Genomics Goes Read-Write

One of Larry Lessig's favourite tropes is that we live in a read-write world these days, where creation is just as important as consumption. Well, hitherto, genomics has been pretty much read only: you could sequence the DNA of an organism, but creating entire genomes of complex organisms (such as bacteria) has been too tricky. Now that nice Dr Venter says he's gone and done it:

A team of 17 researchers at the J. Craig Venter Institute (JCVI) has created the largest man-made DNA structure by synthesizing and assembling the 582,970 base pair genome of a bacterium, Mycoplasma genitalium JCVI-1.0. This work, published online today in the journal Science by Dan Gibson, Ph.D., et al, is the second of three key steps toward the team’s goal of creating a fully synthetic organism. In the next step, which is ongoing at the JCVI, the team will attempt to create a living bacterial cell based entirely on the synthetically made genome.

The team achieved this technical feat by chemically making DNA fragments in the lab and developing new methods for the assembly and reproduction of the DNA segments. After several years of work perfecting chemical assembly, the team found they could use homologous recombination (a process that cells use to repair damage to their chromosomes) in the yeast Saccharomyces cerevisiae to rapidly build the entire bacterial chromosome from large subassemblies.

He even gives some details (don't try this at home):

The process to synthesize and assemble the synthetic version of the M. genitalium chromosome began first by resequencing the native M. genitalium genome to ensure that the team was starting with an error free sequence. After obtaining this correct version of the native genome, the team specially designed fragments of chemically synthesized DNA to build 101 “cassettes” of 5,000 to 7,000 base pairs of genetic code. As a measure to differentiate the synthetic genome versus the native genome, the team created “watermarks” in the synthetic genome. These are short inserted or substituted sequences that encode information not typically found in nature. Other changes the team made to the synthetic genome included disrupting a gene to block infectivity. To obtain the cassettes the JCVI team worked primarily with the DNA synthesis company Blue Heron Technology, as well as DNA 2.0 and GENEART.

From here, the team devised a five stage assembly process where the cassettes were joined together in subassemblies to make larger and larger pieces that would eventually be combined to build the whole synthetic M. genitalium genome. In the first step, sets of four cassettes were joined to create 25 subassemblies, each about 24,000 base pairs (24kb). These 24kb fragments were cloned into the bacterium Escherichia coli to produce sufficient DNA for the next steps, and for DNA sequence validation.

The next step involved combining three 24kb fragments together to create 8 assembled blocks, each about 72,000 base pairs. These 1/8th fragments of the whole genome were again cloned into E. coli for DNA production and DNA sequencing. Step three involved combining two 1/8th fragments together to produce large fragments approximately 144,000 base pairs or 1/4th of the whole genome.

At this stage the team could not obtain half genome clones in E. coli, so the team experimented with yeast and found that it tolerated the large foreign DNA molecules well, and that they were able to assemble the fragments together by homologous recombination. This process was used to assemble the last cassettes, from 1/4 genome fragments to the final genome of more than 580,000 base pairs. The final chromosome was again sequenced in order to validate the complete accurate chemical structure.

But the real kicker was this comment:

“This is an exciting advance for our team and the field. However, we continue to work toward the ultimate goal of inserting the synthetic chromosome into a cell and booting it up to create the first synthetic organism,” said Dan Gibson, lead author.

Yup, you read that correctly: we're talking about porting and then *booting-up* an artificial genome, aka digital code of life.

The Genome Goes Read-Write

Good Craig:

Craig Venter, the controversial DNA researcher involved in the race to decipher the human genetic code, has built a synthetic chromosome out of laboratory chemicals and is poised to announce the creation of the first new artificial life form on Earth.

...

Mr Venter said he had carried out an ethical review before completing the experiment. "We feel that this is good science," he said.

Bad Craig:

He has further heightened the controversy surrounding his potential breakthrough by applying for a patent for the synthetic bacterium.

The old dichotomy....

Open Source Self-Governance

A little while back I wrote about the idea of using wikis for open government. Peter Suber - about whom Bill Hooker commented recently "not a sparrow falls in the OA world but PS knows about it!" - emailed me with some interesting news about an earlier project of his called Nomic:

Nomic is a game I invented in 1982. It's a game in which changing the rules is a move. The Initial Set of rules does little more than regulate the rule-changing process. While most of its initial rules are procedural in this sense, it does have one substantive rule (on how to earn points toward winning); but this rule is deliberately boring so that players will quickly amend it to please themselves. The Initial Set of rules, some commentary by me, and some reflections by Douglas Hofstadter, were published in Hofstadter's "Metamagical Themas" column in Scientific American in June of 1982. It was quickly translated into many European and Asian languages. Games were regularly played, and kicked off, the ARPANET, the Defense Department network which sired the Internet. Nomic has been used to stimulate artistic creativity, simulate the circulation of money, structure group therapy sessions, train managers, and to teach public speaking, legal reasoning, and legislative drafting. Nomic games have sent ambassadors to other Nomic games, formed federations, and played Meta-Nomic. Nomic games have experienced revolution, oppressive coups, and the restoration of popular sovereignty. Above all, Nomic has been fun for thousands of players around the world. For me, it was intended to illustrate and embody the thesis of my book, The Paradox of Self-Amendment, that a legal "rule of change" such as a constitutional amendment clause may apply to itself and authorize its own amendment. (Nomic is the third appendix of the book.)

The connection with open governance is clear. Peter passed on the news that people are trying to apply a Nomic-based approach to open source:

Just last week, by chance, a total stranger proposed a Nomic-variant as a serious system of "Open-Source Self-Governance" (his words).

Here's what that site has to say about the project, which is called Efficasync:

Efficasync is a method of open-source self-governance, where all the members of a group have the ability to examine, discuss and modify their group’s set of operational goals, reasonings, constraints, procedures and arrangements. In computer lingo, each member of such a group has both ‘read’ and ‘write(2)’ permissions to this set of governing statements. As demonstrated by the previous two lines, this document occasionally recasts a few traditional views of governance into a computer programmer’s frame of reference. The programmer’s paradigm holds a new, and potentially valuable, perspective for democratic governance. This document’s purpose is to describe a specific way, based on this new perspective, that a directly-democratic group’s governing infrastructure could be arranged. In doing this, the three main components which constitute Efficasync are explained: a Nomic, a particular graphical interface, and a starting set of ‘rules.’ This document was written with the intention of presenting a prototype for emulation and extension by groups wishing to operate as open-source selfgoverning entities.

Fascinating stuff.