Interview Questions on Synthetic Biology and Ethics In total 20 European key scientists were interviewed, representing the “core group” of the European synthetic biology community, which we defined as those persons and institutions that coordinate (or participate in) one of the EC-FP6-NEST1 funded synthetic biology projects (European Commission 2007). Of these 18 synthetic biology projects funded, 13 are larger R&D projects2 and 5 are smaller support activities dealing e.g. with community building, safety and ethical aspects, and future funding needs. We managed to interview 12 out of 13 coordinators from the R&D projects, plus 5 key R&D project partners, and 1 support activity project partner. Also we included the coordinator and a key project partner of the first EC-FP7 synthetic biology project (HZI 2008). Age: at the time of the interview, 5 interview partners (or 25%) were between 30 and 40 years old, 8 (40%) between 40 and 50, and 7 (35%) were 50 or older. Gender: most of the interviewed experts, 19 out of 20, were male. Place of work: 5 experts were working in Germany, 4 each in the UK and France, 3 in Spain, 2 in Italy, and 1 each in Switzerland and Belgium. Professional background: 11 out of 20 experts stated that they had more than 1 disciplinary background (such as biology, genetics, chemistry, engineering, biomedical engineering), revealing the highly interdisciplinary expertise of these people. 50% of them have a background in chemistry, 40% in biology, 35% in genetics, 15% engineering, and 30% in other areas (e.g. physics, mathematics, computer science, philosophy). Given the geographic distribution of the experts, the interviews were carried out by phone (VOIP) and were recorded using Call Recorder software. In two cases the interviews were done face to face using a videocamera to record the interview. The interviews were performed by Markus Schmidt and Agomoni Ganguli-Mitra, as part of the SYNBIOSAFE project. Below is a compilation of the answers given by respondents, in the form of notes, phrases, catchwords and quotations. These notes, taken by the scientists who performed the interviews, served as a background of the analysis described in the paper. QUESTIONS 1. How would you –in brief sentences - define synthetic biology? (Is synthetic biology fundamentally different from traditional bio-engineering?) #1 1 Design and fabrication of biological component s and systems, not existing in nature as such, large difference to metabolic or genetic engineering, large component of design, SB is cristalisation, engineering counterpart of system biologies. To design and achieve certain functions See: http://cordis.europa.eu/nest/home.html The names of these 13 R&D projects are: BIOMODULAR H2: Engineered Modular Bacterial Photoproduction of Hydrogen; BioNano-Switch: A Biological Nanoactuator as a Molecular Switch for Biosensing; CELLCOMPUT: Biological Computation Built on Cell Communication Systems; COBIOS: Engineering and Control of Biological Systems: a New Way to Tackle Complex Diseases and Biotechnological Innovation; EUROBIOSYN: A modular platform for biosynthesis of complex molecules; FuSyMEM: Functional Synthetic Membranes for GPCR based Sensing; HYBLIB: Human monoclonal antibodies from a library of hybridomas; NANOMOT: Synthetic Biomimetic Nanoengines: a Modular Platform for Engineering of Nanomechanical Actuator Building Blocks; NEONUCLEI: Self-assembly of synthetic nuclei: key modules for semibiotic chemosynthetic systems; NETSENSOR: Design and Engineering of gene networks to respond to and correct alterations in signal transduction pathways; ORTHOSOME: An Orthogonal Episome: an Artificial Genetic System Based on a Novel Type of Nucleic Acids; PROBACTYS: Programmable Bacterial Catalysts; SYNTHCELLS: Approaches to the Bioengineering of Synthetic Minimal Cells 2 Traditional GE, single genes, not take into account the network the context it is embedded, more than sum of parts #2 The organisation, arrangement and understanding of biological system using the techniques, skills and precision of conventional engineering. #3 I would like to emphasize that synthetic biology (SB) “should be different” from traditional bio-engineering in two major respects: a) SB differs from genetic-engineering in one important issue: it deals with cell biological circuits from which they to develop standards. The notion of standardization is critical in SB, because we assume that the particular circuit will always function as expected, i.e., it is much more controlled and, up to a point, we have a deeper knowledge of it than under the classical genetic-engineering framework. b) It is an objective of SB to work with the full cell system. If we are able to develop different biological circuits of the cell, as stated in a) we will also be able to combine all these circuits within a full cell system. The way to proceed is by building minimal cells #4 Like GE to the extreme, but much beyond, using computational methods, biological parts. We can modify organisms many genes in one shot Cheaper Aspect: construction of synthetic molecules Both qualitative (systems engineering, design, like airplane, something new) and quantitative (larger quantities, high troughput, new developments, reduced costs) Pers. Interested in in vivo SB, re-engineering of the cell #5 Production, construction of living systems, living organisms with evolutionary stability! (this is an important point). Different to biomimetics, biotech (conventional one) is not evolutionary stable Drew Endy (he means the biobrick foundation and its concepts) is not doing evolutionary stable constructs, variations can be selected for. Parts design + evolutionary improvements, failed attempt bona fide Design from scratch, evolutionary stable (mentioned again), understand biology #6 Creation of biological systems, products not known in nature, it is more interventionistic than traditional GE, SB has more ambitious goals, like metabolic engineering, but much ambitious many definition on SB, not much different from existing definitions on traditional biotech, from chemical point of view, origin of life problem, how to design new systems that do not exist in nature, production of chemicals / molecules, redesign and re-engineer systems to make new things possible, simplify systems to understand them better. Application and fabrication will be important, synthetic = not natural #7 #8 #9 coming from the material science background: take manmade matter in contact with nature and see how this can be to the advantage of material approach e.g. we work on membrane structures, replace some components of membranes, mimic ampiphilic stuctures. 1. Use existing building blocks in nature (that have evolved) to perform a different function, to misuse them for biotechnical purposes #10 Application of genetic engineering to produce novel pathways that are designed to perform a specific function. And in this process engineering criteria are used in the modelling and planning of the circuit #11 Technically similar to genetic manipulation: construct living beings of the simplest kind in order to re-programme them. Organisms are still recognizable but reprogrammed to so something to do something other than they usually do. Other people try to understand why the organisms don’t do what they are programmed to do…to find out why they are doing what they are doing, independent of the original success. Difference between gen. Eng and SB is the complexity level. #12 Building artificial cells/systems- we assume this can be done but we need to figure out the constraints in getting there. Understanding biology through failure #13 Synthesis of bio-structures and systems that do not exist in nature with the aim of understanding out basic knowledge of life. The basic science aspect is important #14 Activities converting biology in a true engineering discipline, by that I mean o Modular design o Identifiable systems boundaries o Hierarchies of abstraction o For example separation of design and manufacturing That was not available in biology or biotechnology. Traditionally it is like in a dark room where you feel your way around and sometimes you are lucky enough to make a step forward. True SB could change that to a much more rational design and approach Typically we have a complex system, that is difficult to understand and to design rationally Want to address big challenges: sustainable chemical industry, medicine, energy… Today biotechnology fails frequently, it is inefficient In contrast engineering, has innovation cycles of few months, SB is the attempt to work towards these aims #15 Synbio is emerging. It has some new and some old aspects. First mentioned in the early 20th century, but in a different context, the term has since then undergone a metamorphosis. Now it is understood as “ discovery of biological systems with the eyes of an engineer”. Molecular biology was the creation of physicists, because of interest in biology. Synbio is the creation of engineers, who rediscover biological systems as a matter/as an object of study/analysis with tools and conceptual framework of bona fide engineering. Interface engineering (science) and molecular biology. Before the term “engineering” In genetic engineering was used as a metaphor , as an analogy. Now for Synbio engineering is the real methodology. What is new? The engineering aspect. Not taking pieces and putting them somewhere. Now Synbio is meant to have a plan, a blueprint, hierarchies of action, simulation, ways to predict how systems behave. Traditional GM: trial and error approach. Try many combinations and see what works. Synbio: development of biological systems, start with first principles that come from a engineering body. Solving problems with planning, blue print. Like trial and error vs. direct design. Comparable to medieval architecture. Wonderful building but no science behind it. Trial and error. Modern architecture: complete design, you know everything. That is also the dream of SB: to predict behaviour of biological systems, before they exist. #16 It is systems oriented, in comparison to Genetic engineering (GE). GE is to modify one part , Synbio is modification of many interacting parts. Modification and design of systems. That way it is an extension of GE. #17 Rather than to study biological systems by taking them apart and to try to study individual components, it is to build new systems from scratch and to study those, quasi-biological systems. Synthesis is the ultimate test of understanding. Applies to all levels of biology (chemical, macromolecule, systems) #18 MIT definition is a bit too narrow. Would like things that we and others do…e.g. building synthetic anti-bodies, would like to look beyond the genetic definition. Anything that uses building blocks outside /inside organisms, to create a library, e.g. to be screen for some properties etc. That’s not just the building of new living org. , building blocks that do something (e.g. binding to cancer cells, harvesting light, induce electric current). Library of recombinant anti-bodies were a kind of SB too. #19 Production or use of biologically-derived parts in non-standard biological contexts. In Bio. Eng. one would be using and adapting living organism to do things, whereas this is taking sub-systems out of biological systems and using them in a different context, e.g. using it as part of a device or using the organisms themselves as part of a device which is outside the normal BE approach. #20 SB , the rational modification of living systems. Wrote an article about this in xxxx. Using rational design, no big difference from what has been done over the past years, apart from the engineering component. 2. What would you expect to be the most important development/application of synthetic biology in 5 years? in 15 years? #1 Developments at level of understanding, streamline circuits Production of chemicals, health applications, regulation of certain processes, switches tumour regulation, novel sources of energy (BP project, hydrocarbon molecules instead of petrol) Applications will take longer than we expect, In 5 years we can understand better, but no break through applications #2 The ability to provide a catalogue of biologically active components, which can be assembled in a well-described manner, so as to allow the production of novel constructs. AND The ability to provide precision positioning to the localisation of key biological components, which will allow self-assembly of novel biologically-based devices and machines. #3 5 years: a) Building more and more complex and sophisticated standard biological cell circuits. b) Deriving minimal artificial cells by deleting genes from natural cells with already reduced genomes. c) In close connection with Systems biology to have a full knowledge, in silico based, on a minimal cell. d) Increasing number of biotechnology and biomedical applications associated to specific biological circuits properly introduced in biological vectors. 15 years: a) To have a full comprehension on the functioning of a bacterial cell. This is Systems Biology. b) This knowledge will allow us to build a cell from very basic molecular components #4 Short term: bioproduction of compounds (chemicals) in a cheap way, e.g. malaria artimisinin, or ellagic acid against cancer, synthesis into bacteria Biofuel production (his EU project) 10 y. medical applications, for different tissues, tumor cells long term bioremediation #5 5 year time frame: overcome agricultural hurdles, e.g. yield, utilization of biomass, chemical engineering more than nanotechnology, which is naiv 15 year time frame: nitrogen fixation by plants (engineered) #6 In an early stage, something like in the Keasling lab (artimisinin-malaria) microbial. Based production of useful molecules, artimisinin and the like, production of small biomolecules, e.g. for energy, liquid bio-fuels, hydrogen, realistic for the short term 5-10 years. More than 10 years from now: more directed on human health, interaction with larger organisms (not so much small molecules) drug delivery, targeting of drugs, #7 Not an easy field, rather difficult, not much is understood in networking (genes) in biological systems, if you change something what happens? Be rather realistic, many dreams around, currently still many exercises (first steps) My point of view (chemical and medicine): reengineer bacterial systems to produce interesting biological molecules, this is feasible on the short term, there are some examples #8 Very limited and personal view 5 yrs Aiming at understanding how e.g. photosynthesis works so the energy source can be made of synthetic tools #9 I don’t make predictions …too difficult. Nobody can predict the future in 15 years #10 5yrs biotechnology: modifying bacteria or fungi to perform some novel metabolic pathways (production of energy, waste removal, novel vectors for research in mammalian biology) 15 yrs medical applications (for sure). Would be great to use it for gene therapy (if that still exists). Engineered cells to reproduce some drugs etc. #11 I don’t think synthetic biology will be really successful within the first 5 years. I am not looking for any application in the literal sense. 15 yrs SB will vanish due to the lack to widespread application (there may be some applications that I don’t know about). Not revolutionary in terms of applications, but because of many concerted efforts, we will learn a lot about complex systems. #12 5 yrs- establishing the conceptual framework- do we know what life is? e.g. why does an artificial phage work less well? 15 yrs- maybe a (artificial) cell / or set of DNA to put inside cells #13 5 yrs Synthesis of minimal living cells: understanding whether we need such complexity in life as we have now? 15 yrs evolving systems capable of interacting cognitively with environment (loop to evolution) #14 Ones that are talked a lot about and that Biotech wants to deliver for the last 20 years , but with SB we have a higher chance of doing so, e.g. CO2 neutral fuels, bioenergy, novel chemical processes, novel polymers, novel compounds, drugs. But today there is a gap of delivery of these new things. BENEFITS: Pragmatic ones: save time and money. 10 years from now, e.g. large scale manufacturing of oxalic acid would be a very interesting process. Production of fine chemicals, bacteria that does what we want it to do, try to have some demonstrator projects within the next 5-10 years. Long term vision: tremendously difficult to say what is going to happen in the future. Comparison to the people who first connected computers, they didn’t imagine that at some point in the future the internet was going to come out of it. The possibilities are tremendous, to use biology with rationality goes far beyond what we to today. SB (the project SB) will have lot of impact (e.g. chemistry, energy, pharma) but it is difficult to say. #15 Now we are in the game state. We are developing parts, or bacteria that flash, that become green, that become red. But for the moment the applications are limited to metabolic engineering of biological entities that execute reactions that normal systems don’t do. There is the success story of bacteria/ yeast that can produce artimisinin (anti—Malaria) Main applications 1) remain to be seen and 2) to be materialized Now we study the potential. No difference in our life I the coming (5 maybe 10) years. What are the general benefits? Biofuel production, ethanol, hydrogen, bioethanol. But intense discussion of bioethanol diverting resources from food crops! Growing energy crops instead of food crops could have negative effects on food security especially in poor countries. --> big challenge for SB: being able to come up with a solution, to convert cellulose residues (straw, wood, leftovers from harvest) directly into ethanol. And avoiding kidnapping food resources also: production of new material, valuable things, e.g. silk, plastics. Genetic design to produce it. Great potential. But be cautious. Expectation areraised very high. Been around long enough (since 70ties) to know that only part of the promises have been fulfilled. Community is excited . but stick to data what can be done. Taken away be enthusiasm #16 Difficult, well everything that needs the systemic approach and that needs a highly regulated pathway, and its engineering E.g. in vivo in o Medicine, regulation is very important (more than e.g. in white biotech where you have one enzyme doing something). Production of pharmaceuticals depending on the environment (context). E.g. Insulin production is highly regulated. Also in o Environmental technology, where you need sensoric characteristics, highly differentiated switches (not just on/off) o Detection (Nachweisreaktion) in vivo In vitro: o Complex biomolecules that can only be produced by biological systems (because they are so complex). Or when you need pathways to generate something (e.g. 5-6 enzymes on a nano bid (?)) #17 If anybody would know that, they would work on it! 5 yrs: organisms with a modified chemistry at some level (DNA or protein). To see if the type of molecule life chose is optimal or by accident. Will get novel pharmaceuticals, nucleic acids, amino-acid drugs, natural chemical drugs. 15 yrs: ultimate question is what is life. We will be able to take chemical off the shelves and put them together to get an entity that grows, can divide and possibly also evolve, would then fulfil most of the criteria we associate with life. #18 5 yrs: we assemble various building blocks in cell lines, screen monoclonal anti-bodies. Might lead to maybe therapeutics. We are learning, that we can harvest the power of the synthesis machine to make bacteria and cells to “do something”. Library of different molecules, DNA molecules can already be synthesised. This would work with other building blocks as well, then screen for a novel enzyme 15 yrs solve our energy problems in the future 5 yrs: design of an organism that performs functions that are not normally performed by other existing organisms, e.g. produce large quantities of hydrogen or mop up some toxins. Borderline of BE. Put together genomes like Venter application 15 yrs: applications which make use of components of living systems interfaced with solid state devices, e.g. provide onboard power sources for micro-devices, are likely to be the real applications, because they will have the facility of being robust of being able of self-repair, which is not available to organic systems at the moment. #20 5 yrs: synthesis of chemical compounds using bacteria, remediation, at least in small scale. Theoretical: experimental one see Venter, chromosome synthesis like we have oligosynthesis. Simulating and engineering tools. No big bio-revolution theoretically. ETHICS 3. What do you think are the most important ethical issues related to synthetic biology, if any? #1 Don’t really see other than general ethical issues in science. The use of SB technology per se not poses additional issue. Working with gene like in nature, no special ethical issues, Depends on applications, ethic and common sense No new ethical issues, technology can be misused Bioterrorism and associated ethics, already there. The ethical questions are the same now applied to this field. #2 The greatest problem, which has important ethical issues, is the availability of cassette-like biological systems, and the additional information on the internet, which may allow the easy production of dangerous and even lethal biological constructs and associated delivery systems. #3 a) As in traditional engineering, but probably much more, the ethical issue raised by the possibility of building new cellular entities or species. b) The capacity to intervene in the nature of biological entities, under the framework of SB, will be of greater impact than classical genetic engineering. In this field we slightly modify a given organism by introducing a given gene or set of genes. With SB we will move to implementing in a given cell more and more complicated biological circuits and, finally, we will address the possibility of building a cell. c) If we are able to build a cell: what will be our status? Scientists? Creators? #4 Short term: related to safety and security Cell: the human cell, similar debate to stem cell, maybe some ethical issues For the moment no big issues, issues already handled by other debates, enough control in the medical community #5 Only one: No application for human genome manipulation, this is the only important one. Preserve natural habitat, prevent genetic pollution #6 difficult question. Wholesale change to genome, creating life to do something useful, not aware of all consequences. Cross over of higher and lower organisms, maybe some problems (also safety) , mess around with stem cells could be a problem when close to human life. Not clear what will be done #7 Starts to talk about the “xxxxx” project he is working with xxxxx, chemistry and boil. Eng., the idea started out of the GMOs debate: gene flow, control question, xxxx does synthetic biology with non-natural molecules but that have the same function. Interaction (between synthetic and natural) with no problems, circumvent problems in ethics and safety Most SB work done with bacteria, but not many ethical issues involved in bacteria, therefore no problem, but different situation with higher animals (e.g. stem cells) Not see so many ethical issues personally Synthesis of Human DNA it is an ethical problem As long as being used in bacteria, no problems, in humans it would be at the level of gene therapy, stem cell biology, then you have the same problems Not the technology, but the application matters (whether it is an ethical problem or not) #8 There are some: translation form systems and genomic biology. Cannot be sure that the information we are using to build up the system are completely harmless. could come from anthrax organisms. Main concerns biosafety and biosecurity. In favour of control of this information, how effective I don’t know. Big effort to make, do not accidentally use “wrong” information. We are of course not at the level of organism, so e.g the stem cells issues etc. does not apply to my field but these concerns are not special to SB. #9 I would not claim any important ethical issues at present. Partly due to the lack of ability to predict….no other than usual: safety, misuse etc issues. Not like stem cells…but that can change of course. #10 Yes of course there are ethical questions. We will need ethical committees to approve the creation of synthetic organisms (what purpose of these ?) to approve each project. how we can control the organism etc. and why we are doing this. This is needed both for the public (Frankenstein factor) and also because we are modifying something we don’t understand yet. We need to be careful #11 not asked #12 Have heard many worries about re-constructing life etc.: I actually think artificial is dangerous. Worry is regarding misuse and abuse Is this a new approach to life? What would be interesting is if we put the concept of biology into computers: computers making computers! #13 We have to be very very careful about modifying existing forms of life (disturbing, modifying, transforming). Do not oppose it as a matter of principle but we need a committee to say yes or no to certain things (you only need one crazy scientist) Regarding the involvement of the private sector: it is surprising how much investing is taking place. Partly fashionable idea- to make lots of money through pharma, energy etc. #14 Referred to previous answer(s) #15 Ethics: we can keep on discussing, but I thing it is not terribly important. However I see one major issue in synbio: Intellectual property rights! Synbio is s production of western rich nations (US; EU, Japan, little bit China) but synbo can have benefits for the whole world. We need serious reflection. But this is , however, not specific to Synbio. Patets are kept in western systems. We have to make sure the technology benefits everyone. (What happens if IP would be ignored in 3rd world countries?) IP could limit innovation, 20 years ago much easier for a scientist Today you have to sign 100 papers, to make sure that whenever a benefit arises… (See- research exemption!) This is contra-productive! Sooner or later we have to change that. #16 Ethics means Misuse Cell differentiation, cell systems, creation of strange new animals by interchanging the homeo-boxes of insects and mammals, creation of segmented mammals. Dogs with 6 legs. This could trigger the reaction of humans. Talks about stem cells and how good they are to treat humans, but people don’t want them for ethical reasons. #17 Ethics really comes into play if SB is applied to human cells/tissue, who owns such cells etc. Not quite sure if stems cells are part of SB…? But issues would disappear if not ESC (embryonic). Nothing as such within the next 5 yrs. Most of the cases it is an extension of GE and Mol. Bio practised before with application of engineering, with genomics we have a wider variety of components available. Security is also covered by existing frameworks. #18 I don’t envision…apart from maybe religious people, e.g. novel synthetic organism (something that God should do), not really an ethical problem for me. #19 Some activities are equated by some parts of the population as creating life (not saying correct or incorrect), need to carry out such activities in a responsible manner against the background of this perception is going to raise some ethical challenges. This has to be handled sensitively rather than in a regulated form. #20 not to engineering molecules to do something nasty. Apart from the religious view (even that is not so important). So only worry is about release to do something nasty (intended release). 4. Can you foresee any ethical issues with the creation of artificial systems, such as novel genes, bacteria or organisms? #1 No, No ethical issues related to that #2 Refered to previous answer #3 Absolutely. Abounding in my last comment, humans have an increasing capacity to nature intervention and, of course, self-intervention. We are progressively moving from the area of ‘we understand how nature works’ toward ‘we not only understand but are also able to change it more and more’ or ‘we are also in position to create new natures’. As creators we will have the ethical responsibility to delimitate what and what not should be ‘created’. If, in the Western tradition, God has have ethical responsibilities on the nature of things He has created, imagine ours as ‘Creator Beginner’s” #4 Creating ethical issues: how do we sell that? Difference between creating life (which will trigger a reaction) vs. creating self replicating biological complex entities (machines) #5 New diseases, more difficult (to combat) But answer is: NO. look at domestication of mammals, which is on a deeper level comparable. There are not so much ethical issues, but more metaphysical and philosophical issues arising #6 humans have been creating life before, not first time, but now some more significant changes, big grey area, not sure what ethical issues are, how is it different from things done before? (some things are not, but now more rapidly and more rational changes). when is it correct (benefits)? #7 bacteria: no, higher organisms: be careful #8 Referred to previous answer(s) #9 No, those will be in the foreseeable future so low among life forms that it will take quite a while until we can construct something that is comparable in complexity to a single cell and I don’t see any ethical issues with single cells, except that it is a single cell with human DNA. I know Craig Venter is trying to make a simple bacterium…no ethical issues with that, no problems. SB is not so much about creating some living systems, but using the machines, proteins, for a different purpose make drug, drug delivery. This will come out of SB. But not things that will have ethical issues. #10 the process has to be supervised and controlled. Something that needs to happen. One has to be cautious #11 Novel genes in themselves are not living. Bacteria and organisms yes of course. Depends on what we mean by living. The more “living” it is…the more concern. If you have something “living” only under very stringent conditions, you have to ask yourself whether this is good or bad (ethics). But then again I don’t believe we’ll get there (e.g. organism developing their own will). Important but hypothetical question. #12 Not different from any other artificial objects. Part of what man does We may now get living organisms with different codons etc. We might want to reflect on the way we (should) occupy the earth. The nature of man is to be artificial , to escape the natural. There are no new ethical questions. If there is question of patenting, patenting has to involve inventing #13 Bioethical issues will arise. We cannot expect to have a field with new life and ignore bioethical aspects. We need to avoid fundamentalism one way or another. Those who are opposed to it might be ignorant but should be taken into account. #14 Referred to previous answer(s) #15 Referred to previous answer(s) #16 The only question is the one of uncontrollability, fear stems from not being able to control things. SB answers to this as a way to design things more accurately. Synbio is the quest for higher controllability, e.g . it can provide containment for metabolism. That way sybio is the answer to the fears. Synbio is totally harmless, it is the solution to all problematic questions (of uncontrollability) #17 not genes, sequencing genome has show how plastic it is, this goes on in nature all the time. New organism: animal breeding has been around for a long time (see some existing breeds of dogs and cats). So there are ethical dilemmas but they are not new. #18 Referred to previous answer(s) #19 no (Referred to previous answer(s)) #20 no (Referred to previous answer(s)) 5. Do you see any ethical issues related to the interaction between “natural” and synthetic life forms? #1 Not more than e.g. hypothetical cloning, baseline: SB per se no additional ethical or security issues Depends on applications and control, “unexpectibility”, there is a rational design behind, but we don’t know all emerging properties, this is more of a risk assessment issues #2 The unpredictable nature of natural selection and hostile environments may produce unexpected outcomes through fusion of natural and artificial systems. #3 Yes, a lot. The issue is not different between the potential conflict between natural entities and robots, although at lower extent. We can design a synthetic life form able to outcompete natural ones. If we systematically proceed, in the near future, with new synthetic life forms, better ‘designed’ than natural ones to work in specific environments and/or circumstances, we must consider both, the right to do it (ie., the replacement of natural biodiversity with synthetic one), and the environmental and biomedical consequences on it. I told you that in SB we eventually will be able to build a cell and to perfectly know the precise behaviour of the synthetic cellular system, but I’m not sure we will be able to predict the consequences or impact of such new system when freely liberated to the environment. #4 No more ethical issues (than elsewhere), see e.g. Alisaster, an algae that escaped from the aquarium into the Mediterranean sea. Invasive species similar to synthetic organisms (but synthetic are less adapted, have to compete for survival) #5 No, but have to be conscious about, Technical prevention of “cross talk” #6 Interactions, as long as it is in the laboratory not so much of a problem (confined) But when released into the environment: we don’t know the interactions that will be. #7 What we would like is to avoid that out of biosafety reasons, not so much ethical issues Currently production of proteins, using recombinant DNA Better if done by a parallel world, that does not interact with natural world, there should be two different systems #8 You are completely right but we are so far away. It is an issue. The moment you are able to create a synthetic organism, critical ethical issues. Don’t see it a the moment, think about it in 10 years. Don’t kill SB by thinking of something so far away! #9 Referred to previous answer(s) #10 We have the technology in place (precautions) to make sure this does not happen. We have been doing this for ages now…just the normal rules that apply to labs. Also these organisms are not pathogenic. But if there are released in the environment as an application, e.g. removal of waste…there are preventive methods…an external ethical committee can decide whether we can do it or not #11 Not more than is already the case. As I said the world is full of synthetic organisms (dogs, etc.). If you detach synthetic from whatever now in SB is …. (the case??) Artificial: dangers are fewer. We know more and can control more We are in a new area (new form of life). Safety is a less of a problem. There may be concern of lay people facing the idea of new life being created (especially from a religious point of view) #12 #13 #14 Referred to previous answer(s) #15 Referred to previous answer(s) #16 There are not going to be artificial life forms. The probability is too low. OK you have evolving RNA and the minimal life experiments by Luisi but LIFE is not going to be produced by them. Can not produce it outside of life (only modification but not de novo) Transgenic maize for example could have some unpleasant characteristics but it is not very dramatic. Development like with chemistry. Only useful things, not damage, it is a “tool”. You can even use nerve gas to produce some useful polymers, intelligent rules, use it meaningful, like a stone that can be used to make fire or hit someone in the head. #17 No ethical questions but we should make them so that they cannot survive outside lab (safety issue), most organisms will be like that anyway (just can’t survive outside #18 Once again , maybe just safety problems, I don’t see any other problems #19 Yes, This is where there are serious issues that that need to address. Interaction with ecosystem at an unprecedented scale. #20 release …the same as what we are doing with GMOs, we need to check … same kind safety measures, controls. 6. Have you encountered similar ethics debates regarding earlier technologies? Which ones? #1 Many examples: GMOs, nuclear energy, stem cells, all kind of these discussion could be similar, essential the same question behind all these debates #2 Genetic modification of organisms. Bionanotechnology. #3 Yes, when talking about the release of genetically modified organisms to environment. However, the issue will be of higher ethic impact when we release full synthetic organisms #4 GE, Asilomar, stem cell, but not familiar with it. #5 Yes, the civil (use of) nuclear technology. There confinement issues were taken into account. Non-proliferation act (for military use): should be similar for SB Technology is helping the world, I trust technology But: What is experimented should be discussed. Like a panel of people that should discuss that Asilomar: I don’t trust them, they were political bodies, was used as a self voting enterprise There should not be self regulation, scientists are not more moral than e.g. taxi drivers (or whatever) #6 GM crop debate intense in the past, some people don’t like the idea, synthetic organisms is worse, because of more radical changes (embryonic) stem cells (ethics behind it, especially in the US), human stem cells cloning, dolly the sheep, cloning plants, animals Asilomar (heard about it, but doesn’t know it) #7 Genetic engineering, recombinant DNA, might be very close #8 I come from the green GM background eg GM debate. This is what happened in Germany. Of course you can talk about it but the debate turned in such a way that the whole research was stopped, now you can’t even talk about it. The press was somehow killing the whole field by giving the wrong information. So you can discuss about issues that are existing now. I hope this will not happen again. #9 Not really…my background is theoretical physics… so I haven’t followed this closely Mentions stem cells which he has observed as an outsider. #10 Similar but GM debate was in the public. The larger public does not know about SB yet. These issues have to be solved before…it goes to the public to prevent a GM-like debate. #11 Yes of course, Basel, Biocenter Prof. Gehring didn’t get the Nobel prize, but…lot of attention with flies that grow legs instead of antenna. Easy to publish on BBC…. students hated and criticised him would you like to have instead of eyebrowns fingers…ethical issue. Because of that a position was created for ethical issues at the Biocenter. Should become part of the normal…discussion in this field. #12 Public reacts in different ways: somehow GM animals are more worrying that GM food but people will react in the opposite way. I doubt that the public is really that concerned. Controversy is usually created by lobbies, not the general audience. The main problem is not what is done but how—this kind of research is usually done by profit driven companies #13 This is a new modern form of genetic engineering. We might have insurgence of reactionary groups bound to creationism, intelligent design, who might be powerful politically speaking. #14 GE debate was very similar #15 GE, many others (uses a analogy with pain killers and anesthetics from the past) #16 Stemcells, also chemistry (harmful for health), Gentechnology, nuclear energy Talks about general ethical aspects: Shall men do everything that he can? Question since Renaissance (Aufklärung). What God has only given to man.The brain is a computer. Maintain positive things for our species Technology has always been questioned and challenged, like a hydroelectric damm, flying to the moon (some said men should not go to the moon, we are not god). Religious believes. It is a fundamental inclination to technology. Like in nuclear energy and the climate change CO2 discussion . UK will build new power stations. Produces a conflict in Germany: Green-mania (Grünheitswahn) #17 most relevant is Asilomar, much less was know then about the consequences might be of starting to hold such a genetic info. We didn’t know to what extent nature does it anyway. GM is different : there is a difference between what you would give to your children to eat, and making a potentially life-saving drug that requires some manipulation. This is why there was so much resistance. Would not have been a problem if the first GM plant was created to produce a cancer drug. Tomato easier to transport (frivolous) #18 There are similarities with GM Rec. DNA etc. Same issues #19 GM crops in Europe, especially UK. Debates on cloning, Artificial insemination, which are not at least in the UK legislated or regulated by HFEA (human embryonic and fertilization association) #20 no answer