Team:ULB-Brussels/Debate

Presentation:

In the beginning of July 2011, we were contacted by the KULeuven team, the other Belgian team participating in the iGEM competition. They proposed we meet to organize a joint debate on bioethics and our respective projects.

We immediately accepted! then began the preparations for this event. We had to contact professors, politicians, medias and so on. We quickly agreed on a date regarding the teachers’ availability, the 1st September. Even though we had different types of organization, we succeeded in making this debate as nice as possible for both of the teams. We finally had 4 professors come to our event. Hereunder, you’ll find a brief description of each:

• Prof. PhD. Filip Rolland is professor at the K.U.Leuven in molecular physiology of plants and microorganisms. His research topic is plant metabolic signaling, mainly on ‘sugar signaling’. The department of molecular physiology of plants and microorganisms, functional biology is further investigating the SnRK1 (discovered in Arabidopsis thaliana) signaling pathway and its role in controlling plant metabolism, development and stress resistance.
• Prof. PhD. Jacques van Helden is professor at the Université Libre de Bruxelles, and director of the Laboratory of Genome and Network Bioinformatics (http://www.bigre.ulb.ac.be/). Initially trained as agronomic engineer, his PhD thesis focused on the genetic regulation of nervous system development in Drosophila. Since 1997, his research activities have been dedicated to the development of bioinformatics approaches to analyze genomes and networks of molecular interactions (regulation, metabolism, protein interactions).
• Prof. PhD. Johan De Tavernier is a professor at the K.U.Leuven. He has a degree in Moral Theology and since 1996, he has been the director of the Centre for Agricultural Bio- and Environmental Ethics (now the Centre for Science, Technology and Ethics). In one of his books ‘science, ethics and society’ (published in 2004) he discusses whether biotechnology is necessary to solve world hunger.
• Prof. PhD. Bruno André is professor at the Université Libre de Bruxelles, and director of the laboratory of Molecular Cell Physiology (IBMM, ULB). The research of his laboratory mainly focuses on the yeast S. cerevisiae which is a paradigm model system for dissecting the molecular mechanisms of basic cellular functions in eukaryotes.

After we found a moderator and an auditorium, we agreed on a program and a schedule. We began on 7 p.m. by presenting the teams, the professors and so on. Then, a student explained what precisely iGEM is and what kind of things it implies. He continued by giving a definition of the synthetic biology: « the design and construction of new biological parts, devices and systems that do not exist in the natural world and also the redesign of existing biological systems to perform specific tasks » (the ETC group, an Action Group on Erosion, Technology and Concentration). After this brief introduction, the K.U.Leuven team presented its project.

The KULeuven team is eagerly working on E.D. Frosti. This is a modified E.coli bacterium that the students will engineer to stimulate and prevent ice formation, depending on the given stimulus. The ice nucleation protein (INP) is responsible for the making of more stable ice. When E.D.Frosti forms this protein, the bacteria cells will turn into a red color. A different stimulus is responsible for the production of the Antifreeze Protein (AFP). To be sure that the right protein is expressed, these cells will turn into a different color. We can use bacteria cells which produce AFP to make roads ice- and snow free during winter. A very important feature of the bacteria is its cell death mechanism, which makes sure that the cells will not overgrow the environment. When E.D. Frosti is exposed to cold temperatures, the bacteria will self-destruct. It is essential that both proteins are not produced at the same time. To avoid this, the KULeuven team engineered E.D. Frosti in a way that the production of one of the two proteins makes the formation of the other protein impossible.

It was afterwards our turn (the ULB-Brussels team) to present our projet, the so-called “Pindel”, coupled with our bioethics project. It was actually difficult to present all our work within five minutes, but we managed to do so. Here is our presentation text:
“The bricks of synthetic biology are fragments of DNA. Just to remind you, DNA contains instructions to construct every molecules of your body. It is as a plan that every organism has inside all of his cells.

Actually, the major intention of synthetic biology is to manipulate DNA of unicellular organisms (composed of only one cell) to make them able to produce useful molecules for therapeutic or industrial matters, among others.

Sadly, it’s not as easy to do as it is to explain. In fact, manipulate DNA consist in two fundamental acts: insert and delete fragment. It is exactly similar to Legos, when you put and withdraw brick to build; except that difficulties appear because biologists don’t handle plastics bricks. They handle living matter in living organism. Therefore they have to exploit natural mechanisms to manipulate DNA.

For instance, the iGEM standards use a “cut and paste” system. But, in that sense, you need to have the right scissor, which cuts at the right place and it is often problematic.

The most effective and appropriate mechanism is called “homologous recombination”.

To explain it simply: if you have two little regions that board a fragment of DNA and if those regions are the same than two others in another fragment, we say that those regions are homologous and there exist a mechanism that switches those fragments: recombination.
It is already used in yeast, which is a unicellular mushroom. Therefore, to do every complex assembly easily, biologists have to use yeast. But yeast is bigger and grows slower than bacteria. The problem is that E.Coli, our favourite bacterium, doesn’t allow constructing anything because it has an enzymatic system that removes every linear DNA.

We found the solution in a virus of E.Coli, the lambda phage. It has a molecular gadget to save linear DNA and to allow homologous recombination. We took the plan of this gadget and we constructed an entire plasmid around it, that we called Pindel.
We designed Pindel to be removed after use and to express his genes when we want. We also constructed an additional plasmid and wrote a protocol that allows insertion or deletion leaving no resistance to antibiotics.

In conclusion, we build a tool that allows every searchers, druggist or industry, to do manipulate easily, properly and precisely, DNA in E.Coli. It will be a fantastic tool to produce molecules in large quantities or to study E.Coli genome, manipulating one gene without any impact on neighboring regions.
To ensure a high quality of work, we build our project on three complementary and parallel axes: a first group called “wet lab” which manipulates and construct, a second called “modeling team” which works on characterization and third called “Human Practice Team” which will speak now.”

Another member of the ULB team took the word to explain the bioethics part of the project:

“We will structure our defence in two parts. In a first part, we worried about the antibiotic resistance that was inserted in the genome of our bacteria. For the anecdote, the bad reputation of GMO’s is due to the use of antibiotics resistant genes in corn BT176. After a few years of exploitation, it appeared that this sort of GMO could have a negative effect on human health and on earth. Some people who ate this corn were sick and cultivating it could contaminate the ground with the resistance to antibiotic (but it wasn’t proved). Since these days, people are frightened by this new way of cultivating that they associated as dangerous for themselves. The problem comes from the fact that no one ever told them that the danger comes from these antibiotics resistant genes and not from the organism itself. So today, we would like to reassure people about the fact that this gene can be removed from an organism. And that is how we want to defend our project, by removing this gene from our bacteria.

The second part of our bioethics project consists in collecting the public opinion about GMO. That is why we made a survey composed of three parts. The first consists of 16 items that measure the people’s acceptance and tolerance of GMO’s. The second part is an informative text about the advantages of GMO’s. The third part contains the same 16 items. Thanks to this questionnaire, we’ll observe the influence of positive oriented information about GMO on public opinion. After a statistic study of the results, if we measure an effect, we would like to create an information brochure, available everywhere, about the benefits that we can take from the research and the development of GMO’s.”

Reflexion following the debate:

After this presentation of both the projects, the professors (panel members) presented themselves and gave to the public their opinion about synthetic biology and bioethics. They also asked questions to the teams, in order to better understand notions which weren’t presented in a clear way during the projects’ presentations. They expressed critics which were very constructive. For instance, they talked about notions such as horizontal transfer, a notion which wasn’t, at that time, taken into account by the KULeuven team. That’s why our debate was so important. It helps the Belgian teams to develop a reflexion about their projects. Thanks to this debate, we were confronted to others points of view than ours and it helps us to improve our projects.

The professors gave us some ideas, which turned out to be perfect reflexion sources for us. Therefore, we decided to go into these notions in depth, in the following section. These notions are the precaution principle, the communication between society and science, probabilities and at last, the legislation.

The precautionary principle (McCullum et al., 2003) has its origins in the German word “Vorsorgeprinzip”, which is freely translated as the obligation to “foresee and forstall” environmental harms. A 1998 consensus statement characterized the precautionary principle in this way: “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”. The 4 central components necessary to achieve its implementation include (1) taking preventive action in the face of uncertainty, (2) shifting the burden of proof to the proponents of an activity, (3) exploring a wide range of alternatives to possibly harmful actions, and (4) increasing public participation in decision making. As noted by Applegate, “properly construed, this principle defines a process for taking environment- and health-protective actions while the dangers of not taking such protective action remain uncertain…. It seeks to anticipate the risks of new and existing technologies so as to avoid or minimize them.” In December 2002, the British Medical Association (BMA) issued a statement on GE foods in which it reiterated its support for the precautionary principle. Adherence to the precautionary principle is consistent with at least 3 different tenets of scientific analysis.

First, it fits with the desire to minimize type II error (false-negative). 40 Scientists in the fields of ecology, conservation biology, and natural resources management have been increasingly concerned about the tendency to downplay type II error in studies that aim to inform environmental policy. As explained by Kapuscinski, this is because the potential for harm is greater if conclusions commit a Type II error (false negative) compared to a Type I error (false positive) since recovery from most harm to ecosystems or human health involve large time lags, and are sometimes irreversible. Type I errors, on the other hand, are usually limited to short-term economic costs borne by the developers and marketers of GEOs.

Second, the precautionary principle assists in accounting for another type of uncertainty that arises from ecological systems research, something that is inherent in all biological systems. With regard to the release of GEOs into the environment, uncertainty arises from gaps in current knowledge about the behavior of a GEO, the novel traits modified, ariability in the environment, and limits in predicting the evolution of GEOs subsequent to their release in the environment. Third, by broadening participation in the risk characterization process, the precautionary principle may be helpful in reducing type III error, which occurs when scientists provide an accurate answer to the wrong problem, that is, they ask the wrong question. A realistic way to cope with such inherent uncertainty in complex biological systems is to implement an adaptive management approach to biosafety governance. Such an approach for assessing the ecological and human health effects for the release of GEOs into the environment that is consistent with the CBD adherence to the precautionary principle has been developed by the Scientists’ Working Group on Biosafety. It should be acknowledged that the precautionary principle has been criticized by some as being overly vague. Other criticisms of the precautionary principle include (1) current regulatory processes are already precautionary, (2) the precautionary principle is not scientifically sound because it advocates making decisions without adequate scientific justification, and (3) if it were implemented, the precautionary principle would stifle innovation by requiring proof of safety before new technologies could be introduced. However, a recent analysis has concluded that implementing the precautionary principle is not only good science, it is also good economics for at least 4 reasons: (1) precautionary action benefits workers, (2) precautionary action does not impose damaging costs on industry, (3) precautionary policies can stimulate technological innovation, and (4) economic logic supports timely action to avoid substantial health and environmental costs.

As regards society – scientists’ communication, it has rightly been raised by Professor Bruno André. It stated: "the information is available everywhere thanks to the new technologies but you can communicate only to those who are interested. The question is how to stimulate their interest? ". We think that the iGEM is a good way to stimulate the interest of people. An international competition that involves students from different backgrounds and from all around the world is a perfect opportunity to have the media attention we need to touch many people.

Probabilities, in turn, have been invoked by Jacques Van Helden. He drew our attention to the fact that the KUL had not fully measured the probabilities related to the fact that they can spread bacteria in nature. He said that although there is a low probability, when it comes to bacteria, we speak directly to millions and the low probability then has a big chance of happening. In addition, these low probabilities may have a large impact on the world. So, how do you measure this? Must we write a stringent law on this? We think that probabilities are crucial, mainly for organisms which are apt to go in the outside world. That’s why it must be developed by team composed by people with different backgrounds to don’t forget taking every part of context into account. Well, our project don’t really need this kind of mathematics because we developed a tool which will stay in the lab but if we had constructed an organism which had to be send in the outside world, we surely would worried about horizontal transfer or contamination and probabilities would be in the center of our defense project.

Finally, for the legislation, it emerged from the debate that it is imperative to develop specific legislation for what happens in the laboratory and what is destined to one day leave the laboratory. These laws must be different to allow science to evolve in the laboratory without the risk of contaminating the outside world. We might consider developing bacteria that dies outside of the laboratory. We tried to inquire about the current legislation but it’s not easy to found it. After hours of research, we threw in the towel. It appears that if the legislation exists, it’s not accessible and well known from everybody. So after defining a specifically legislation for the lab and for the outside world, it is imperative to make sure that it is accessible and understandable for everyone. Writing this legislation is good but it won’t help if it’s not closely monitored. People need to know that limits exist in synthetic biology, they can’t do everything they want without an external system which controls what they do. So our last request is this external controlling system which would monitor the well known and the respect of the legislation.