Biodesign: a Prevalent Cultural Trope

A new science or technology field really starts to capture the imagination and become mainstream when it seeps into art and culture. This is increasingly evident with bioart, bioprinting, and synthetic biology.

In bioart (using biological materials to make art), there have already been several phases starting with bacteria drawings in petri dishes and more recently culminating in DNA manipulation, live cells growing into cultured shapes in galleries, and the Algae Opera (an opera singer’s CO2 producing algae in real-time for audience consumption).

Bioprinting is an emerging field which marries the 3D printing revolution with biohacking and DIYlabs in the 3D printing of designed human materials for aesthetic and functional purposes.  

Synthetic biology (the design and construction of biological devices and systems) is being featured in art shows alongside industry conferences and in film festivals, including in its own Bio-Fiction, an international synthetic biology science, art, and film festival series.

Not only are we making art with biology as an artistic material, culture is being made in new ways through biology. 

The theme of biodesign is becoming prevalent as a cultural trope through the rapid expansion of designed biology into the arts, culture, collective human consciousness, and science and technology. These ideas are becoming quite normal, which can only mean that their demise through kitschification and cliché could be coming soon in a subsequent era of anti-bioart, post-bioprinting, post-synbio!

Blood tests 2.0: finger-stick and microneedle array

The farther future could include smartpatches - non-invasive, invisible, continuously-worn health self-monitoring skin patches. In the nearer future, a killer app for synthetic biology and other new chemistry and biology 2.0 methods could be the ability to create one's own vitamin supplements, and possibly innovate low-cost, non-prescription based finger-stick blood tests, and saliva and urine panels for self-testing.

Barrier to Citizen Science
A significant barrier to the wide-scale adoption of citizen science in the context of health self-management, intervention exploration, and preventive medicine implementation is the high cost, inconvenience and discomfort involved in obtaining traditional lab tests. While many tests may be ordered in a direct-to-consumer fashion through DirectLabs, the Life Extension Foundation, and other websites, it still costs ~$100 per test.

The challenge is to identify the requisite chemistry and processes involved and see if it may be possible to make simple consumer-friendly finger-stick blood test cartridges, similar to the glucose and HDL measurement kits sold at drug stores, which self-experimenters may perform at home or at community biolabs. Continuous monitoring via microneedle arrays would be useful for self-tracking glucose levels and other markers. For example, there could be consumer-targeted versions of the devices being developed by Orsense.

Figure 1. Non-invasive glucose monitoring device from Orsense

Community labs and high-end home labs may include the (CLIA-waived) Cholestech LDX machine (~$2,000 for the machine + ~$5-10 per measurement cassette) which can assess eight different lipid profiles.

Figure 2. Cholestech LDX finger-stick lipid measurement device

There is an urgent opportunity to expand the range of finger-stick measurement tests. Below is a Wish List of basic tests for one-off or comprehensive panel delivery.

Traditional Blood markers:

• Homocysteine
• Vitamin B-12
• Folate
• Vitamin D
• Creatinine
• eGFR
• Cortisol
• Calcium
• Iron
• Aldosterone

Hormones

• Estrogen
• Progesterone
• Testosterone
• Estradiol

Personal genome citizen science

Enough people are in possession of SNP genotype data from direct-to-consumer genomic services (e.g., 23andme, deCODEme, Navigenics) that collaborative citizen science genomics is starting to make sense. Participants could contribute genotype data for individual SNPs or their genotype data file (600,000 – 1 million SNPs) to secure peer collaboration platforms, with different levels of permissioning to different groups of ‘gene friends.’

Personal genome citizen science could be carried out in a number of domains ranging from ancestry to health to athletic performance. Research could both replicate and extend existing academic studies and look for new associations between genomic profiles and disease. Citizen scientists could explore and identify different kinds of phenotypic data to collect and apply in attempts to make genomic data meaningful and useful. The proven benefits of opening up datasets to the wisdom of the crowds could be expected with open personal genome research too.

Personal genome citizen science examples taken from the DIYgenomics Citizen Genomes Project list:

• One fun citizen science genomics project could be applying the information in the WIRED article “Don’t tell Geico, you may be a natural born bad driver.” DIY scientists could look up their genotype value for the relevant SNP (rs6265) on the BDNF gene and match this with actual driving records.
• Another project a Silicon Valley-based DIYbio team is starting to look into is Vitamin B12 deficiency. The two relevant SNPs on the MTHFR gene, rs1801133 and rs1801131, are genotyped by 23andme and maybe also by deCODEme and Navigenics. The first step is looking up genotype values for these SNPs, (AG and GT for one participant, for example). For more information on being a peer participant in this study, please contact m AT melanieswan.com
• A third opportunity concerns the application of existing genetic association studies to peer cohorts. For example, the long-awaited results from a Boston University centenarian study were presented in November 2009. Part of this study found 18 SNPs on the ADARB1 and ADARB2 genes for RNA editing associated with centenarians. Citizen scientists could identify individuals with the favorable genotypes for these SNPs and investigate whether these people have corresponding lack of phenotypic biomarkers of aging.
• Even better than having low-cost DNA sequencing tests for consumers would be being able to self-genotype in DIYbio labs. An early example of this was Katherine Aull genotyping herself for hemochromatosis.

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.

Synthetic biology – what is next?

Synthetic biology is the engineering of biology, re-designing existing biological systems and designing new ones, for a myriad of purposes. The most obvious killer apps are the improved synthesis of drugs and other medicines and the synthetic generation of biofuels.

Right now the most exciting aspect of synthetic biology –suggesting that the field is getting some traction – is that three key community constituents are getting more heavily involved: traditional academic researchers (SB 4.0 conference videos and agenda), undergraduates and high school students through the annual iGEM (international genetically engineered machines) competition (1200 students from 112 teams are expected at this fall’s iGEM Jamboree at MIT, and a growing group of non-institutionally affiliated enthusiasts, diybio’ers, the 2000s version of the Homebrew Computer Club, for both wetlab (an interesting recent example) and computer modeling, simulation and data management projects.

Venture capitalists are slowly starting to realize that synthetic biology could be a huge growth industry and could be the next generation of biotechnology. Amyris is probably the best-known synthetic biology company, estimating to launch its biofuel (ethanol) business publicly in Brazil and the US in 2011.

The long road to automation
Other waves in the history of biotechnology have shown that life sciences problems tend to be much more complex, take much longer than expected to solve and ultimately underdeliver results. There is no reason to think that synthetic biology would be any different, but it is obviously not futile to work on the challenges. When the synbio community analogizes their status to the heterogeneous screws and bolts of the construction industry circa 1864, they are not kidding.

The DNA synthesis process is astonishingly unautomated, unstandardized and expensive ($0.50-$1.00 per base pair) at present (it would be $15-30 billion to synthesize the full genome of a human (ignoring ethical, legal, etc. issues)).

Synthetic biology is a new field and the demand for synthesized DNA is still small; the 2,000 or so iGEM community members are the biggest market. Ginkgo Bioworks is working to deliver robotic synthesized DNA assembly and other startups would be likely to spring up in this area. Ginkgo has also helped to expand and improve one of the main synbio tools, the Registry of Standard Biological Parts.

Status of cancer detection

The Canary Foundation’s annual symposium held May 4-6, 2009 indicated progress in two dimensions of a systemic approach to cancer detection: blood biomarker identification and molecular imaging analysis.

Systems approach to cancer detection
A systems approach is required for effective cancer detection as assays show that many proteins, miRNAs, gene variants and other biomarkers found in cancer are also present in healthy organisms. The two current methods are one, looking comprehensively at the full suite of genes and proteins, checking for over-expression, under-expression, mutation, quantity, proximity and other factors in a tapestry of biological interactions and two, seeking to identify biomarkers that are truly unique to cancer, for example resulting from post-translational modifications like glycosylation and phosphorylation. Establishing mathematical simulation models has also been an important step in identifying baseline normal variation, treatment windows and cost trade-offs.

Blood biomarker analysis
There are several innovative approaches to blood biomarker analysis including blood-based protein-assays (identifying and quantifying novel proteins related to cancer), methylation analysis (looking at abnormal methylation as a cancer biomarker) and miRNA biomarker studies (distinguishing miRNAs which originated from tumors). Creating antibodies and assays for better discovery is also advancing particularly protein detection approaches using zero, one and two antibodies.

Molecular Imaging
The techniques for imaging have been improving to molecular level resolution. It is becoming possible to dial-in to any set of 3D coordinates in the body with high-frequency, increase the temperature and destroy only that area of tissue. Three molecular imaging technologies appear especially promising: targeted microbubble ultrasound imaging (where targeted proteins attach to cancer cells and microbubbles are attached to the proteins which make the cancerous cells visible via ultrasound; a 10-20x cheaper technology than the CT scan alternative), Raman spectroscopy (adding light-based imaging to endoscopes) and a new imaging strategy using photoacoustics (light in/sound out).

Tools: Cancer Genome Atlas and nextgen sequencing
As with other high-growth science and technology areas, tools and research findings evolve in lockstep. The next generation of tools for cancer detection includes a vast cataloging of baseline and abnormal data and a more detailed level of assaying and sequencing. In the U.S., the NIH’s Cancer Genome Atlas is completing a pilot phase and being expanded to include 50 tumor types (vs. the pilot phase’s three types: glioblastoma, ovarian and lung) and abnormalities in 25,000 tumors. The project performs a whole genomic scan of cancer tumors, analyzing mutations, methylation, coordination, pathways, copy number, miRNAs and expression. A key tool is sequencing technology itself which is starting to broaden out from basic genomic scanning to targeted sequencing, whole RNA sequencing, methylome sequencing, histone modification sequencing, DNA methylation by arrays and RNA analysis by arrays. The next level would be including another layer of detail, areas such as acetylation and phosphorylation.

Future paradigm shifts: prevention, omnisequencing, nanoscience and synthetic biology
Only small percentages of annual cancer research budgets are spent on detection vs. treatment, but it is possible that the focus will be further upstreamed to prevention and health maintenance as more is understood about the disease mechanisms of cancer. Life sciences technology is not just moving at Moore’s Law paces but there are probably also some paradigm shifts coming.

The three most suggestive areas for coming life science discontinuities are genomic sequencing, nanoscience and synthetic biology.

Genomic sequencing contemplates the routine scanning of each individual and tumor at multiple levels: genomic, proteomic, methylomic, etc. Nanoscience is the ability to design, construct and render mobile a large variety of molecular [biological] devices. Synthetic biology is designing new or modifying existing biological pathways in order to produce systems with superior or different properties, exercised by both traditional practitioners (recent conferences: Advances in Synthetic Biology, Synthetic Biology 4.0) and diybio’ers.