II.a. Biosafety in synthetic biology: anything new?

[e-conference]

In order to focus on the biosafety risks from a scientific point of view it is necessary to distinguish as clearly as possible the safety issues that arise in synthetic biology from those associated with other life science activities. Many scientists argue that synthetic biology opens up fascinating new opportunities for the future bioeconomy while on the other hand when asked about the biosafety risks they unenthusiastically comment that these will remain the same as before.

Is it really possible that such a promising new enabling technology will only yield useful and desired outcomes and doesn’t automatically create new unintended consequences?

Does synthetic biology raise new biosafety questions, and if yes, which ones?

[stevensynbiosafe]

Nothing in academic science is fought over more than a trademark. At present, three very different groups are attempting to claim the "synthetic biology" trademark as their own. The first is the modern version of the "synthetic biology" defined by Waclaw Szybalski, who used this term in the 1970's to describe the use of recombinant DNA technology to reassemble existing genetic elements into a single life form. This is effectively what Jay Kiesling is doing in a new department of synthetic biology at UC, for example. It carries with it the same biosafety issues as those discussed in Asilomar over 30 years ago, as it is the same thing. The somewhat fragile compromise crafted at Asilomar (that the hazards of synthetic biology were minimal, but that the scientific community would responsibly handle whatever risks existed, and would use these tools only to address significant problems) is being undermined in the public perception by some organizations attempting to use the tools for trivial things (e.g the videos of giggling high school students using recombinant DNA technology to make bacteria that smell like bananas because "making new organisms is cool"). But notwithstanding the social problems that this cavalier attitude creates, in fact, making bacteria that smell like bananas does not present any real biosafety issues. And although the ready accessibility of synthetic DNA makes it easier to do malicious things with recombinant DNA technology, this creates only a quantitatively larger biosafety issue, not a qualitatively new one. Likewise, the Smith-Venter minimal organism goals is synthetic biology in this vein, and delivering the same value that synthesis has done for a century: Pursuit of a difficult goal drags scientists across uncharted terrain where they are forced to encounter and solve unscripted problems. Thus, synthesis drives innovation and discovery in ways that analysis cannot.

A second, quite different, use of the "synthetic biology" trademark describes attempts to create a Darwinian chemical systems not by recombining existing parts of natural systems, but by building these from the ground up. In practice, natural biological systems are used in this process (at the very least, the graduate student doing the work). Eric Kool defined this use of "synthetic biology" in 2000 at the lowest level: getting these artificial chemical systems to work within natural living systems. At a higher level, one refers to thoughts by George Church (and others) to make E. coli that use a different genetic code, or use D-amino acids to make proteins by translation. Work in the Benner laboratory is at a still higher level: making artificial genetic systems with 12 letters in the DNA alphabet (instead of four), for example. The farther these systems move away from standard biochemistry, the less they would be able to parasitize natural living organisms, and the less of a biohazard they present.

[Markus Schmidt]

Steven, you mentioned an important point, namely that there is more to synthetic biology than the biobricks/metabolic engineering approach: the creation of biochemical systems or new life forms that are based on a different biochemical set of "components".
Changing the genetic code by using more and or different base pairs (e.g. Benner lab), or creating a new sugar backbone for the gentic code (e.g. Herdewijn lab in Leuven). This work finally aims to create a parallel biosystem, a parallel world that cannot directly interact with life as we know it. It could help to improve current biosafety problems e.g. by circumventing the problem of unwanted gene flow. In that respect the challeges are qualitatively new.

What was called a rather quantitative change is the inherent de-skilling agenda of the standardized bioparts approach, to make it ever more easier to design living biochemical systems. In case this appraoch proves to be successful, a much larger circle of people will be able to do "cool" and useful things. By that you would not only create a quantitative change but also a qualitative change, because then you would have new groups of people able to generate biosystems a la carte outside the current small and regulated circle of people (biotech companies, university labs etc.). This means that even high school students, and practically everybody would be able to design their own bug. Oversight would then be hardly possible (maybe even unwanted) but the biosafety risks would remain the same. That I think is also a qualitatively new biosafety issue.

[a.forster]

Does synthetic biology raise new biosafety questions, and if yes, which ones?

Yes. For example, the synthesis of poliovirus and the 1918 influenza virus from synthetic oligodeoxribonucleotides. These experiments were simply not possible until a few years ago. Given that they were performed and published within currently existing regulatory frameworks, and given the dangers associated with accidental release of the flu or deliberate resynthesis of it for bioterrorism, new regulations are sorely needed.

Anthony C. Forster, MD, PhD
Vanderbilt University