March 8, 2009

Biological standardization of functional modules

My exploration into genetic engineering for my M.Sc. thesis has led me to an interesting path of new exciting research in gene synthesis. For those of you that have not been in contact with this topic before, it can simply be described as the synthesis of gene-length DNA from chemically derived oligonucleotides, which in turn are short Feb 23 posting in McKinsey&Company: What matters: ”Over the past few decades, most new jobs, wealth, and growth were created in the knowledge and digital realm. And while venture capital represented only about 0.2 percent of US GDP, the companies it created generated about 17 percent of economic activity. The Internet changed virtually every industry. Yet as far-reaching as the digital revolution was, the ability to code life will likely reach even further.“.

BioBrick Standardization Process
DNA cannot currently be fabricated purely using an in vitro process (it still requires an intermediate step using a host organism, e.g. yeast or E.Coli). Nevertheless, a transition period has certainly begun. An interesting model in regards to this is the BioBrick Foundation that was introduced (according to Wikipedia) by Tom Knight (MIT), Drew Endy (Stanford) and Christopher Voigt (UCSF). The trademarked words BioBrick and BioBricks refer to a specific brand of open source genetic parts, defined via an open technical standards setting process;
1. You develop some scheme for standardizing some aspect of synthetic biology work.
2. You convince at least one other person, at a different location from you, that the scheme would help them with something that they care about.
3. You each demonstrate that the proposed standard works for each of you (i.e., the standard must work and be good for something).
4. You document your scheme in writing.
5. You request a BBF RFC number by asking for one (email the list)
6. The BBF technical standards group (i.e., the folks on this list) comment on the standard, try it out, propose revisions.
7. You revise the standard if necessary.
8. The standard is formally accepted as part of the definition for BioBrick parts. Congratulations, you win (publishers are standing by), the BioBricks technical standards suite is updated.
9. New, possible standards tremble before you! Goto 1.

Productification of Functional Modules
BioBrick parts are DNA sequences held in circular plasmids with precisely defined up- and downstream sequences (both of which are not considered part of the actual BioBrick part). Larger BioBrick parts are simple to create as the up- and downstream sequences contain six restriction sites for specific restriction enzymes allowing for ”chaining together“ of smaller ones. According to the Guardian, there are 3 levels of BioBrick parts;
1) Parts: encode basic biological functions
2) Devices: made from a collection of parts and encode some human-defined functions (such as logic gates in electronic circuits)
3) Systems: perform tasks (such as counting)


I have not been able to find any IPR policies or ownership governance, but according to an article in Nature Biotech it seems as the objective is to create openness and accessibility: ”Quantitative descriptions of devices in the form of standardized, comprehensive datasheets are widely used in the electrical10, mechanical, structural and other engineering disciplines. [...] We propose to adopt a similar framework for describing engineered biological devices. [...] Finally, because the receiver can be used in many systems and because we hope to promote the collaborative development and unfettered use of open libraries of standard biological parts and devices, all of the information describing the receiver is freely available through the Registry of Standard Biological Parts

Value Extraction
It will be interesting to see what type of interesting value extraction models that may arise from this open standard. Some early models related to education include;
* The International Genetic Engineered Machine (iGEM) competition
* The Build-A-Genome (BAG) class at John Hopkins University

To paraphrase Barry Schuler in his TED talk Genomics 101, about the fact that it is a fine line between playing god and learning the laws of nature. We are not creating anything artificial we are only changing around the already existing building blocks in nature to understand what the rules of the game are.

Tobias Thornblad

More state-of-the-art gene synthesis:

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