Publications: Science Omega Review UK Issue 1

The synthetic springboard

Test tubes
It is clear that synthetic biology will change the nature of energy storage, construction materials, information processing and, of course, pharma and medicine.
Dr H Bernauer & M Fischer
International Association Synthetic Biology Board Members Dr Hubert Bernauer and Markus Fischer provide insight into the scope and practical applications of synthetic biology…

The vast number of different organic biomolecules that contribute as the building blocks of the natural organic world are functional all-rounders. Besides their pure structure and structural information, they provide physiological bioactivity and biocatalysis (coding information) of the highest importance. In addition, they can harvest light and (semi-)conduct current, creating colours by absorbing specific wavelengths of light and fluidic crystals to electronically induce mixed patterns of colours for our imaging technologies. These biomolecules are also involved in bio-mineralisation processes.

An important fact is that most reactions within organic matter are performed at moderate temperatures, pH and water pressure with low energy consumption by the biocatalysts. This is a natural process dating back at least 3.5 billion years.

All organic matter in the world is created by self-assembly that finally ends in its decay, the products of which are channelled back into the global cycle of matter as carbon, nitrogen and phosphorous (among other things), without any waste. In contrast, traditional human technologies, such as metallurgy, classical synthetic (an-)organic chemistry and silicon technologies, are in principle linear, producing non-biodegradable toxic waste. Recycling of such dead-end waste consumes a huge amount of energy, requiring highly toxic solvents and creating substantial environmental and health risks. Over the next four years, the production of electronic waste is expected to double to 90 million tons a year.

Synthetic biology tremendously increases the technological potential of handling organic matter in the form of artificial molecules, which have been produced before using natural processes.

Some technological breakthroughs in other fields prepared the fertile ground for synthetic biology, such as the explosion of capabilities in molecular technologies, DNA synthesis chemistry and gene assembly as well as analytical high throughput sequencing and mass spectroscopy.

Primarily, synthetic biology is the extension of the capabilities of natural bio-organics towards all possible organo-chemical compounds mediated by information processing molecules such as natural DNA. However, the true scope of the discipline goes far beyond optimising existing chemistry.

Applied synthetic biology has an impact on all variants of biosyntheses, such as small molecules (fine chemicals, biofuels), biological active compounds (biopharmaceuticals) on variants macromolecular applications, as well as a high impact on medical applications in all indication fields and prosthetics, bio-mineralisation, bioelectronics and biorefining. However, the major breakthrough is that at the end of its life, recycling the synthetic biology technology requires low energy consumption and there is no waste production.

In all fields of human life, synthetic biology can have a substantial and beneficial impact, but its most imminent impact is in the revolution of medical therapy, companion diagnostics, individualised medicine and medical supply. Real cures for genetic ailments, such as metabolic and neurodegenerative diseases, as well as infections, could be built on effective gene-based therapies and stem cells.


Advances in the field

A plethora of important prerequisites of synthetic biology were discovered and invented decades ago, such as basic cloning strategies, restriction enzymes and DNA synthesis techniques. However, recent years have seen breathtaking new concepts and breakthroughs in synthetic biology. This started with a standardisation and commoditisation of the underlying building blocks (genetic elements such as promoters and enzyme-coding genes, but also bacteria and other organisms serving as ‘chassis’), and goes on to high level concepts such as orthogonal biology, cell-free biology and fully synthetic systems that blur the boundary between living and mechanical entities.

The traditional gradual, piecemeal modification of natural biological systems is being complemented by more radical changes that are designed rationally onto cells that have been stripped of large parts of their natural genetic programme.

Synthetic biology-based advances in real-world applications are presently most visible in the pharmaceutical drug pipelines. Even with a field as young as synthetic biology, the number of applications in the pharmaceutical industry cannot be overlooked, where basic synthetic biology technologies are making inroads in biopharmaceutical drug development and are becoming increasingly important.

Other fields are also starting to adopt synthetic biology technologies and synthetic biology-based development approaches, ranging from the production of synthetic rubber precursors by fermentation, to advanced biosensors built on a bacterial chassis, to biofuels and renewable bulk chemicals. It is clear that synthetic biology will change the nature of energy storage, construction materials, information processing and, of course, pharma and medicine.

Overcoming the challenges

Synthetic biology is a set of powerful new technologies, and as such, it also brings with it the potential for misuse and accidents. A challenge for this new field, therefore, is the safeguarding of current and future synthetic biology processes, both in terms of biosafety and biosecurity. Fortunately, scientists and industry players in synthetic biology have shown exceptional initiative and responsibility, in addressing questions of safety and security very early on. In elaborate community processes, The International Association Synthetic Biology (IASB) and others have created codes of conduct for the responsible handling of DNA synthesis and other aspects of synthetic biology. Law enforcement, safety agencies and international stakeholders have collaborated very early on in order to ingrain biosafety and biosecurity into synthetic biology right from the start. As opposed to many other disruptive technologies, synthetic biology safety was implemented even before the first industrial applications became available.

Other challenges are more mundane. Despite a nice line up of early real-life applications, take up of synthetic biology techniques by established industries – be it manufacturing, pharma, fuels or electronics – remains slow. Some of the most exciting academic concepts in synthetic biology are still waiting to be adopted by industry and translated into tangible products. Even in the 21st Century we are still surprisingly dependent on steel and coal, and many industrial fields are using the same approaches as they did 100 years ago. It is therefore important for synthetic biology to interface more directly with traditional industry sectors and to highlight the benefits to be reaped from a new synthetic biology-based economy: highly sustainable closed production circuits, highly customised materials and properties at commodity costs, and technical systems that feature the adaptability, homeostasis and fault tolerance of biological systems.

Support and funding within the field

Funding for synthetic biology is, at the same time, both abundant and scarce. Comprising a wide range of technological building blocks, it is often difficult to decide whether a particular project actually falls into the domain of synthetic biology. This confusion leads many public funding agencies to steer clear of it, focusing instead on the individual building blocks, such as orthogonal biology, metabolic engineering or biosensing.

Public funding for synthetic biology is very limited, and while the entry barriers are low due to low prices for synthetic DNA and molecular biology components and services, cutting-edge synthetic biology projects are still notoriously expensive and highly risky. Considering the substantial societal benefits synthetic biology could bring in the mid and long term, more public funding is desperately needed. This is especially true in continental Europe, where synthetic biology has strong roots, but which is currently being outpaced by ambitious initiatives in the US and the UK. There is a silver lining, though: synthetic biology features prominently in the EU’s ambitious Horizon 2020 programme.

However, public funding can only play the role of a facilitator for an emerging market. Much more important in the long run will be the development of synthetic biology in the commercial sector. Prime target customers for synthetic biology are the manufacturing industry, biotech and pharma. All three sectors have so far been outrageously slow in approaching synthetic biology, even at a time when conventional manufacturing is facing severe sustainability problems and pharma’s development pipelines are drying up. Synthetic biology could refuel these industries and possibly even break the age-old paradigm that economic growth can only happen at the expense of non-renewable resources.

Therefore, the time is right to create a strong interface between synthetic biology stakeholders and traditional industry – which is where the main priorities of networking activities must lie.

Dr Hubert Bernauer
Member of the Board

Markus Fischer
Member of the Board

International Association Synthetic Biology (IASB)

[This article was originally published on 20th March 2013 as part of Science Omega Review UK 01]


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