subota, 16 Juli 2016 08:09

Synthetic Biology

By Nermina Lamadema, Postdoctoral Research Associate at King's College London

Human beings have been altering the genetic code in animals and plants for millennia by selective breeding for desirable traits. All characteristics of a living being are determined by the set of instructions (genetic code) which resides in their DNA and is sometimes referred to as the genome.

Nowadays the process of developing new plant and animal breeds is speeded up as a consequence of recent technological advances in the field of biotechnology.  Scientists are capable of reading, understanding and manipulating one organisms’ genome to select useful features and add it into another organism in a process called genetic engineering. With the advances in the DNA sequencing technology which is becoming more powerful and less expensive new insights can be gained into the ways of potentially improving health of humans and domesticated animals, preservation of endangered species and advancing agricultural applications.

Most recent advances are occurring in the field of synthetic biology where the scientists have been able to make new sequences of DNA from scratch. By combining modern engineering, IT, and chemistry with basics of biology novel organisms can be designed to do new things--like produce biofuels or excrete the precursors of medical drugs. This field is rapidly expanding with novel advances being made continuously and the field definitions are being updated as the progress is being made. According to the SynBERC which is a US based research program dedicated to the research in Synthetic biology

"Synthetic biology is a maturing scientific discipline that combines science and engineering in order to design and build novel biological functions and systems. This includes the design and construction of new biological parts, devices, and systems (e.g., tumour-seeking microbes for cancer treatment), as well as the re-design of existing, natural biological systems for useful purposes (e.g., photosynthetic systems to produce energy). As envisioned by SynBERC, synthetic biology is perhaps best defined by some of its hallmark characteristics: predictable, off-the-shelf parts and devices with standard connections, robust biological chassis (such as yeast and E. coli) that readily accept those parts and devices, standards for assembling components into increasingly sophisticated and functional systems and open-source availability and development of parts, devices, and chassis."

The possibilities are therefore limitless and vast. Scientists may soon be able to design programmed biofuel producing or toxin sensing living cells. Another exciting possibility is design of cells that will release precise quantities of insulin depending on body’s requirement.

Biological circuits composed of reusable genetic components open the door to the possibility of engineering versatile toolboxes which can be used to design cellular versions of transistors and switches. According to the Synthetic Biology database ( there are around 116 synthetic biology product so far generated with over 50 already on the market or very close to it and the remainder on the horizon in early development. The products that are already on the market have found wide range of applications ranging from industrial processes in cosmetics manufacturing, food flavourings, improved properties biofuels, antibiotics and medicine production, phthalate free plastics, synthetic rubber for tyre manufacture, ethanol production, bio-based moulding material etc.

One of the most cited success stories come from anti-malarial drug Artesiminin. The precursor compound Arteseminic acid traditionally derived from Chinese Sweet Wormwood Plant used to involve long and expensive extraction process yielding low quantities of material. However, a company called Amrys has created yeast strains capable of large scale production of the same compound using standard fermentation procedure.

Another famous albeit controversial example is a Synbio Vanilla produced from genetically engineered yeast programmed to produce synthetic vanillin destined for food flavourings amongst many other things.

The only limits in the field are biology itself which provides serious challenges to the engineering approaches. The hype is often very far from the reality. For example Lego images presented in the press to depict how different parts of biological systems may fit and lock in a simple way do not realistically convey the challenges related to the fact that much of the genome sequence remains uncharacterized which poses a problem especially when dealing with protein coding sequences. Furthermore, it is not always clear how does the performance and configuration of different components used in circuit change depending on the cell type used or under different laboratory conditions.

Furthermore, it’s not always clear if the parts once assembled together will interact as expected as a whole because of the complexity of biological systems. It may be possible to predict the cell behaviour using computer modelling algorithms but the cell is still a living operating entity with endless levels of complexity.

For example when the scientists at Boston University in Massachusetts tried to create a bacterial cell with a genetic timer that controls expression of two genes they encountered problems relating to balancing of promoters where no matter what they did one of the promoters overpowered the other. Another important issue to consider is that as the size of the circuit becomes larger the testing and construction process becomes more complex. At Arymis it took 150 scientists many years to bring anti-malarial compound near to the market due to the process requiring refinement and research of many pathways involved in gene regulation. Finally many components used in the synthetic biology are not compatible and can cause unintended side effects where sometimes a foreign gene that is inserted into a host cells can lead to the changes in the behaviour of the host system such as cell growth, health and so on. Synthetic biologists are developing solutions to these issues to ensure that the circuits can function reliably for any given system be it a yeast or bacterial cell. Long term circuit use could potentially give rise to genetic mutations which may cause the circuit to cease function altogether which is another issue to contend with. So despite many potentially exciting usage possibilities for synthetic biology this area of science remains progressing albeit at a very slow pace dictated by the complexity of biology systems in nature.

This technology sometimes called extreme form of genetic engineering is not without its opponents. Concerns exist over the synthetic biology products entering food chain with calls for more stringent regulation and evaluation of potential risks vs. benefits. Friends of the Earth argues for putting more pressure on the key stakeholders such as the US government, oil and agricultural business which invest heavily into this kind of research in a drive to generate a new ‘bioeconomy’ based on living factories. The demand is for more stringent control and research to be put into what effects on the environment and human health will this new technology have once it is fully unleashed.

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