Synthetic Biology: Engineering Life or Engineering For Better Life?

Mention the term synthetic biology to a non-specialist audience and you will no doubt evoke a range of responses, from enthusiasm, inspiration and inquisitiveness to suspicion, frustration and fear. In response to a survey question by the Royal Academy of Engineering, “What words come to mind when I say synthetic biology?” the most common answer turned out to be “don’t know” or “nothing”. Why does the public perception of synthetic biology remain so hazy?

Synthetic biology as a science has been around long before the term became popular in the media. As early as 1912, the French biologist Stephane Leduc published la biologie synthetique, where he sought to model and understand the physical forces governing life, like cell division. This was several decades before Watson and Crick proposed their model of DNA (1953), or the ability to manipulate DNA with restriction enzymes was realised (1971).

Today the field of synthetic biology has grown to encompass two broad research areas linking biology, chemistry and engineering  – the first concerns itself with the redesign of existing natural biological systems, whereas the second focuses on the construction of new biological parts or devices from scratch. The overall goal is to understand the living world around us by rebuilding parts of it – either through reverse engineering or a bottom-up approach, with the underlying aim of engineering molecules for applications in medicine, energy and the environment.

Perhaps one of the most well publicised efforts in this field is the work of Craig Venter on the construction of a self-replicating cell containing artificially synthesised DNA. Using gene sequencing techniques, Venter and his colleagues duplicated the million base-pair nucleotide sequence of the bacterium Mycobacterium mycoides. After modifying the DNA by adding deliberate mutations and certain “watermark” genes, they inserted the genes into a close relative, Mycobacterium capricolum, lacking any of its own genetic material. The artificially synthesised DNA was able direct the metabolism of its host cell, and replicate, creating a new type of M. mycoides cell.

Other scientists have adopted a plug-and-play approach to synthetic biology, by constructing an off-the-shelf registry of standardised biological parts. Designing a cell to perform a specific function from scratch can be fiddly and time-consuming, but it is much easier to work with a universal pre-fabricated chassis, with the flexibility to plug-in one or more well-characterised genes. One such example is the BioBricks project, started by scientists Tom Knight, Drew Endy and Christopher Voigt. Using this approach, scientists have been able to program cells to perform customised functions, including mine detection and the ability to solve mathematical problems.

The generation of clean, energy-efficient, low-cost fuel ranks high in the current priority areas of synthetic biology applications. Solar energy is an example of an energy source that is readily available, yet difficult to harness.  Plants only utilise a tiny fraction of the available light energy available to them. Now a group led by Travis Bayer is attempting to redesign the photosynthetic systems found in nature. Their strategy involves linking photosynthetic bacteria to chemotrophic bacteria using electrically conductive nanowires – the photosynthetic bacteria absorb light energy and convert it to electrons, which are shunted along the nanowire to the chemotrophs, capable of efficient fuel production.  Another group, headed by Jay Keasling, have succeeded in engineering E coli to produce biodiesel directly from cheap, readily available sources like sugars in plant waste.

Synthetic biology also offers new hope for the treatment of diseases like malaria and cancer.  One of the most promising leads in this area is the production of low-cost anti-malarial drugs. Using gene segments from three different organisms, the Keasling lab engineered a new metabolic pathway in yeast cells, giving them the ability to synthesise amorphadiene, a precursor of the anti-malarial drug artemisinin. This strategy will allow for artemisinin to be produced in large quantities at a fraction of the current cost. In another recent development, the pharmaceutical company Ziopharm tied up with the biotech company Intrexon to treat cancer using artificially synthesised DNA capable of producing anti-cancer proteins on cue, with minimal toxic side effects.

What are the risks in this new era of engineered biology? Will our technology allow us to programme any type of living cell with the desired function? The reality is far more humbling – the current technology only allows us to manipulate cells at a very basic level. Trying to recreate more complex cells, like human cells or even more complex bacteria, will require a lot more work.

What concerns people is the lack of official safeguards and the easy of availability of “off-the-shelf” parts. While scientists advocate an open-source ethos, ethicists urge caution till more stringent regulations are in place. Is a compromise, in the form of regulated research, possible?

In 2010, President Obama called on the US bioethics commission to do a 6-month study on the “potential medical, environmental, security, and other benefits of this field of research, as well as any potential health, security or other risks.”  The commission found that the current uses of synthetic biology did not pose any novel safety or ethical issues, but recommended self-vigilance by synthetic biologists and the incorporation of “suicide-genes” which would limit growth of the organism outside the laboratory. Recently, open-source software from Virginia Tech, called GenoTHREAT, has become available, which allows gene synthesis companies to scan incoming DNA sequences for potentially harmful sequences.

Ultimately, synthetic biology and society must find a way to interact with each other, if the technology is to flourish. Good, clear, factual science communication should outweigh sensationalism of science, and public understanding should take equal priority with publishing new developments in the field.

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