Engineered Negligible Senescence) conference in Cambridge, U.K., September 3rd – 7th, 2009 (program) (full conference report).

Epeius Biotechnologies, San Marino, CA, USA: Rexin-G, a tumor-targeted injectable gene delivery system
FoldRx, Cambridge, MA, USA: small molecule therapeutics to treat protein misfolding diseases, and bind and clear undesired molecules
Gencia Corporation, Charlottesville, VA, USA: mitochondrial DNA rejuvenation using the rhTFAM (recombinant-human mitochondrial transcription factor A) protein
Genscient, Fountain Valley, CA, USA: novel chronic disease therapeutics by combining genomics and selective screening (a large Alzheimer’s Disease genetic study is in progress with Kronos and TGen)
Knome, Cambridge, MA, USA: whole human genome sequencing (consumer offering)
Neotropix, Malvern, PA, USA: oncolytic viruses for the treatment of solid tumors
Pentraxin Therapeutics Ltd, London, UK: small molecule drug CPHPC specifically targeting SAP (serum form of amyloid P) and removing it from the blood and brains of patients with Alzheimer’s Disease
Repeat Diagnostics, Vancouver, BC, Canada: telomere length measurement for total lymphocyte and granulocyte populations (consumer offering)
Retrotope, Los Altos Hills, CA, USA: using isotope effect to slow down damage pathways and control metabolic processes associated with oxidative stress
StemCor Systems, Inc., Menlo Park, CA, USA: bone marrow harvesting system
T.A. Sciences, New York, NY, USA: telomerase activation via the single molecule TA-65, licensed from Geron Corporation (consumer offering)
TriStem Corporation, London, UK: retrodifferentiation technology to create stem cells from mature adult cells

So discontinuous a discontinuity

2009-09-06T04:10:00.000-07:00

A key aspect of thinking systemically about the future is being able to see how rapidly advancing technologies across many fields interrelate. Whatever next Internet-like discontinuity or singularity occurs will influence whatever comes thereafter. It is likely that some high percentage of what are now thought to be expected future advances will recede or be reshaped at minimum, for example:

If all chronic disease and aging becomes controllable and there is effective immortality, does uploading matter as much?
If artificial general intelligence is achieved, how does that change the exigency and requirements of molecular nanotechnology?
If affordable space launch and space-based solar power is achieved, what happens to ethanol, electrical and other terrestrial alternative vehicle and transportation infrastructure solutions?
If immersive virtual reality and post-material scarcity are achieved, does molecular nanotechnology matter and what happens to global political systems?
If whole human genome testing is available, do single SNP tests go away? If there are home health monitors and nanodiagnostics, do primary care physicians go away?

Real-time unified search

2009-08-30T09:59:00.000-07:00

It is surprising that a unified search application across different types of web content does not yet exist.

According to OneRiot, 40% of web searches at present are for real-time content such as that from Twitter, FaceBook, PeopleBrowsr, digg, bookmarking sites, blogging and microblogging sites (friendfeed, etc.).

Megafeed
One vision of a unified search 'megafeed' app would be a customizable html page with search across many types of web content, automatically updated and delivered together or organized into categories such as events, articles, comments, people, etc. The types of web content to search would be:

Traditional web search: Google, Bing, etc., which could be more richly granularized with content-tagging per a variety of parameters such as information type (news, blog, video, book, event, etc.), time (time added to web, time of occurrence), original vs. subsequent post and other distinctions.

Real-time web search: The emerging real-time content search engines should be extended and unified into one digital social interaction feed for Twitter, FaceBook, LinkedIn, bookmarking, email, blogging, microblogging and possibly IM/SMS notification AND response. User-permissioned credentials can be browser-stored for such a unified action platform. In addition to usability, the fast-growing real-time web search companies are also focused on monetization, ~~reinventing~~ generating AdSense-like models.

Local search: New restaurant and retail notifications, events, craigslist and other commercial postings of interest, friends traveling to the area (links to feeds from GeckoGo, Dopplr and other travel social networking and public calendaring websites).

Academic search: notification of new papers, articles or news. Federated PubMed, ArXiv-like journal portals are needed for all academic fields, including economics and liberal arts.

Multimedia search: notification of non-text postings of photo, music, podcast and video content.

Content demand mechanisms: ambience to supersede keywords

Content could be searched by the usual user-entered keywords or a deeper variety of content demand-interaction mechanisms could be developed, for example, permissioning-in by users such that ambient profiles from hard-drive content and previous web interactions automatically form and evolve (a precursor to pre-AI web interactions).

Automatic Markets

2009-08-23T09:34:00.000-07:00

At Singularity University, one of the most pervasive memes was the “routing packets” metaphor; that many current activities are just like routing packets on the Internet. This includes areas such as people in driverless cars, electrons in electric vehicle charging and power entry, load-balancing, routing and delivery on smartgrid electricity networks.

Fungible resources and quantized packet-routing
The packet-routing concept could be extended to neurons (routed in humans or AIs), clean water, clean air, food, disease management, health care system access and navigation, and in the farther future, information (neurally-summoned) and emotional support (automatically-summoned per human dopamine levels from nearby people or robots). It is all routing…directing quantized fungible resources to where they are needed and requested.

Automatic Markets
Since these various resources are not uniformly demanded, the idea of markets as a resource allocation mechanism is immediately obvious.

Further that automated, or automatic markets with pre-specified user preferences, analogous to limit orders, could be optimum. Markets could meet in equilibrium and transact, buying, selling, and adjusting automatically per evolving conditions and pre-programmed user profiles, permissions, and bidding functions.

Truly smart grids would have automatic bidding functions (as a precursor to more intelligence-like utility functions) that would indicate preferences and bid and equalize resource allocation, the truly invisible digital hand.

The key parameters of a working market, liquidity, price discovery and ease of exchange would seem to be present in these cases with large numbers of participants and market monitoring and bidding via web or SMS interfaces. The next layer, secondary markets and futures and options could also evolve as an improvement to market efficiency, if designed with appropriate incentives.

Automatic markets are not without flaw, they exist now in traditional financial markets, causing occasional but volatile disruptions in the form of quantitative program-trading (blamed for exacerbating the 1987 Black Monday stock market crash) and flash-trading. Speculative aspects are not trivial and would be a critical area for market designers to watch, particularly managing for high liquidity and equal access (e.g.; faster Internet connections do not matter).

Markets to grow as a digitized resource allocation tool
At present, markets are not pervasive in life. The most notable examples are traditional financial markets, eBay, peer-to-peer finance websites and prediction markets. Being in a global digital era with the ability to use resources in a more fungible and transferable way could further promulgate the use of markets as a resource allocation tool.

A focus on preference rather than monetary value, and other currencies such as attention, authority, trust, etc. could vastly extend the range of implementation of market principles.

iPhone Biodefense App

2009-08-16T11:02:00.000-07:00

Right now it would be nice for people to be able to perform a detailed inspection of whatever environment they are in, and of themselves internally. As the future evolves, it could become an exigency. Portable personal biosensing devices for biothreat defense and medical self-diagnosis could become de rigueur, most logically as an extension of current mobile device platforms.

Hardware Requirements:

Integrated Lab-on-a-chip module with flow cytometer, real-time PCR, microarray and sequencing unit (genome, proteome, metabolome, lipidome, etc.)
Disposable finger-prick lancets

Software Requirements:

Data is collected and perhaps digitized locally, then transmitted for processing and interpretation via web services

What is the current status of the iPhone Biodefense App?

A. Order online
B. DIY with components from Fry’s
C. Have a roadmap, getting supplies and building tools
D. Homesteads and landgrab available to pioneers
E. “Ahead of the science,” aka it’s always 20 years out!

Answer: C. Have a roadmap, getting supplies and building tools
Single-cell identification, extraction and genotyping is starting to be possible from a research perspective (ex: Love Lab, MIT). Lab-on-a-chip functionality has been miniaturized (e.g.; small flow cytometers, small PCR machines). Now the trick is to integrate and add features to these systems, extend the functionality, shrink them further and reduce constraints. Microarrays and sequencing also have several innovation cycles ahead.

Key constraint: time
In addition to moving down the cost curve (most relevant for sequencing), performance time is the key constraint. Substances, expressed genes, blood biomarkers, etc. can be detected but it is taking hours and days when it needs to be immediate.

Declassify custom biodefense microarrays
Lawrence Livermore National Laboratory has one of the most advanced biodefense labs in the country. Custom microarrays have been developed for government agencies that the lab would now like to transfer into the public health domain. This could revolutionize and hasten commercial biosensing applications much like the declassification of adaptive optics revolutionized astronomy. At least three custom microarrays have been developed:

Microbial Detection Array: identify what a substance is
Virulence Array: identify how much damage a substance could do
Microbial Defense Genotyping Array: identify SNPs, indels

Open Global Courseware

2009-08-09T13:03:00.000-07:00

The U.K., long an adopter of surveillance technology, announced recently that high-definition CCTV cameras from Classwatch have been installed in 94 schools. The result has been improved classroom management and there are plans to install hundreds more cameras nationwide in primary and secondary schools.

Free global education resource
With minimal effort, this internal surveillance initiative could be expanded into a worldwide sousveillance victory. A global education resource could be generated by broadcasting and archiving the live feeds to the web for access by teachers and students worldwide in their own classrooms and via cell phones. This is essentially an extension of MIT’s open courseware concept.

Language imperialism and the return of the British Empire?
The U.K. might briefly enjoy the notion of re-establishing the British Empire by exporting English-language education, but

language is becoming more fungible over time

The issue of language imperialism could be avoided with the use of audio translation tools (Google Translate – audio version?) and by opting in CCTV broadcasts from schools in other countries. The pilot project phases could be U.K. transmissions targeted at India and Beijing, etc. transmissions targets at rural Chinese schools.

PenPal 2.0 flattens the world
Classroom broadcasts could quickly become interactive with commenting and messaging on the streams. Students worldwide could get to know each other and work on team projects together in virtual world classrooms like Second Life’s Teen Grid; a multi-dimensional PenPal 2.0. Students in India could come up with ideas to work on problems in the U.K. by interviewing British students and vice versa. Teacher and student exchange programs could arise. Students could vote on the curriculum.

The real way to raise test scores would be to have live head-to-head competitions between different schools in a district, country or around the world (“The class in Chennai did 5% better….”).

Local community engagement tool
Internet broadcast could also enable the local community. Parents could tune in to their children’s classrooms (“Mom, did you see what I did around 10:30?”…”What happened at school today?” “Mom, just watch the feed archive…”). The social networking dimension could deepen student, teacher and parent interaction as many are already managing homework assignments colaboratively on the web.

American Idol Teacher: injecting abundance
Classroom broadcast could bring more abundance to teaching by providing acknowledgement (whuffie) for good teachers. Innovative and engaging teachers could reach a global audience and become YouTube celebrities. There could be competitions for the Best Teacher of the Pythagorean theorem, Best Teacher in Swindon, etc. as nominated through video clips. Videos could be linked to teacher ranking websites. From a policy perspective, education could become easier to evaluate and standardize. Countrywide best practices could be culled to train new teachers.

Conclusion: inevitablility of full-life recording

It seems inevitable that video surveillance/sousveillance will increasingly penetrate public and private areas for a variety of reasons ranging from safety and crime control to life-logging. One classic opposition argument is that recording inhibits ‘natural’ behavior, however most people quickly forget and adjust and it could be likely that the ongoing recording of society will advance without much opposition as long as there is a balance between surveillance and sousveillance (e.g.; there is popular access to the technologies and streams).

Bio-design automation and synbio tools

2009-08-02T08:59:00.000-07:00

The ability to write DNA could have an even greater impact than the ability to read it. Synthetic biologists are developing standardized methodologies and tools to engineer biology into new and improved forms, and presented their progress at the first-of-its-kind Bio-Design Automation workshop (agenda, proceedings) in San Francisco, CA on July 27, 2009, co-located with the computing industry’s annual Design Automation Conference. As with many areas of technological advancement, the requisite focus is on tools, tools, tools! (A PDF of this article is available here.)

Experimental evidence has helped to solidify the mindset that biology is an engineering substrate like any other and the work is now centered on creating standardized tools that are useful and reliable in an experimental setting. The metaphor is very much that of computing: just as most contemporary software developers work at high levels of abstraction and need not concern themselves with the 1s and 0s of machine language, in the future, synthetic biology programmers would not need to work directly with the Ac, Cs, Gs and Ts of DNA or understand the architecture of promoters, terminators, open reading frames and such. However, with synthetic biology being in its early stages, the groundwork to define and assemble these abstraction layers is currently at task.

Status of DNA synthesis
At present, the DNA synthesis process is relatively unautomated, unstandardized and expensive ($0.50-$1.00 per base pair (bp)); it would cost $1.5-3 billion to synthesize a full human genome. Synthesized DNA, which can be ordered from numerous contract labs such as DNA 2.0 in Menlo Park, CA and Tech Dragon in Hong Kong, has been following Moore’s Law (actually faster than Moore’s Law Carlson Curves doubling at 2x/yr vs. 1.5x/yr), but is still slow compared to what is needed. Right now short oligos, oligonucleotide sequences up to 200 bp, can be reliably synthesized but a low-cost repeatable basis for genes and genomes extending into the millions of bp is needed. Further, design capability lags synthesis capability, being about 400-800-fold less capable and allowing only 10,000-20,000 bp systems to be fully forward-engineered at present.

So far, practitioners have organized the design and construction of DNA into four hierarchical tiers: DNA, parts, devices and systems. The status is that the first two tiers, DNA and parts (simple modules such as toggle switches and oscillators), are starting to be consistently identified, characterized and produced. This is allowing more of an upstream focus on the next two tiers, complex devices and systems, and the methodologies that are needed to assemble components together into large-scale structures, for example those containing 10 million bp of DNA.

Standardizing the manipulation of biology
A variety of applied research techniques for standardizing, simulating, predicting, modulating and controlling biology with computational chemistry, quantitative modeling, languages and software tools are under development and were presented at the workshop.

Models and algorithms
In the models and algorithms session, there were some examples of the use of biochemical reactions for computation and optimization, performing arithmetic computation essentially the same way a digital computer would. Basic mathematical models such as the CME (Chemical Master Equation) and SSA (Stochastic Simulation Algorithm) were applied and extended to model, predict and optimize pathways and describe and design networks of reactions.

Experimental biology
The experimental biology session considered some potential applications of synthetic biology, first the automated design of synthetic ribosome binding sites to make protein production faster or slower (finding that the translation rate can be predicted if the Gibbs free energy (delta G) can be predicted). Second, an in-cell disease protection mechanism was presented where synthetic genetic controllers were used to prevent the lysis normally occurring in the lysis-lysogeny switch turned on in the disease process (lysogeny is the no-harm state and lysis is the death state).

Tools and parts
In the tools and parts session, several software-based frameworks and design tools were presented, many of which are listed in the software tools section below.

Languages and standardization
The languages and standardization session had discussions of language standardization projects such as the BioStream language, PoBol (Provisional BioBrick Language) and the BioBrick Open Language (BOL).

Software tools: a SynBio CrunchUp
Several rigorous computer-aided design and validation software tools and platforms are emerging for applied synthetic biology, many of which are freely available and open-source.

Clotho: An interoperable design framework supporting symbol, data model and data structure standardization; a toolset designed in a platform-based paradigm to consolidate existing synthetic biology tools into one working, integrated toolbox
SynBioSS - Synthetic Biology Software Suite: A computer-aided synthetic biology tool for the design of synthetic gene regulatory networks; computational synthetic biology
RBS Calculator: A biological engineering tool that predicts the translation initiation rate of a protein in bacteria; it may be used in Reverse Engineering or Forward Engineering modes
SeEd - Sequence Editor (work in progress): A tool for designing coding sequence alterations, a system conceptually built around constraints instead of sequences
Cellucidate: A web-based workspace for investigating the causal and dynamic properties of biological systems; a framework for modeling modular DNA parts for the predictable design of synthetic systems
iBioSim: A design automation software for analyzing biochemical reaction network models including genetic circuits, models representing metabolic networks, cell-signaling pathways, and other biological and chemical systems
GenoCAD: An experimental tool for building and verifying complex genetic constructs derived from a library of standard genetic parts
TinkerCell: A computer-aided design software for synthetic biology

Future of BioCAD
One of the most encouraging aspects in the current evolution of synthetic biology is the integrations the field is forging with other disciplines, particularly electronics design and manufacture, DNA nanotechnology and bioinformatics.

Scientists are meticulously applying engineering principles to synthetic biology and realize that novel innovations are also required since there are issues specific to engineering biological systems. Some of these technical issues include device characterization, impedance, matching, rules of composition, noise, cellular context, environmental conditions, rational design vs. directed evolution, persistence, mutations, crosstalk, cell death, chemical diffusion, motility and incomplete biological models.

As it happened in computing, and is happening now in biology, the broader benefit of humanity having the ability to develop and standardize abstraction layers in any field can be envisioned.

Clearly there will be ongoing efforts to more granularly manipulate and create all manner of biology and matter. Some of the subsequent areas where standards and abstraction hierarchies could be useful, though not immediate, are the next generations of computing and communications, molecular nanotechnology (atomically precise matter construction from the bottom up), climate, weather and atmosphere management, planet terraforming and space colony construction.

(Image credits: www.3dscience.com, www.biodesignautomation.org)

Ethics of brainless humans

2009-07-26T08:23:00.000-07:00

As a thought experiment, if it were possible, would it be ethical to make humans without brains for research purposes?

The idea arises since a more accurate model of humans for drug testing would be quite helpful. Drugs may work in mice, rats and monkeys but not in humans or in some humans but not others. Human biology is more complex and the detailed pathways and mechanisms are not yet understood.

Of course by definition, a brainless human is not really a human; a human form without a brain would be more equivalent to a test culture of liver cells than a cognitive agent.

Tissue culturing, regenerative medicine and 3D organ printing
The less contentious versions of the idea of growing brainless humans is currently under initial exploration in taking tissue from a human, growing it up in culture and testing drugs or other therapies on it. A further step up is regenerative medicine, producing artificial organs from a person’s cells such as the Wake Forest bladder and Gabor Forgacs 3D organ printing work.

Brain as executive agent may be required
The next steps for testing would be creating systems of interoperating tissue and organs (e.g.; how would this person’s heart and liver respond to this heart drug?) and possibly a complete collection of human biological systems sans brain. One obvious issue is that this might not even work since the brain is obviously a critical component of a human and that a brainless human could not be built, that some sort of executive organizing system like the brain would be needed. Also medical testing would need to include the impact on the brain and the brain’s role and interaction with the other biological systems and the drug.

Ethical but impractical
Where it is quite clear that generating a full living human for research purposes would be unethical, it is hard to argue that generating a brainless human, a complex collection of human biological systems without a brain, which is not really human and does not have consciousness or personhood, would be unethical. Certainly some arguments could be made to the contrary regarding the lack of specific knowledge about consciousness and concepts of personhood, but would seem to be outweighed.

Unlikely to arise
It is extremely unlikely that the situation of manufacturing brainless humans for research purposes would ever arise, first since a lot of testing and therapy may be possible with personalized tissue cultures and regenerative medicine, and informed by genomic and proteomic sequencing. Also, in an eventual era where it might be possible to construct a brainless human or a collection of live interacting tissues and organ systems, it would probably be more expedient to model the whole biological system digitally.

The biomolecular interface and the definition of living

2009-07-19T09:01:00.000-07:00

Definitional and classification issues often arise in any field of heightened focus and progress (e.g.; what is a planet?). For the many fields integrating organic and inorganic materials, an interesting issue comes up as to what is the definition of life. Many different gradations of living things are emerging.

Some interesting new cases of living materials are the idea of organic sensors made of biomaterial placed on buildings, self-replicating crystals and biological scaffolding for stem cell grown organs and 3D tissue printing.

De novo materials synthesis
One exciting aspect of the living/non-living classification is the new synthesis of both organic and inorganic materials. Scientists are creating de novo engineered proteins and other biological materials, non-naturally occurring inorganic materials with superior properties using molecular manufacturing techniques and hybrid organic-inorganic materials, with the best of organic and inorganic properties in one object, for example rotaxanes which could be used in quantum computing.

Definition of integration
Not just the definition of what is living arises, but also the definition of the integration of organic and inorganic materials. Alan H. Goldstein proposes that a true integration of organic and inorganic material involves communicating back and forth, not just a system which has properties or components of both organic and inorganic systems.

The future of biomolecular interfaces

The future of biomolecular interfaces is probably a further blurring of the underlying substrates as the focus is more relevantly on the properties and requirements of any challenge at hand.

Ethics of the future: self-copies

2009-07-12T11:35:00.000-07:00

Just as the future of science and technology is rife with legal opportunities and psychological study possibilities, so is it with ethical issues. One interesting example is the case of individuals having multiple copies of themselves, either embodied or digital.

1. Can I self-copy?

The first issue is how different societies will set norms and legal standards for having copies. The least offensive first level would be having a backup copy of mindfiles for emergency and archival purposes, much like computer backups at present. People take pictures and videos of their experiences, why not of their minds? The other end of the extreme would be the most liberal societies allowing all manner of digital and embodied copies. The notion of regulating copies brings up an interesting potential precedent, that currently, the creation of children is largely unregulated on a global basis.

2. When and where can I run my self-copy(ies)?

A second issue is, given copies, under what circumstances can and should they be run. A daily backup is quite different from unleashing hundreds of embodied copies of oneself. Physically embodied copies would consume resources just as any other person in the world and there would likely be some stiff initial regulations since national population doubling, trebling or more overnight would not likely be a useful shock to society. Not to mention the difficulty in quickly obtaining and assembling the required resources for a full human copy; despite the potential advances in 3D human tissue and organ home printers by then.

Digital copies is the more obvious opportunity for running self-copies and could be much more challenging to regulate. In the early days, the size and processing requirements of uncompressed mindfiles would likely be so large that a runtime environment would not be readily available on any home machine or network but would rather require a supercomputer.

3. Am I a copy?

A third interesting problem is whether it would be moral for copies to know that they are copies, and the related legal issues regarding memory redaction as explored in Wright's "Golden Age" trilogy. Depending how interaction between originals and copies is organized, it may not matter. Psychologically for the originals and the copies, it may matter a lot. The original may 'own' the copies or the copies may have self-determination rights. In the case of an embodied copy, it is hard not to argue for their full personhood but somehow a digital instance seems to have fewer rights, although it may come to be that shutting down an instance of a digital mind, even with a recent full memory backup and integration, is just as wrong as a physical homicide.

Interesting ethical issues could arise for originals and copies alike as to what to share with the others; should horrifying experiences be edited out as Brin's Kiln People do at times? There would be both benefits and costs to experiencing the death of a self-copy, for example. It would not seem ethical to make self-copies explicitly for scientific research purposes to garner information from their deaths, but it does seem fully ethical to have multiple self-copies for with different life styles, some healthier and some less healthy to investigate a) whether a healthy life style matters and b) to selfishly share exciting experiences from less risk averse copies back with the longer-lived healthier copy.

Indeed in the new medical era of a systemic understanding of health and disease where n=1, what better control examples to have than of yourself! However, epigenetic mutations and post-translational modifications may be much harder to equalize across copies than memories and experiences.

The issue of the definition of life arises as some people may want the abridged meta-message or take-away from experiences, indeed this is one of the great potential benefits of multiple copies, while others may wish to preserve the full resolution of all experiences. The standard could accommodate both, with the summary being the routine information transfer with the detail archived for on-demand access.

4. What can I do with my self-copies?

Societies might like to attempt to establish checks and balances to prevent originals from selling copies of themselves or others into slavery to reap economic benefits, as dystopially portrayed in Ballantyne's "Capacity". Especially in a potential realm of digital minds, there are many potential future challenges with rights determination and enforcement.

The 'AI abdication' defense is the argument that societies that are sufficiently advanced to have the ability to run self-copies would also have other advancements developed and in use such as some sort of consciousness sensor identifying existing and emerging sentient beings and looking after their well-being, a beneficent policing. There are numerous issues with the AI abdication defense, including its unlikely existence from a technical standpoint, whether humans would agree to use such a tool, whether a caregiving AI could be hacked and other issues. However, technology does not advance in a vacuum and society generally matures around technologies so it is likely that some detriment-balancing counter initiatives would exist.

For example, would it be moral to create sub-sentient beings as sex slaves or personal assistants? This may be an improvement over the current situation but is not devoid of moral issues. At some point, as more about consciousness has been characterized and defined, a list of intelligence stratifications and capabilities could be a standard societal tool. Animals, humans and AIs would be included at minimum. A future world with many different levels of sentience seems quite possible.

Next-gen computing for terabase transfer

2009-07-05T11:53:00.000-07:00

The single biggest challenge presently facing humanity is the new era of ICT (information and communication technology) required to advance the progress of science and technology. This constitutes more of a grand challenge than do disease, poverty, climate change, etc. because solutions are not immediately clear, and are likely to be more technical than political in nature. The raw capacity in information processing and transfer is required and also the software to drive these processes at higher levels of abstraction to make the information useable and meaningful. The computing and communications industries have been focused on incremental Moore’s Law extensions rather than new paradigms and do not appear to be cognizant of the current needs of science, and particularly the magnitude.

Computational era of science
One trigger for a new ICT era is the shift in the way that science is conducted. The old trial and error lab experimentation has been supplemented with informatics and computational science for characterizing, modeling, simulating, predicting and designing. Life sciences is the most prominent area of science requiring ICT advances, for a variety of purposes including biological process characterization and simulation. Genomics is possibly the field with the most ICT urgency; genomic data is growing at 10x/year vs. Moore’s Law at 1.5x/year for example, however nearly every field of science has progressed to large data sets and computational models.

Mindfile deletion

2009-06-28T06:02:00.001-07:00

How do you know that your mindfile will not be deleted, either on purpose or by accident? What would you do if your mindfile is stored in memory and not allowed to run? How would you know that you are not being run? Is not running the equivalent of being dead? How will you know that you are getting the processing power and bandwidth in your contract when reality is simulated and hardware test results could be simulated too?

There are at least two levels of challenges to address, akin to current physical world needs, first, survival needs and second, needs and rights when interacting with others.

Establishing rights for mindfiles
There will need to be ways to assure basic ‘human’ rights in a potential era of uploading brains to digital software files. There could be many misuses of massive databanks of mindfiles: they could be deleted at will (digital genocide) or by mistake by careless ISPs/data center managers, sold, kidnapped, copied, bred, hiveminded or discriminated against via less bandwidth and processing power. If the reality experienced by mindfiles is simulated, how would anyone know that the virtual reality they experience is the one they want to experience? A code or key could be created so that individual mindfiles could not be copied without the owners permission, agreement or knowing; perhaps like the telomere-shortening system used by biological cells. Pervasive externally run audit software could maintain lists of mindfile citizens (a future role for the nation-state) and periodically query each mindfile to determine its status and whether it is running. As usual, the white hats would need to stay ahead of the black hats.

Reducing naked Darwinism
With less transparency and social pressure, it is possible that the behavioral smoothing that has arisen in contemporary society would dissolve. Codes of conduct for mindfiles could be developed, probably with a much heightened awareness and refinement of the respectful treatment of consciousnesses. If virtuality is 100% sousveilled, this should not be a problem. In addition, mechanisms such as barriers, permissioning tiers and firewalled gardens could arise to prevent stronger minds from terrorizing and controlling weaker minds or different minds. The real goal would be to rearchitect social pressure in ways that are continually empowering to all individuals. Some mindfiles may prefer heavily controlled virtual environments, others may wish to venture onto the interstitial wildnets.

Health Literacy Toolkit

2009-06-21T09:08:00.000-07:00

With one key life sciences focus shifting to health as opposed to healthcare (as HealthCamp founder Mark Scrimshire exhorts) and to preventive, predictive health management as opposed to therapy and treatment, there should be the concept of a health literacy toolkit that would be a component of standardized knowledge, such as how to write, drive or get a job.

Definition of health literacy
Surprising but emblematic of the traditional health mentality (e.g.; treat illness) is the prevailing definition of health literacy…”a patient’s ability to acquire and understand information about a condition and options once diagnosed…” Moving into the preventive era, the definition of health literacy needs to shift from being backward-looking to forward-looking. Having health knowledge ahead of time could inform behaviors to prevent, slow or lessen the development of disease. Health literacy should be a general set of knowledge for everyone to know, not related to a condition once a patient has it.

Gap between health literacy and demand for health information
A U.S. Department of Health and Human Services (HHS) study finds that only 12% of adults have proficient health literacy (p. 26); that nearly 9 out of 10 adults may lack the skills needed to manage their health and prevent disease.

The biggest reason for low health literacy could be a lack of appropriately accessible and presented health information.

A Pew Internet Study “The Social Life of Health Information” in June 2009 finds that 61% of U.S. adults are looking for health information online. The gap between health literacy and the demand for health information suggests that there is a substantial opportunity for a range of health information services and management tools, many of which could be fee-based such as the LIVESTRONG nutrition and exercise management program.

Health literacy toolkit
What should be the components of a standard health literacy toolkit? Many professionals (e.g.; physicians, academicians, etc.) believe that even HDL/LDL cholesterol information is too complicated for the lay public, but this just cannot be correct. When simple numeric information is presented clearly, people of any background and capability are often quite able to understand it and take action. For example, when utility bills started to provide straightforward quantitative data regarding power consumption, including day/night usage and costs, many people shifted their behavior in a positive informed way.

Figure 1: Ongoing Total Cholesterol readings for one individual

Figure 1 illustrates an example individual’s ongoing total cholesterol readings presented in a clear and informative way. Anyone inspecting the chart can easily identify the overall trend, down, which is good, wonder about the range of numeric measurements (157-185) vs. the average and how this translates into good or bad health tiers (e.g.; under 200 is generally good, but a rising trend that is still under 200 could be an indication of arising health issues for that individual), and inquisitively wonder about the peaks. The next level of information would be HDL and LDL readings, small lipids as is now de rigueur and triglycerides, but even this simple plot of total cholesterol measures is understandable, useful and potentially actionable. It is also the perfect level of information for individuals who are interested in being responsible for self-managing their health but from an efficient, easily-actionable level that does not require deep engagement of time or knowledge acquistion.

Some of the most obvious aspects to include in a health literacy toolkit would be nutritional information and its interpretation, caloric consumption and expenditure and ongoing quantitative measures of health from blood analysis and other tests (e.g.; blood pressure, glucose, cholesterol, BMI, weight, VO2 max, etc.). The data can be summarized (with detail available) and directly linked to actionable explanatory information (e.g.; measures may go up or down if they were not measured at the same time or situation, for example if a meal had been eaten before some but not all of the measurements). Other components of a standard health literacy toolkit could include where and how to obtain information and tools for self-tracking, how to integrate multiple data sources into a unified view, and how and what to expect when interacting with the medical community. Genomics is already part of the health literacy toolkit for early adopters and could become a standard toolkit component for everyone within five years, already helpful Genetics 101 sites are emerging.

Automated health monitoring tools
Health-self management in large quadrants of the population could accelerate with the advent of automated health monitoring tools that would capture frequent datapoints and aggregate the information into easily viewable web-based charts. Many devices such as blood pressure monitors, heart monitors and scales are now battery-intensive Bluetooth-enabled which is a nice intermediate step but what is really needed is for all of these monitoring devices to be directly on home WiFi networks. Where possible, having the monitoring applications directly on the smartphone is another obvious step rather than having separate devices. There are some WiFi-enabled devices, for example the FitBit calorimeter, which has been delayed in launching, and glucose monitors such as the GlucoMON, however its $75/month subscription fee appears exorbitant.

Genomics: highest-impact near-term advance

2009-06-14T09:47:00.000-07:00

Genomics is making faster progress than any other technology in recent history. Usually the vista from any point on an exponential curve looks flat to the experiencer but not so with consumer genomics, the field is exponentiating from any vantage point. Genomics scientific research and commercialization issues were discussed with excitement at the first-ever consumer genomics conference in Boston, June 9-11, 2009. (A PDF of this blogpost is available here.)

Summary

Advent of the whole human genome: Automatic whole human genome sequencing of all individuals could likely be a reality in the next few years
Medically actionable now: Genetic data is medically actionable now and becoming increasing more so, particularly in routing higher-risk individuals into earlier screening. It is estimated that each individual is in the upper 5% risk tier for at least one chronic disease.
New ICT era (information and communications technology): Genomic data requires a significant new level of information processing, storage and transfer. One whole human genome can range from 6GB-8TB in terms of the data currently transferred between researchers.
Social inevitability: Widespread genomic sequencing appears to be inevitable which has great benefits together with social challenges such as revealing non-paternity (10-15% in the U.S.), terminal disease conditions and reproductive issues (e.g.; recessive carrier status).
Heightened role of the consumer: Consumers will have unprecedented access to health information about themselves and could take a much more active and self-directed role in their health management, more likely responding favorably than being consumed with their ‘incidentalome.’

Genetic tests – what is now available

Physician-ordered tests (generally insurance-reimbursed)

For some time, physicians have been ordering any number of one-off genetic tests for specific conditions such as Cystic Fibrosis, Huntington’s Disease, breast cancer (mutations in the BRCA1 and BRCA2 genes) and other conditions. Physicians can also order any of the below tests for patients.

Consumer-ordered tests (no doctor-order required, unreimbursed)

Single condition tests (DNA Direct, $200-1,000)
SNP Chip risk assessment tests (23andme ($399, down from $1,000), DeCODEme ($985), Navigenics ($2,499))
Whole genome scan (Knome ($99,500)) or whole exome scan (Knome ($24,500)) [The price just dropped from $350,000 to $99,000, but it would still seem silly to purchase now when a few more zeros might drop off within months]
Personal Genome Project (PGP), Harvard Medical School, genome sequencing for free in exchange for open data publishing, now expanding from ten subjects to 100,000
Family planning genetic screening: Counsyl
Mate compatibility analysis based on immune system variation: ScientificMatch, GenePartner (The next obvious component would be including recessive disease carrier status in the back-end matching algorithms of dating services)

Out of work due to technological advance:

elevator operator, stock broker, physician(?)

Current genomic testing issues: validity and utility
Validity
There are differing levels of data validity depending on which chip array and methodology is used to sequence the genomic data. Illumina reports being at two 9s now (e.g.; 99.99% error free; experiencing one error per 1,000 reads) and is hoping to move to four and then six 9s of quality. Sequencing is done at different levels of coverage ranging from 1x to 30x coverage, meaning how many times a sequence is read; 30x coverage is the most accurate and highest industry standard at present.

A few people who have tried multiple DTC (direct-to-consumer) SNP chip offerings have found consistent genotyping data (e.g.; having a ‘CT’ at a certain SNP), but different interpretations in lifetime risk probabilities as different markers are evaluated and rolled up into risk assessments across the companies. The risk of false negatives and false positives abounds.

Direct-to-consumer genomic testing companies:

Heterogeneous breast cancer markers assessed

Sources: Navigenics, DeCODEme, 23andme

Not only do different services map different markers to meta conditions like cardiovascular disease, but the most relevant medical SNPs are often not included in DTC SNP chips, probably due to patent and cost issues. A notable example is Myriad, which owns patents on the breast cancer-related BRCA1 and BRCA2 genes. This has become the focus of a timely lawsuit brought by the ACLU regarding the patentability of natural materials such as genes and industry norms of how genes are licensed for diagnosis and therapy.

Whole human genome sequencing renders the patented-gene issue moot as anyone having access to their raw data could look up their genotypes for particular SNP/rsid numbers such as those corresponding to the BRCA1 and BRCA2 genes. (Knome customers can do this now). There will be a need for interpretation tools appropriately aggregating multiple risk alleles. Fee-based or open source genomic data interpretation tools like the SNPedia’s Promethease report could proliferate.

Utility

People would like to know definitively if they are going to have a disease but aside from monogenic conditions (for example, Muscular Dystrophy, Huntington’s Disease, sickle cell disease and Cystic Fibrosis), most chronic diseases are polygenic and influenced by many factors. The current genetic testing for these conditions does not deliver a simple Yes/No, but rather assesses the lifetime risk probability for an individual and whether the individual is at higher or lower risk than the average.

There is ample room for risk interpretation mechanisms for polygenic conditions to become more sophisticated, right now the practice is a multiplicative technique, taking the risk value for each genotyped allele associated with the condition and multiplying them together; weighting and cluster-evaluation would be obvious refinements that research may support over time.

Genetic variation and disease causality
NHGRI and other GWAS (genome-wide association studies) researchers find that genes, as they have been studied so far, only account for a small percent of explaining disease. However, studies have been preliminary, the 1,000 genomes studied may not be enough for complete understanding, for example, about 35 common diseases have been found to have widely replicated common variants. One next step targeted by the NHGRI is to look at rare variants, low-frequency (e.g.; 1-2%) GWAS variants with intermediate penetrance, to possibly explain a larger percentage of disease causality. Simultaneously, our systemic understanding of biology is slowly improving, it seems that in many disease cases it may not be the gene or genotype, but rather the number of copies of the same gene (CNVs), translocations, inversions, and other problems with gene expression and DNA repair that are responsible for disease.

Knowledge gap
Genomic technology has been moving so fast that at present, most physicians do not have genetic training. The genetics community is the primary party helping to generate, interpret, present and monitor genomic data. Over time, other communities like physicians and genetic counselors (one of the world’s fastest-growing job categories) will hopefully become helpful in interpreting data together with patients. Genetic training is a key target area of CME (continuing medical education), for example the National Coalition for Professional Education in Genetics' "Genetics Education for Health Professionals: What are the Key Messages? How do we deliver them?” (Sep 2009) and Harvard Medical School’s “What the Primary Care Provider needs to know about the Genetic Basic of Adult Medicine” (Oct 2009).

Medical relevancy
That disease has a molecular basis is now undisputed and medicine is slowly shifting to reorganize around this. Presently, 1,400 genes can be tested to inform various clinical decisions, and 225 are deemed clinically significant. 100 new tests are being added annually. In some cases, medical information exists but is not being used, for example a straightforward marker for poor drug metabolizers, CYP2D6. About 10% of Caucasians are poor metabolizers however this is not routinely tested for ahead of time (nor in the DTC SNP chip tests mentioned above) and the same drugs are given to all patients in a trial and error process, sometimes in lower doses (e.g.; warfarin) due to fear of overdosing those for whom it could be harmful.

Another example of medical relevancy in genomic testing is the NHGRI’s GWAS study finding of the first nine genetic risk variants for type 2 diabetes: TCF7L2, IGF2BP2, CDKN2A/B, FTO, CDKAL1, KCNJ11, HHEX/IDE, SLC30A8 and PPARG; particularly the first one, TCF7L2. Higher-risk individuals identified early in life could receive targeted healthcare.

Additive statistical approach
So far, general genomic testing suggests that on average, each patient is in the upper 5% risk tier for at least one chronic disease (e.g.; cancer, cardiovascular disease, myocardial infarction, etc.) and that there is value in understanding genomic risk factors earlier in life. Whole human genome sequencing automatically at birth could mean a lifetime of personally relevant healthcare.

Although genomic tests do not predict polygenic disease definitively, they are medically actionably in taking conventional risk percentages (e.g.; American female lifetime breast cancer risk = 12%; American male lifetime prostate cancer risk = 16%) and layering on the specific genetic risk of the individual to route higher-risk individuals to screening and therapeutics earlier. Several researchers estimate that the earlier identification of higher risk patients could reduce overall healthcare costs by about ~$100,000 per person per condition.

Patient behavior: a key component of medical actionability
Although there is no known cure for Alzheimer’s Disease, and even a firm diagnosis can only be made at autopsy, Boston University’s REVEAL study has shown that people do change their behavior after receiving a positive diagnosis for Alzheimer’s Disease (mainly through purchasing supplements and some increase in exercise). It is also known that mid-life cholesterol levels correlate with Alzheimer’s Disease, so the highly actionable behavior for someone with an APO E4 positive allele could be more closely managing cholesterol intake.

Family history
The role of family history is another important component of disease prevention, diagnosis and management, and there are starting to be helpful web-based tools for consumers to assemble, manage and access family history data such as My Family Health Portrait.

Technology status
Technology advance has been the key enabler of the genomics revolution. The first genome sequencing project, completed in 2003 cost $3b. Now, the cost of genetic sequencing is dropping to the point where a $100 whole human genome may be available in the next few years, in 2010 according to Pacific Biosciences. There are several next-gen sequencing platforms in process now to supercede the current array-based method.

Next-gen sequencing platforms
Next-gen genomic sequencing platforms are generally falling into two categories, those using synthesis (specifically multiplex cyclic sequencing by synthesis) and those not using synthesis. Some of the most interesting next-gen companies using synthesis are Pacific Biosciences, Ion Torrent Systems and RainDance Technologies. Some of the most exciting non-synthesis-based next-gen sequencing companies are Oxford Nanopore Technologies, and NABsys and Halcyon. NABsys and Halcyon are electromagnetically-based rather than optically-based which means they are not dependent on light or fluorescence so the cameras can go much faster, perhaps 10,000 frames per second. Harvard Medical School maintains a nice overview of current and emerging gene sequencing technologies.

Transcriptome, proteome, metabolome, microbiome…
In addition to improving the cost and speed of existing genomic scanning, sequencing advances could open up the way to the eventual characterization of the whole cell and its interactions through the sequencing of the transcriptome, the proteome, the metabolome, the microbiome and other biological features. In the farther future, histone modification sequencing, DNA methylation, acetylation and phosphorylation are other characterization processes of interest that could be included.

Petabyte data era: processing, storage and transfer challenges
The biggest challenge consuming national genomic research labs at present is data processing and network communications. Genomic data is growing at 10x per year (vs. Moore’s Law growing at 1.5x per year). Research labs have problems with data storage, mapping and access, together with intra-site data transfer and external transfer. Shipping terabyte drives via fedex is the best current data transfer method, and at least one lab finds resequencing data cheaper than storing it.

The raw data of the 6b base pair whole human genome is 6GB, not challenging to store, but challenging to work with, it is not like just opening up and manipulating a word document. New data processing algorithms will need to be developed to interact with whole genome data, link it to reference tools and make it searchable and meaningful. Whole businesses can be formed to focus on genomic data curation alone (a second wind for Google?).

Even though the most basic raw data version of the whole human genome is 6GB, the full collection of files in use by researchers for one whole human genome may reach 8TB. The full works may include an intensity file, a BAN file (binary), a SAN file (searchable) and other files with coordinates, variations and other aspects. Part of the challenge is that appropriate data abstractions from the raw sequencing output are not yet known so all the data is kept. There is not yet a good reference model. Apparently, the Archeron X-Prize for genomics (sequencing 100 human genomes within 10 days or less at a maximum cost of $10,000 per genome) remains outstanding not because it cannot be done, but because the results cannot be recapitulated.

Testing inevitability and social implications
It seems quite possible that initial and ongoing whole human genome sequencing (and eventually, on-demand proteome, metabalome, microbiome, etc. sequencing) would be a routine component of everyone’s EMR (electronic medical record) available to both patients and physicians for ongoing predictive, preventive healthcare monitoring. There are some important social implications of widespread whole human genome testing, for example:

Non-paternity
One genetic issue is non-paternity (studies suggest 10-15% is the ongoing rate of non-paternity in the U.S.). In the era of whole human genome sequencing, paternity would be quite easy to trace. One possible impact is that the divorce rate could increase and single mothers could be stratified into lower economic tiers.

Right not to know
Another genetic issue is that of a person’s right not to know about their medical situation. With improving remedies, the right not to know becomes a lot less important. Also it may be quite straightforward for practitioners to deliver healthcare without breaching the patient’s right not to know their genetic information as they do currently. With more actionable treatments, it could become the social norm to know your genetic profile, to learn about potential conditions and work collaboratively with others with similar conditions in attempts to mobilize long-tail medicine, as PatientsLikeMe health social network participants are doing to run their own clinical trials.

Discrimination
GINA, the Genetic Information Nondiscrimination Act of 2008, protects U.S. citizens from discrimination by employers and insurance companies. It is a step in the right direction, but many are not reassured. The law has some holes, such as not covering long-term care providers, and will have to be strengthened via interpretation as real-life cases arise.

DNA Forensics – Gattaca?
In an age of inexpensive genomic testing, the on-demand testing of other people (such as a prospective mate, business partner, supervisor or tenant), as portrayed in the movie Gattaca, could easily occur; one such example provided decisive evidence in a recent divorce case. DNA privacy would become impossible as a practical matter. DNA privacy would become impossible as a practical matter. However, precisely because everyone would be subject to genetic openness and since the present world is not one of scarcity and control as the dystopian Gattaca, it may be that DNA testing and knowledge would not be a substantive issue. Already, several individuals in support of hastened scientific advance and open medicine have open-sourced their genomic data on the SNPedia or via the Personal Genome Project.

Venture capital investment opportunities
There are many exciting potential opportunities for venture capitalists, entrepreneurs and researchers in helping to realize the genomics revolution. The money is already arriving before the physicians as companies, backed by varying degrees of research, seek to monetize genetic risk. The potential demand for personal genomic products and services could be enormous, for example, the marker for weight-loss products is a $40b/year. Here are some potential opportunities:

Personalized genetic testing, counseling, supplements and other action programs and remedies, for example, Inherent Health’s Weight Management, Heart Health and other tests, and the APO E Gene Diet.
More DTC (direct-to-consumer) genetic testing and interpretation offerings stratified towards differing enduser tiers (e.g.; the aggressive early adopter, the lay person, the Boomer, the Gen Y’er)
A line of genomic testing services to be offered by spas and private clinics; positioned as a luxury item vs. a medical necessity to accelerate adoption
Next-gen sequencing, and next-next-gen sequencing, innovating the technology and the applications to commercialize the technology
Web-based tools for integrating medical records, family history and genomic data, facilitating data collection, entry and access
Genetic literacy products and services for physicians and consumers
Web-based tools to appropriately and dynamically aggregate multiple risk alleles into chronic disease meta conditions such as cancer and cardiovascular disease
Fee-based genomic data interpretation tools like the SNPedia’s Promethease
Data processing algorithms to interact with whole genome data, making it searchable and meaningful with links to external reference databases
Genomic data curation
Cloud computing for genomic data analysis
Health social networks or other tools for deep longitudinal monitoring over time by consumers/patients of many complex health factors

Conclusion
As our molecular understanding of disease progresses and genomic testing continues to decrease in cost and become increasingly medically relevant, adoption could become extremely widespread almost overnight. Physicians could start to see the additive, precise information conferred by genomic testing as a means of improving the care they now deliver, finding themselves initially encouraged and eventually forced into the genomic revolution. Pharmaceutical companies could start to use genomic testing and pharmacogenomics as a means of improving efficacy in drug discovery and delivery, providing some much-needed assistance to their ailing cost models. Consumers could be radically empowered to become curious about and responsible for self-managing their health with automated easy-to-use tools. Genomics as an enhanced approach to healthcare could transform the quality of life worldwide for all humanity.

Aging is solvable

2009-06-07T05:18:00.000-07:00

That aging is understandable and solvable, not necessarily immediately but ultimately, was one topic not seeing a lot of opposition at the American Aging Association (AGE) conference in Phoenix AZ May 29 – June 1, 2009. Key research highlights are below.

Aging is a key contemporary concern, on the order of climate change, as all countries worldwide have populations increasingly stratified towards aging. Aging is not just a medical condition but a key challenge to be resolved for advanced societies to be successful in the long-term. Productivity, healthcare costs and happiness and comfort could all be improved with advances in the remedy of aging. Aging has advanced from a nebulous concept to concrete mechanisms that can be understood and managed. Thematically, most of the bioparts impacted in aging (cells, genes, proteins, neurons, etc.) seem to still be present in older organisms, just not functioning the way they did when the organisms were younger, suggesting that it may be possible to manage and reverse aging processes, and confirming the systemic nature of aging including, for example, the role of a healthy microenvironment and cell-cell signaling. Reductionism as an approach has proved unsuccessful.

Aging is a multidisciplinary phenomenon, involving different deterioration processes in different tissues over time. Aging involves a variety of fields (immunology, cancer, regenerative medicine, cognition, micronutrients, etc.) and a variety of levels of research species (C. elegans (worms), Drosophila (flies), mice, rats and humans). At AGE, the organizational structure was a focus on systems pathways, particularly signaling and hormones, together with a look at the role of proteins in aging.

AGE was an excellent place to obtain a broad and deep comprehension of how aging works. The systemic rigor required to characterize the process-intensive nature of aging has been making significant progress, with a much more detailed understanding of the complex nested multifactor pathways now existing as compared with that of even a few years ago. It is clear that the painstaking characterization work could be further improved with automation and quantitative tools, especially for example, digital linkage of aging pathways across organisms.

As with other life sciences areas, the potential widespread quick and cheap availability of the sequencing of genomes, proteomes, etc. is likely to dramatically change how the science of aging is conducted, though not guarantee quick solutions. As pathways continue to be confirmed, they can be digitized into software and nearly indefinite simulated iterations could be run before conducting time-consuming and expensive bench experiments in confirmation.

Many interventions work for extending the lifespans and healthspans of lower order organisms, for example knocking out any one of 200 known genes may extend the lifespan of the C. elegans worm but the specifics and replicability of the mechanisms in higher order organisms are not known. It does not make sense to directly translate point solutions up to mammals given the systemic nature of the organisms and aging processes. Even moving one biomarker for alcohol consumption from monkeys to humans is not direct.

Exciting new research findings
Reference links below and conference abstracts here

3D organ printing: Use only biologics (cells and cell products) in a scaffold-free tissue engineering process to print 3D tissues and organs which can be vascularized prior to implantation, relying on developmental biology to trigger the cells to fuse and self-assemble into organs. (Gabor Forgacs, video, lab, organ printing)
Stem cell antibodies: Improve existing cardiac stem cell therapies (only 1% of cells reach the intended destination) by using specific antibodies for better targeting and retention of stem cells at sites of tissue injury. Replace cardiomyocytes with adult stem cells. (Jim Larrick, paper, general information)
Stem cells: Amplify and rejuvenate adult stem cells for injection into knees and hips as an alternative to surgical replacements. (Regenexx)
Bioremediation: Use natural enzymes to remediate biological build-ups; cholesterol oxidase from Brevibacteria to reduce 7KC cholesterol in atherosclerosis and A2E-degrading enzymes to improve macular degeneration. (John Schloendorn, research program, paper)
Life extension: Examine the mechanisms of dietary restriction (DR) with further elucidation of TOR (target of rapamycin) pathways, a fast growing area of research. Find that inhibiting a downstream gene in the TOR pathway, HIF-1 (a transcription factor important for growth and metabolism), extends lifespan in worms. (Pankaj Kapahi, paper)
Life extension: Generate a 10x lifespan extension in C. elegans by silencing many components of insulin/IGF-1 signaling (IIS) possibly via the disruption of PIP3 (a key signaling molecule required for the membrane tethering of many signaling molecules). (Puneet Bharill, paper)
Amyloid plaque reduction: Use a known plaque imaging agent, ThT (Thioflavin T), as a therapeutic for amyloid plaques. (Silvestre Alavez, lab affiliation, paper)
Cancer protection: Find that naked mole rats have two layers of anti-cancer protection, humans have only one. p16 is the first-line-of-defense anti-cancer protection mechanism found in naked mole rats. Humans (and other organisms) also have p16 (a suite of three genes), perhaps the mechanism for its upregulation (probably a cell:cell signaling dynamic) in naked mole rats could be understood and turned on with an enzyme in humans. (Andrei Seluanov, earlier research)
Cognitive function: Find that neurogenesis is possible in aged organisms with exercise followed by cognitive stimulation (e.g.; tackling a puzzle or challenge); organisms can benefit by building up a larger reservoir of brain cells earlier in life by being exposed to a variety of external stimulation. (Gerd Kempermann) This author’s speculation: Perhaps neurogenesis could be further harnessed for brain enhancement beyond currently realizable human capacities as this mechanism is better understood.
Aging biomarkers: Upstream the aging focus to prevention by measuring biomarkers and introducing interventions. Some suggested biomarkers of aging are p16 gene levels (which can be decreased with exercise), telomere length, the level of senescent cells, and the number of circulating lymphocytes in the immune system (measure total T cells (CD3+), B cells (CD19+) and CD28 absolute numbers on CD8+ T cells). (Kronos research projects, test menu; telomere length measuring)
Hormones-IGF: Find no conclusive evidence of insulin-like growth factor's (IGF) ability to retard natural aging, though on an individual basis some people may find it useful. (Marc Blackman)
Hormones-HRT: Find that hormone replacement therapy (HRT) can be good for improving cognitive function and bone loss in women that do not have a risk of heart disease; HRT should be started with the onset of menopause, not later. (Barbara Sherwin, Eef Hogervorst)
Cost of reproduction: Find that ovary removal in grasshoppers resulted in a 25% increased lifespan, contributing to existing evidence regarding the high cost of reproduction. (John Hatle) This author’s speculation: In the farther future, in humans, it could be quite desirable to closely manage fertility, turning it on and off at will, if fertility is even necessary.
Micronutrients: Find tremendous nutritional benefits from the consumption of fruits with skin, especially blueberries (pterostilbene that reduces oxidative stress), blackberries, raspberries, red grapes, pomegranates, cranberries, plums, strawberries, cherries, pears and apples (phytochemicals that provide cancer prevention), walnuts (preventing the inflammation and oxidative stress of brain aging:), green tea (catechins that reduce cardivascular and cancer risk) and tempeh (fermented whole soy bean with folate is healthier than tofu (processed soy bean curd)). (Blueberries: Agnes Rimando, Rolf Martin; Apples: Rui Hai Liu, Walnuts: James A. Joseph, Green tea: Vojo Deretic, Tempeh: Eef Hogervorst)
Calorie restriction (CR)/dietary restriction (DR): Find that in humans, improved biomarkers for CR/DR, vegan and raw food diets that result in the extension of the onset of aging challenges. (John Holloszy)
Aging mice testbed: A mouse type that sufficiently recapitulates early aging, the human WS phenotype (Werner syndrome), has been created which could hasten mammalian aging research. (David Kipling)

Conclusion
Aging is a key contemporary issue. Research is advancing both incrementally and radically in every area of aging. The highest immediate impact could come from working on aging problems upstream at important fulcrum points that impact everything below them, such as genetics, epigenetics and the immune function. The research is progressing and it is starting to be time for VCs, big pharma and DIYbio’ers to take advantage of the many interesting and actionable possibilities.

The future of computing – rotaxanes?

2009-05-31T22:09:00.000-07:00

One of the great human endeavors at the moment is being able to work at the molecular scale (e.g.; 1-100 nm), using organic and inorganic materials for a variety of purposes ranging from basic materials to computing to electronics to life sciences therapeutics to energy. This includes the designed direction of existing molecular processes (e.g.; biology) and the synthesis of novel materials, structures and dynamic behavior.

Three of the most interesting advances in working at the molecular scale and examples of bio-infotech convergence are described below…

1) Hybrid organic-inorganic rotaxanes
First is the March 2009 work of David Leigh’s lab at the University of Edinburgh in creating hybrid organic-inorganic rotaxanes. A rotaxane (rota/wheel + axis) is a mechanically-interlocked molecular structure, essentially a dumbbell shape with a ring around its middle (Figure 1), often man-made but occasionally existing in nature. In this case, the dumbbell portion of the hybrid organic-inorganic rotaxane is an organic amine, the ring around the middle is a metal.

Figure 1: Rotaxane graphical schematic and crystal structure (source)

The benefit of metal-organic frameworks is that they have the properties of both organic and inorganic materials; structural and functional properties from organic materials and electronic, magnetic and catalytic properties from inorganic materials. This rotaxane molecule has directed shuttle-like behavior, where the metal ring around the center can be pushed to bind at either end, with its biggest potential application being in quantum computing.

2) Bio-inorganic interfaces
A second interesting example of molecular scale work and bio-infotech convergence is biocomposites/GEPIs (genetically-engineered peptides for inorganics) which regulate cell behavior and improve binding at bio-inorganic interfaces by modifying surface chemistry and immobilizing infection-causing bioactive molecules. Candan Tamerler’s lab at the University of Washington is doing some interesting work in this area. Improved bio-inorganic interfaces are needed for reduced infection and seamless interaction between human wetware and implants: heart, hip, prosthetics, eye, brain, etc.

3) DNA nanotechnology
The third interesting bio-infotech convergence example is DNA nanotechnology, the notion of using DNA as a structural building material (for example, for self-directed rapid templating) rather than as an information carrier. One key use is employing DNA as a programmable scaffolding for the self-assembly of nanoscale electronic components, meaning that scaffolds comprised of self-assembled DNA serve as templates for the targeted deposition of ordered nanoparticles and molecular arrays. DNA is formed into tubes and then metallized in solution to produce ultra-thin metal wires. John Reif’s lab at Duke University, Erik Winfree’s lab at Caltech and many other groups are working on DNA nanotechnology. Moving to the molecular scale for electronics manufacture is imperative for maintaining Moore’s Law computing performance improvements.

Future implications
It seems likely that working at the molecular scale and bio-infotech convergence will continue to grow. Organic-inorganic hybridization approaches could proliferate to exploit the full suite of properties afforded by organic and inorganic inputs, and as researchers suggest, lead to novel properties and the ability to harness molecular dynamics for human use.

Expanding notion of Computing

2009-05-24T11:07:00.000-07:00

As we push to extend inorganic Moore’s Law computing to ever-smaller nodes, and simultaneously attempt to understand and manipulate existing high-performance nanoscale computers known as biology, it is becoming obvious that the notion of computing is expanding. The definition, models and realms of computation are all being extended.

Computing models are growing
At the most basic level, how to do computing (the computing model) is certainly changing. As illustrated in Figure 1, the traditional linear Von Neumann model is being extended with new materials, 3D architectures, molecular electronics and solar transistors. Novel computing models are being investigated such as quantum computing, parallel architectures, cloud computing, liquid computing and the cell broadband architecture like that used in the IBM Roadrunner supercomputer. Biological computing models and biology as a substrate are also under exploration with 3D DNA nanotechnology, DNA computing, biosensors, synthetic biology, cellular colonies and bacterial intelligence, and the discovery of novel computing paradigms existing in biology such as the topological equations by which ciliate DNA is encrypted.

Figure 1. Evolving computational models (source)

Computing definition and realms are growing
At another level, subtly but importantly, where to do computing is changing from specialized locations the size of a large room in the 1970s to the destktop to the laptop, netbook and mobile device and smartphone. At present computers are still made of inorganic materials but introducing a variety of organic materials computing mechisms helps to expand the definition of what computing is. Ubiquitous sensors, personalized home electricity monitors, self-adjusting biofuels, molecular motors and biological computers do not sound like the traditional concept of computing. True next-generation drugs could be in the form of molecular machines. Organic components or organic/inorganic hybrid components, as the distinction dissolves, could be added to many object such as the smartphone. A mini-NMR or mini-Imager for mobile medical diagnostics from a disposable finger-prick blood sample would be an obvious addition.