Passive cognizance: outsourcing thinking to computers

Product manufacturing went offshore from the US and Europe to China. Infotech services were outsourced to India. What is next in this flat world? [Even more] thinking could be outsourced to computers. Memory already has been…spelling, navigation, and fact recall, for example. Several forms of thinking have been already been outsourced to computers too, fraud detection and geological data review in oil exploration are the canonical examples. Passive cognizance could be the futurepath of humans; even more on autopilot than at present, behavior facilitated by personal digital assistants like SIRI based on continuous incoming lifecam and biomonitor data and utility function reassessment.

Reality: analog, digital, or information compression continuum?

The Foundational Questions Institute (FQXi) has a thought-provoking new essay challenge for seasoned physicists, cosmologists, and lay-persons to answer: “Is Reality is Digital or Analog?”

In one sense, analog and digital is not an either/or question but two points on a continuum. Analog and digital are different information compression algorithms, using frequency and amplitude as levers for modulating information onto electromagnetic spectrum. As analog has progressed to digital, so too could there be several subsequent phases of information compression algorithms that are denser than digital.

Along the electromagnetic spectrum (Figure 1), analog communication uses radio waves, analog and digital satellite communication uses microwave frequencies, and digital communication uses fiber optics in the visible spectrum. Next-gen terahertz communications systems are already under development.

Figure 1. Electromagnetic spectrum

Quantum computing modulates atoms with information. Eventually, maybe all atomic and energy quanta could be modulated with information (smart matter). In the farther future, modulating information onto the other three forces (strong, weak, and gravitational) could be explored, along with the modulation of dark energy and dark matter. Gadget of the future: dark energy multiplexer.

Figure 2. Harnessing gravity waves through muons despite their 1.56 microsecond half-lives?

Transcranial magnetic stimulation

An emerging technique for working with the brain is transcranial magnetic stimulation (TMS). In TMS, an electromagnetic coil is placed on the scalp and delivers short painless bursts of energy to stimulate nerve cells in the brain.

TMS has been suggested as clinical tool for the neurorehabilitation of many conditions including depression, hallucination, pain, tinnitus, Parkinson’s disease, and stroke, and possibly for neural enhancement in improving focus and concentration. NeuroStar, a TMS device used in the treatment of depression, was cleared by the FDA in 2008.

The non-invasive nature of TMS also makes it useful as a research tool. Some recent research using TMS has improved knowledge of motor control and perception:

1. adaptive motor learning in humans is related to cerebellar excitability and depression; motor learning could possibly be enhanced by noninvasive brain stimulation (paper)
2. the right parietal and frontal eye fields play a key functional role in the spatial updating of objects in trans-saccadic perception (TSP), the process of constructing an internal representation of the world from successive saccadic eye movements (paper)

New class of drugs: stapled peptides

Stapled peptides refers to a computational drug design technique that may create a whole new class of drugs by being able to more effectively target substances within cells and increase the number of proteins which can be targeted. Stapled peptides are generated through the synthetic enhancement of a 3-D alpha-helix protein segment with hydrocarbon bonds to make proteins more rigid and able to penetrate cell walls. The more rigid structure also gives stapled peptides longer lives through greater protease degradation resistance.

The two current classes of drugs, small molecules and biologics, are limited in that they can only target 20% of all proteins. Stapled peptides could allow a wider range of proteins to be used in drug-targeting. They are currently in clinical trials for the inhibition of a BCL-2 family protein, oncogene MCL-1, using an exclusive inhibitor, the MCL-1 BH3 helix, which could unblock caspase-dependent apoptosis in cancer cells (paper).

Synbio update: reference standards, protein fusions, and bioscaffolds

One of the core tools developed and used by synthetic biologists is the Registry of Standard Biological Parts which has over 5,000 available parts (paper). A contemporary research focus is on improving methods for working with the standardized parts. Three recent innovations are described below.

1. In vivo reference standards
One advance is in establishing in vivo reference standards for the different biological parts. For example, the absolute activity of different promoters (gene transcription regulators) varies across experimental conditions and measurement instruments. Variation in promoter activity was reduced 50% by using a selected promoter as an in vivo reference standard against which other promoters were measured (paper).

2. Construction of protein fusions
Another advance is in allowing the construction of protein fusions. This is not feasible in the current assembly standard due to an unfavorable scar sequence that encodes an in-frame stop codon. Restriction enzymes BglII and BamHI are employed in a new assembly standard that replaces the scar sequence with a generally innocuous glycine-serine peptide linker (paper).

3. Rapid circuit generation with BioScaffolds
A third advance is in the creation of a new part, a BioScaffold, that can be used in the rapid generation of synthetic biological circuits. The BioScaffold can be inserted into cloning vectors and excised from them to leave a gap into which other DNA elements can be placed. Targeted circuit modification simplifies and speeds up the iterative design-build-test process through the direct reuse of existing circuits (paper).

Regenerative medicine: conduits, augments, and blood-vessel printing

A medical advance that could have as large an impact on disease eradication and life extension as penicillin is regenerative medicine and tissue engineering. The field was perceived as revolutionary even a few years ago, but rapid advances have made it seem almost commonplace today.

Replacement organs grown from one’s own cells are desirable since this would avoid immune system rejection and a lifetime of immunosuppressive drugs and their side effects.

Hollow organs like the bladder are easier to create than the more solid liver and kidney, and the heart is the most challenging. The current status is that several dozens of lab-generated bladders have been implanted in humans.

In the case of other organs, the present focus of tissue engineering is on conduits (e.g.; providing a link to the outside of the body for waste removal (Tengion neo-urinary conduit clinical trials)) and augments (e.g.; providing a supplemental path for normal operations (Tengion neo-kidney augment and other augments)).

Vascularization, or blood-vessel printing, is an intense area of research focus, and there is some promising progress from at least two sources, well-known regenerative medicine research leader Anthony Atala, and tissue engineering startup darling Organovo. This could be a key step in allowing more sophisticated organs to be regenerated.

Cognitive and social enhancement tools

Computer software and the internet have long been cognitive enhancement tools. Spellchecker obviated the need for spelling skills. Wikipedia and the internet obviated the need for fact memorization. There is less reason to earn a PhD if the module might be available as a cognitive plug-in within a few years.

The need to speak foreign languages is reduced with Google Translate for Android.

Social networks like Facebook are acting as a social prosthetic. It is now possible to have a massively larger context-driven social apparatus with deep-interest specificity.

Accessing, assimilating, applying, and interacting around knowledge and information has become the critical 21c skill set.

Android mobile app for 23andMe data

DIYgenomics released a personal genome Android app update on January 9, 2011 adding three new elements of functionality: the ability to upload and store 23andMe data in the app, multiple views for health risk, drug response, and athletic performance (Figure 1), and a quality ranking system for each SNP.

Figure 1: DIYgenomics Android mobile app view categories.

What is this information?
Selecting any item displays a list of variants or SNPs (places of potential genetic typos), such as for Alzheimer's disease (Figure 2). The locus, gene and variant (SNP) details are shown, along with the normal type (e.g.; no mutation) for 23andMe data (if it exists) in black, an individual's 23andMe data (if loaded) with normal alleles in green and mutations (polymorphisms) in red. Stars (from 1-5) indicate the research quality of the SNP (per the journal ranking of the study, the number of cases and controls, etc.). The colored blocks show which service providers cite the SNP (per color legend), and how many studies they cite.

Figure 2: DIYgenomics health condition Alzheimer's disease.

What does this information mean?
In Health Conditions, a mutation (polymorphism) presented in red generally indicated being at higher potential risk for developing a condition. In Drug Response, a mutation could mean that the normal dose of the drug may not work as well, that there could be side effects, or that there could be a higher change of addiction (for substances). In Athletic Performance, the favorable mutation (green), suggests greater than average athletic capability.

Citizen science genomics

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

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

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

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

Top 10 technology trends for 2011

1. Mobile is the platform; mobile payment ubiquity could be next
2. Device proliferation continues; tablets, e-book readers, etc.
3. Connected media and on-demand streaming video, IPTV, live event interaction
4. Social shopping: grouppurchasing, commenting, recommendation, LBS
5. Sentiment engines (ex: Pulse of the Nation, We Feel Fine) are ripe for being applied much more broadly to other keyword domains; sentiment prediction
6. Big data era explosion: machine learning, cloud computing, clusters, supercomputing
7. Labor-as-a-service: microlabor, on-demand labor, global task fulfillment
8. Quantified self tracking gadgets and apps (ex: WiThings scale, myZeo, BodyMetRx, medication reminder, nutrition intake, workout coordination, DIYgenomics, etc.)
9. Personal manufacturing, digital fabrication, 3D printing ("atoms are the new bits"); slow but important niche growth
10. Real-time economics: blippy, crowdsourced forecasting, stock market prediction

(Review predictions for 2010)