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%.

Ubiquitous information technology fields

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

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

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

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.