Precautionary approach to synthetic biology needs to be translated into effective regulation

Algal ponds such as this one in the USA, used as part of efforts to produce bilofuels, pose serious containment risks. Pacific Northwest National Laboratory CC BY-NC-SA 2.0
Algal ponds such as this one in the USA, used as part of efforts to produce bilofuels, pose serious containment risks. Pacific Northwest National Laboratory CC BY-NC-SA 2.0

by Almuth Ernsting ([square brackets])

The Ad-hoc Technical Expert Group (AHTEG) on Synthetic Biology [1] reaffirmed the need to observe the precautionary approach in relation to synthetic biology. Its report lists 15 potential adverse impacts of synthetic biology and emphasises the need for comprehensive case-by-case risk assessments. Disappointingly, no agreement could be reached as to “whether or not current methodologies to address the environmental impacts of the components and products of synthetic biology are adequate or even needed”.

There are many important arguments and reasons why existing regulation of synthetic biology (both for intentional and unintentional releases) is wholly inadequate, highlighted in the “Principles for the Oversight of Synthetic Biology” supported by 111 civil society organisations. [2]

Synthetic and other genetically engineered microorganisms are almost always used in conditions which existing regulations defined as ‘contained’. During the 1980s and 1990s, when governments were developing ‘contained use’ regulations for GE microorganisms, those uses were primarily in the medical sector, and thus inside laboratories. Even then, evidence of how inadequate such regulations were for preventing a release of genetically engineered microbes was emerging. [3] Inherent problems with ‘containment’ are analysed in the Secretariat of the Convention on Biological Diversity’s Technical Report on Synthetic Biology, published March 2015. [4]

Minimal regulatory risk assessments

Today, ‘contained use’ of genetically engineered microorganisms commonly means their use in biorefineries and other industrial plants which are entirely different environments from biotech laboratories. Regulatory risk assessments of supposedly ‘contained’ industrial uses of GE microalgae, fungi or bacteria are minimal, even when safe physical containment appears unlikely and biological containment may not even be attempted. This is illustrated by two examples: The US synbio company Amyris has been engineering bakers’ yeast to produce farnesene, a chemical not naturally produced by any microorganism. According to Amyris, this involved 13 different manipulations
to the genome of S. cerevisiae. [5]

Recently, Amyris has been focussing on another isoprenoid, farnesene to produce small quantities of biofuels and, primarily, personal care products. Amyris is reported to have been creating and testing 400,000 yeast strains per week and shipping the most promising ones to Brazil. The US authorities have waived the requirement for a full risk assessment and regulatory oversight. [6]

In Brazil, Amyris’s farnesene-producing yeast has been approved on the basis that baker’s yeast is generally safe, as is the organism from which a gene was transferred, sweet wormwood. Yet the yeast strains have been subjected to intensive metabolic engineering and bear little resemblance to any natural organism. They are designed to produce chemicals which no microorganism can produce in nature. A risk assessment based on the properties of ordinary bakers’ yeast and sweet wormwood is clearly inadequate to assessing the risks of such a synthetic yeast. Because the GMO has been classed as ‘safe’, there is no regulatory oversight of containment procedures inside Amyris’s refineries. Yet industrial refineries rely on engineers who have no academic background in biosafety and there are many more opportunities for GE microorganisms to escape than there would be in closed laboratories.

Another company which also uses synthetic microorganisms, and which obtained a waiver from regulatory oversight and from the requirement for a full risk assessment in the US, is Joule. Joule has been engineering cyanobacteria of the genus Synechococcus so that they directly convert carbon dioxide contained in seawater into hydrocarbon fuels. [7] According to one peer-reviewed article, Synechococcus is one of two genera of cyanobacteria which “dominate the photoautotrophic picoplankton over vast tracts of the world’s oceans where they occupy a key position at the base of the marine food web and contribute significantly to global primary productivity”. [8]

Despite the keystone role of Synechococcus in marine ecosystems, not a single assessment of their potential ecological impacts or likelihood of genetically engineered strains surviving in nature has been published. All that separates Joule’s genetically engineered bacteria from the open environment are two thin tubular plastic sheets, which need to be flushed out regularly. [9]

A precautionary approach to synthetic biology will be meaningless unless it is translated into effective regulations that include so-called contained industrial uses of GMOs, in line with the Principles of Oversight developed by civil society.

[3] See for example
[7] The initiation ketosynthase (FabH) is the sole rate-limiting enzyme of the fatty acid synthase of Synechococcus sp. PCC 7002, James Kuo and Chaitan Khosla, Metabolic
Engineering, March 2014
[8] Molecular biology of the marine cyanobacterial genera Proclorococcus and Synechococcus, David J. Scanian and Nyriee J. West, FEMS Microbiology Ecology, 1 April 2002