Synthetic Biology

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= Synthetic Biology is A) the design and construction of new biological parts, devices, and systems, and B) the re-design of existing, natural biological systems for useful purposes. [1]

See: DIY Bio


What we should be afraid of

Dr. Mae-Wan Ho:

"Collins is upbeat about medical applications of synthetic biology, moving from synthetic biology of microorganisms into mammalian system, and engineering microbial communities that colonize the digestive system for therapeutics. These are exactly some of the applications that give me reasons to be afraid. Although microbial systems can be modified quite precisely, all attempts to target genetic modifications in eukaryotic cells have so far failed (which is why genetic modification of plants and animals is inherently uncontrollable and unpredictable), and methods to monitor the precision of gene targeting in mammalian cells are just now being developed [18]. Engineering microbial communities in the digestive system that we hardly know about is sheer recklessness, as these microbial communities are intimately intertwined with the physiology and immunity of the human host (see [19] Genetically Modified Probiotics Should Be Banned, ISIS scientific publication).

Profit before safety

In June 2011, the US Defense Advanced Research Projects Agency (DARPA) announced a $30-million, three-year programme called Living Foundries to support academic and corporate researchers bringing products to the market. “It's too early to predict the commercial importance of such a young field,” Collins remarked [16], “whether it will turn out to be the next semiconductor industry is hard to say.”

Not to be outdone, Britain issued A Synthetic Biology Roadmap for the UK in July 2012 [20] - commissioned by the Department for Business and Skills and published on their behalf by the Technology Strategy Board - citing an estimate that the global synthetic biology market will grow from $1.6 bn in 2011 to $10.8 bn by 2016, and calling for substantial public investments into establishing multidisciplinary centres, synthetic biology networks, and a “leadership council” with appointed subgroups to direct, coordinate, and oversee it all, and to ensure smooth passage from research to commercialization. It sounds like a potential bureaucratic nightmare of managed science by those who have little or no understanding of science, let alone safety, which is why I am thankful to have left academia.

Although the words “responsible” and “ethical” appear often enough, no civil society organisations were involved in drafting the document, only representatives from industry and research councils plus a few academic synthetic biologists and social scientists. There was no mention of public consultation at all. Being “responsible” seemed nothing more than adhering to “existing regulatory guidelines”, i.e., those applying to genetic modification for contained use and deliberate release, which may well be relaxed in future, in order not to unduly hinder commercialization. And the word “safety” does not appear anywhere.

Stranger dangers than conventional GMOs

While increased precision and reliability can improve the safety of genetic modification, the greatly expanded possibilities for engineering novel constructs and organisms also multiplies the dangers of intentional or accidental releases.

It is now possible to construct whole genomes of viruses and bacteria out of sequence information freely available on the web. Apart from the poliovirus synthesized from its published sequence in 2002 (see above), the virus responsible for the 1918-19 flu pandemic was similarly reconstructed in 2005 [21]. In 2008, Craig Venter Institute synthesized the first bacterial genome of M. genitalium; and in 2010, the team assembled the genome of M. mycoides and transplanted it into a M. capricolum cell to create new M. mycoides cells [22] (see also [23] Synthetic Life? Not By a Long Shot, SiS 47)

Many of the genetic constructs and organisms involved are novel in kind, such as the new bases for DNA, and new amino acids to be incorporated into proteins (see above), the safety of which is entire unknown. At the same time, ethical issues surrounding genetically modified animals and even human beings are brought into much sharper relief (see [24] Unspinning the Web of Spider-Goat, SiS 54).

In the present series, I highlight two flourishing areas that are on the point of exploding. One is the expanding use of nucleic acid aptamers, short sequences of RNA or DNA that bind to proteins or small molecules ( [25] Aptamers for Biosensing, Diagnosis, Druge Delivery and Therapy, SiS 56). The second is the rapid modification of entire genomes for practically any required use ([26] Mass Genome Engineering, SiS 56). These are developing so fast that safety is in real danger of being left behind.

As Ball remarked in 2004 [3]: “The expanding toolbox of ways to re-engineer microbes — and even construct new ones — has opened up extraordinary possibilities for biomedical discovery and environmental engineering. But it also carries potential dangers that could eclipse the concerns already raised about genetic engineering and nanotechnology.”

In July 2011, the Synthetic Biology Project at the Woodrow Wilson International Center for Scholars in Washington DC assembled a group of synthetic biologists and ecologists to explore the possible risks of introducing novel organisms into the environment, and how to assess those risks. These scientists are developing an eco-risk research agenda to help move the field forward in a productive fashion, while aiming to avoid serious ecological impacts.

They propose four areas of risk research:

  • Differences in physiology of natural and synthetic organisms, in the production of toxic substances or other harmful metabolites
  • How escaped microorganisms might alter habitats, food webs or biodiversity;
  • The rate at which the synthetic organism and its genetic material evolves,
  • Horizontal gene transfer.

They suggested a (very) minimum investment of $20 to $30 million over 10 years on risk research.

What the group of scientists have failed to propose is a moratorium on all environmental releases until the synthetic molecules and organisms are proven safe.

The issue is pressing, as pointed out in a report submitted to the Subsidiary Body on Scientific, Technical & Technological Advice of the Convention on Biological Diversity by an International Civil Society Working Group on Synthetic Biology [8]. There is at present no legal instrument that covers the regulation of the new constructs in synthetic biology, and no risk assessment protocol. There is a general assumption in the field that physical containment of synthetic organisms is not practical, especially within large scale commercial production systems. Natural disasters such as floods, earthquakes could readily lead to unintentional releases, as in the foot and mouth outbreak in the UK traced to broken waste-water pipes from Pirbright Laboratory. The behaviour of the novel constructs and organisms are simply unpredictable. It is now recognized that horizontal gene transfer is much more extensive than previously thought. A report published in 2010 documented horizontal gene transfer frequencies in the ocean thousands to hundreds of million times higher than previous estimates [27]. There should be no doubt that genetically modified DNA can spread readily by horizontal gene transfer with unpredictable and potentially uncontrollable consequences (see [28] Scientists Discover New Route for GM-gene 'Escape', SiS 50).

We should indeed be afraid of the lack of public consultation and regulation of an endeavour that may yield many beneficial and useful results, short of creating life; but could also unleash exotic deaths and destruction on people and planet." (