How safe is safe enough: towards best pratices of synthetic biology
Our team was baffled by the new and exciting bacteria undergraduate students created during the summer, and presented to the world during the yearly iGEM competition. Auxin (Imperial 2011), AgrEcoli (Bristol 2010), and E.D Frosti (KULeven 2011), but also hundreds of other bacteria could prove very useful. However, some need to be taken out of the lab so they can be used. We want to take genetically modified bacteria out of the lab because we see huge potential benefits. However, we are not willing to do that “no matter what”. This is why we decided that the project we would present to the 2012 iGEM competition would be one that would help us get closer to that goal: putting genetically modified bacteria in the environment in a safe, responsible and acceptable way.Our “human practice” and “wet lab” parts are complementary. We identified some technical issues such as HGT and excessive proliferation that we believe can be solved by synthetic biology. This is what our bench work is about: trying to build a master system to diminish the probability of HGT and bacterial proliferation. However, we are not so naïve as to think that technique can solve everything. We know that they are many non technical issues when it comes to releasing bacteria created by synthetic biology in the environment. This is where our human practice part takes all its meaning.
When discussing putting genetically modified bacteria in the environment, it is crucial to differentiate the concern that are in fact just about synthetic biology and the ones that really concerns the application in the field. The debate on the technique should happen, and then be closed once and for all so we can move forward to discussing the applications.
If we do not proceed in that order, the debate gets very messy, like it has been when debating about GMO crops in Europe. Europeans never really had a say on the recombinant DNA technology so when applications were discussed, since the technique had never been properly been discussed per se, the whole debate about recombinant DNA technology re emerged each time.
We are afraid the same thing could happen with Synthetic Biology if citizens are not properly informed and given the opportunity to debate on Synthetic Biology as a field. Of course, we are not starting from 0 because fears about genetic engineering have already been voiced during the GMO crops episode, and as Synthetic Biology is an extension to genetic engineering, we can only imagine that the fears raised by the first are mainly extensions of the ones raised by the latter.
For all of the above reasons, we decided to separate this essay into two distinct parts. The first one will address the concerns raised by synthetic biology per se, that is, as a technique. Then, in our second part, we will analyze the specific concerns that arise from synthetic biology’s potential applications in nature.
In our human practice report, we discussed putting genetically modified bacteria in the wild.
When discussing such a question, it is crucial to differentiate the concerns that are just about synthetic biology and the ones that really involve applications in the field. The debate on the technique should happen, and then be closed once and for all so we can move forward to discussing the applications.
Therefore, we decided to separate our human practice report in two distinct parts. The first one will address the concerns raised by synthetic biology per se, that is, as a technique. Then, in our second part, we will analyze the specific concerns that arise from synthetic biology’s potential applications in nature.
I Debate on synthetic biology as a technique
Firstly, we studied the historical background of synthetic biology. We presented synthetic biology as an extension of genetic engineering, and examined the shared controversies around recombinant DNA technology. We showed that scientists handled the situation in an exemplary way, and we provided a detailed analysis of the 1975 Asilomar conference.
Secondly, we studied the concerns raised by synthetic biology nowadays. We used numbers from the 2010 Eurobarometer on biotechnologies and Hart Research Associates’ 2010 poll on “Awareness & Impressions of Synthetic Biology” to study awareness, perception, and approval of synthetic biology in the European and American populations. We showed that the level of awareness of synthetic biology in Europe is incredibly low (only 17% of participants had already heard of synthetic biology previous to the poll), that the approval rate is low to average in both Europe and the US, that these populations want tight government regulation, and that the main concerns raised by synthetic biology are: unnaturalness, playing god, status of artificial life, potential physical harms, regulations. We then provided a detail analysis of these concerns. We came to the conclusion that:
- (a) The “unnaturalness” and “playing God” arguments convey the population’s fear of novelty and of the unknown, and should not just be tossed aside;
- (b) Religion is in favor of synthetic biology and does not consider that synthetic biologists are “creating life”;
- (c) Questions such as “is there such a thing as artificial life?”, “what will be the status of this artificial life?” will have to be addressed someday, and probably sooner than later;
- (d) Biosafety measures to prevent bacteria from harming workers or escaping the lab and proliferating in the wild are efficient;
- (e) George Church’s proposal seems to be a good starting point for biosecurity;
- (f) Synthetic biology should not be regulated by the free market.
Thirdly, we examined the common question “will rising awareness change anything?”, and its implications. We came to the conclusion that
- (a) Skepticism is not necessarily due to lack of awareness;
- (b) Education on new technology should be provided so people can be more aware of what is happening around them. Educating middle and high school students could be one way, amongst others, to achieve this goal.
- (c) The education on new technologies do not has to be use so that the population can accept them better, only to provide them tools to be able to judge by themselves.
See: Contribution 1, Proposals 1 & 2
II The debate on putting genetically modified bacteria in the environment
Firstly, we examined issues around horizontal gene transfer (HGT), excessive proliferation and risks assessment. We showed the difficulty of assessing risk when it comes to putting genetically modified bacteria in the wild, and that from the very start (beginning of recombinant DNA technology), people have been concerned about HGT and excessive proliferation and tried to create security systems. This is in the spirit of the precautionary principle: “When an activity raises threats of harm to human health or the environment, precautionary measures should be taken even if some cause and effect relationships are not fully established scientifically. In this context the proponent of an activity, rather than the public, should bear the burden of proof. The process of applying the Precautionary Principle must be open, informed and democratic and must include potentially affected parties. It must also involve an examination of the full range of alternatives, including no action.”(Wingspread Consensus Statement on the Precautionary Principle). We screened the literature and previous iGEM teams’ wikis to identify security systems that had already been constructed. Systems proposed by previous iGEM teams are very often kill switches, toxin/antitoxin systems, aggregation modules, and usually one mutation away from failure. Our literature screen indicated that such systems were used at first, but that scientists then started combining different system (for e.g. two different toxin/antitoxin systems), which made the systems more efficient, but still quite close from mutation. Some more elaborate mechanisms are being created now: they are systems that make synthetic bacteria’s genetic information not universal anymore, preventing communication with wild type bacteria (for e.g. semantic containment, xeno-nucleic acids). We then discussed the master safeguard system we designed to try and decrease the probability of HGT and excessive proliferation. See Contribution 2 & 3
Secondly, we examined other concerns that could be raised by the release of genetically modified bacteria in the environment. We started by doing a case study on GMO plants and crops and looked at the lessons that could be learned, so as not to make the same mistakes when releasing synthetic bacteria in the wild. We concluded from that case study that
- (a) Populations want to be informed of what is going on;
- (b) They need to perceive some benefits which justify taking a risk;
- (c) They want issues like that to be submitted to public debate. And they want the public’s opinion is taken into consideration;
- (d) They do not want to feel pressured in anyway by big lobbies to buy things that were created by biotechnology. They want labeling and they want alternatives. They want their right to free choice to be respected;
- (e) Some feel very strongly about the fact that industrials are the one funding the scientists to test their products. People would have more trust in an independent comity;
- (f) Biotechnology should be used to help the third world, and so research should be oriented in that way too.
We then listed conditions that we find necessary for a responsible release of genetically modified bacteria in the environment:
- (a) There should be a real effort to inform citizens on this subject; See Contribution 4
- (b) There should be a real dialogue between the general population, the scientists, the politicians and the biotechnology firms. They should agree on goals, benefits, and tolerable side effects. Physical harms, but also ethical aspects should be considered. The dialogue should take place as soon as possible, before too much money is at stake; See Contribution 1bis
- (c) Thirdly, no concern should be brushed away before thorough investigation; See Proposal 3
- (d) Everyone should be able to benefit from synthetic biology's applications; See proposal 4
- (e) Applications of synthetic biology that require releasing in the environment should be tested by an independent comity of scientists; See Proposal 5
- (f) The status quo of evaluating projects case-by-case before enabling release in the wild should be maintained
Proposal 1: We would like that in the future, collaboration with a middle school or high school be a requirement for an iGEM gold medal. This would drastically raise the world level of awareness about synthetic biology.
Proposal 2: Extend proposal 1 to a mandatory high school course called “new technologies”.
Proposal 3: A real discussion with all the actors of society about synthetic biology and its applications.
Proposal 4: We would like to see the creating of a committee similar to the French advisory council for the protection of people in biomedical research (“comité consultatif de protection des personnes dans la recherche biomédicale”), but for biotechnology. It would be called “advisory council on synthetic biology and genetic engineering”. Biotechnologies industries could go and consult this comity before they start the research on the product they wish to develop. This council would take ethical issues into consideration.
Proposal 5: some researchers should work on applications of synthetic biology that can be useful to the third world. We believe that this should be publicly founded. However, the state would get the money through taxing biotechnology firms on the income they make by selling to the first and second world products that use synthetic biology.
Best Research practice
Proposal 5: applications of synthetic biology that require releasing in the environment should be tested by an independent committee of scientists. When an industry wants to test a new product where synthetic biology is involved, it will not be able to test it with its own scientists. An intermediary will have to be involved: the state. The industry will pay a tax to the state, who will, in exchange, ask its independent comity to test the project. We hope that thanks this will relieve the pressure on the scientists to produce results that go in the sense of the industry, as they will not be funded by the industry anymore.
Proposal 6: Safety modules ans risks assessments has to be part of every synthetic biology projects from the very beginning.
Proposal 7: Each synthetic biology application should assess and disclose a list of application specific risks and hazards.
Contribution 1: We organized a workshop on synthetic biology for high school students in order for them to discover this new field. We also gave them a tour of our lab.
Contribution 1bis: Here, we decide to take the contribution 1one step further. After the introduction to synthetic biology, we would discuss with students what they would consider as benefits and acceptable risk. This would take the form of discussing synthetic biology projects they brainstormed. See wiki page on the workshop for additional details.
Contribution 2: We tried to engineer a master safeguard system. We wanted this system to be as robust as possible against mutations. We decided to add up containment systems in order to increased robustness. We relied on three levels of containment: - Physical containment with alginate capsules - An improved killswitch featuring delayed population-level suicide through complete genome degradation. - Semantic containment using an amber suppressor system We acknowledge that our system is not perfect or infallible. However, we believe that it is a good starting point, and that next year, teams can build up from this like we built up from previously existing systems.
Contribution 3: We created a safety page on the registry. Teams can put the safety circuits they created there, and assess its efficiency. In the future, we would like that the standard plasmids contain safety elements (for e.g: autodestruction system, etc). Our aim is to promote safety in future iGEM projects.
Contribution 4: We organized a debate involving 10 university students from very various background (law, politics, etc), but no one studying synthetic biology. 70 people came to see the debate. They had to debate on the following motion: “This house would allow environmental release of genetically modified bacteria for applications in the following fields: medicine, pharmacy, agriculture, energy, bioremediation”. 5 students were assigned to be for, 5 students were assigned t be against. They had one week of preparation. We were impressed by the level of the debate. See the debate page for further details.