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This study described this report reviewed ethical considerations in the open source synthetic biology student science competition called “iGEM”. As a case study, the opinions of the participants of the TU Delft 2008 team on moral issues that play a role in this project were monitored. The goals were twofold: firstly to investigate which ethical considerations play a role in the iGEM project; secondly to create awareness among the participants on these ethical issues. With the results of the study, some discussions are possible, some of which are brought up in this chapter.

5.1 The general ethical issues in iGEM

From a literature review it appears that four main ethical issues constantly return in synthetic biology. Two relate to the novel character of the scientific backgrounds used in synthetic biology, being biosafety and ethical considerations around artificial life. The other two relate to the open source approach that is proposed (and partially implemented already) in synthetic biology, being biosecurity and intellectual property.

The issue of biosafety involves a guarantee for safety in development, in production of the application, upon use of the application and for the environment it is developed, produced or used in. The question here is to what extent absolute safety can be guaranteed. Currently, much research and development of application probably revolves around risk analysis, rather than the possibilities in terms of projected benefits (in terms of money, general good for society, safety, etc.). It cannot be stated that this is a bad or good development, but at least it can be observed that this is reflected in society (or the other way around), which is probably one of the main reasons why biosafety currently is an ethical issue in synthetic biology and, more specifically, in the iGEM project.

The issue of artificial life relates to the level of naturalness in synthetic biology research. More and more “unnatural” components can be added to “natural” cellular systems. The level of artificialness generally increases in synthetic biology application, more so than was the case in the more classical “metabolic engineering”. Currently, components that can not be found in nature can be incorporated into biological systems. Biological subsystems can be integrated into other biological systems, creating new, complex and more or less “natural” (or artificial) systems. The question is how “synthetic” biology (the study of life) can actually be. Should recombinant DNA techniques be the solution to all the world’s problems? This makes artificialness or naturalness an issue to discuss within the iGEM project.

The issue of biosecurity revolves around the open source character of the iGEM project. Participating teams are expected to be fully open and honest about their research setup and their results. This open source approach, together with standardized biological parts and recombinant DNA techniques becoming cheaper and more easy, has some consequences in terms of biosecurity: applications can be developed that may cause intentional harm to the environment, human life, etc. Currently, any DNA sequence can be ordered from synthetic DNA manufacturing companies all around the world. Pathogenic systems may therefore easily be developed. The question is how much attention a team participating in iGEM can give this issue and to what extent the teams are responsible for what other people do with developed applications.

The issue of intellectual property rights also involves the open source character of the iGEM project. To some, it is somewhat unclear what may be patented and what may not. But one may also question whether the open source (in comparison with closed source) is a good development from a scientific point of view. Will fundamental or applied science really benefit from complete openness? These questions are also to be considered within the iGEM project.

5.2 Recombinant DNA techniques: going too fast?

But one may question whether it is good to consider these issues in synthetic biology, while many ethical concerns in the predecessors of this novel technological approach with recombinant DNA techniques, are still not addressed. Is society ready for this new, extreme form of genetic engineering ? It sometimes seems as if under the “banner” of synthetic biology, all the science is morally justified. But don’t issues relating to public opinion, like religion, trust in science, naturalness concepts, globalization, need to be resolved first? Then the question lies deeper, e.g. whether science should always depend on public involvement. But still, science has advanced, so probably the thing to do now is take these new ethical considerations into account, in addition to the previous ethical considerations. But this also means that we cannot forget about the previous issues. In that sense, synthetic biology can be a PR stunt to get the science appreciated by the public, but when presented incorrectly, it may result in public backlash, because the public is perhaps not ready yet for the next step in “biology”.

5.3 Designing with biology: the points of ethical decision making

Ethical decisions are made throughout the entire project. The project has different stages. In the initial stage, the project has to be defined. In this stage, different ethical issues play a role than in the next stage, when a project is slowly starting to lead to an application. That is exactly the stage the project is in during the time this report is written. Hereafter, product development and potentially commercialization will play a role, which also involves different ethical decisions. But even before the iGEM project has started, participants have to be found that are willing to participate. Deciding to participate of not can be an ethical decision: the team will be working with recombinant DNA techniques, play with nature or natural biological systems, etc. Even though this probably doesn’t play a role for students who just need the credits for participating in a scientific project, the choice to become involved can still be a moral one (see Chapter 3.4). Before the project was defined, already some minimal moral values to take into account were defined by the team. These values helped to bring more guidance in the brainstorming sessions and also helped defining the project after brainstorming (see Chapter 4.2). But also in design of the project, ethical decisions are made.

Also in designing the bricks themselves ethical decisions are made. One can question why certain sequences from certain source organisms are used, or whether or not DNA should be ordered from a company (Chapter 4.3). Also, during the project, interviews were held with the participants to investigate their opinions on ethical issues that play in synthetic biology and simultaneously making them more aware of these ethical issues. In these interviews the participants also learn about their ethical decisions.

Whilst the project is slowly evolving, the team is starting to think about realistic applications. In thinking about these applications, some people are slowly thinking towards market introduction and related issues of biosafety and security, public opinions, etc. These are also ethical decisions, but in different future stages of design.

5.4 Conceptualization in design: standardized BioBricks or standardized science?

Synthetic biology is currently largely about making standard biological parts that can be used to make any sort of application. The iGEM organizers cry for large scale standardization in an open source setting with a publicly accessible database. But some criticists have stated that biology cannot be standardized, for different reasons: biological processes may be too complex, behave unpredictably, etc. But one can wonder to what extent biotechnology research has already been standardized or conceptualized. In the weekly meetings with the TU Delft team, typically once or twice remarks like “and than we can easily check that with an assay” or “but there are methods for that” are heard, without further defining what actually has to be done. This conceptualization also means that the biological side of research is suggested to be easier than it may actually be, since these vague conceptualized statements need to be interpreted, investigated, incorporated into the project. All these steps take additional time and may give participants unschooled in biotechnology the wrongful idea that the biological science is predictable.

5.5 Ethics in the 2008 TU Delft iGEM team

The outcome of the survey was already described in Chapter 4.4. Some issues about which there can be much discussion are further analyzed in this paragraph. First, the feasibility iGEM project is discussed. Hereafter, the relation between fundamental science and applied science will be further examined. Then, how ethical considerations come back in the project is described into more detail. Next, the role of value sensitive design in the project is discussed. Subsequently the team’s responsibility in safety and security is further discussed. The last topic of this paragraph regards the difference in opinions that scientists have on the values that play a role in the project.

5.5.1 A little too ambitious?

In the introduction of this report it was stated that synthetic biology generally has two approaches: the constructing approach and the deconstructing approach. In the first, biological subsystems are used to build a certain application. In the latter, an organism is used to analyse these subsystems and to learn about living systems. The participants in iGEM mainly use the constructing part, while in fact the team is also learning about the biological subsystem that is used. In trying to make an application, actually fundamental science is involved. This can be observed in many iGEM teams. On their WIKI websites, the teams start off with the wildest biological ideas, with most promising applications. But when time goes by and projects evolve, the teams are conducting more and more fundamental science to prove basic biological principles. In fact, many proposed applications are not actually made by the end of the project, because the fundamental biological principles are not fully understood and still under investigation. It is questionable whether the façade of iGEM as being an applied science project (implicitly represented in the “building with biology” slogan) can be justified from this point of view.

5.5.2 A fundamental conflict

Continuing on the ambitious usefulness on the project, this gives some difficulties within the TU Delft team. When asked whether the participants preferred the fundamental scientific approach of developing an RNA structure dependent switch or the more applied color output research, all but one participant stated that the fundamental science was more interesting for them (Chapter 4.4.10). To some extent is in contrast with the requirements and the value sensitive design as assessed before the project was defined. These requirements stated that a useful, Delft related application was to be investigated, and usefulness was a minimal moral value. Now that the project has been defined and research is being carried out, the participants generally think the fundamental science is more interesting.

Of course, fundamental knowledge is needed to develop an application. But even making an application doesn’t seem to be a goal anymore for some team members (Chapter 4.4.5): commercialization and the application are not stated as an iGEM goal, so the team doesn’t have to think about them anymore, according to some. Others still think the application needs to be considered, along with ethical issues like biosafety, biosecurity, public opinion, intellectual property and commercialization. Others think that thinking about an application has nothing to do with commercialization and money. But the relation between open source and usefulness and the relation between open source and commercialization are largely unclear for the participants, and all have a different opinion on these relations (Chapter 4.4.4).

To make this difference more general: there seems to be a clash between those who think in consequences (consequential ethics, e.g. if the team does “this”, we should take into account “that”) and those who think in principles (deontological ethics, e.g. “we should always take “that” into account).

This fundamental science vs. application oriented science conflict seems to be something that also needs to be considered by the iGEM competition organizers. It is currently largely unclear for the participants to what extent they have to investigate patents and commercialization. One may not expect this science project to also involve making business plans for starting companies with the developed application. In fact, it was also stated that it is questionable whether iGEM will really generate useful applications (Chapter 3.9) and the team members also don’t agree on this matter (Chapter 4.4.4).

5.5.3 Why does a dog lick itself? Because it can…

Whether anything useful will come from the TU Delft project or not, still some ethical issues need to be considered. Here the focus is on science for the sake of science. It seems that the iGEM competition has a very strong focus on modern biotechnology, in all its facets. But participants need not be biology or biotechnology students. The TU Delft team also consists of an informatician, a mechanical engineer and a biomedical engineer. But can people from different disciplines really participate in this project? One striking finding was that one of the participants, not schooled in biotechnology, was not happy with the idea that human genes (without questioning what makes a human gene a human component, scientifically speaking) could theoretically be used in this project, because of personal moral beliefs. What if the TU Delft team had decided to use a gene responsible for human eye colour for the output of the thermometer? The question than is whether these matters of personal beliefs should be investigated before participating in the project. Should iGEM be responsible for letting the participating teams decide on participation because of moral restrictions? Perhaps this should be investigated.

But besides these personal beliefs conflicts, it can also be questioned whether or not it is a good development that people without a background in biotechnology start working in synthetic biology research. From the interviews it can be concluded that the participants schooled in biotechnology have less difficulty in formulating their opinions on ethical issues than the participants without a biotechnological background, indicating a very limited overview of the ethical concerns in biotechnology research. Together with the large scale conceptualization of biological principles and biotechnology research becoming more and more standard and more and more easy, one may wonder whether this is a good development for the future. Is scientific research becoming science for the sake of science, or can ethical considerations play a role in modern biological research?

A different issue regarding ethics in science regards the biological design of the project. In the project proposal the goals of the project are clearly described. The benefits for society are mentioned, but the methods in how to achieve the goals are still somewhat vague. The group has to come from any starting point to a certain end point (metaphorically, from A to D). The ethical conditions under which this is possible have been assessed and the ethical considerations are defined in value sensitive design. But still, the steps to go from A to D, being B and C, have to be defined. In this intermediate research stage, also new or other ethical principles are appearing, some maybe conflicting with the initially defined ethical conditions. For example:

In value sensitive design it was assessed that the design should be simple: an RNA structure in front of a gene should regulate gene expression and hence functionality of the biological part. But how does one check this principle? The output system, the color pathway, is also still under development, so “easy” testing methods should be found. Let’s say the team comes up with a testing method where a human gene is used that is easily incorporated in the part to be tested, but requires a little more effort to analyse. A balance has to be found between checking the functionality in a good, quantitative way, and the ease of checking this functionality. Here, in deciding on how to get from A to D, ethical considerations seem to play a minor role, in comparison to technological possibility. In other words, in the intermediary steps, science is becoming science for the sake of science in stead of science for the sake of society, as it was previously defined in the project proposal.

5.5.4 Value insensitive design?

But does the above this mean that the value sensitive design concept has failed completely for this project? All participants stated that it was necessary to consider ethical issues during the project, so in that sense probably it is useful to consider ethics. Also the value sensitive design session was appreciated by all team members who were present. Also the participants did not mind talking about ethical issues during the project. But taking into account the values from the value sensitive design setting is a different matter. Apparently it’s not that the team doesn’t want to consider it, it may be just (too) hard to implement during the project, or at least during the initial phase of the project. Some participants stated that currently the focus of the project should be on making functional subsystems and thinking about applications. Others stated that the values from value sensitive design should be taken into account after applications were developed. All in all, this seems to indicate that the team members recognize different stages in design. Before the project has been described, values can be mentioned that are important to incorporate into the project, but perhaps during the project these values become irrelevant, because of the nature of the proposed applications. Also, new ethical issues may arise during development of the project.

The values as assessed in the value sensitive design session currently do not come back in the current stage of the project. While the functional units are being developed, the team starts to think about applications, and when these applications have been found, the general expectation is that the values are going to play a more prominent role. It can be expected that the value sensitive design will play a more prominent role in future stages in design. Also, all iGEM teams may benefit from experiencing value sensitive design sessions. In that sense, it may be useful for the iGEM organizers to incorporate values in the project participation requirements.

5.5.5 The misuse dilemma

Two of the values that were considered important to consider beforehand, are also proposed major ethical considerations in synthetic biology in general, being safety and security (also described above in Chapter 5.1). But one has to question to what extent biosafety or security can be guaranteed, from a scientific point of view: it depends on many different aspects, like the proposed application. It may seem easy to assess whether or not an application can have harmful effects or may be used in terrorist activities, but how is this to be assessed? E.g., evaluation of “likeliness to be misused” in terms of errors or terrors is quite an arbitrary, intuitive assessment. But also one should question what can be done to prevent misuse to prevent safety or security issues. What can be designed into the developed application to actively prevent misuse? Participants proposed being clear in documentation and giving detailed manuals on how to use the application is all you can do. Others state that maybe failsafe systems need to be developed, but that first a functional unit needs to be developed before this can be considered.

Probably, scientifically, not much is possible to prevent misuse. It seems that currently we have to rely on people’s morality and sense of responsibility. The team members did feel responsible for the safety of the application that is being developed, but opinions on where this responsibility officially lies are somewhat diverse. Some even state that the iGEM organizers could be held responsible for misuse, because the organization sends the DNA around. Others state the laboratory in which the research is conducted is responsible. Nevertheless, a little clarity on liability from the iGEM organizers would be very much appreciated.

5.5.6 Scientific homogeneity

The most obvious general conclusion of the conducted interviews is that the “scientists” (students and supervisors) in the iGEM project have dissimilar opinions on various ethical issues. Apparently, like “the public”, “the scientific community” doesn’t ventilate a single, homogenous opinion. One may question what can be done with this information, since relating this finding to ethics in technology goes much further than just the ethics in synthetic biology. One may for example wonder whether it would be wise to let the public know, explicitly, that scientist also do not always agree on the way science is conducted. But at the least this finding indicates that it is very useful to think about ethics in a project like iGEM, or perhaps even in general in working with innovation. Thinking about ethics can change the course of research in such a way that values are taken into account, that the good for society is always considered, and that not always the scientific principle of efficienty ruled the course of science conduct.

The 2008 TU Delft iGEM team members indicate that ethicists and scientists probably need to work together in the future to make sure that ethics are taken into account in natural science (Chapter 4.4.6), and that is exactly the area where currently much research by science and technology studies (STS) researchers is done. It is probably a good development that the iGEM organization values taking human values into account, since it is a “gold medal requirement”. But perhaps it should be obligatory to think about ethics for all participating teams.

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