Do you remember, what you have been doing in 2003? I was 14, hanging out in a German High School and having a lot of different things in my mind but I certainly couldn’t have imagined that this year was about to be a milestone year for Synthetic Biology. In 2003, Tom Knight published his ideas on standardized DNA parts for Synthetic Biology. He called them BioBricks and while the publication itself seems to tell a story of simpler times, the BioBrick standardization became a huge success and probably everyone who came in touch with Synthetic Biology has at least heard about the basic concept.
Knight’s reasoned from an engineer’s standpoint. Standardization accelerated the innovation process in engineering and libraries of well described and standardized DNA parts have proven to be of great value for thousands of scientists. The original BioBrick assembly standard might seem nowadays laughably inefficient compared to modern multi-part, scarless assemblies. Everybody who participated in an iGEM competition knows the dreads of removing restriction sites from genes and then assemble pathways piece by piece. Nevertheless, the sheer number of different (not always compatible) DNA assembly methods and standards forces every scientist over and over to decide which standard will be the one for them.
Does this mean that we will never have one unifying standard for Synthetic Biology? Maybe we don’t even need one standard that suits all. But the issue of the many standards highlights how engineers and scientists don’t always speak the same language.
Knight cited in 2003 the Franklin Institute which developed in the mid-19th century the standards which make up today the regulations describing the size and form of screw threads (and many more things). This top-bottom process of standardization is fundamentally different from the open access approach that is practised by the Synthetic Biology community. Nobody could imagine or would want a state regulatory institution to tell scientists which DNA assembly method they should use.
Another reason why we might never see one universal standard for Synthetic Biology is the inherent higher complexity of nature. The BioBrick standard assumes that there is a simple relation between the “code” and the “output” in form of an amino acid sequence, we know that it’s more complicated. The 5’ untranslated region (5’UTR) has a huge influence on translation and the codon usage of different organisms can make the difference between efficient gene expression and none at all. If we are forced to tinker with those parameters because we have to remove a certain restriction that is not tolerated by the DNA assembly standard. That makes any standardization effort much harder.
Is then any standardization attempt fruitless? Not at all. A very promising approach is the standardisation of the design process which is being pushed by the Synthetic Biology Open Language (SBOL). ACS Synthetic Biology has already adopted SBOL and more journals might follow. While it doesn’t abolish all the drawbacks of different DNA assembly standard it is a promise for the future: All assembly standards rely on repositories where the DNA parts are stored physically because DNA synthesis of larger pathways is still too expensive for most labs. In a golden future, the costs will be so low that we design multi-part assemblies in the morning and get the physical DNA the next day. Until then, I will still ask myself: “What assembly now?”
I will probably touch on some of these topics in more detail in future blog posts. Let me know in the comments or on twitter (@sachsdaniel), what you are interested in most: State regulation vs Open Access in Synthetic Biology? Engineering approaches for Synthetic Biology? Future of DNA synthesis? I guess, you might call this the beginning of a series.
Knight, T. (2003). Idempotent Vector Design for Standard Assembly of Biobricks https://dspace.mit.edu/bitstream/handle/1721.1/21168/biobricks.pdf
Casini, A., Storch, M., Baldwin, G. S., & Ellis, T. (2015). Bricks and blueprints: methods and standards for DNA assembly. Nature Reviews. Molecular Cell Biology, 16(9), 568–576. https://doi.org/10.1038/nrm4014
Synthetic Biology Open Language, http://sbolstandard.org/