Bleb envisioned the creation of a platform technology which future researchers may utilise for the implementation of synthetic biology systems addressing world problems.
The UNSW iGEM team undertook the challenge of creating an ideal strain of E. coli for producing functional OMVs with a number of potential applications in mind. An essential element of our human practices was therefore to pre-emptively explore these applications, in order to produce a directive guide for future research into these areas, and determine what avenues may be best suited to the technology.
After exploring and analysing the potential applications of our project, we also wanted to evaluate what factors, beyond laboratory research, may constrain or influence future implementation of the Bleb technology. We decided to investigate two key areas that we felt would have a large impact in this respect - not only our project, but the emerging field of Synthetic Biology holistically: Sociology and Biolegalities.
As a culmination of our human practices endeavours, we aimed to present our discussions and findings to the wider community, in a public Synthetic Biology Symposium with panel speakers and open debate. We found the discussions to be extremely beneficial to our project design, with the ideas explored applicable across platform technologies and synthetic biology research. As such, we wanted stimulate increased investigation in this area, and encourage participation in the conversation by not only researchers, but members of the public. Therefore, we created educational videos, briefly outlining some of the poignant aspects of discussion, to further engage the debate in this area.
A fundamental issue with the application of synthetic biology research in real world scenarios is our inability to safely use engineered bacteria outside of the lab, for fear of repercussions regarding biosafety and biodiversity. As a foundational advance project, Bleb aimed to address this issue through the creation of a new platform technology for synthetic biology. Our projected was centred on the creation of a strain of E. coli that can overproduce outer membrane vesicles (OMVs), which can be functionalised for a multitude of future applications without fear of the impact of release into the environment. This is because OMVs are non-living and non-replicative, whilst still able to carry proteins and thus perform functions.
As part of our human practices, we wanted to assess the possible suitability of OMVs for application in environmental bioremediation and medical biotechnology. By talking to researchers in these fields, we assessed important factors to consider in these applications, and gauged the suitability of OMVs for these uses. Our conversations enabled us to highlight some essential points of product design which need to be considered, should research into OMV application in these fields be pursued in the future.
Environmental Bioremediation
As a non-replicative, stable transport mechanism able to carry functional proteins and molecules, the potential for OMVs to aid in bioremediation without posing a biosafety risk was evident since inception of our project. To investigate this application, we met with Mike Manefield, a researcher and founder of Environmental Biotechnology company Micronovo, which specialises in bioaugmentation of polluted environments.
A key question our team had for Mike was how environmental biotechnologies can successfully be implemented into Australian industries, and what barriers exist to this implementation. The first issue he identified was the disconnect which exists between research, classically conducted at university institutions, and businesses. In Australia there exists a need for greater interdisciplinary integration, so that the foundational research is able to be developed effectively into useful products for society. The difficulty of regulation, particularly environmental regulation, was flagged by Mike as a definite difficulty he faces in the continued implementation of his own work. Liaising with environmental protection agencies is necessary, and requires effective scientific communication, not only about the mechanics of the project, but the risks which have been evaluated. Mike found himself often dispelling preconceived notions, which had caused bias against the progression of environmental biotechnologies. Another hurdle to effectively creating a market for environmental bioremediation was the inclusion of terminology in legislation which unintentionally impacted the use of bioremediation technologies.
Lessons learnt & implemented into Bleb:
Identifying a gap in the market is necessary to create a successful product. Particularly in Australia, where the biotechnology industry is relatively small, thoughtful technology design is very important. For our project, continued market research will be necessary to determine the scope of its applicability in this area.
Industrial optimisation is an essential factor to consider. Particularly as our product does not replicate, the viability of the product to be produced on a large scale must be assessed. Additionally, the benefit of biosafety against the need to place large amounts of product in polluted sites should be balanced, and research into companies who have considered similar ideas in the past need to be studied.
The potential by-products of OMV biodegradation in the environment must be adequately tested in order to comply with environmental protection laws. This testing will be part of our future research
As an industrial product, the longevity of OMVs both in the environment and on the shelf need to be investigated. When functionalising OMVs for industrial use in later research stages, stabilisation will be considered as a key design element
Medical Biotechnology
Our OMV platform technology could be customised for various medicinal uses by using OMVs for the uptake, delivery or transport of biologically significant molecules. For example, we hypothesised the potential functionalisation of OMVs into a drug delivery system, biosensor, or vaccine carrier.
To discuss such applications, we met with Lawrence Lee, an ARC Discovery Early Career Research Award Fellow at the UNSW, specialising in the artificial synthesis of complex nanoscale biological machines and other bio-inspired technologies. As supervisor of the Biomod Australia team, Lee has a keen interest in synthetic biology, and the potential it holds for the future of medicine.
From our dialogue with Lawrence, we came to appreciate the potential for synthetic biology in the medical field. By utilising nature as a blueprint, as we have done with the design of our project, we are able to capitalise on exisiting biological processes, and optimise them for novel uses. Some advantages which Lawrence identified from our initial ideas was the clear potential for targeted drug delivery which OMVs provide. Additionally, potential customisation of a biosensor could be optimised to provide point to care diagnostics, and greatly improve patient care.
Lessons learnt & implemented into Bleb:
A significant point of consideration for our team's future work will be biophysics, and how this could possibly affect the success of creating functionalised OMVs. Importantly, such considerations should involve an investigation into the kinetics involved in the uptake of periplasmic-localised proteins into our OMVs, and assessment of whether this is energetically favourable for the system
Another point of consideration raised was the effect of lipopolysaccharide (LPS), found on the outer membranes of gram-negative bacteria, on the ability of OMVs to be utilised for in vivo medical applications. LPS is highly immunogenic, thus in the future its effects need extensive research before attempt of medical functionalisation of OMVs
Contact with clinicians, to discuss the desirability of the technology, and its potential effectiveness, will be essential when the product reaches the stage of development into the medical field
As an industrial product, the longevity of OMVs both in the environment and on the shelf need to be investigated. When functionalising OMVs for industrial use in later research stages, stabilisation will be considered as a key design element
The success of any emergent technology, particularly within a relatively new field of research, depends not only upon sound scientific practice, but also consideration of social factors influencing its direction. We therefore decided it was essential at this early stage of our research to investigate the sociology factors effecting synthetic biology, and determine how to best approach our project to ensure its future success.
Our investigation into the sociological factors influencing the progression of synthetic biology began in discussion with leading academics in the field of environmental humanities. Matthew Kearnes is an ARC Future Fellow at UNSW in the School of Humanities and Languages, focusing upon the intersection between science and social theory, including research into the social dimensions of bionanotechnologies. Eben Kirksey is a Senior Lecturer and DECRA Fellow at UNSW, researching the boundaries of nature and culture, and the political influences on the imaginative processes.
The subtle connections between science and society are often overlooked, with researchers assuming that the main issue with public acceptance of new technologies, especially in biology, is a lack of scientific communication and understanding. However, as our team discovered in conversation with Matthew Kearnes, this was an over-simplification of a multifaceted problem. Although a clear presentation of the research is important for establishing the trust of the wider community, and this contingent upon effective scientific communication, it was noted ‘when publics are given more information about genetically modified crops, or perhaps in this case synthetic biology, their concerns are amplified rather than diminished’. Broader concerns exist with the public which often are not considered at the research stage, as they should be. These concerns include issues of ownership, who controls and profits from the product, responsibility, who can be held accountable if technology goes awry, and frameworks for regulation of synthetic products.
The limited scope with which scientists approach the calculation of risk, and the effects of this restricted inquiry, was identified by Eben as a major issue in the field. The impacts on groups apart from humans, on the environment, plant, and animal species, due to unexpected side-effects of technologies, should be more thoroughly investigated, ‘trying to do imaginative work, speculative work is what needs to be done at the risk assessment phase… we need to start thinking more creatively, outside of the box’. Risk assessment should be performed not only by regulatory bodies, but by the scientists themselves. Thoroughly evaluating and balancing the risks and benefits at the research level would encourage conscientious practices, and hold scientists more accountable for their research.
The external factors influencing research were also an interesting point of tension discussed. Although we had not consciously realised this during the design of our project, political and economic pressures direct the progress of research in specific ways. As Matthew explained, ‘[synthetic biology] only impacts society as much as it’s driven by a set of social, political, and economic forces’. These external forces, and the limitations or bias they enforce of directions of research, should be kept in mind when developing new technologies. Who does this research benefit? And why should it benefit this particular group? These are questions which should be addressed at the early stages of development to clearly establish the moral groundwork of technological directions.
In the same way they societal values influence research, technological developments also have the potential to change societal structures and ideals. Drawing analogies to the development of amniocentesis and the subsequent decline of down syndrome individuals in the population, Eben prompted us to consider that ‘We have to think forward to how emerging technologies are almost legislating what the conditions of life could and should be’. As the tools of synthetic biology continues to improve, and innovations such as CRISPR/Cas9 enable gene editing not only in bacteria, but in plants and animals, classically defined moral and ethical boundaries begin to blur. Investigation into the reasons behind innovation should be made, and questions asked about whether products should be developed.
How did this effect our approach to research?
From our discussions, we were able to identify a number of important social considerations which need to be made not only for the success of our project, but for the success of all research in foundational technologies. From this we developed the following suggestion of good practice:
Explore varying vested interests
Find out exactly who would be interested in or affected by both your research and your desired product. Consider exactly why they are vested in your research, and how you can adapt your product to best address these needs. A number of different groups, including communities, industry partners, and collaborators may be interested for a variety of different reasons. The success of a product will be determined when most or all of these interests are considered.
Consult widely in the community
All products will exist in a social dimension, and their integration into specific sectors of society therefore should be assessed. The unique concerns of all social groups, including minorities, should be considered to improve targeted product design.
Investigate risks broadly and inventively
Thoroughly consider the ways in which your research may go awry when exposed to unexpected variables outside the laboratory. This should be conducted with not only human health in mind, but environmental and ecological risks.
Identify the aims of the research honestly
The motives and realities of technological developments should be honestly conveyed to stakeholders in the project. By accurately identifying why research is being undertaken, and creating clear implementation projections, a more realistic and open conversation about research is allowed.
Share progress with stakeholders
A dialogue model should be established, where the community has a voice in product design and implementation, with progress sharing integral to this. Consultation will enable consistent re-evaluation of research progress, risks, and barriers to implementation, ultimately resulting in the creation of a technology best suited to its purpose.
After considering this for our project, we decided that at this stage in the development of our technology the most effective way to open up a dialogue with the pubic would be to hold a public panel discussion on synthetic biology (Here's how it went!). As clear applications of our project begin to be realised in the future, we intend to follow the good practices outlined above, and continue an honest dialogue with the community to improve our processes of scientific practice.
To edit, rearrange, and disrupt the basic structures of life implicates a fundamental change to the structure upon which our moral, ethical, and therefore legal systems are built. As projects, such as our own, have the potential to revise legal concepts, and are equally limited by legal limitations, we thought it essential to investigate the way in which synthetic biology research and the law interact for our human practices.
In order to closely examine the complexity of Biolegalities, we began discussions with academics in the fields of law and philosophy. Marc de Leeuw is a senior lecturer in the UNSW Law Faculty, specialising in the field of legal, moral, and political philosophy. He established the UNSW Initiative for Bio-Legalities, aiming to further explore the complexity of emerging relations between Law and Biology. Lyria Bennett Moses is an associate professor in Law at UNSW, whose research explores the relationship between technology and law, and the issues which arise as technologies evolve and change within Australian jurisdictions. In conversations with these distinguished academics, we were able to examine both the structural and theoretical aspects of the concurrent evolution of law and synthetic biology, and the impacts they may have on one another.
To fully conceptualise how the law regulates emergent technologies such a synthetic biology, we felt it was important to understand the way in which the law allows for integration new technologies. This was discovered to be a complex process, as explained by Lyria, ‘When legislation is passed there is an imagined set of technologies that it will apply to… Where you have a new technology come onto the scene the law wont be perfectly adapted to that technology’. Therefore, to accommodate any new technology, there may be a need to prohibit, restrict, clarify (through legislation or judgment) or repeal existing laws. Laws in Australia which currently apply to synthetic biology technologies specifically include the Gene Technology Act 2000, as well as a number of broadly applicable laws including negligence, property, ethics, environmental, and nuisance laws. We found that the ways in which our research activity is regulated was broader than initially perceived. This reaffirmed the discussions had with sociologists, that research is never truly isolated to the laboratory, but may have serious effects upon wider communities which need to be considered.
Regulation of research exists not only in legislation, or ‘hard law’, as outlined above, but in the form of protocols or good practices, ‘soft law’. The combination of both hard and soft law was discussed with Marc, ‘In general the scientific community would rather have soft law, because that means they more or less self regulate, and that allows for more forms of innovation’. Different forms of hard and soft law in similar fields across nations creates difficulties for scientific collaboration, and therefore standardisation was identified as an area of tension to which increased should be paid by the community.
Law and biology also have a very interesting relationship, as biology redefines legal concepts. Where biological understanding becomes increasingly enriched, legal concepts are re-evaluated and evolve with new knowledge. As shown in the example of the notion of ‘parenthood’, Marc explained how developments in synthetic biology may lead to a new understanding of legal concepts, and the law needs to react accordingly. ‘Biotechnology and synthetic biology changes the ordering of the rest of the world by law, because it needs to include the way that biology has re-ordered a particular legal concept’. This co-constitution of law and biology co-produces new orders, and displays how synthetic biology research has the potential to really impact social arrangement.
The particularly unique culture of synthetic biology, and its push for open-access sharing of information, has resulted in the emergence of ‘biohackers’: backyard scientists looking to create their own technologies and organisms. Although widespread scientific capability and curiosity is considered a positive influence on research and field advancement, the reluctance of States to proactively regulate the experimental processes has lead concerns about biosafety in the wider community. Marc noted that 'It would be very useful to have a permanent exchange between those working in synthetic biology and legal scholars,' to address such issues as they arise, and be able to provide clear legal structures should intervention be needed.
Ultimately, as identified by Lyria in our discussions, the law is not the only regulator of new technologies. How a technology is accepted into society is also regulates its success, as assessed on the moral concerns of communities at large. ‘From an ethical standpoint as scientists its important to think beyond "What am I allowed to do," to consider "what is socially acceptable for me to do?"’. If the public is averse to utilising a product, despite being grounded in sound science, the social morals will hinder its future progression.
How did this effect our approach to research?
Apart from identifying relevant laws we should be aware of during development of our OMV technology, the moral and ethical inquiries we should be having were made quite apparent throughout these discussions. As our target product, OMVs, are non-replicative, there are fewer legal barriers in place to restrict their use than for live bacterial cells. However, identification of the legal parameters only emphasised the need for comprehensive consultation with communities and parties who will be using or effected by our technology.
Additionally, a need for consultation with legal professionals and policy makers was made apparent. Understanding the framework within which our technology exists into the future will be paramount. Helping those designing laws for its regulation to understand our technology’s aims and progress will only aid the positive integration of technology design and protection of those using such developments.
Synthetic Biology Symposium: Perspectives and Progress
The UNSW iGEM team held a Synthetic Biology Symposium at the conclusion of our Human Practices, in a rare opportunity to bring together professionals in scientific research, biolegalities, and social theory. The symposium was in the form of a panel discussion, open to the public, in order to allow for open discussion and engaging debate.
The evening was extremely successful with those in attendance coming from a variety of disciplinary backgrounds to learn about the potential of synthetic biology, not only for scientific advancement but its effects on social and legal structures. The combination of panellist enabled a critical and interesting debate, where synthetic biology was examined from a variety of unique perspectives. Individuals across science, commerce, arts and law knowledge bases engaged with the panellists, to gain a greater understand of synthetic biology as a whole.
Take a look below!
UNSW IGEM @ STEM Talk
As part of Ku-Ring-Gai rotary’s youth education initiative, a series of talks about science, technology, engineering and mathematics (STEM) were held at Gordon library. We were fortunate enough to be invited to present a talk about synthetic biology and our project. A huge thanks to Matt from the 2015 Sydney University iGEM team for arranging this opportunity! The talks were organised for high school students with the main focus to enlighten them to the possibilities in a STEM career. Members of the 2015 and 2016 USYD iGEM teams and members of the 2015 UNSW iGEM team also joined us at this event, which prompted the start of our collaborations with them.
UNSW IGEM @ B.Inspiring
As a part of our outreach efforts we were able to secure a one-hour workshop opportunity with the organization B. Inspiring Inc. to present and educate their audience about this growing field of science, synthetic biology. B. Inspiring runs an annual three-day conference addressing high school students between years 10 to 12 who aspire to work in the field of STEM (science technology engineering and mathematics). Throughout the three days, students are required to develop a pitch solution to one of the UN sustainable goals. They are also given workshops and presentations by guest speakers from leading companies in STEM, which help them develop their pitch and also inspires them with the merits of a career in STEM.
As representatives of the iGEM competition as well as the synthetic biology community, the goals of our presentation were to interest high school students and allow them to appreciate the world of synthetic biology.
Due to the audience’s diverse backgrounds in STEM, we started by explaining the basic and most fundamental concept of biology: the central dogma. From this we introduced the analogy that synthetic biology is very similar to computing, where the ‘coding language’ of ATGC, and Bio Bricks made out of DNA represent the instructions. With these fundamentals laid down, we explained the different types of Bio Bricks focusing on promoters and open reading frames.
We then provided them with an activity (built upon that of last year’s team), which was to construct a bio-synthetic organism by using bio bricks. We applied this towards the conference’s theme, UN sustainable goals, and told them to create an organism which would help achieve their designated UN goal.
After this activity session, we then discussed the ethical issues that must be addressed in any synthetic biology project. This ranged from concerns in biosafety (which included factors such as environmental damage), sociology (which dealt with cultural and social attitudes) and finally economic factors (such as the matter of patenting). With this in mind we allowed the students to look back on their newly created organism and consider the possible ethical impacts their project may need to take into account.
The audience of high school students at first approached this activity with a lot of questions, as the concept of a genetic circuit was very new and bizarre to them. However, with the one to one guidance from our presenters, their creativity proved to be limitless as they designed some very novel organisms. With the use of a feedback form, from this presentation we were able to gather the general perception of synthetic biology from the students. It had seemed that they were very intrigued by the ability to manipulate life however due to the sophisticated nature of biology, it was hard for them to grasp the whole picture through our ‘basics of synthetic biology’ presentation.
UNSW IGEM @ Aspire
At the end of June we took part in Aspire’s conference for high school children from rural and disadvantaged areas. This conference brings year 10 students from these areas together at UNSW to introduce them to university life in a welcoming and friendly environment in an effort to make university less daunting. Through this the students would hopefully become aware of the range of options available to them after they leave school, and what pathways there are into university. Students prior to the conference chose a stream that they thought most interested them (Law, Business, Medicine, etc.); we were privileged to be included, along with this year’s BioMod team, in the Medicine stream.
We gave a short presentation giving an overview of our project, simple introduction to Synthetic Biology, and then a basic explanation of how promoters and genes worked together to produce different proteins. We then gave the students some cut-outs and balloons to ‘manufacture’ their own proteins which they packaged into the balloon, a substitute for an outer membrane vesicle (OMV). Students then presented their creations to the class; there were some very creative ideas, including OMVs which created glow in the dark zombies or broke down methane.
We left the conference with a sense of achievement, having felt we connected well with the students and engaged them in the idea of Synthetic biology. The feedback we recently received happily reflected this, and we hope the students enjoyed the other days of the conference as much as they appeared to enjoy ours.
