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)

Human morphology-changing technologies

To date, most technology has been human-created. It can be grouped into two categories, technologies that are not likely to have an immediate direct impact on human morphology, and those that might.

Technologies that would likely not change human morphology
There could be the rapid advent of significantly more dramatic technologies than have been experienced to date. While these new technologies could change some aspects of life, human biological drives could remain unchanged, and therefore the structure and dynamics of human societal organization, interaction, and goal pursuit could also remain unchanged. Some examples of these advances could include the realization of molecular nanotechnology, quantum computing, cold fusion, and immortality. Even with several of these revolutionary technologies implemented, the seemingly different world would not actually be structurally different if humanity is still ordered around the same familiar biologically-driven goals.

Technologies that might change human morphology
The other group of technologies is those which could possibly have a near-term impact on the structure and form of what it means to be human, for example, cognitive augmentation, genomic therapies, and synthetic biology. The area with the greatest possible change is improving human mental capability. There have been several significant advances in a variety of neurology-related fields in the last few years that if ultimately realized, could potentially alter human morphology. Even the resolution of all mental pathologies such as Parkinson’s disease, depression, stroke rehabilitation, and addiction would constitute morphological change at a basic level. Augmenting cognition and deliberately managing biophysical states would constitute morphological change at other levels.

Morphological reach of technology

Is technology simply the tools that humanity has created to further its will or a force that can change humanity? Whether arrowheads or supercomputers, humans have made technology to enable and reinforce human nature and evolutionary tendencies. However, it is possible that advanced technology could actually change humans, human nature, and biological drives, both unintentionally and by design.

Supercomputers surpass 2.5 petaflops

The biannual list of the world's fastest supercomputers was released on November 13, 2010. For the first time, supercomputing capability surpassed 2.5 petaflops with the world's fastest supercomputer, the Tianhe-1A - NUDT TH MPP, X5670 2.93Ghz 6C, NVIDIA GPU, FT-1000 8C NUDT, at the National Supercomputing Center in Tianjin China, clocking in at over 2.5 petaflops.

Figure 1 illustrates how supercomputing power has been growing in the last five years, starting at (a paltry) 136.8 gigaflops in June 2005, and experiencing four solid doublings in growth. This rate of progress is estimated to continue, and usher in the exaflop era of supercomputing by mid-decade. The IBM Roadrunner at Los Alamos was the first to achieve speeds over one petaflop in June 2008 and held onto the fastest computer seat for three measurement periods, then was surpassed by the Cray Jaguar at Oakridge for two measurement periods. China has now captured the fastest supercomputer ranking with its NUDT MPP.

Figure 1. Growth in Supercomputing Capability: Jun 2005 - Nov 2010

Source: Top 500 Supercomputing Sites List Releases

The world's supercomputers are working on many challenging problems in areas such as physics, energy, and climate modeling. A natural question arises as to how soon human neural simulation may be conducted with supercomputers. It is a challenging problem since neural activity has a different architecture than supercomputing activity. Signal transmission is different in biological systems, with a variety of parameters such as context and continuum determining the quality and quantity of signals. Distributed computing systems might be better geared to processing problems in a fashion similar to that of the brain. The largest current project in distributed computing, Stanford protein Folding@home, reached 5 petaflops in computing capacity in early 2009, just as supercomputers were reaching 1 petaflop. The network continues to focus on modeling protein folding but could eventually be extended to other problem spaces.