Unlocking the Potential of SynBio for Improving Livelihoods in Africa

Synthetic biology (SynBio) is an interdisciplinary field that has developed rapidly in the last two decades. It involves the design and construction of new biological systems and processes from standardized biological components, networks and synthetic pathways. The goal of Synbio is to create logical forms of cellular control. Biological systems and their parts can be re-designed to carry out completely new functions. SynBio is poised to greatly impact human health, environment, biofuels and chemical production with huge economic benefits. SynBio presents opportunities for the highly agro-based African economies to overcome setbacks that threaten food security: The setbacks are brought about by climate change, land degradation, over-reliance on food imports, global competition, and water and energy security issues among others. With appropriate regulatory frameworks and systems in place, the benefits of harnessing SynBio to boost development in African economies by far potentially outweigh the risks. Countries that are already using GMOs such as South Africa and Kenya should find the application of SynBio seamless, as it would be a matter of expanding the already existing regulations and policies for GMO use.


Introduction
The past two decades have been characterised by a boom in a new interdisciplinary field anchored on the application of engineering principles in biology called synthetic biology These can be in biosensing, biomanufacturing and biotherapy. They follow a typical designbuild-test cycle (Xiang et al., 2018). Inspired by computer science and electronics, synthetic gene circuits have been designed to control the flow of information in biological systems.
SynBio offers the ability to redesign existing biological systems or their parts to carry out new functions (Enyeart et al., 2013;Lu et al., 2009;Chen et al., 2017). It makes use of interchangeable and standardized "biological-parts" so as to construct complex genetic networks that allow robust and tunable transgene expression in response to changes in signal input (Young and Alper, 2010; Guiziou et al., 2018). Using the same engineering principles, existing organisms can be redesigned for new or enhanced purposes to satisfy human needs.
The key for development of biocomputing SynBio based approaches is in Boolean logic functions design and implementation in cells (normally encoded into genetic material). Logic gates, counters, multiplexers, adders, and memories have been engineered in cells. Through There is tangible evidence demonstrating that SynBio is poised to have major impacts in a number of fields such as human health, environment, biofuels and chemical production (Mcdaniel and Weiss, 2005;Serrano, 2007;Khalil and Collins, 2010;Schmidt, 2010).
Engineering principles are now being applied to complex multigene constructs that include pathways and whole genomes. Where genes that are essential for a minimal bacterial genome are synthesised and at times transplanted into microbial cells. This has made feasible and simple previously impossible tasks (Goold et al., 2018). SynBio offers technologies such as whole cell biosensors that can be used in environmental monitoring, bioremediation, landmine detection as well as production of safer alternatives such as biodegradable plastics (Lee et al., 2006;Gogerty and Bobik, 2010;Teo, 2014, Belkin et al., 2017Goold et al., 2018). SynBio is being propelled into prominence by the ever-decreasing costs of DNA sequencing and DNA synthesis and the increasing speed at which they are being accomplished. This is facilitating a paradigm shift in molecular sciences (Goold et al., 2018).
Of particular interest, in this paper, is the applicability of SynBio in agriculture extending beyond crop development. The far-reaching applications stretch from farm management to agri-intelligence systems right up to post-harvest stages to reduce risks of product spoilage (Liu and Jr, 2015). SynBio poses a huge economic potential with the global market expected to be valued at US$38,7 billion by 2020 (Allied market research, 2019). Agriculture, which is one of the bedrock of African economies, faces an increasingly challenging future due to a lot of factors among them climate change, land degradation, over reliance on food imports, global competition, water and energy security issues (Conceição et al., 2016). With the continent's population continuing to increase, demand for food will also increase. Hence, food security becomes a paramount economic issue. Africa's present food production approaches are not capable of providing sufficient food without posing serious adverse environmental impact (Funk et al., 2008).
SynBio can be an investable utility technology capable of ensuring that Africa meets and sustains its food security needs. However, while SynBio applications from areas other than agriculture have been predicted to offer great benefits by making products, they have also given rise to concerns about new safety, ethics and socio-economic risks (Dana et al., 2012;Edwards, 2014;Ribeiro and Shapira, 2018). Whilst SynBio may present benefits for the economy at large, its use in the production of compounds commonly extracted from natural   and near term biosynthetic production of numerous ingredients or chemicals to replace these crops has relevance for Africa. This often involves the use of genetically engineered microbes such as yeast or algae, which feed on sugar. There is potential for negative effects on biodiversity as a result of adoption of SynBio. These can include a reduction in demand for natural plants such as shea, cocoa and cassava and a huge demand for sugar which is used to produce the genetically engineered microbes for production of SynBio products. The sugar is often produced by agribusiness using unsustainable methods and high amounts of water which is becoming difficult to get because of climate change (ETC Group et al., 2018).
Small-molecule natural products produced by endangered organisms that are on the verge of extinction may need alternative methods of production. This is because a continuation of their extraction from natural sources will not be viable. This approach has been used for heterologous production of many complex and high-value phytochemicals in microorganisms (Gandhi, 2019). Yeast can be engineered with ease and it has high growth rates. There is an abundance of infrastructure and industries with expertise in yeast fermentation. Thus, together with bacteria they can be used as hosts for production of medical and non medical bio-products. Also use of plants for production of high value compounds such as flavourings, medicines and oils bring caveats such as long generation rates, dependence on arable land and water and seasonality. Genetic engineering of plants is plagued by long generation times and large polyploidy genomes such as wheat. Using SynBio, multigene pathways can be This review is aimed at providing an overview of recent progress in the application of SynBio in agriculture as well as on arguments and evidence related to their possible benefits to the African continent while also outlining the risks and governance implications.

Food issues faced in Africa
Africa, especially ''The Horn of Africa'' and Sub-Saharan Africa, is among the most food

Possible applications of SynBio to food and agriculture in Africa
SynBio has a number of applications in the food sector across various sub-sectors. SynBio can be applied for the production of metabolites and health products such as vitamins.
Artificially produced health products can be packaged as supplements which might be cheaper and more readily available than naturally occurring vitamins and other health products. Another food sector potential application is the production of processing aids in the manufacture of food and food derivatives such as nutraceuticals, probiotics and glycol, nutrients used to raise the value of certain foods or nutrient enriched plants. Nutrient-enriched plants are ideal for people in Africa living in poverty as one plant would be able to address several nutrient needs. It can be used in the production of preservatives such as nisin and artificial flavours and fragrances. Vanilla has been successfully produced from baker's yeast (Hansen et al., 2009) and synthetic saffron has been produced for commercial use at a fraction of the price of natural saffron (Pretorius, 2016). Thus, SynBio can potentially reduce prices of some commodities on the African continent.
SynBio surpasses the application of conventional genetic engineering for crop development and farm management. Drought monitoring and prediction systems (DMAPS) in Africa use various indicators at different temporal and/or spatial resolutions. They are based on remote sensing, land surface modeling, and seasonal climate forecast. These are efficient but drought preparedness remains low (Hao et al., 2017). The development of engineered tomato plants that are able to activate drought protection mechanisms on application of fungal spray can help African farmers prepare for drought (Goold et al., 2018). This helps abate crop loss due to climate change induced droughts and ordinary droughts that have been occurring at least once every ten years in many African countries (Hao et al., 2017).
There is still low adoption of mineral fertilisers use in some African countries due to reasons that include high costs. However, when they are coupled with some good agricultural practices, they can help increase yields (Donkor and Owusu, 2019). Using SynBio, nonleguminous crops that are able to fix atmospheric nitrogen reducing the need for fertilizers were developed (Goold et al., 2018). The technology can be transfered to crops grown on the African continent thereby helping to reduce nutrient associated losses and hence costs of production for many crops. This is because fertiliser is a major cost driver in agriculture and there are periodic shortages that lead to yield losses.
More smart crops with various other advantages such as high yield, drought resistance, and pesticide resistance amongst other adaptations, can be engineered into the synthetic plants (Park et al., 2015). The benefit to farm management from SynBio comes through the development of biosensors and the use of agri-intelligence systems that reduce the use of pesticides and fertilizers. The plants will detect when there is a drought or weed threat and activate necessary response mechanisms. This will reduce yield losses and wastage of herbicides which pollute the environment. Food waste processing methods are able to take advantage of this technology and increase the amount of toxic waste removed from the environment (Pretorius, 2016). This will help increase the amount of arable land being cultivated and its productivity as most farmers in Africa cannot afford fertilizers and pesticides.
Given that more than 80% of the poor Africans keep livestock (

Risks, advantages and disadvantages of using SynBio
Risks should be thoroughly assessed before large numbers of synthetic organisms are released out of the laboratory, taking into consideration self-replication, crossing over events and recombination. Thus, there is need for strict monitoring of the technology and its products. Research and development teams should include multiple safeguards in synthetic cells, such as giving them strictly limited life spans or on/off switches, and engineering them to depend on laboratory-specific conditions. They should also keep using unique identifying marks, so that products can be traced back to their "creators". SynBio offers the advantage of removing the use of selectable markers which are a requirement in many genetic modification applications. It can achieve this using retargetable mobile group II introns commonly called 'targetrons'. These have very high efficiency such that there is no requirement for selectable markers (Lambowitz and Zimmerly, 2004).
Targetrons function in a wide variety of bacteria. Beyond suicide plasmids which have low efficiency and are unstable, targetrons are first genetic tool of significant utility (Heap et al., 2007).
Non-coding RNA molecules used in RNA interference crops can survive mammalian digestion. They then go on to regulate genes of mammals that consume them. They can also have off target effects. When created using SynBio non-coding RNA molecules will likely have similar effects unless it is addressed in the design stages.

One of the biggest challenges with SynBio is biopiracy of Africa's vast genetic resources.
Biopiracy is "the unethical or unlawful appropriation or commercial exploitation of biological materials native to a particular country or territory without providing fair financial compensation to [its] people or government" (Merriam-Webster). Technologies in DNA synthesis and sequencing now mean that genetic information can be transmitted electronically across borders. There may be no need to transport a physical seed or plant.

The current state of regulation of SynBio
SynBio is a rapidly evolving, multidisciplinary and promising techno-science field. In particular it is anticipated that it may lead to the 5 th industrial revolution (Peccoud, 2016).
Strikingly, the technologies have enormous potential to significantly alter genomes of viruses, prokaryotes and eukaryotes. It is thought that when these altered organisms are released into the environment, they can become a biodiversity risk as they may become invasive. Biosecurity risks may also arise if biological weapons are made using SynBio (Trump, 2017). All these concerns raise environmental, health, social, legal and ethical issues

Regulation of SynBio in Europe
The regulations governing their use in Europe exist at various levels of implementation. In the majority of the cases, the regulations originally produced for the regulation of GMOs and their derivatives are revised to suit the current technological innovations. In this regard, for the last two decades, two EU GMO directives namely the Contained Use Directive

Regulation of SynBio in the United States of America
The United States of America (USA) is using the same regulatory frameworks for GMOs for the regulation of SynBio. The present state and form of the legal regulatory framework for GMOs is applied to SynBio and products derived thereof. Agencies involved in the implementation of the regulatory system are the U.S. Department of Agriculture's Animal and Plant Health Inspection Service (APHIS), the U.S. Environmental Protection Agency (EPA), and the U.S. Food and Drug Administration (FDA) (Carter, et al., 2014). Elsewhere, these agencies are viewed as organizations who have limited regulatory authority to regulate some SynBio products. For instance, APHIS regulates organisms in which plant pests or components thereof have been used to modify the plant. It is most likely that development methods of SynBio derived organisms will not be covered by these regulations (Carter et al,   2014). Thus, the products will go without regulatory oversight because they are not explicitly covered by the existing statutes. The responsible and enforcing agency is thus rendered 'powerless'. In the case of EPA, as modified microbes become more complex, risk assessments will become more difficult, requiring more financial resources and expertise.

Regulation of SynBio in Africa
Despite the potential positive impact of SynBio, it is important to note that the regulatory framework for SynBio products including synthetic organisms still has to be developed by some African countries. There is no distinctive line between what is traditionally labelled 'natural' and what should be labelled 'synthetic'. Even African countries with wellestablished systems for regulation of genetically modified organisms (GMOs) such as Kenya, and South Africa, are yet to put in place regulations which are specifically meant for SynBio.
It is worth noting that certain provisions contained in their current GMO regulations may be extended to SynBio since it builds on modern biotechnology methodologies and techniques.
As more complex organisms are produced by SynBio there will be a need to develop Furthermore, future reviews of the regulations will be motivated by the fact that globally the definition of SynBio and products is ambiguous and SynBio produces more complex products which potentially present legal issues. The NBA Act does not make specific reference to SynBio and to avoid any ambiguity, a statutory instrument which supports the NBA Act requires gazetting.
The African continent needs to assume a harmonized position on regulation and governance of SynBio, whether it should be case specific or not, process based or product based. These gaps in the regulatory frameworks need to be addressed if Africa is to derive maximum benefit from SynBio whilst minimizing the risks associated with the technology. This is critical given that fellow African countries such as South Africa are among the leading researchers of SynBio (Oldham et al., 2012).

International treaties
Misuse of SynBio presents threats to international peace and security hence this section looks There are a number of capacity limitations and challenges that need to be addressed globally if the countries are to effectively regulate SynBio products. Addressing these issues would go a long way in ensuring that countries benefit from these technologies whilst protecting human and animal health and the environment. SynBio is rapidly advancing and current regulations may not adequately cover future products of the technologies. Taking cognisance of both benefits and risks of the technology (Good et al., 2018), countries need to come up with allencompassing regulatory frameworks which will not stifle development, at the same time making sure that adequate biosafety and biosecurity measures are put in place to prevent misuse of the technologies. In the case of Africa, it is worth noting that the judicious application of synthetic biology can alleviate food and energy security, reduce poverty, boost industrial growth, reduce greenhouse gases and promote environmental conservation (Garang and Onkware, 2016).

Future perspectives and conclusion
Adoption of SynBio has the potential to improve food security and livelihoods in Africa.
Considering that most African countries are yet to accept genetically modified organisms, the adoption of SynBio might seem arduous. However, there are countries like Zimbabwe where, growing of GE's is not permitted but controlled research on and food processed from GE's is permissible. It is important that stakeholders' perspectives on GE's are investigated: the understanding of GE's definition(s), methods employed in obtaining GE's, knowledge of SynBio, source of information and willingness to fund research of GE's. This will improve platforms for knowledge transfer, identifying key challenges and mapping solutions. It is knowledge that will assist in developing informed polices that have meaningful impact of the socioeconomic factors.  SynBio thus offers great opportunities although it can result in many adverse effects on the environment and economies in Africa. Its adoption is however still low. It seems to be following the trajectory of GMOs which to date are being legally cultivated in Sudan and South Africa only out of about 50 African countries. These limited experiences therefore provide limited data on the effects of some of these GM technologies on the continent.