How Daemon/Freedom is starting to happen

The books by Daniel Suarez, Daemon and Freedom, portray a possible extension of the world of today. Some elements contemplated in the books are obviously already in place such as worldwide gaming communities like World of Warcraft (11 million subscribers as of December 2008) and other MMORPGs. Botnetting of government and corporate computers is another existing feature of the contemporary world. High-magnitude financial crises (e.g., 2008) and dissatisfaction with the way they are handled is another obvious parallel, with grassroots responses such as the Move your Money movement to use local banks that did not receive bailout funds.

At a broader level, one of the most interesting ways that fundamental economic transformation could happen is the way that humans worldwide are starting to behave like a vast complex adaptive system (CAS).

1) Location-based services check-ins
Mobile-device users are checking in at the different physical locations they visit using FourSquare, Loopt, and other location-based services (LBS). People are shifting their physical-world behavior to unlock certain badges and points. In addition to earning badges and mayorships for the number of check-ins to a particular location, opt-in communities could develop using LBS platforms to award the type of check-ins, giving points and badges for behavior valued by the community. FourSquare's API is available and new applications are already being created. A simple example of rewarded behavior would be receiving double points for gym visits, escalating levels over time as visits accumulate. Another example for certain user communities might be earning double points for check-ins at local coffee shops vs. Starbucks. Starbucks actually comprises over 30% of all check-ins for LBS service Loopt.

Not just the geographical location, but also the type of activities could be rewarded. For example, there could be creativity, collaboration, learning, and teaching badges from check-ins at places like the TechShop, BioCurious, Hacker Dojo, or the Hub (social venturing collaboration). There could be time and location tagging for event attendance interpolation. Not every user would want this detail or would make their activity public, but this functionality could be useful for life-logging too. There could be sensors on public transit registering user behavior or some other way to ‘check in’ to transportation-based behavior.

There could be both incentives for positive behavior and disincentives for negative behavior. For example, users could receive points for not doing behaviors like checking in at fast-food restaurants, not going to gas stations (congratulations, you only went to a gas-station once this month!). A trustable automated check-in system could provide behavior validation, although there are obvious hacks such as not bringing the mobile device when going to fast-food locations. Finally, the spirit of incentivized check-ins should be opt-in, fun, and empowering, not didactic.

2) Real-time economy feeds
A second interesting complex adaptive system element that is arising is a real-time economy feed in the form of Blippy. Parts of the feed are publicly open and other parts just to the user community. The feed provides immediacy, transparency, and detail regarding economic activity, like real-time game-like granularity. Features could be added for zooming into views of more or less detail (e.g., real-time to-date, Amazon’s sales are down this month vs. last month). The user community can comment and interact around specific purchases.

In addition to the democratic openness of a real-time economy feed, this platform could be used the same was as LBS check-ins to reward certain behaviors. Blippy users could earn points for certain types of purchases, like carbon-neutral products certified by GoodGuide, Green Home, or ClimateCooler. Lower energy usage could be rewarded. With detailed purchase granularity, behavioral goals could be facilitated (e.g., Congratulations, you did not buy cigarettes this month! Congratulations, you bought less ice cream this month!)

3) DIYBio email list
A third fascinating development of humans as a complex adaptive system for change is the DIYbio movement. DIYbio is a worldwide self-sustaining collaborative community arising to build a new or complementary scientific order in biology. The story is told through these snippets of recent postings…

• DIYbio meeting Wednesday Jan 13th at 7PM: So all the DIYbio groups have hacked 300X microscopes out of $7 webcams.
• Plant stilbenes, SIRT1 activators; request for assistance: Hi, I am looking for tropical crop plants that produce phytoalexins called stilbenes; phenolic chemicals, that among other things, include molecules that activate the SIRT1 deacetylase. For the moment I am restricting my search to plants of the Fabaceae subfam. Faboideae (pea group). Currently, I am looking at the literature on Cajanus cajan (pigeonpea) & Arachis hypogaea (peanut, groundnut). I am also looking at literature on non-resveratrol stilbene activators of SIRT 1. I have linked two relevant papers for context.
• DIY movement in Shenzhen, China: I'm looking for a previous post about a DIY movement in Shenzhen, China, somebody posted it before but I can't find it now? It wasn't bio focused, more about electronics.

Aging research: systems biology, genomics and new tools

Three important themes emerged from the Buck Institute’s Systems Biology Symposium of Aging held November 10-13, 2009. The themes were progress in the overall understanding of aging as a systems biology problem, the role of genomics in aging, and new tools development for aging research. Happily, some immediately applicable tidbits were discussed: the findings of the protective response of endurance exercise, and the use of resistance exercise as a countermeasure to sarcopenia. (Mark Tarnopolsky)

Theme 1: Aging is a systems biology problem
Inflammation
Increasingly, aging is being understood as a systems biology problem involving cascades of signals across multiple pathways, many of which break down with aging. In younger organisms, problems are managed automatically as they arise, but in older organisms, the resolution processes do not work as well. When cells become damaged as a consequence of aging, they can either self-destruct through apoptosis (regulated cell death) or become senescent (living on without dividing). Senescent cells persist in tissues, where they may secrete inflammatory proteins. Many major age-related diseases, including atherosclerosis, heart attack, stroke and metabolic syndrome, share an inflammatory pathogenesis. The build-up of senescent cells can lead to both degenerative disease (aging) and hyper-proliferative disease (cancer). There are some efforts underway to facilitate the removal of senescent cells, for example, using an MMP inhibitor to kill senescent cells.

Dynamic regulatory continua
It is being suggested that more and more aspects of living systems such as humans are dynamic regulatory continua, and that there may be optimum points on the continuum which become harder to maintain with aging. One example of a dynamic regulatory continuum is the interrelation of cholesterol, fats, and Alzheimer’s disease. Having lower levels of the 142 alpha-beta plaques is neuroprotective, for example, but higher levels become harmful. One technique for understanding dynamic regulatory continua is to look at explaining the events at one biological level in terms of the events at the levels above and below them. (John Tower)

Signaling pathways
There is more of an effort to examine whole processes such as pathway networks and the chain of events in DNA transcription and translation. Current knowledge of signaling pathways is fairly primitive. The role of mRNA translation is being investigated as it is known to be related to growth promoting activities like cancer. There is the general translation of RNA, but this can be further modulated by the cell. In addition, signaling pathways are not working alone, there are probably many pathways converging. For example, there is likely cross-talk between several important signaling pathways such as the insulin pathway, the TGF-beta pathway, the IGF-1 pathway, and the TOR pathway. (Heidi Tissenbaum) In another example of the systemic interactions of aging, amyloid-binding compounds were found to suppress protein aggregation models in concert with homeostatic function (i.e., autophagy, chaperones, etc.). (Gordon Lithgow)

Theme 2: The role of genomics in aging
As with many areas of biology and medicine, the role of genomics is becoming increasingly important in aging. While it is known that there is little variation (0.1%) among SNPs in human genomes, 12% of the genome may vary structurally (copy-number variations, deletions, inversions and insertions of genes). On the threshold of whole human genome sequencing, it is being realized that SNP data alone is insufficient for a genomic understanding of health; more levels of data and annotated data, potentially including RNA sequencing to see protein expression will be needed. (Mike Snyder)

Variation in genomes
Three areas of research were presented regarding genome variation and aging. First were the long-expected results of Boston University's genome-wide association study (GWAS) on centenarians. The study found 150 SNPs in the genetic signature of longevity, 33 of which meet genome wide significance and are replicated. The most important longevity genes, most already associated with aging pathways, were: IL7 (immune system), CDKN2B (tumor suppressor), and APOE, CTNNA3, TOMM40, SORCS1, and SORCS2 (Alzheimer’s disease). (Tom Perls)

Related results were confirmed by personal genomics company 23andme. A study of senior athletes found that this cohort exhibited lower risk than the database in general. Ten chronic disease conditions were reviewed including coronary artery disease, breast cancer, prostate cancer, heart attack, type 2 diabetes, high blood pressure, high cholesterol, and macular degeneration. (Joanna Mountain) However, other research found that there is not a full overlap between genes conferring longevity and genes conferring increased healthspan. (Monica Driscoll)

Variation in genomic expression
Four interesting research findings found variation in genomic expression between older and younger organisms. First, another centenarian study found significant diversity of microbial communities in different age groups. For example, there was a high level of expression of certain miRNAs in older livers (miRNA-200c, miRNA-141, and miRNA-31). (Claudio Franceschi) A second study found that a full third of genome expression changed with age in worms. (Simon Melov)

A third study found a general relaxation in translational control and protein production during aging. It was proposed that increased or sloppy protein expression might contribute to proteotoxicity. (Monica Driscoll) Applying a systems biology and network analysis approach, a fourth study looked at how the structure of biological networks declines with age. The AGEMAP (a gene expression database for aging in mice) was reviewed, finding 26% fewer edges (edge nodes on the network) in 24 month old mice vs. 16 month old mice. It is possible that gene expression networks could lose integrity with age. An unexplored but possible explanation is that if there if less transcription, then network edges disappear. (Daniel Promislow)

Theme 3: New tools development for aging research
New approaches and tools are critical to advancing the study and potential remedy of aging, and three interesting talks were presented. First, progress in microfluidics and microscopy was discussed, particularly an exceptional development in electron microscopy that may allow the noninvasive molecular-resolution imaging of live samples (Figure 1). Usually electron microscopy is a destructive technique as the electron beam destroys the sample in the process of inspecting it. (paper: Noninvasive Electron Microscopy with Interaction-free Quantum Measurements). (Fatih Yanik)

Figure 1: In vivo noninvasive molecular imaging.

Image credit: http://www.rle.mit.edu/bbng

A second area of improvement has been in the targeted analysis of specific proteins. Now that there are robust measures for mRNA, proteins and post-translational modifications are the next areas of interest. Traditional shotgun analysis techniques are being improved upon by targeted analyses of specific proteins using mass spectrometry. The process is to take a protein mixture, produce peptides through proteolysis, collect a snapshot of multiple peptides at once, and use mass spectrometry to separate them by their mass. This method greatly expands protein identification and analysis capabilities, including the ability to do time course experiments. (Mike MacCoss)

Third, a genomic database tool, PharmGKB, was presented. The database facilitates a systems approach to pharmacology. Researchers can search for pharmacogenes, for example, given a drug and putative indication, ranking all genes in the genome for the likelihood of interactions. The database contains information regarding over 500 drugs, 500 diseases, and 700 genes with genotyped variants as of November 2009. (Russ Altman)

Top 10 technology trends for 2010

Some of the freshest ideas in 2009 were botnet futures (Daemon, Daniel Suarez), a variety of neuro scanning applications (The Neuro Revolution, Zack Lynch), a systems approach to Earth (Whole Earth Discipline, Stewart Brand), accelerating economic development through charter cities (Charter Cities, Paul Romer), automatic markets for fungible resource allocation (Broader Perspective, Melanie Swan), and the notion that the next-generation of technology needed to solve intractable problems could be non-human understandable and come from sampling the computational universe of all possible technologies (Conversation on the Singularity, Stephen Wolfram).

Heading into a brand new decade, there are several exciting technology areas to watch. Many are on exponential improvement curves, although from any viewpoint on an exponential curve, things may look flat. Most of this blog’s big predictions for 2009 came true. Here’s what could happen in the next year or so:

1. Closer to $100 whole human genome
Third-generation DNA sequencer Pacific Biosciences estimates that they are still on track for a late 2010 release of single-molecule real-time sequencing technology that could eventually lead to less than $100 whole human genome sequencing.

2. Mobile continues to be the platform
There will likely be a greater launch and adoption of addictive location-based services (LBS) like FourSquare, Gowalla and Loopt, together with social networking, gaming, and video applications for the mobile platform. Continued trajectory of smartphone purchases (one in four in the U.S.). iPhone and Android app downloads double again. Gaming expands on mobiles and on the console platform with Avatar and maybe other 3-D console games. Internet-delivered content continues across all platforms.

3. 22nm computing node confirmed for 2011
Intel possibly confirming and providing more details about the 22nm Ivy Bridge chip planned for commercial release the second half of 2011. The September 2010 Intel Developer’s Forum may feature other interesting tidbits regarding the plans for 3-D architectures and programmable matter that could keep computing on Moore’s Law curves.

4. Supercomputers reach 15% human capacity
Supercomputing capacity doublings have been occurring each few years and could likely continue. As of November 2009, the world’s fastest supercomputer was the Cray Jaguar, running at 1.8 petaflops (1.8 x 10¹⁵ flops), approximately 10% of the estimated compute capacity of a human.

5. Confirmation of synthetic biology fuel launch for 2011
Pilot plants are running and the commercial launch of the first killer app of synthetic biology, synthetic fuel, could be confirmed for 2011. Sapphire Energy and Synthetic Genomics are generating petroleum from algal fuel; LS9, petroleum from microbes; Amyris Biotechnologies, ethanol, and Gevo, biobutenol.

6. Smart grid and smart meter deployment
In energy, more utilities moving to deploy internal smartgrid network management infrastructure and starting to replace consumer premises equipment (CPE) with advanced metering infrastructure (AMI) for automated utility reading and customer data access. Dozens of efforts are underway in the U.S. (Figure 1).

Figure 1: U.S. Smart Metering Projects Map as of Jan. 2010

7. Increased choice in personal transportation
More electric vehicle offerings, greater launch of alternative fuels, a potential Tesla IPO announcement, and more widespread car share programs (i.e., City CarShare, Gettaround).

8. Real-time internet search dominates
More applications allow real-time search functionality through content aggregation, standards, and more granular web searches. Search could be 40% real-time, 40% location-based, 20% other.

9. Advent of health advisors and wellness coaches
Hints of personalized medicine start to arrive with the unification of health data streams (i.e., genomics, biomarker, family and health history, behavior, and environment) into personalized health management plans. Early use of health monitoring devices (i.e., FitBit, DirectLife) as a prelude to biomonitors.

10. WiMax roll-out continues
Clear adds more markets to its current 26. Increasing importance of integrated data stream management (video, voice, etc.) on fixed and mobile platforms.

Probably not happening in 2010 but would be nice…

• Kinko’s buys high-end 3-D printer (i.e., ZPrinter 650 or Dimension Elite or uPrint) and DIY product design communities go professional (i.e., Shapeways, Ponoko)
  
• Nanotechnology demonstrations of mechanical synthesis and positional assembly

Still waiting for significant progress regarding…

• 4G/LTE roll-out
• Driverless cars, on-demand personal rapid transport systems
• Ubiquitous sensor networks
• OLEDs

Advances in robotics

Robotics can be defined as the integration of sensors, computation, and machine systems to manipulate matter. Some of the most important current applications are in military use, factory automation, telepresence, entertainment, and human interaction. Some contemporary trends include bipedal robots, autonomous robotics, and swarm computing. Walking, instead of navigating around on wheeled or multi-legged bases, could open up a variety of new applications for robotics. Similarly, autonomous robotics could handle tasks at a higher level of abstraction with less of a control burden. Swarm computing could allow the efforts of multiple robots to be coordinated, for example in warehouse automation or RoboCup soccer.

Military robotics
The U.S. military’s current deployment of robots includes 7,000 unmanned aerial vehicles (UAVs) such as the Predator drone and 12,000 unmanned ground vehicles (UGVs) such as the PackBot (P.W. Singer, Wired for War). Boston Dynamics has developed several interesting robots for military use. One is the BigDog, a quadruped robot that can walk, run and climb on rough terrain and carry heavy loads. More recently, the company has been working on the PEDMAN bipedal robot which balances dynamically using a human-like walking motion and is to be used initially for testing chemical protection clothing by walking and climbing like a human. Another example of military robotics is the DARPA Grand Challenge, where there have been three rounds of competition for unmanned navigation vehicles, lastly in an urban environment.

Industrial robotics
A second important area is industrial robotics, extending automated machines by making them mobile. One leader in mobile robotic solutions for warehouse automation is Kiva Systems who uses robots to organize, manage and move inventory. The robots cooperate using swarm behavior by reading barcodes on the floor and other messaging systems. There are other examples of robots for potential use in corporate or health care environments. Willow Garage’s PR2 (Personal Robot 2) can autonomously open doors and locate and plug itself in to power outlets. AnyBots offers a corporate telepresence robot and a bipedal robot under development.

Personal robotics
There is also a research focus on creating robots with emotional intelligence for human interaction. Two notable examples are MIT’s Personal Robots Group and Hanson Robotics. MIT has robots such as Leonardo which has 50 independently controlled servo motors creating a full range of facial expressions. Hanson Robotics’ Zeno and other robots which have life-like skin created from frubber, a nanoporous materials advance in elastic polymers. For consumer use, robots are starting as small appliances such as the Roomba and Neato Robotics unit for home vacuuming and the Rovio for home security, and toys such as the Furby, Aibo, and Kondo.

Engineering life into technology

Information optimization, presently known as intelligence, is a centerpiece phenomenon in the universe. It arises from simplicity, then continuously breaks symmetry and cycles through instability on its progression to increasingly dense nodes of complexity and diversity.

A contemporary imbalance has arisen that exponentially growing technology is potentially poised to be a sole successor to human intelligence. A complex dynamical system is emerging in response, the engineering of life into technology. Numerous macroscopic and microscopic elements are under development which could together stimulate advancement to the next node of symmetry and stability, creating a phase transition in intelligence which could broadly include many varieties of sentience.

The macroscopic and microscopic network elements that comprise the complex adaptive system, engineering life into technology, are illustrated in Figure 1.

Figure 1: Elements of engineering life into technology

Progress in Aging: Secretome, mRNA and Nutrients

The U.S. National Institute on Aging held a Systems Biology of Human Aging conference in Baltimore, MD on December 8-9, 2009. Several interesting topics were considered including the complexities of modeling the process of aging, the role of RNA in gene regulation, neurodegenerative disease and vascular compromise, and gene expression and signaling networks.

Aging: break-down in signaling networks
Aging is a systems biology problem where signaling networks break down. As part of the signaling break down, senescent cells secrete inflammatory proteins which together can be thought of as the ‘secretome.’ Judy Campisi has found that the secretome, the senescence-associated secretory phenotype (SASP), can provide a common biological explanation for the related phenomena of aging, degenerative disease and cancer. Senescent cells produce the SASP, essentially inflammation, which can then trigger degenerative disease (aging) and hyper-prolific disease (cancer). A potential solution is to remove the 10-15% of senescent cells that are not naturally killed by the immune system. Some secretome research has been applied specifically to vascular smooth muscle cells which have the tendency to unhealthily proliferate and migrate with aging, in a process called the pro-inflammatory age associated arterial secretory phenotype (AAASP).

RNA and gene regulation
With mRNA analysis it is possible to obtain the transcriptome, the complement of DNA that has been synthesized into RNA and exists in a cell at any given time snapshot. This is starting to allow findings that the process of transcription and translation is probably more tightly coordinated than previously thought, and that translational control could be a dominant force in transcription. The norm is starting to be that RNA binding protein and non-coding mRNA expression should be identified too in analysis, not just protein expression. Generally, DNA is much more active than initially thought with perhaps 90% of the human genome being actively expressed in some cell of the body. The level of certain mRNAs can be an upstream pathway indicator of aging as mRNAs may increase or decrease with aging which can cause the level of damaging proteins to increase. For example, MKK4 increases with the overexpression of four mRNAs.

Alternate day fasting and nutrients
Alternate day fasting may potentially confer the same benefits as calorie restriction in animals and humans, both in physical and neurological health. Neurodegenerative disease and neurological decline are part of aging pathologies. A countermeasure may be to increase the levels of certain proteins, especially BDNF, brain-derived neurotrophic factor, which is neuroprotective, neurogenerative and important in plasticity and synaptic activity. Some nutrients that may help to increase BDNF levels are sulforphane (broccoli), curcumin (tumeric), catechins (green tea), allicin (garlic), hypericin (St. John’s Wort) and plumbagin.

Digital personas

There are more machines than humans on the internet, and more machine-to-machine traffic than human-to-human traffic despite the trillions of text messages sent every year. Perhaps the most interesting category of messaging is machine-to-human. There are many mundane examples of this such as RSS feeds, automated email notifications and status updates from entities (groups, companies and other organizations). Coming innovations in machine-human communication could be quite fun and life-enhancing.

There are already fan-run Twitter accounts, FaceBook parodies and other interaction sites for fictional characters, often contemporary television characters. The next step could be creating digital emulations that could automatically respond in character. For example, subscribing to the Ben Franklin feed – “ooh-zapped the heck out of myself with my kite last night.”

There could be many uses for digital personas in addition to entertaining status updates, for example, having kids hang out with Marie Curie and the Wright Brothers as role models. It could be interesting to have a society where dead or fictional characters become part of the conversation, having a voice and a lasting ongoing presence. Digital personas could be managed with sliding parameters (e.g.; amp up Churchill’s humor), and have add-on modules (get the early-adopter technophile package for the great-grandmother persona...”I’m off to text in my response to Dancing with the Stars.”)

Digital personas would not need to be exclusively reserved for dead or fictional characters, anyone could create one as a facsimile with some sort of fidelity from current digital content, data and other artifacts. Celebrities could possibly earn greater remuneration by renting their emulations rather than through live engagements involving their actual physical persona.

As robotics continue to advance, digital persona overlays could be applied so that Franklin Lloyd Wright or Frank Gehry could walk around and discuss home renovation plans with you, Lady GaGa could be at your next soiree or Einstein and Feynman could join a scientific brainstorming session. A new field for productive and entertainment endeavor could emerge to create and bring together the digital personas of historical figures for problem-solving and fun. Would ‘Lost’ be better with Genghis Khan, Ella Fitzgerald, Moctezuma, Rosalind Franklin and Sherlock Holmes in the cast? Lawmakers could obtain measured input by running the Thomas Jefferson and John Adams personas simultaneously. The world’s great scientific and intellectual minds could be assembled to focus on current problems.

Genomics – The Global Opportunity

Genomics is particularly interesting as a candidate area for possibly making the most difference the most quickly to the most people worldwide by contributing to developments in energy, food and public health.

A full understanding of genomics, the instruction set for life, could mean a more comprehensive ability to manipulate both the world around us and the world within us. Biology evolved to be just good enough to survive and genomics provides the critical next-generation toolkit for its greater exploitation. With the possibility of a complete understanding of biology and the ability to engineer life to be optimum, traditional limits can be overcome, moving from the gene therapies of today (replacing or silencing one gene) to working with whole genomes and possibly creating new ones.

The global challenge and opportunity is for humanity to move safely and expediently into the genomic era of biological manipulation.

The agricultural applications of genomics have been underway for some time in the form of genetically-modified crops. Energy applications of genomics are in development using synthetic biology to generate fossil fuel replacements and are estimated to be ready for commercial launch in 2011. The public health application of genomics is especially promising, using genomics to further understand and eradicate disease. Genetic information is already starting to be medically actionable and is likely to become increasingly useful over time. Its two main current uses are in pharmacogenomics, personalized therapeutics, categorizing drug responders and non-responders for tailored treatment, and in routing higher-risk individuals to earlier screenings for chronic diseases such as prostate cancer and breast cancer. It is estimated that each individual is in the upper 5% risk tier for at least one chronic disease and that $100,000 per person per condition could be saved as a result of earlier detection. By 2010, according to a World Health Organization (WHO) report, cancer will surpass heart disease as the world’s greatest killer, and in fact, developing countries could be at the highest risk due to smoking and high-fat diets.

As our molecular understanding of disease progresses and genomic technologies continue to decrease in cost and become increasingly medically relevant, the use of genomics could become quite widespread. Physicians could start to see the precise, additive information conferred by genomics as a means of improving the care now delivered, finding themselves initially encouraged and eventually regulated into incorporating genomics in care regimens. Pharmaceutical companies are already using genomics as a means of improving efficacy in drug discovery and delivery, providing much-needed assistance to their ailing cost structures. Individuals worldwide could have unprecedented access to their health information which could prompt a much greater level of responsibility-taking and health self-management.

Humanity: hedgehog or fox?

Isaiah Berlin discusses an interesting paradigm for understanding different kinds of thinkers, the hedgehog and the fox. The hedgehog operates under a single vision while the fox incorporates many ideas into a worldview. Philip Tetlock applies this framework to an analysis of political predictors and finds that while all expert predictors are bad, foxes are not as bad as hedgehogs. The success of the fox is perhaps partly due to Bayesian updates, adjusting the synthesis-oriented worldview per new information, as opposed to the hedgehog being stuck trying to fit all new developments into the same model.

Humanity: hedgehog or fox?
It could be argued that so far all of human history has been organized around certain grand hedgehog visions such as mastery over matter, immortality or evolution, to name a few.

Mastery over Matter
Over time, humans have been continually demonstrating increasing mastery over matter. The current focus is on improving control of biology and indeed reengineering it with genomics and synthetic biology, matter with 3D printing and eventually molecular nanotechnology, the brain with fMRI technology and smart-drugs and space with a next-generation understanding of physics. Perhaps the most intense version of mastery over matter is the present focus on the biomolecular interface, the integration of organic and inorganic matter. However mastery over matter may not persist as a paradigm, a future redefinition could include mastery over information.

Immortality
Immortality is another grand vision, persisting from the time of the Pharaohs and earlier to long-established religious beliefs to the contemporary notions of life extension, uploading and cryonics. In some sense, immortality is just another kind of mastery over matter.

Evolution
Evolution is a strong paradigm, explaining many things, and connotes a higher order than just mastery over matter since not everything is matter. Evolution can examine more phenomena, including the progression of intelligence, possibly across substrates as is contemplated with artificial intelligence. However, despite myriad application attempts, it is not clear yet whether evolution can explain everything, for example the laws of physics and how the universe developed.

Conclusion
Since even in a simple analysis, no one model can explain everything and there are multiple ideas relating to a composite explanation of human activity, the conclusion would be that humanity bears more resemblance to the fox model than the hedgehog model. Tetlock’s finding that the multi-viewed more adaptable foxes are better could likely hold true for societies and humanity in general as well as for individuals.

MMP inhibitor to kill senescent cells

Important work in the understanding and remedy of aging at the Buck Institute’s Systems Biology Symposium of Aging held November 10-13, 2009 was presented by Judith Campisi in a keynote talk, “The Four Horsemen – Damage, Inflammation, Cancer and Aging: Integrating Aging and Age-Related Research.”

Summary
Campisi has found a common biological explanation for the related phenomena of aging, degenerative disease and cancer: the senescence-associated secretory phenotype (SASP). Senescent cells produce the SASP, essentially inflammation, which can then trigger degenerative disease (aging) and hyper-prolific disease (cancer). A potential solution is to remove the 10-15% of senescent cells that are not naturally killed by the immune system by using matrix metalloproteinase (MMP) inhibitors.

Background
Humans are much longer-lived than other organisms such as flies because they have evolved cell-dividing mechanisms for tissue regeneration and repair. However, mistakes in the form of mitotic mutations occur during this process and build-up cumulatively which can cause cancer. To counter the build-up of mutations, tumor suppressor mechanisms evolved. One action of gate-keeper tumor suppression mechanisms is to direct damaged cells to senesce, or lose function.

Senescent cells are not harmless, they amass at sites of inflammation and pre-cancer and secrete up to 40 different cytokines (immunoregulatory proteins) which together can be thought of as the SASP secretome. All major age-related diseases share an inflammatory pathogenesis including atherosclerosis, myocardial infarction, stroke and metabolic syndrome. The build-up of senescent cells can lead to both degenerative disease (aging) and hyper-proliferative disease (cancer).

The purpose of the cytokines is to repair tissue. In the SASP secretome, they are perhaps trying to summon the immune system, communicating to the rest of the tissue that there is a problem. The immune system does arrive and kill most senescent cells, but 10-15% survive, perhaps due to the over-expression of matrix metalloproteinases (MMPs) which can cleave the ligands off the cell surface where natural killer cells would bind, allowing the cell to escape the immune system.

Solution
Extending the existing research and application of matrix metalloproteinase (MMP) inhibitors, chemicals that mimic the binding site, Campisi’s lab has been able to drive senescent cell killing to 95%.