Académie des technologies

Synthetic biology and (white) industrial biotechnologies

ADVICE NOTE ISSUED BY THE NATIONAL ACADEMY OF TECHNOLOGIES OF FRANCE (NATF), approved by vote at the October 10, 2012 plenary session

The National Academy of technologies of France (NATF) in this Advice Note throws light on issues that have accompanied the emergence of synthetic biology (SB) into the field of industrial biotechnological applications. The aim of the advice note is, on one hand, to identify the potential of this historic changeover from ‘naturalist’ biology to technology-intensive biology, in the contemporary context of industrial and societal challenges and, on the other, to propose various measures which if taken would favour the emergence of a knowledge-based bio-economy.

Synthesis biology

SB is defined by the OECD as: (1) the design and construction of new biological parts, devices, and systems, and (2) the re-design of existing, natural biological systems for useful purposes (definition from; it can be seen as a pursuit and extension of biochemistry.
The origin of the recent development of SB lies in the extraordinary progress made in techniques enabling reading and writing of genetic information, as associated with the upsurge of available computing power, of possibilities to analyse data from genomic sequencing, modelling of living matter, characterization of cellular metabolism, robotics and miniaturization of sensors. The end result is a systemic approach to cellular biology and absolutely new capacities in protein molecular engineering, notably with enzyme catalysers that combine rational a d combinatory approaches, metabolic engineering that allows scientists to introduce new metabolic paths and general erasing of parasite paths in a given microorganisms to produce new compounds that offer attractive industrial prospects.
Several research teams are pursuing the dream of assembling a « minimum » genome microorganism that remains viable and has the capacity to reproduce itself. The idea would then be to integrate, on demand, various metabolic paths creating, in essence, cell factory. We must emphasis here not only are we still a long way from understanding fully how even the simplest bacteria function, but that also, as far as the “synthetic bacteria” announced by Craig Venter in 2010 is concerned, only the chromosome was synthetic (albeit it was a formidable scientific achievement) and that the cellular ‘machinery’ in fact pre-existed. Synthetic living matter is still a very distant aim.
We can also envisage new forms of coding for genetic data, as well as the assembly of proteins made of non-natural amino-acids, illustrating the new possibilities of intervening on living matter that are not based on nature. SB could potentially lead to breakthroughs and new products that otherwise would not be accessible via classic genetic engineering.
These news to modify living matter, of course, raise numerous ethical, safety and intellectual property rights questions, which must be taken into account as soon as possible. The recent commissioning of the Observatory for Synthetic Biology at the Conservatoire National des Arts & Métiers, should place the actors in a position to answer the societal questions involved.
(White) Industrial Biotechnologies
Biological tools have been used my Men since very early, bygone days, to obtain interesting products from renewable raw materials, whether they be of animal or vegetable origins, firstly in a purely empirical manner (drinks, foods …); more recently, these same tools have been used in a rational manner to produce industrial molecule (antibiotics, organic and amino acids, enzymes, chemical additives and sweeteners). Thus a global scale industry for fermented products and processes using enzymes developed as of the 1950’s, with a production level measured in M tonnes/year. This is still a well-represented sector in France, even if we take into account the capital acquisitions that have also taken place in the past 2 decades.
Today, the possibilities to change living matter via BS processes has multiplied the application of biological tools in the chemical, materials and in energy sectors, with an economic context that is doubly marked by the forecast depletion of fossil fuel raw materials, and the need to limit, as best we can, the carbon print of industrial processes to preserve the environment. By 2050, some 15% (volume) of chemical products could have “bio” sources. We can already note the industrial success of synthons for polymer chemistry (lactic acid, 1,3-propanediol, succinic acid, isobutene …). One of the main challenges, apart from a necessary bolstering of those processes that enable the industrialists to attain efficient outputs, productivity and final concentration levels of the products, is to be able to access and exploit reliable sources of renewable carbon that prove economical to operate and which do not compete with foodstuffs. The valorisation of ligno-cellulose biomass (which are the bye-products or more accurately the co-products of agriculture, of forestry work and specific crops …) integrated to an overall “bio-refinery” concept is very necessary.
NATF Recommendations
France saw some considerable industrial developments in this field in the past, but we must now concede that the level of public and private investments remain low – if we disregard a few isolated initiatives. Implementing BS, which is above all other consideration a technology-intensive issue is a step our country must engage, as has been done in the USA and other EU countries. In order to encourage a rapid development in this new bio-economic field based on the valorisation of renewable carbon material, the following measures would be more than welcome:
• To provide support for research that will enable and facilitate access to microbial biodiversity to identify new genes and new metabolic paths : functional meta-genomics, metabolomics, bio-computer sciences, advanced modelling … it is important to underscore that classic microbiology still hold promise and can prove of major interest to pursue research work.
• To support the gene sequencing establishments and or associate data processing.
• To launch of engineering school cursus that integrate in a determined and original way BS within bio-technologies, modelling techniques, chemistry and process engineering.
• To create of critical R&D mass concentrations: the poles at Evry (the Genoscope, CEA), at Toulouse (Toulouse White Bio-Technology) are being set up thanks to financial incentives made available under the French Government’s ‘Investments for the Future’ programme.
• To support for development of industrial process pilot demonstrators and through fiscal incentives.
• To set up a process that would engage ethical and sustainable development reflections for all new industrial biotechnological processes.