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| - | =Ethical issues in Synthetic Biology= | + | =Reductionism in Synthetic Biology, an Ethical Issue= |
| - | | + | Since genetic engineering was first applied in 1973, research on enhancing micro-organisms has taken a leap. The ability to change the behavior of biological systems by modifying the genetic code has been the basis for research in synthetic biology. Although the possibilities of synthetic biology seem promising and applications are virtually endless, concerns are raised about the fast progression, possible risks and ethical implications. |
| - | ==Introduction==
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| - | The marriage between technologies in molecular and cellular biology together with genetic and chemical engineering gave life to a new phenomenon called synthetic biology. Since then, a lot of ethical questions were raised. Although the definition of synthetic biology is not yet clear and future implications are yet uncertain, research in the field of synthetic biology is at its peak. Different articles claim that synthetic biology is the answer to curing cancer and the production of bio-fuel, and several leading universities assembled specific departments for this field of research. An OpenWetware created by the Massachusetts Institute for Technology, gives free access to a large registry of BioBricks: basic “ready to use” biological machinery components. The most important resource for these BioBricks comes from the yearly iGEM (international genetically engineered machine) competition, in which teams of students can compete on building the best microorganism machine by combining, describing, implementing and/or designing these biological standardized parts.
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| - | ==Definition==
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| - | 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 intangible characterization. An attempt by the European Commission to describe synthetic biology resulted in partial acknowledgement by the scientific community. The EC tried to reflect how synthetic biology differs from other emerging technologies and focused on constructing of artificial life forms with use of engineering principles applicable in biology. Their working definition of synthetic biology is as follows:
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| - | <br>''“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”'' ([ftp://ftp.cordis.europa.eu/pub/nest/docs/syntheticbiology_b5_eur21796_en.pdf EC, 2005]).
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| - | ==Frameworks==
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| - | There is a lot of literature on ethical issues in synthetic biology. A road map to illustrate these main concerns is shown in Figure 1. This road map (based on a paper of [http://www.synbioproject.org/library/publications/archive/synbio3/.com Parens, 2009]) is generally applicable for emerging technologies, but is currently designed to focus on synthetic biology. The ethical concerns that are mainly addressed in literature are "physical harms" and concerns gained by researchers "closest to action" in synthetic biology. The first concerns on bio-safety and bio-security, where the latter involves matters such as intellectual property rights and transparency.
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| - | Unfortunately the scientific community lacks an appropriate attitude towards themselves and the rest of the world. An undervaluated but nevertheless important subject in synthetic biology is the fact that we might change the perception of life when we try to (re)engineer life or even try to create it from scratch (Craig Venter's [http://www.pnas.org/content/103/2/425.abstract minimal genome project]). The reductionist approach (a method of understanding complex systems by analyzing the subsystems that it is composed of) has brought a lot of benefits in understanding physics and chemistry, and has definitely helped in understanding biological systems. But now we have come to the point that we are designing living systems. Some even believe we are at the brink of defining and even creating life. The consequences of this progression should be described and discussed elaborately.
| + | A rough division of the different main concerns in synthetic biology is shown in Figure 1. Ethical and political issues concerning bio-safety, bio-security and intellectual property rights have been discussed elaborately. Ethical discussions concerning the top-down (reductionist) approach towards understanding living systems and the bottom-up approach of enhancing/creating biological systems are lagging behind. Craig Venter, one of the lead researchers in synthetic biology, is working on a controversial project with a goal to create artificial life. He is one of many that use the reductionist and bottom-up approach in biology to search for the foundation of life. |
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| - | [[Image:Framework1.jpg]] | + | [[Image:Framework4.jpg|thumb|550px|Figure 1. Road map illustrating a rough division of the main issues in synthetic biology, based on a [http://www.wilsoncenter.org/index.cfm?topic_id=166192&fuseaction=topics.event_summary&event_id=492968 presentation] of Dr. Arthur Caplan.]] |
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| | + | Reductionism can be explained as an approach to understand complex systems by reducing them to their subsystems. In biology, a way to understand the nature of complex living entities is by looking at the function of individual components (e.g. DNA, proteins) and their relations. The bottom-up approach of (re-)engineering biological systems is the modifying of such components, mainly by genetic engineering techniques. How the different approaches are related to understanding life and creating artificial life is shown in Figure 2. More information on ethical issues in synthetic biology can be found in the [https://2009.igem.org/Team:TUDelft/Ethics_background Background] section. |
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| - | Parens et al. also describes a framework that distinguishes two groups responding differently to questions concerning physical harms. The pro-actionary people think more of the benefits of the research than its possible implications. The pre-cautionary community are concerned about safety and security instead of rather thinking about the opportunities. As it comes to regulation and policies, the enthusiasts would keep the authority to themselves, whereas the critics would rahter see external regulation on safety and security issues.
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| - | ==Concerns==
| + | [[Image:Framework5.jpg|thumb|550px|Figure 2. Road map illustrating the connection between the reductionist and bottom-up approaches in understanding and creating life respectively.]] |
| - | The concerns in synthetic biology that typically appear in literature include bio-safety, bio-security, transparency and intellectual property rights. Topics concerning the attitude towards life, reductionism and public involvement that are relatively hard to address but nonetheless important, do not obtain the attention they deserve. A list of the ethical concerns:
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| - | * Bio-safety (Regulations for working in synthetic biology)
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| - | * Bio-security (Consequences of synthetic biology, e.g. bio-terrorism)
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| - | * Intelectual property rights (conflict of interest, fair distribution of benefits and who owns what?)
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| - | * Transparency (open source, availability)
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| - | * Communication (towards public and media)
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| - | * Naturalness (or artificialness)
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| - | * Attitude (towards life)
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| - | * Reductionism (consequences and implications when reducing biological systems)
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| - | Since the introduction of synthetic biology, ethical issues have been addressed and different opinions, frameworks and solutions have been proposed. To get an overview of opinions and responsibilities relevant to different topics, we propose a framework that describes the main ethical considerations from a personal perspective, as shown in Figure 2.
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| - | [[Image:Framework2.jpg]] | + | |
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| - | The personal view describes features on how we perceive synthetic biology, what is our attitude towards life, and why do we participate in such research. The believes, perceptions and reasons for people to understand and work in the field of biology will vary between individuals. It is good to give these different subjects some thought, to make evaluation of the research somewhat easier. Moreover, when working together in a team it is important to know that team members can have different opinions. A healthy discussion can help the research because you can respect each others differences, learn of other viewpoints. Furthermore, it shows peoples personal qualities.
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| - | Externally, researchers are responsible on a social level for communication and security of the public. On a scientific level they should concern the safety of themselves and co-workers. In synthetic biology specifically they have to think about the consequences of making biological components freely available, how to deal with intellectual property rights and to what extend the research should be transparent to the community.
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| - | ==Responsibility==
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| - | The proposed framework can function as a guideline for what is important and what are our responsibilities when working on synthetic biology. Although most of the topics are addressed in literature, policymakers are lagging behind in making regulations concerning these topics. Specifically a lot of questions are raised concerning bio-safety and bio-security. For example, what are the possibilities for bio terrorist or what are the consequences of do-it-yourself synthetic biology, where people can engineer organisms in their own backyard. Regulations and policies should clear up this uncertainty. But the problem is: who is responsible? Should the government create certain guidelines, or should the scientific community self-regulate their own research? Are existing guidelines and safety measures on genetic engineering enough, or do we need to extend this? What about the open source properties, what if somebody patents a gene? Another question that follows from this discussion is whether synthetic biology is as new as some papers make us believe. Do we really need new guidelines? Did we not already describe safety regulations to keep modified organisms in the laboratories?
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| - | These are difficult questions, certainly because key stakeholders will have different opinions and demands. Although these questions have an ethical undertone, they are better categorized in the policy and regulatory field. The ethical aspects have been described extensively. It is now up to the policymakers to identify the problems, see where guidelines are needed and implement clear regulations when necessary.
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| - | ==Reductionism==
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| - | As has been stated by Arthur Caplan (Director of the Center for Bioethics at the University of Pennsylvania) during his speech at the Woodrow Wilson Center for Scholars, [http://www.wilsoncenter.org/index.cfm?topic_id=166192&fuseaction=topics.event_summary&event_id=492968 Synthetic biology: is ethics a showstopper?], the key ethical issues in synthetic biology are reductionism (when life is reduced to genetics) and playing God (the bottom-up approach of creating living systems). Issues concerning safety, security and handling of intellectual property rights should be related to politics not ethics. These topics need good regulation, but ethics does not play a role there. Instead, bio-ethicists should focus on questions concerning life. 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, the ethical questions become much more important. To get an overview of what plays a role in evaluating reductionism in synthetic biology, we propose a framework in which we display the connection between evolution, life, and reductionism.
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| - | [[image:framework3.jpg]]
| + | How do the public and the scientific community feel and think about life-related questions and the reductionism approach in biology? These are difficult questions. But now that we are directing evolution and trying to artificially create life, we have come to a point at which we need to discuss these issues. We will never get a clear answer on philosophical questions such as, "what is life?", even the scientific community is much too homogeneous for that. Still, a discussion to raise awareness and make us think about these questions could help in the debate on whether researchers should pursue the controversial goals that are present in synthetic biology. Furthermore, communication to the general public should be much easier if an overview of the different believes and opinions within the scientific community are available. |
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| - | Since Darwin's work On the Origin of Species in 1859, a lot of scientific theories suggest that the world as we know it is a product of millions of years of evolution. This phenomena that mankind will probably never be able to fully understand has produced a complex biological world with an entangled network of many different living systems and (non)organic materials. Science indicates that only a relatively short period of time the homo sapiens have walked the earth (surprisingly on two legs) and have evolved to a sophisticated heterogeneous community with thoughts, believes, opinions, consciousness, and the ability to adapt and improve survival chances better then any other organism. The property that made mankind the top of the food chain is its ability to use the brain efficiently. One of the things that humans have used their brain for, is to give definitions to the things that they saw and heard. So what about LIFE? Society came to a point where it made a distinction between living systems (with the potential to expire) and non-living systems. The problem is to make a clear cut between these two. The scientific community has come up with some properties that are specific for living systems, such as the ability to reproduce, evolve and metabolize. Although these properties are quite clear, it is also suggested that this list is insufficient. We still don't know for certain what constitutes life. Moreover, scientist tend to look at living systems with a biochemical approach. But what if biological systems are fundamentally special in some way? Is there more to life than we can imagine? Is there a higher power? Is life holy or sacred? We just don't know. However, it is definitely important to distinguish how life is perceived by the general public and what is believed and proven in science.
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| - | Synthetic biology is a key player in the search for answers regarding life. The reductionism approach that has proven itself to be very useful in physics and chemistry is now applied in biology to get to know the foundation of life. Fundamental research on the molecular level has given us indication that DNA is the basis of all life forms and genetic engineering has given researchers the ability to change this genetic code. But is this all? Or is there more to it? Should we go on with this chase for answers? What happens if we find out?
| + | A qualitative and quantitative analysis on the opinions of researchers on reductionism in synthetic biology could be achieved by approaching many people in this particular field of science (mostly iGEM supervisors and participants). To pursue the quantitative analysis, I have invited many iGEM teams to complete a short questionnaire. <br><br> |
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| - | One of the results of the top-down approach towards understanding living systems is that we can now understand how certain substructures of complex living systems work, and sometimes even how they interact with other substructures. But there is still a very long road (if not endless) to completely understanding the complicated superstructure called life. A different result is that understanding substructures of living entities proceeded in creating these substructures artificially. It did not take long before they were implemented in simple organisms and were proven to function there, in some cases even more efficiently than the original "natural" system.
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| - | The bottom-up approach of enhancing organisms has been going on since genetic engineering was applied first in 1973, although mankind has been altering live since they were able to manipulate crop growth and directed the reproduction of animals. What they did not know then was that they were manipulating DNA of descendant live forms, and thereby enhancing evolution. So what is different now? Are the attempts to manipulate DNA directly and implement it in an organism one step too far? Or is it nothing different from genetic engineering as researchers have been doing since the 70s? Research proposed by Craig Venter and others indicate that we are about to open the door to understanding what life is all about, and synthetic biology is the key. Why does this next step scare people? Are we afraid of the possible results? Do we care too much about our present perception of life? Scared of possible disappointed? But then again, should we be anxious? It could well be that the reductionism approach is limited in defining life. Maybe life has this property that does not let it explain in chemical and physical principles. Whether or not this might be true, getting to this point in evolution makes us morally obliged to think about such questions. Why? You will find out soon...
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| - | ==Approach==
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| - | How does the public and the scientific community feel and think about life-related questions and the reductionism approach in biology? This is difficult and always has been difficult. But now that we are directing evolution and trying to artificially create life, we have come to a point at which we need to discuss these issues. We will never get a clear answer on phylosophical questions such as, "what is life?", even the scientific community is much too homogeneous for that. Still, a discussion to raise awareness and make us think about these questions could help in the debate on whether researchers should pursue the controversial goals that are present in synthetic biology. Furthermore, communication to the general public should be much easier if an overview of the different believes and opinions within the scientific community is available.
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| - | A qualitative and quantitative analysis on how the opinions of researchers on reductionism in synthetic biology, could be achieved by approaching many people in this particular field of science (mostly iGEM supervisors and participants). To pursue the quantitative analysis, I would like to invite as many iGEM teams as possible to complete a short questionnaire. | + | |
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| - | ==Interesting links==
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| - | '''Synthetic biology in general'''
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| - | [http://www.springerlink.com/content/q561r1113xk10750/ Pleiss, 2006]
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| - | [http://www.nature.com/nrg/journal/v6/n7/abs/nrg1637.html Benner, 2005]
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| - | [http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6VRV-4GM45W4-2&_user=499885&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_searchStrId=978595215&_rerunOrigin=scholar.google&_acct=C000024500&_version=1&_urlVersion=0&_userid=499885&md5=c6095815cab1e416590eb6f2018682ed McDaniel and Weiss, 2007]
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| - | [http://www.nature.com/msb/journal/v2/n1/full/msb4100073.html Andrianantoandro, 2006]
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| - | [ftp://ftp.cordis.europa.eu/pub/nest/docs/syntheticbiology_b5_eur21796_en.pdf European Commission, 2005]
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| - | [http://www.nature.com/doifinder/10.1038/embor.2009.76 Deplazes, 2009]
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| - | <br><br>
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| - | '''Ethics in synthetic biology'''
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| - | [http://www.is-journal.org/V02I01/2ISJLP053.pdf Gorman, 2006]
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| - | [http://www.thenewatlantis.com/publications/the-promise-and-perils-of-synthetic-biology Tucker, 2006]
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| - | [http://www.synbioproject.org/library/publications/archive/synbio3/ Parens, 2006]
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| - | [http://www.nature.com/nature/journal/v438/n7067/full/438423a.html Church, 2005]
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| - | [http://www.nature.com/embor/journal/v10/n1/full/embor2008232.html Samuel, 2009]
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| - | [http://www.bbsrc.ac.uk/organisation/policies/reviews/scientific_areas/0806_synthetic_biology.pdf Balmer, 2008]
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| - | [http://www.mtzstiftung.de/sites/mtzstiftung.de/myzms/content/e162/e356/e1417/e1988/nbt0408-387.pdf Boldt, 2008]
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| - | [http://www.nature.com/nbt/journal/v27/n4/full/nbt0409-321.html Mitra, 2009]
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| - | <br><br>
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| - | '''Reductionism'''
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| - | [http://www.nature.com/nature/journal/v421/n6919/full/421118a.html Benner, 2003]
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| - | [http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0060095 Caplan, 2008]
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| - | [http://science-mag.aaas.org/cgi/content/summary/286/5447/2087 Cho, 1999]
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| - | [http://www.independent.co.uk/news/science/playing-god-the-man-who-would-create-artificial-life-773859.html Conner, 2008]
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| - | [http://dsc.discovery.com/technology/my-take/synthetic-biology-caplan.html Caplan]
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| - | [http://findarticles.com/p/articles/mi_m1374/is_3_60/ai_62111884/ Clark, 2000]
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| - | [http://camtriplehelix.com/magazine/synthetic7.pdf Pace, 2009]
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| - | <br>
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| - | [http://www.nature.com/nbt/journal/v15/n13/abs/nbt1297-1322.html Short, 1997]
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| - | [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1299179 Regenmortel, 2004]
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| - | [http://www.rsc.org/delivery/_ArticleLinking/ArticleLinking.asp?JournalCode=MB&Year=2009&ManuscriptID=b901484e&Iss=7 Agapakis, 2009]
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| - | [http://www.thehastingscenter.org/Publications/BriefingBook/Default.aspx The hasting centre, 2008]
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| - | [http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=2872712 Calvert, 2008]
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| - | [http://genomebiology.com/content/2/2/COMMENT2002.1 Peterson, 2001]
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| - | [http://www.nature.com/nature/journal/v420/n6914/full/420350b.html Check, 2002]
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| - | [http://www.scribd.com/doc/24588/Zen-and-the-Art-of-Creating-Life Ray, 1993]
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| | + | The [https://2009.igem.org/Team:TUDelft/Ethics_methods survey] on reductionism in synthetic biology is now closed. We are grateful to all the people who took the time to participate in the survey. Thanks to them we now have a total of '''242''' [https://2009.igem.org/Team:TUDelft/Ethics_results responses] of iGEM students, supervisors and advisors.<br><br> |
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| | + | [https://2009.igem.org/Team:TUDelft/Ethics_conclusions Conclusions], the headlines: |
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| | + | * Participants believe that the value of life cannot be changed by synthetic biology |
| | + | * Craig Venter's research is presumed not to involve creating new life forms, but rather applying genetic engineering |
| | + | * Safety and security issues are acknowledged and additional regulation should minimize their risks |
| | + | * Synthetic biologists are generally careful, but the public wants more |
| | + | * There is no relation between the existence of a God and sacred or holy properties of life |
| | + | * Communication with the general public is difficult but perceived necessary |
| | + | * Life can possibly never be explained by mankind |
| | + | * The reductionist approach towards understanding life is limiting |
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| | + | '''References''': [http://www.synbioproject.org/library/publications/archive/synbio3/ Parens, 2006] | [http://www.nature.com/nature/journal/v420/n6914/full/420350b.html Check, 2002] |
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