From 2009.igem.org

Revision as of 00:04, 22 October 2009

Project

Introduction Current therapies Gene therapies DVS Concept Tissue Vector Cell Vector Therapeutic plasmid Conclusion Implementation Tissue targeting Antitumor action Treatment modeling Conclusion

Ressources

BioBricks Material & Method Bibliography

Ethics & Safety

Ethics Safety

Ethic

The international competition iGEM gathering each year together more and more teams (110 teams for the 2009 session) added to 18 Europeans programs, 70 industries, 10000 laboratories in the world which have all the same common objective: the construction of living systems, following the assembly principle of functional modules.

The emergence and the fast development of this discipline require reflection, to put a regulation system in place ready in the next 5 to 10 years for safe practices.
Thus at the occasion of the iGEM concourse, we realized this debate to think about ethic stake linked to synthetic biology.

The debate program

Debat program :

1. Introduction to synthetic biology, François Le Fèvre
   
2. Introduction to the Double Vectorization System (DVS) project developed by the team
   
3. Round table leaded by Thierry Magnin, and the Sup’Biotech Paris team:
   
   • Synthetic biology / DVS Project - Formulation of risks and benefits: what are the risks, can we get round them, what are the effects on Human, animal and environment, the advantages of this discipline, where stop science and where start creation? The populations fears...
     
   • Regulation, Access and right : at which point the knowledge should be protected, put in advance the « non patent » concept as well as regulations...
     

Discover videos of the debate !

Summarization of reflections

« Ethic is the movement itself of the Liberty which searches a well life, in the solicitude toward others is in just use of social institutions »; Paul Ricoeur quotation, philosopher of the 20th century. In other terms, ethic represents the philosophical field gathering moral values which define the way we have to behave.

Applied to synthetic biology, ethic indicates the way to follow to allow this discipline development by avoiding its drifts. Indeed, even if it lets dream to large perspectives like clean energy sources, accessible therapies to all or biological remediation methods, to manipulate the living rises regularly to a certain number of ethic questions . François Le Fèvre mentions « it is the first time that human is confronted to the possibility to create new forms of life ».

It seemed important to us to interest to these points, beside the biologic engineering technic aspect. In this way, we organized an ethic debate based on the topic of the synthetic biology, in which some different expert key figures of the domain were invited. During this debate, different problematics were raised. Like emphasized Thierry Magnin, some of them are of metaphysical order, and concern notably what «this gives us as the living representation, as life »; some others concern direct applications and their technical aspects which can push us to imitate them. At the occasion of this debate, we presented our project to our guests in order to take out ethic questions.

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Metaphysic problematics

Aim of the synthetic biology

It convinces first to interest in finality of this science. What are we trying to do? Are we looking to reach a perfection state? When we are working to the improvement of a living organism, in addition to technical difficulties, we have to ask if what are we doing is desirable. Without the egocentric drifts we can easily imagine, we could try to correct our weaknesses, handicap, diseases. Dorothée Benoit Browaeys put in advance that the context can change a « tare » in asset: « there are diseases which give you certain advantages. So to take up the titer of Alain Gras’ book on the fragility of the power, we could speak of fragility power ».

However, potentials advantages seem sometimes negligible copared to the handicap: it is for example the case when we are affected by the HIV. And the engendered disease will not be controled, in Willy Rozenbaum opinion, « if we are not using synthetic biology ». More generally, this last one does not imagine « how we could do without it if we want to go towards an improvement of the human condition». The perfection myth seems not to worry him, because he affirms that we still very vulnerable and far to be perfect.

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Modification of the living representation

Search to synthesize and to modify fundamentally organisms push to wonder about the definition itself of the living. Craig Venter affirms that « we pass from the capacity to read our genetic code to the capacity to write it». But understand and generate life mechanism can demistify it; and the fact to create living machines, in a precise goal, risk to give us a determinist vision of the living. Thierry Magnin wonders « in a context where life is assemble with bricks, what is doing the real difference between vegetal machinery, animal machinery and human machinery? ». After all, we can consider the difference between the three does not come from interactions between « bricks » which compose them. « How can I recognize a certain dignity of Living if all is built by blocs » ?

Synthetic biology can reveal a play aspect, and this aspect can alter the respect that we carry to living organism : to quote one more time Thierry Magnin, « Those with what I am used to play, I often have difficulties to respect it». We can create « pieces » of living organism without of their context, stock, reproduce, transmit and assemble them. If we create biologic systems like we assemble “legos”, do not we risk considering living organisms, whose human, like simple assembling of pieces? And in this case, the respect that we consider to have face to them can be altered. Of course, we can consider that our creations are only biologic engines, synthetic distinctive machines of « natural » life forms.

But where is the limit between these ones and the artificial life? The way of one and the other were created change their natures? It is however necessary to qualify the impact what biological synthesis could have on the way we consider life: how reminded François Le Fèvre, when «we synthesized urea, the first organic synthetic molecule, it has an entire debate to know if we created life or not»; and, how emphases Lluis Mir, we could ask same questions at the beginning of of chemistry. Two hundred years later, it can make smile.

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Problematic linked to applications

Evolution control synthetic biology products

Synthetic biology leads to the creation of living organisms which should not have exist without the human intervention and are not the fruit of a natural evolution. Will be able to control it? We are not controlling mechanism of the information storage in the living world, and we are far to be able to predict how will behave a group from its separate elements. We create parts, but will be able to predict emergent properties of their assembling? Furthermore, synthetics organisms, because they are living, evolve; will we be, asked Thierry Magnin, « in measure to control propagation of these lively engines that we construct? » Thanks to their capacity to evolve, do they risk to escape to our control? Willy Rozenbaum observe that the pression responsible of the evolution will exist even for organisms which are not due to this pression; and that « it is more performant and less nocive that will go out of this; because these presion will stay ».

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Bioterrorists drifts

The loss of control of living systems syntheticaly created could be intentional. The synthetic biology and the diffusion of knowledge that it put at disposal of a large public of genomes, notably pathogenes can be modified at low cost. In the case of our DVS project,some changes could transform our vector in biologic weapon like mentionned François le Fèvre: « we can imaginethat instead of target a cancer, we target neurons to send drogues that permit to weaken someone ». From 2003, a CIA report mentionned risks linked to live science development and the difficulty to limit the bioterrorism developement. It is necessary to limit access to data at the risk of slowing down progress of the knowledge in synthetic biology?

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The benefits/risks ratio

To assess the risks and benefits of a science, we have to wonder for what it is intended, and if the risks are taken by beneficiaries. In the case of synthetic biology, risks are taken by the society and it must be the same for benefits. The financial interest of a small community does not have to harm the majority. Currently, the scientific community manages synthetic biology, but some applications, provided to generate significant revenues, might be developed despite the nuisance they cause. Therefore, as stated by Lluis Mir, "it remains the vision of science and society, and not markets." It is also important that involved researchers retain their critical thinking and continue to communicate the progress of their knowledge even if they work in an industrial or commercial context.

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Intellectual properties

Thinking about the intellectual property of our project. We wanted that our treatment could be available at the lowest price. In this context, we asked about the open source development or patenting at least a part? The first option would allow any company to develop and improve it, but a private company could then patent a more rounded version of it, and impose prices that benefit the most. Furthermore, Willy Rozenbaum confirmed us that the clinical development would be very difficult to finance, "if you can convince a manufacturer to begin the preclinical tests, you will already have protected your model because otherwise you will not find manufacturers to develop it. " This last point would be less problematic with the second option as the funds generated by a patent would help persuading manufacturers, but access to data would be much more limited.

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Problematics related to the DVS project

One of the objective of this meeting was to discuss some issues related to our project DVS. The general points have been mentioned above, since these point apply to the whole synthetic biology. Specifically, we examined relative risks underlying the introduction of potentially pathogenic agents in the organism.

Let’s begin with the importance of this risk. Mycobacterium avium is sometimes responsible for serious infections in humans. But, as noted by Willy Rozenbaum, "it is a bacterium that is ubiquitous, it is found in tap water, we are almost all contaminated" but this contamination has rarely consequential effects. The cases reported involved immunodepressed patients, for example. We also planned to analyze the effects of infection on tumors. Anyway, Willy Rozenbaum believes that "all that is not very annoying”. In addition to numerous tests and simulations that have to be conducted before the use of our treatment, this statement is justified by the fact that bacteria are lysed when there is a release of the phage, it does not persist in the body.
Francois Le Fevre has legitimately questioned about the possibility that the phage infect other bacteria already present in the organism. We have therefore explained to him that our cell vector encapsidate only the therapeutic plasmid, not its genome. If it infects bacteria of the commensal flora of the organism (which may be limited by changes in protein internalization), the bacteria will receive just the therapeutic plasmid, and the phage will not be able to multiply We can also worry about the drifts, and abuses of the transgene integration, as the risk of homologous recombination or risky integration. Lluis M. Mir supported us about this idea, that our phage is a prokaryote, but cells of human body are eukaryotes. It can therefore be no risk of homologous recombination or integration between its genome and our cells genome, as they do not belong to the same "world": "there is no possible integration. That's the real advantage of being at the crossroads between eukaryotic and prokaryotic.

Furthermore, Willy Rozenbaum reminded "this type of subject is very well controlled today in terms of security": the product would obviously not be marketed until being subjected to numerous tests to check its innocuousness. Organizations as Afssaps, in France manage the safety of health products / / / / If we consider that the risk is not negligible, we must ask whether it is worthwhile to be taken into account. Thierry Magnin gave a translation of the principle of responsibility made by Hans Jonas: "Before trying to estimate the risk, I'll try to work up on the most serious risk." Does the targeted disease justify it? According to Bernard Baertschi, "Cancer is an extremely serious disease, for which we accept to take risks even now." Francois Le Fevre acknowledged: "Anyway, if I have lungs cancer, I think I should take your medicine...” To conclude this section, we can quote Bernard Baertschi again: "We can take a risk if the person consents and if there is an expected benefit.

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Conclusion

Synthetic biology can become a very powerful tool if it remains under control. Risks exist, of course, but some causes for which it is an asset that justifies the taking. It is without doubt the scientific community to make the community accept this idea, by transmitting the knowledge. Some problems, such as various diseases, seem also to be resolved through it. But the sought interests are those of the entire society, and not particular groups. It might be beneficial to put quickly in place a regulation to avoid abuses, without limiting the development of this promising science

Survey

Today everything is patented or patentable, and worse it is possible to patent in simple concepts that have not been applied. Thus the purchase, exchange, submission and management of the patents bank of a company is a real business activity and it can be really profitable. Patent an invention, a concept or a brand is there real consequences on the daily progress? That is what we asked students to respond Sup'Biotech.

• 32% believe that patents represent a barrier to innovation, while 43% disagreed. The opinion seems pretty divided, which is quite surprising because in theory the patent is a tool for encouraging innovation. Indeed, the temporary monopoly allows to finance investment in R & D. However, in practice the patent appears as a secondary tool, some do not even have little confidence, while others do not hesitate to follow the example of the law fragmentation when innovations are cumulative and / or complementary as computing, biotechnology or electronics.

• As part of a therapeutic application, we may wonder if we can patent a living thing, giving it a value? This is the question that is facing synthetic biology.
• Like other technologies, synthetic biology would show us a new era, that of "Biolithic", where the living is becoming the tool. A tool that could be greatly promising to cure many diseases. But what is the therapeutic goal legislates she use? Synthetic biology thus challenges our life conception. Where is the boundary between natural and artificial? Can we afford to create everything from the living? Evolution can be "diverged"?
• 50% of students tend to reject this possibility of free manipulation with therapy pretext, however, 31% would consider it and 19% of students are wondering. As for a drift of evolution, 50% of students are quite convinced that evolution cannot be compromised by synthetic biology, however, 31% of students disagreed.
• Researchers must ask themselves these questions and beware of unethical uses that could be made of such technologies, even for the purpose of curing diseases; this fear of a student speaks to the questions raised by the living instrumentalization facing synthetic biology.
• Indeed, each advanced biological research contains a lot of questions on the health implications, environmental, social and ethical implications of possible applications of these discoveries. Are we able to control the living? Are we able to control the spread of systems that we built? While they are a majority think that researchers are capable of manipulating life, we remain skeptical with control its spread.
• Faced with these questions, how the company will position itself and how to respect the ethics rules. Because of the life control, the public is faced with a control by research area while having the feeling of being dispossessed of research results. How the company is going to express their wishes on these issues?
• Given the stakes, the debate should be pluralist and collective, we have to know who will control and how? Do we need new regulations, while those for existing GMOs are already far from perfection and unaccepted? Can we aspire to global governance? 46% of students believe that such governance is possible, while 31% think otherwise.

The survey draws the attention of politics, researchers and lawyers, reminding them that the innovation and therapeutic goal arguments are often wrongly used by supporters of a world where everything is protected and deposits. A collective discussion should take place to decide together how to maximize the positive applications of these technologies while minimizing the abusive risks.

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