Summary and Conclusions

Executive Summary

Synthetic biology is becoming the dominant term in describing an innovative multidisciplinary field with both promising scientific benefits and important ethical issues at the same time. The surge of interest in engineering living systems is largely due to a reduction in gene sequencing and synthesis costs as well as the completion of the human genome project and developments in automation techniques.

Although the term has been abundantly used for almost a decade, there is no consensus on a definition for synthetic biology. Different practical approaches to synthetic biology research and engineering emanate from different disciplines, resulting in an almost intangible characterization. An attempt by the European Commission to describe synthetic biology resulted in the following working definition: “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”.

The goals in synthetic biology range from creating an open source registry for standardized biological parts (initiated by the Massachusetts Institute of Technology ) to environmental control, development of pharmaceuticals and renewable fuel production. There are two main practical approaches involved in pursuing such goals. The bottom-up approach starts by creating synthetic biological systems out of partially artificial components, whereas the top-down approach reduces existing life forms down into its individual components.

Now that research has enabled to change individual biological components, focus lies on constructing complex networks in single-cell and multi-cellular systems. Recently realized accomplishments include the development of nonnative behaviors such as bi-stability, oscillations, bio-sensing and spatial-pattern formation. Furthermore, as the capabilities of synthetic biology advance, applications within biotechnology, pharmaceutics, environment, information technology and renewable energy will emerge.

The issues concerning synthetic biology are partially acknowledged by the scientific community. Unfortunately different stakeholders usually raise only a limited number of concerns, dependent on personal interest or due to insufficient data or unfamiliarity. The concerns that typically appear in literature include bio-safety, bio-security and intellectual property rights. Topics concerning attitude towards life, reductionism, transparency and public involvement that are relatively hard to address but nonetheless important, do not obtain the attention they deserve. Therefore we have propose different frameworks of the major ethical issues involved in synthetic biology, which can function as a potential reference for regulation and policy making. The different road maps illustrate a rough division of the main ethical issues in synthetic biology, differences between physical and non-physical harms in emerging technologies, ethical considerations from a synthetic biology practitioner's point of view and the connection between evolution, life, reductionism and the bottom-up approach in synthetic biology research.

The undervalued but key ethical issues in synthetic biology are mainly concerning reductionism and the bottom-up approach of creating living systems. Issues concerning safety, security and handling of intellectual property rights should mostly be related to politics not ethics. Although these topics need good regulation, ethics does not play a major part there. Instead there should be more focus on questions concerning life, specifically the reductionist (top-down) approach towards understanding life, and the bottom-up approach towards creating life. The reductionist approach in general, is a method to understand complex systems by understanding its subsystems, in synthetic biology specifically the molecular level is targeted to see how biological systems work. In the bottom-up approach systems are pieced together to give rise to bigger systems, as can be done in biology with genetic engineering principles. What happens if the reductionism approach will eventually show us what life is all about? What happens when humans can create living systems? We cannot foresee if research in synthetic biology will be able to reach those goals but since the scientific community is getting closer en closer to the foundation of living systems, these questions become much more important.

We have evaluated these omitted topics and reflected on them quantitatively by carrying out and analyzing a survey amongst 60 supervisors (and advisors) and 168 students, participating in the 2009 International Genetically Engineered Machine competition. The aim was to raise awareness on these particular subjects. Moreover, the collection of many opinions from this particular scientific community contributes to understanding synthetic biology, to see how ethical issues are perceived and to recognize which concerns should be addressed in regulating synthetic biology.

Conclusions from the survey

The first few questions were introductory to the main ethical issue: whether the reductionist approach in biology has any effect on our current perception of life and if so, how. The questions meddle with traditional and established viewpoints.
It seems that the possible negative effects of the pursuit of understanding life (the devaluation of life) are not a reason to stop research, mostly because people argue that the value of life cannot be changed (but might even be enhanced) by understanding the mechanisms of life. A majority of 90% would not pull back from fundamental research on the principles of living matter even if the the value of life cannot be secured.
Modifying organisms by the using genetic engineering tools should be available because of the (possible) benefits that it carries along, as outlined by the majority of the group. Only a small group is worried about the consequences that these techniques might have when meddling with evolution. Although the techniques are well studied, the complexity of DNA and the translation system are not yet completely understood and should make researchers use genetic engineering with care, and only apply it for beneficial purposes. A risk/benefit assessment could help identifying when these techniques should be applied.

One of the biggest contributors to synthetic biology research and possibly one of the most controversial researchers in (synthetic) biology is Craig J. Venter. His project on creating a minimal genome is groundbreaking and raises a lot of questions, primarily by media machinery. Whether the research of Venter is new or not is a difficult question, the surveyed group does not have a universal answer. Reasons for that can include that more specific knowledge on his research is needed, and that it is hard to define when an approach or technique is typically new. Nevertheless, the technical challenges that Venter faces are acknowledged.
Although he is pushing the technology as far as it goes, over 80% does not believe that Venter is playing God by creating life artificially. Nevertheless, the majority also thinks that the public will perceive the research as controversial, thinking that Venter is trying to create new life forms. A relatively large minority of think that the public will presume that he is only putting biological components together. An important point is to focus on the importance of proper communication in order to inform the public objectively. Using statements such as "playing God" might draw the wrong attention.

Amongst the main issues in synthetic biology are bio-safety and bio-security. Both the dangers of errors and terrors are addressed in the survey, as well as the attitude towards risk-taking in this emerging field of science.
The majority acknowledges the possibility of the production of a biological system containing some hazardous error and most believe there is regulation needed to prevent this. 34% does not see this possibility as a real thread and think either that there is sufficient regulation already, or just does not fear this at all. It is hard to say whether new regulations can overcome the unforeseeable problems that come with synthetic biology. An issue in respect to safety is the emergence of DIY biology, which can increase the risk of errors significantly.
Most people acknowledge the risk of synthetic biology principles being used for terrorist purposes, but in contrast to the previous question, there are much more people that think new regulation will not be the answer, mostly because they have the feeling that if terrorist want to use synthetic biology as a means to their own ends, they will find a way of doing that anyway. Nevertheless the plurality of the group believes that enforcing additional policies can minimize this risk.
Synthetic biologists are generally careful. Only a very small group can be described as optimistic and fearless, whereas the plurality would conduct additional research to minimize any risks. Moreover, the majority thinks that the public is even more fearful and risk-averse than researchers are. They believe that the public first wants proof that a certain project is safe, before pursuing any goals. Furthermore, the influence of communication between researchers and the public on risk assessment is important.

How does the synthetic biology community thinks about life, what values they give to it, what does it means to them, and to what extend can it be explained (reduced) in terms of science? To a certain extend, these questions should make the reader aware that they are working with living systems with a certain worth but and make them think about how research may effect the value or perception of life. The ultimate way of applying the reductionist approach could well explain life, consequently have certain implications. Whether this point will ever be reached is doubtful. What is the scientific opinion? If research proves that life is reducible and independent of any non-materialistic properties, then most participants would believe this. Conceivably, a large plurality of the group does not believe that God has a hand in life.
In contrast to the previous question, the statement saying that life is holy/scared is answered more diversely. The group that rejects the statement is equally big as the group that embraces it. Even though the majority of the group does not think that God has a hand in life, the believe that life is holy/sacred is still very much divided, which indicates that there is not a necessary relation between the existence of a God and sacred or holy properties of life.
Although many people think that the reductionist approach can reveal the properties of biological systems, there is an almost equally big group that is not yet sure about this. The lack of a majority that either agrees or disagrees with the statement shows that there is no concise answer for this question. Contrastingly, the majority of the scientific community does support the holistic approach of describing complex biological systems with emerging properties. The questions remaining: can we ever characterize the emerging properties? Can a living system ever be explained completely materialistically?
Materialists believe that all things are composed of matter and all phenomena are the result of material interactions. A plurality of 40% believes that life can be explained materialistically, versus 19% that rejects this statement. A rather large group does not choose sides and keeps his answer in the middle. There might be a conflict between the traditional perception of life where it is thought that living systems are just too complex to understand and the breakthroughs in science getting closer and closer towards explaining life. Will the scientific community ever be able to reveal the principles of life completely, or will there always be things we cannot understand? Supposedly time will tell. Or not, depends on what you believe. Although research has given us indication that life is purely physical and can be explained materialistically, there is a chance that we will never figure out its foundation.

Insight in the goals of synthetic biology can help in defining the fields where possibly more regulation is needed. The most popular reasons to work in synthetic biology appear to be sharing knowledge of fundamental processes in biology and social objectives, using synthetic biology for applications in fields such as medicine and the bio-fuel industry.

One of the problems in science in general is the way to communicate research to the public. It gets even more difficult when controversial subjects raise ethical issues that might be hard to understand without any scientific background knowledge. Informing the public is perceived to be necessary, but the media apparatus and the scientific community should generally work together on getting a clear unbiased and easy-to-access story out, rather than publishing controversial and misleading headlines to draw attention. Moreover, debating ethical issues in synthetic biology together with the general public is assumed to be even more important. Researchers have to work together with governmental institutions to identify, characterize and possibly find solutions to issues emerging from synthetic biology.

When discussing ethical questions concerning the implications of the approaches in synthetic biology, the ultimate questions that always come up are: "what is life?" and "what is natural?". Furthermore, can the reductionist approach ever lead to an explanation of life? The prospects of synthetic biology re-initiates the discussion, a result of researchers working on the brink of understanding and creating life. How do the people involved in the iGEM competition think about life and the reductionist approach? Following the statements of the group, the properties of "life" include the existence of: negative entropy, the ability to adjust to environment, reactions to external stimuli, interaction of biochemical processes, the ability to proliferate, an information storage system, metabolism, a defined outer-limit (such as a membrane), the sum of components and its interactions, self-sustaining properties and emerging properties. Although the list is very comprehensive, many people still argue that there is no description nor a complete set of specific criteria that can define life. We are part of what we assume is life and are therefore never capable of objectively characterizing it.
Although no one suggests that it is infeasible to understand life without a definition for it, there are numerous other suggestions why understanding life might or might not be possible in the future. What seems exceptional, is that many use human life as the standard of understanding life, most probably of its complexity.
First of all, there is the problem of the observer, we cannot define life because we are life. The reducionist approach is limited because mankind is limited.
Second of all, some believe that we consist of a complex series of biochemical reactions that lead us to interact with our environments the way we do. Although synthetic biology might help us to understand the mechanisms behind the operation better, it runs the risk of becoming too detached from humanity and life, which could be dangerous in reducing the image of ourselves as the sum of our parts. Others think that life is the results of molecules bumping into each other and positive and negative charges interacting, which is perceived as sublime. They are not afraid of taking religiosity, mysticism, or magic out of human existence, but rather focus on taking a moment to appreciate the true magnificence that is a human being. New questions are proposed, such as "Where do atoms come from?" and "Why are we here?".
Science strives to understand life mechanistically, but there is a feeling amongst some survey participants that there will always be elements that mankind cannot understand as we are unable to see the entire picture. The reductionist approach is limiting because there is always "room to go deeper". However, as innocent as reducing life may appear to be it also has the ability to devaluate our perception of life itself. It is this fate, more than any other possible negative consequence, that is the true threat of synthetic biology and science as a whole.
The reductionist approach is also believed to be limiting because it does little to explore the emergent properties of complex systems which may be at the core of our perception self-awareness and other concepts usually considered to be meta-physical in nature; the nature of our soul and the need to assign meaning to life.
As described by others, combining biological subsystems to make a bigger system that is considered to be living, such as a bacterium, is more than just the combination of their properties. The constituting subsystems are not inert with respect to each other. Instead there is crosstalk, which results in emergent properties of the entire system, none of which were part of the subsystems. This concept has nothing magical or superstitious about it. Emergence adds a layer of complexity that is much more difficult to unravel than to understand subsystems individually because it requires a full understanding of all subsystems and their mutual interactions. In any case, the reductionist approach is necessary to get to this stage because it simplifies the initial characterisation of subsystems.

Finally, one statement describes the relation between consciousness and life through a paradox: although life is not consciousness, strangely enough, for us, consciousness is life, referring to the fact that consciousness is not a necessary property of life.

Recommendations

As described in the conclusions, a big issue that comes back in different subject areas is communication. There is not only the issue of communicating scientific advances, but also discussing (ethical) issues that have emerged from synthetic biology and assessing the risks involved in certain projects. The current communication of synthetic biology by the media is generally not objective. Statements such as "playing God" draw attention but can give synthetic biology a bitter taste. We have experienced some issues with media because of biased description of synthetic biology in general and our project specifically. We recommend in the future, scientists and media work closely together to overcome these issues.

Secondly, both for biosafety and for biosecurity the scientific community has expressed its perception towards the risks involved in synthetic biology and they believe that additional regulation can limit or even reduce these risks.

At last, with our survey we aimed to raise the awareness on ethical issues mainly focusing on the extreme application of the reductionist and bottom-up approach. We got great feedback from many participants and when looking at the amount and the content of the open-answers, most people find this subject very interesting and seemed to appreciate the survey. Although no consensus will be formed on questions like whether life can be explained materialistically, the ongoing research in synthetic biology and specifically on the principles of life makes us obliged to keep the debate going and possibly prepare ourselves for whatever science will bring us next.