Contents 1 3 Ethical issues in synthetic biology on a macro level 1.1 3.1 A definition of “Synthetic Biology”: a discourse in semantics? 1.2 3.2 Risks related to synthetic biology: bioerror or bioterror? 1.2.1 3.2.1 Risks and risk perception 1.2.2 3.2.2 Synthetic biology as a novel technology 1.2.3 3.2.3 Synthetic biology and open source databases 1.3 3.3 Implications of terminology: a contradictio in terminis? 1.4 3.4 Implicit assumptions in synthetic biology: forgetting what’s currently important? 1.5 3.5 The “banner” implications: a pragmatic point of view. 1.6 3.6 The media: a PR stunt or time for a public backlash? 1.7 3.7 From contradictio in terminis to oxymoron: the hype or promise of synthetic biology? 1.8 3.8 Intellectual property rights: usefulness or commercialization? 1.9 3.9 iGEM, open source technology and the intellectual property: impossible or naïve? 1.10 3.10 Prospective: solutions to ethical problems?

3 Ethical issues in synthetic biology on a macro level

Discussing synthetic biology

Since the “reintroduction” of term synthetic biology in 2005, several reports have appeared in which the ethical and social issues related to this field of research are described. Ethical and social reflections in a stage this early in scientific development have not been observed in other novel technologies, like nuclear energy and genetic engineering, some decades ago. Yet with the recent introduction of nanotechnology, experts tend to see the necessity of these considerations. This report will not describe into detail why these social and ethical reflections are said to be necessary; rather, it will describe what has been stated in literature on the ethical and social challenges in modern literature, which questions and values are considered and how this applies to the emerging field of synthetic biology.

To do this, this chapter will start by describing what is meant by “synthetic biology”. Thereafter, the risks associated with synthetic biology will be mentioned. Hereafter, the implications and implicit assumptions made in synthetic biology research will be explored. Subsequently the relation between constructive biotechnology in an open source setting and intellectual property rights will be discussed, followed by a brief prospective on synthetic biology.

3.1 A definition of “Synthetic Biology”: a discourse in semantics?

Stakeholders in synthetic biology do not use a single definition of synthetic biology. Therefore, the boundaries of the scientific area that can be called “synthetic biology” are also not 100% clear. In this report the moral values related to the technology are described without defining into detail what is meant by “synthetic biology”. Further, the used technologies that converge in synthetic biology are also not very clearly defined. E.g., what is meant exactly by industrial biotechnology, nanotechnology, nanobiotechnology, etc., is also not clearly described. To give an impression of what synthetic biology involves, several definitions as defined by different stakeholders are given below.

• European Union – “Synthetic biology is the engineering of biological components and systems that do not exist in nature and the re-engineering of existing biological elements; it is determined on the intentional design of artificial biological systems, rather than on the understanding of natural biology.”

• Dutch COGEM – “Synthetic biology focuses on the design and synthesis of artificial genes and complete biological systems and on changing existing organisms, aimed at acquiring useful functions.”

• Jay Keasling – “The development of well characterized biological components that ban be easily assembled into larger functioning devices and systems to accomplish many particular goals.”

• Steven Benner & Michael Sismour – “Synthetic biologists come in two broad classes. One uses unnatural molecules to reproduce emergent behaviours from natural biology, with the goal of creating artificial life. The other seeks interchangeable parts from natural biology to assemble into systems that function unnaturally.”

• Berkeley University – “The design and construction of biological parts, devices and systems and the redesigning of existing natural biological systems for useful purposes.”

Only by looking at these examples, one can observe that what is meant with the term “synthetic biology” involves different things. Therefore, it is probably more appropriate to speak of the “field of synthetic biology” combining different life science related technologies, rather than classify it as a single technology in itself. At least, one can claim that synthetic biology encompasses constructing and deconstructing biological processes of “life”, with life in different gradations of naturalness or artificialness. Exactly this suffix, which states that there are several levels of what is considered natural or artificial (synthetic), implies that perception and hence ethical considerations related to the autonomy of life are important topics to consider in the field of synthetic biology. How synthetic can biology actually be? To what extent can biology be engineered? To give at least some answers to these questions in the following paragraphs, one must first analyze which risks are concerned in synthetic biology. These are described in the next paragraph.

3.2 Risks related to synthetic biology: bioerror or bioterror?

As is probably the case with any “new” technology, besides a number of new applications synthetic biology also comes with a number of new risks. In this paragraph, the term “risk” is introduced first. Hereafter, risks associated with new technologies like synthetic biology are mentioned. Finally, risks associated with open source technology are brought up.

3.2.1 Risks and risk perception

When making a decision, like the decision whether or not to use Synthetic Biology in an application, one balances the risks against the benefits. But is actually meant by “risk” isn’t always clear. Textbooks state that the Risk is the magnitude of the Hazard when it takes place, multiplied by the Frequency in which these hazards actually occur (R = H * F).

These risks are partially factual risks, which can be scientifically assessed, like assessing the chance that an organism will share DNA with surrounding organisms upon deliberate release into the environment. There are also virtual risks, like exploring the probability of creating a biological weapon with open source BioBricks. When the future impact of a certain decision, like in the case of using Synthetic Biology in increasing levels of artificialness, risk assessment actually becomes risk perception: the response of the public, NGOs or consumers are unknown, as well as the scientific possibilities and application areas. If the risk is “low enough” (and one has to wonder who decides that), a certain action can be justified. Some would calculate the Justification of a decision as the Impact of something going well, times the Chance of it going well, minus the actual risk (J = I * C – H * F).

The problem with these kinds of analyses is that the (financial) impact or hazard can be calculated, or well estimated, but the occurrence of the events generally cannot. Then, values for impact or hazard are chosen arbitrarily, attributing a certain value to what a stakeholder deems important. Many individual assessments play a role. Experiences of the company or academic institution, experiences of others, experiences of individual employees, public attitudes, litigation, fear of bad media attention, activism by NGOs, etc., all play a role in “calculating” the risk or in justifying the actions of the company as a whole and to make money or generate knowledge within all legal boundaries.

It becomes clear that the risk assessment regarding synthetic biology relies on many uncertainties. Some risks can be scientifically assessed, but many other risk assessments related to this new technology take into account many uncertainties. Ethical considerations can help create some structure on what to focus on in risk assessments. By focusing on synthetic biology and its applications, two main fields of risk perception are distinguished in this report: risks associated with new technology and risks associated with open source technology. These two will be addressed in the next sections.

3.2.2 Synthetic biology as a novel technology

As stated before, probably all new technologies give rise to new risks and risk perceptions. This has been observed for genetic engineering, nuclear energy, cars, etc. Modern research on the newest technology may also come with unforeseen risks or possible mistakes. When these potential errors are noticed, it is too late to prevent them from occurring. BioErrors may occur when e.g. a deliberate release into the environment does not work out the way it was predicted, e.g. new pathogens or toxins are released. In that instance, the problems that NGOs like Greenpeace and Friends of the Earth warn for, will turn out to be real problems. Therefore, caution in using new technology like transgenetics or creating more artificial biological systems is always advised. Regulation on genetic engineering techniques like used in synthetic biology is already in place , but BioErrors may not always be foreseen.

Besides unforeseen consequences on a technological level, also new ethical considerations appear in synthetic biology. Creating more artificial systems makes one wonder what “life” actually is and to what extent the autonomy or quintessence of an organism is more important than technological progress. From a biological point, something lives when it has its own energy metabolism and it can reproduce all by itself. From a moral point of view, this may be different, especially with increasing levels of artificialness of “biological” or “natural” systems. That is why in synthetic biology, artificial life is an issue to consider: what is the boundary between “organism” and “machine”?

3.2.3 Synthetic biology and open source databases

Besides issues related to errors in research or application of synthetic biology and issues related to artificial life definitions, ethical considerations on synthetic biology related to the open source character of the technology also need to be examined. The proposed BioBrick approach of the constructing part of synthetic biology gives rise to a number of ethical considerations. One of these is related to the intellectual property issues described below : the relation between open source technology and commercialization of ideas, patent laws, etc. need to be considered.

But besides these IP related issues, one also must deliberate on the deliberate (mis)use of the open source BioBrick database. Some applications or “devices” made out of BioBricks from a publicly available database may have a “dual use” character. This concept can be related to e.g. the sharp edge technology of a knife: a knife-like object can be used to cut a sandwich into peaces or to kill someone. But everyone who has tried to slice bread with a samurai sword knows that’s not really the purpose of this particular device. From the BioBrick database also metaphoric samurai swords may be devised. Then it only takes a small step to consider deliberate misuse or BioTerror of the open source technology.

Also, biotechnology research or genetic engineering gets more and more easy to carry out. It is probably possible to conduct research in your own garage, without anyone knowing what you are doing. Moreover, companies that synthesize DNA can create any sequence one likes, currently possibly without any constraints.

These open source, dual use and DNA ordering freedom makes BioTerrrorism an issue to consider in the light of open source biotechnology or particularly, iGEM. That is probably why this issue is addressed in many papers on synthetic biology specifically.

3.3 Implications of terminology: a contradictio in terminis?

In synthetic biology many different technologies are converging. Some would say that it is just a modern, advanced version of metabolic engineering. In addition, one may recognize scientific approaches from nanotechnology and biotechnology, but also approaches from information technology are used in synthetic biology. The used laboratory practices rely on recombinant DNA techniques which are already used in genetic engineering. Yet still, biology has from a historical point of view probably always been perceived as a study of nature and natural events. A synthetic prefix results in a contradictio in terminis from a “naturalness” point of view. But what then, is considered “natural”? What is considered natural is the topic of much discussion, also in the Genetic Modification (GM) field. To elucidate this statement: Arno van ‘t Hoog, former chief editor of Bionieuws (news paper of the Dutch institute for Biology, NIBI), writes:

“Biologists are moralists. That righteous attitude can be found especially in the term naturalness. Think of natural balance, organic food, etc. Naturalness is an odd mix of ethics and science. Namely, naturalness isn’t a biological term, in nature you can’t see what is natural. You can go and find a certain situation or condition and call it natural. Naturalness always indicates a favored situation. Or the lack of it, and then we hear defying talk of an unnatural situation. And unnaturalness is about the worst sounding biological accusation one can make. It is therefore that the terms naturalness and unnaturalness are always heard in discussions on controversial subjects like biotechnology and nature conservancy. Biotechnology with animals, genetic modification of plants and the cloning of humans are, according to critics, unnatural practices. And thus repulsive. End of discussion. That’s how it goes repeatedly. Ecological farmers attempt to use natural cultivation methods. Artificial fertilizer and pesticides are regarded unnatural. There was a time when homosexuality, contraception and IVF were regarded unnatural, but luckily times have changed. With all kinds of unnatural situations it seems like the world is a better place to live. One who hears the term “naturalness”, should ask questions. […] The power of the naturalness argument is seemingly obvious. Naturalness is so good and unnaturalness so bad, that it seems like no further explanation is required. And often, no further explanation is given. It sounds like a scientific observation, referring to a higher, unchangeable order. Such a discussion strategy is called a naturalistic fallacy. One describes a situation as natural, to conclude without further explanation, that that situation is good. A well-known example is the justification of the existence of social inequality because of the natural process of competition between different groups in society. In short, there is a foul smell around the naturalness argument. In fact, it can only serve as an emotional signal that the people involved think is important. Afterwards, these people really have to explain and give arguments as to why.”

Van ‘t Hoog argues that what is “natural” is a matter of perception. The concept can be used in any context, either for the pro and contra parties in the GM debate. Another theory is suggested by ethicist John O’Neill , who states that naturalness matters to e.g. environmentalists because of its historical context. It can be compared to an object of art, e.g. a painting of a famous artist. Currently one may be able to make exactly the same painting, with the same kind of paint, colors and autograph, but still it wouldn’t be as valuable. That may be exactly why GM can be perceived as “unnatural”.

However, in synthetic biology this discussion can become obsolete, as the “naturalness” level of synthetic systems appears to be decreasing. At first, one may think that this is useful for ethicists in a pragmatic point of view, because there is one less thing to consider. But this appears not to be true: the discussion has only shifted to a more sensitive discourse, a discussion on the value, essence or autonomy of life.

Nevertheless, the level of artificialness or naturalness is difficult to define. Currently, synthetic biology has a metabolic engineering character, with a focus on understanding and using nature and natural systems. Making complete artificial systems is still in a distant future. This does not mean that one should not consider moral issues related to artificial life, but one should also realize that the current ethical issues in genetic engineering techniques cannot be omitted just because other issues are arising in synthetic biology. There are some implicit assumptions in synthetic biology that need to be considered.

3.4 Implicit assumptions in synthetic biology: forgetting what’s currently important?

Between 2005 and 2008 several papers, fact sheets and reports , , , , have been published on the ethical and social reflections related to synthetic biology. Within most of these publications the authors elaborate on the following four issues:

• Biosafety: health and environment
• Biosecurity: biological weapons and terrorism
• Intellectual property rights: commercialization and globalization
• Artificial life: ethical considerations

One should notice that the issues raised here relate to synthetic biology applications in higher levels of artificialness than is currently being researched in most instances. Of course one should realize that there is only a vague difference between advanced metabolic engineering and the more artificial levels of synthetic biology, but what is often not considered in modern papers on the ethics of synthetic biology, are issues related to metabolic engineering practices like genetic engineering.

It seems that implicitly stakeholders working in the (self proclaimed?) field of synthetic biology live under the impression that ethical considerations that relate to synthetic biology should be considered in stead of ethical considerations relating to recombinant DNA techniques. Skipping this field, where there is already much debate on what is or should be allowed from a moral point of view, seems to be the easiest thing to do. But in this case we are only omitting some relevant issues that have not really been solved yet. Of course, this also depends on the application area of the application. E.g. in Europe the GM food debate stirs many souls, while GM techniques in medical research are much more appreciated. Discussion topics that seem to be missing in synthetic biology are highly related to ethical issues in nanotechnology and biotechnology. Some relevant issues and related ethical questions are enlisted below:

• Public knowledge and involvement in scientific development: should the public be informed about science?
• Public awareness and appreciation of the technology: would a highly informed public be more appreciative of scientific developments?
• Trust of all stakeholders in government, governance and enforcement: do NGOs, the public, scientists, etc. have faith in regulations?
• Trust between the stakeholders: can opposing parties in (ethical) discussions on scientific topics come to terms and on which bases?

• Public or consumer freedom of choice in using this technology and related products: do consumers wish to buy products made with synthetic biology (genetic engineering)?
• Naturalness or artificialness issues: when does a natural system become a mechanical structure?
• Religion and genetic engineering technology: what are the religious boundaries for applying genetic engineering techniques?
• Traditional production methods and related employment: is technological development also appreciated in artisanal production of e.g. food products?
• Risk perception and related gut-feelings of safety: to what extent are gut-feelings of safety (“is it really, really safe?”) playing a role in ethical considerations of certain stakeholders?
• Industrialisation and globalisation and related intellectual property rights: will scientific development lead to abuse of third world countries by large multinationals?

Digging into these ethical issues a little deeper shows that what people may really be concerned about, is autonomy, security and safety (of self and nature, for now and for the future): these are the underlying considerations of the ethical issues enlisted directly above. These are exactly the four issues raised in synthetic biology, as stated at the beginning of this paragraph, but these four are on a higher level and much more abstract. The moral values, that people may want satisfaction on before these higher issues can be discussed, are the more superficial issues listed directly above.

3.5 The “banner” implications: a pragmatic point of view.

Yet implicitly it seems that in synthetic biology research, these issues are not considered. Scientists probably know about the issues raised in synthetic biology. However, by working in synthetic biology research, it may seem that the scientists do not consider ethical issues related to the public, religion, trust, tradition, globalisation, industrialisation, naturalness, freedom of choice, etc. Does this mean that under the “banner” or flag of synthetic biology, more is or should be allowed than is the case for genetic modification in metabolic engineering? Let’s elaborate.

With the term “genetic modification” the focus is on the used technology and hence there is a focus on practicing recombinant DNA techniques. Therefore the focus is on changing DNA and hence the autonomy of an organism is much more prominently present in discussions on ethics of genetic engineering. Discussions about the possibilities (technical and theoretical) and regulations (legal framework and enforcement) of genetic engineering techniques therefore are much more logical to be discussed by the parties that in some way or another are in contact with this technology. This is in great contrast with synthetic biology. The term “synthetic” probably makes people perceive that the connection with “life” and autonomy of life is, perhaps partially, already lost. With increasing levels of artificialness (irrespective of where the frame of “naturalness” ends) it may therefore seem that more is allowed in terms of use of recombinant DNA techniques, than was the case in metabolic engineering with “genetic modification”. It seems that just this difference in terminology may have important consequences for the public appreciation of the technology, while in fact, synthetic engineering can be considered “worse” from a technical point of view in terms changing DNA and respecting life and living organisms’ quintessence; it seems that under the banner of synthetic biology, more may be allowed, while forgetting about the ethical issues raised in the previous paragraph.

But nonetheless, before it was argued that currently, synthetic biology and metabolic engineering are not that different. This should also mean that the ethical issues related to genetic engineering should be considered in synthetic biology and should not omitted or forgotten. Indeed, synthetic biology gives rise to new ethical issues that need to be considered, like the afore mentioned moral issues related to biosafety, biosecurity, intellectual property and artificial life. Papers and reports focussing on the ethics of synthetic biology focus on these new issues, but most of them do not elaborate on ethical issues of genetic engineering in general, like mentioned at the end of the previous paragraph.

3.6 The media: a PR stunt or time for a public backlash?

In a different approach, one may also argue that in synthetic biology, the application and related processes within an organism are in the centre of attention, while in metabolic engineering the technology and the organism itself play a more prominent role. This implies that the designer approach of synthetic biology, possibly together with the constructive excitement of this new approach may make synthetic biology appeal more to the public and therefore my be more appreciated by the public. But this is not how synthetic biology is presented in the media. A quick survey on the news paper websites of the BBC, NY Times, Daily Mail and the Guardian, with search term “synthetic biology”, yields a number of articles, which do not put synthetic biology in a particularly good (or bad) perspective:

• Synthetic life 'no terror threat' – “Synthetic biology can help in the fight against emerging infections, rather than aid the design of bioweapons, controversial scientist Craig Venter has told reporters.” – BBC News

• 'Artificial life' comes step closer – “Researchers at Rockefeller University in the US have made the first tentative steps towards creating a form of artificial life.” – BBC News

• Venter revives synthetic bug talk – “Craig Venter - one of the scientists behind the sequencing of the human genetic code - aims to construct a living organism from a kit of genes.” – BBC News

• Biology's New Forbidden Fruit – “The scientific, commercial and destructive possibilities of this synthetic biology are easily as great as those once offered by the transformation of chemistry. But they will make themselves felt far more quickly, raising ethical and moral questions that many biologists have been poorly trained to handle.” – NY Times

• Researchers Take Step Toward Synthetic Life – “Taking a significant step toward the creation of synthetic forms of life, researchers reported Thursday that they had manufactured the entire genome of a bacterium by stitching together its chemical components.” – NY Times

• Custom-Made Microbes, at Your Service – “To be sure, scientists have been putting genes into bacteria and other cells for three decades. The term "synthetic biology" seems to include various activities, some of which are not altogether new. "This has a catchy new name, but anybody over 40 will recognize it as good old genetic engineering applied to more complex problems," said Frances H. Arnold, a professor of chemical engineering at Caltech.” – NY Times

• One step closer to Frankenstein as scientists create artificial life in the lab – “Researchers in the US managed to swap the entire genome of a bacterial cell with one from a different related bug. Given a completely new set of genes, the bacterium was effectively changed into a new species.” – Daily Mail

• Scientists create artificial life in the laboratory - from four bottles of chemicals – “Scientists have made a major step forward in creating life in the laboratory as researchers announce they have rebuilt a living bacterium from four bottles of chemicals. […]The scientists took the natural bacterium and painstakingly replaced its genetic structure, or genome, with DNA stitched together from chemicals. Eventually they had recreated all the genes that had been in the natural bacterium, effectively turning it into an identical but artificial organism.” – Daily Mail

• Synthetic biology aims to solve energy conundrum – “Designer enzymes are big business as the need to produce viable biofuels grows - but can they offer a long-term alternative? […]Even with an agricultural system tuned to extract as much biomass as possible, there will not be enough land to supply all fuel. […] Clearly, our need for designer enzymes is growing urgent.” – The Guardian

• Biologists join the race to create synthetic life – “The new discipline, established by scientists such as human genome pioneer Craig Venter, involves stripping microbes down to their basic genetic constituents so they can be reassembled and manipulated to create new life forms. These organisms can then be exploited to manufacture drugs and fuels or to act as bio-sensors inside the body. However, some researchers warn that synthetic biology - which is accelerating at a dramatic pace - also poses dangers. In particular, they fear it may already be possible to create deadly pathogens, such as polio or smallpox viruses, from pieces of synthetic DNA ordered over the internet. In future, completely new - and highly dangerous - microbes could be made this way.” – The Observer

• Can we create life? – “Our knowledge of, and ability to, alter DNA remains rudimentary, in spite of notable scientific advances and the persistent dream of genetic perfection. […] This technique is called synthetic biology and it combines science and engineering to build new biological functions and systems. The US group J Craig Venter Institute hopes eventually to use engineered genomes to make bacteria that can do useful things, such as produce clean fuels or take carbon dioxide out of the atmosphere. But many people are extremely concerned by the possibilities of bio-error (or bio-terror) that artificial life creates. They say artificial microbes could have dangerous consequences if they escape into the environment or if they are used to manufacture bioweapons. At present there are no international laws or oversight mechanisms to assess the safety of synthetic organisms.” – The Observer

From these articles, it seems that people do see the benefits of synthetic biology, but there is also attention for bio-error, bioterrorism, ethical issues, etc. In a way, the benefits are recognized, but the drawbacks also receive attention.

One can debate whether this attention for the potential risks and risk perception is a good development for advancing science, but at least one can notice that this development is in large contrast with the progress in genetic engineering from the 1970s to 2000: here, much less ethical considerations are generally observed.

Yet still, when we consider scientific evolution of synthetic biology, with a focus on ethical issues such as biosecurity, biosafety, intellectual property and artificial life, one can wonder when the public is going to realize that synthetic biology is not so much different from genetic engineering. Could this lead to a large decrease in public appreciation of synthetic biology or genetic engineering in general? Will the introduction of the term “synthetic biology” in fact cause a public backlash on this technology?

Perhaps different questions should be considered. For example, should we wonder what can be done to prevent this public backlash from occurring? But maybe the questions should be on a different level: is the public interested in this field of science? Should the public know more about the scientific background of this technology? To what extent should the public be involved in scientific development? These ethical/social questions are becoming more relevant when biotechnology (or synthetic biology) applications are going to represent a larger part of our everyday life.

Currently, one may argue that in most products we use, in some way or another, biotechnology is already used, people just don’t know about it. With the decrease in oil supplies and the introduction of biofuels, bioplastics, agro biotechnology, gene therapy etc., a larger part of the things we take for granted will become biotechnology based: from fossil fuel based economy to biobased economy. It is up for discussion whether this is in all cases a good development…

3.7 From contradictio in terminis to oxymoron: the hype or promise of synthetic biology?

The question that arises from the previous paragraph is whether synthetic biology applications can really live up to their promises. In other words: the seemingly mistake of the contradictio in terminis of the term “synthetic biology” may really become the deliberate use of the oxymoron “synthetic biology”. Is it just another hype (like in the past e.g. Y2H systems, DNA microarrays, systems biology), or can scientists really accomplish something with synthetic biology, and than in particular some applications that everyone is happy with and see the advantages of? To achieve this, there are two kinds of challenges:

• A scientific challenge: can we come up with synthetic “living” systems that do not pose biosecurity and biosafety risks? This may be impossible, but the possibilities and advantages of synthetic biology are numerous.
• A social/ethical challenge: can we make synthetic biology applications appreciated by all direct and indirect stakeholders in the discussion on genetic engineering and related topics? Artificial life and intellectual property issues need to be considered, but also general genetic engineering related ethical issues.

The engineering approach of synthetic biology (biological engineering in stead of only metabolic engineering) may give rise to numerous applications. It comprises a big technological field that will probably involve the whole world. This also means that a thorough discussion on ethical issues, regulation and control is necessary to determine the boundary conditions, in both a social and a legal perspective. Still, whether synthetic biology will prove to be a hype with only loose promises, only the future will tell.

3.8 Intellectual property rights: usefulness or commercialization?

Besides the implications of synthetic biology, the terminology and the scientific advantages and disadvantages, another issue needs to be considered in the field of synthetic biology from an engineering point of view. As synthetic biology applications begin to emerge, the applications are also starting to be patented. In our society, scientific research on patented applications is possible without licences, which means in practice that all patented ideas can be researched without financial consequences. Licence fees have to be paid, however, when an investigated application is subsequently commercialized. This has some practical limitations for synthetic biology research: some ideas may already have been patented, without the application being demonstrated to work properly in the lab. This also means that any combination of BioBricks (a “device”) can also be patented (of course under the patent requirements that apply), which makes commercialization of certain applications impossible.

One can wonder whether the constructing side of synthetic biology with increasing levels of artificialness is then only meant to be useful and to prove principles in biology, or whether actual applications can also be commercialized without being limited by patent registrations. But besides intellectual property considerations of open source technology, also more specific concerns regarding the iGEM competition can be considered. These will be discussed in the next paragraph.

3.9 iGEM, open source technology and the intellectual property: impossible or naïve?

Within the iGEM competition, the idea is that BioBricks are added to a database in a completely open source setting. Everyone should be able to use these BioBricks to make a certain application. However, in this approach, there are several things that have to be considered, on which we could elaborate into very much detail. However, these issues will be mentioned and explained below briefly.

• Open source and the role of capitalism in science. Perhaps ideally, all academic science would be open source; financing for universities comes from a central (national) government, all scientific findings are published and progress is made because everyone has access to the latest scientific developments. Unfortunately, this is currently not the case. Universities have agreements with companies, companies finance research carried out at universities and commercial interests need to be considered. A consequence is that research in an academic environment is not completely open or publicly available anymore. On one hand, it is convenient for universities to have some extra money to spend, but on the other hand it is not an ideal situation for open source research: some research cannot be published or only partially. This means that scientific knowledge lingers in company file cabinets, partly perhaps due to possible commercial losses or gain.
• Developing real cash cows? Within this capitalist environment, one can also imagine that developing applications that could really yield a lot of money in the commercial sector, are not made publicly available. It would probably be considered quite obtuse of the inventor of a certain application to not patent it. Of course, the data can still be made publicly available, but one can wonder what than is the eventual point in publishing your secret with which you could make a lot of money. It may therefore also seem unrealistic for constructive open source synthetic biology (iGEM) to expect really valuable inventions to be deposited in public DNA databanks like the BioBrick database.
• Academic interests. Another issue to consider in this respect is the interest of companies that sponsor academic research institutes and the interest of the academic institute itself. Imagine a really potentially profitable application being developed by an iGEM team, which deposits its findings in the database. Would the board of the university be happy with this iGEM team or its supervisors or supervising professor? Probably not, since loads of money could have been generated from this certain project, to the benefit of the entire university. Moreover, would it be in the interest of renowned professors to contribute to this particular iGEM project that could have generated a lot of money? Probably not, the professor may even be sacked by the university, for blunt ignorance.
• Company interests. Besides the issue described above, also company interests may count here. Supervisors of iGEM student teams are sometimes not allowed to talk about different subjects, because they have agreements with companies that sponsor their research. One agreement may be that the academic institution can do research on a topic as sponsored by this certain company, under the condition that the academics do not contribute or work on other projects related to this sponsored topic. This may not be desirable for the progress of technology or contribution to open source science, but it is the case in everyday scientific practice. In fact, lots of money (and/or other company interests) may be at stake.
• Bioterrorism? The last issue related to open source technology that will be mentioned in this report has to do with bioterrorism. For obvious reasons, open source technology is connected to dual use issues and (deliberate) misuse or bioterrorism. These issues are discussed in the next paragraph.

From the issues described above, one may begin to doubt whether the open source approach of the iGEM competition is actually as useful as is sometimes proposed. It may in fact even be naïve to believe in the success of this approach. Still, from a different point of view, the benefits of the BioBrick database may also be recognized, as presented in the introduction of this report. Having discussed al the above, one topic remains to be described, the risks associated with synthetic biology. This topic will be discussed in the next paragraph.

3.10 Prospective: solutions to ethical problems?

By looking at the future of synthetic biology one can identify all considerations presented in this report to play a part in future research and applications, but also in governance, regulation and enforcement issues, where the issues that were mentioned are to be reflected in. Conventions or international agreements may also be considered. Still, technological advancement and governance are somehow related when speculating about the future of biotechnology. When life science activities are tightly regulated and difficult, this will yield a different future than when synthetic biology turns out to have results easily in an unrestricted research environment. This is further specified by Aldrich et al. Here, speculations are made on the likelihood of e.g. deliberate misuse, garage biotechnology and open source approaches towards technology, but no conclusive remarks can currently be made.

Hypothesizing about the future of life science technologies, together with scientific advancement, different stakeholders and many conferences and papers on the ethics of technology may together lead the development of synthetic biology applications into a future with fewer concerns related to synthetic biology.

The discussion on the ethics of synthetic biology classifies as a “wicked problem” , as proposed by dr. Jeff Conklin , director of the CogNexus Institute. He published on shared understanding of wicked problems : this involves problems with many stakeholders, large technical complexity and where no easy solution is available. If this is the case, fragmentation between stakeholders occurs, resulting in different parties with different opposing opinions, which is not a good development for coming together and deliberating on a certain topic in order to achieve social and technological advancement. Defragmenting activities to prevent this from occurring involve deliberations like conventions and reports on ethical considerations, like currently the SynBioSafe program and Synthetic Biology X.0 conferences.