Sins, Ethics and Biology - Review

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The Review : We have prepared a classical review on scientific reports about Synthetic Biology and its ethical consequences. With more thant 30 references, you will get a complete overview of the present status of this new emerging field. Ideas of well-known scientist about different topics are gathered here: Definition of SB, The engineering principles of the field, Applications, new chemically different biomolecules, ethical problems with genetic engineering, Europe and USA and teaching and learning SB.

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Sins, Ethics and Biology - Review

  1. 1. THE REVIEW Synthetic Biology... is a research field tha t In the following pages you will find a review about what combines the investig biology with the cons ative nature of has been written in specialized journals about Synthetic tructive nature of engin eering. Biology and all its ethical implications. Purnick PE, Weiss R.[6] What was and is Synthetic Biology? Bottom-Up Nowadays the term Synthetic Biology is widely used in approaches[3], [4]. The Top-Down approach focuses on the scientific community, but its definition and goals designing and creating working biological devices and, differ among scientists. The French chemist Stéphane to do so, it aims to create a minimal genome (a Leduc was the first to use the term in 1912[1], he was “chassis”) and the standardization of parts of DNA with thinking of creating life from inanimate matter and known function (to make it easier to assemble them). although some might agree (one century later) that this is The Bottom-Up approach tries to understand evolution one of the main goals of the field, there is certainly much and the origin of life by creating it from inanimate matter, more to SB than this. which is why protocells are so important in this new field. But, is Synthetic Biology a new field? For a more recent quotation of the term, we have to go back to 1978, when Szybalski and Skalka extended its Applying Engineering to Biology is not new and, in fact, meaning, bringing it closer to what SB is considered as Synthetic Biology has a lot in common with other today: branches of science. According to David Deamer[5], both Systems Biology and Synthetic Biology have two “The work on restriction nucleases not only permits us easily to construct recombinant DNA common theoretical questions to answer: How did life molecules and to analyze individual genes, but begin? and Can a lab version of cellular life be made? also has led us into the new era of ‘Synthetic For other experts in the field, SB is just an approach to Biology’ where not only existing genes are genetic engineering that tries to make it easier and described and analyzed but also new gene cheaper to genetically modify organisms and can be arrangements can be constructed and evaluated.” viewed as an extension of genetic engineering. Szybalski, W. & Skalka, A.[2] Anyway, it seems that the time for a change of paradigm has arrived. The study of biology has traditionally Nowadays, experts usually agree that there are at least focused on a reductionist way of thinking, where two main ways to look at SB, the Top-Down and the information about single genes and proteins was 6
  2. 2. gathered with no perspective of the 5 categories of whole cell system. Synthetic Biology Synthetic Biology: and other related Top-Down Bioengineering Turning biotechnology into a true engineering discipline. disciplines attempt approach to turn biologists’ Synthetic genomics Creating of organisms with a chemically synthesized genome. minds in this new direction. Unnatural Creating new kind of molecules chemically simillar to the ones molecular biology existing in order to replace them (XNA, different genetic code). Re-engineering Bottom-Up biology Protocells Constructing artificial cells in vitro. approach It is very common In silico approaches Informatic simulation and modelling of the other 4 categories. to hear this concept when Deplazes, A. [8] someone tries to define Synthetic Biology, but, what kind of engineering principles are being considered? Are these principles in concordance with the complexity of living matter? In 2005 Drew Endy wrote a famous article “In an ideal world, desig ning living systems for entitled “Foundations for engineering biology” [7] practical purpose should a be like redesigning a ca to make it more effi r where he tried to explain the engineering cient, or redesigning computer with a faster pro a principles that need to be applied to Biology: cessor. One would have the parts, the right softw Standardization, Decoupling and Abstraction. are, the brains and the knowledge about the tar get system, and ‘voilà!’ a Standards are necessary if we want to design new bacteria that produ ces and construct things more easily. We do not need CO2 and light has been cre ethanol from water, ated.” to design every nut and bolt of our genetically modified organism, instead we only have to take the Serrano, L.[9] 7
  3. 3. THE REVIEW Synthetic Biology... of new biological pa is the design and cons truction standardized parts we are going to use and combine rts, devices and syste and the re-design of ms, them, knowing they are going to fit without difficulty. The existing, natural biolog useful purposes. (http ical systems for Registry of Standard Biological Parts was created by the ://www.syntheticbiol ogy.org) MIT as a place where anyone can find a characterized DNA part that can be mixed and matched to build synthetic biological devices and And what do biologists think about all systems [10]. this? They have been studying the Decoupling means the division of the different molecular complexity of living simple tasks of a problem. The separation of organisms for more than fifty years and design and manufacture is a characteristic of some of them are not so convinced by engineering disciplines. t h e i d e a . G e n e s a re o f t e n n o t interchangeable among organisms and Finally, abstraction is important in order to The pillars of synthetic biology.[14] when they are, there is no guarantee deal with the complexity of living organisms. that their function remains as it was in a The use of abstraction hierarchies in the flow of genetic different context. What is more, if we know so little about information enables engineers to work on just one part even the simplest organism known, how are we going to of the hierarchy without regard for the details of the design a new one?[8]. Organisms replicate and evolve others. These biological hierarchies have been and this will certainly affect the stability of any designed compared to the ones found in computer engineering, system in the long-term. Although an effective solution an interesting analogy made in a recent report[11]. to this particular problem has yet to be discovered, this Of course, the in silico approach is present in every is not a problem specific to Synthetic Biology[12]. aspect of the field and permits computer modeling and Computer modeling of cell behavior is discussed in design. Other works also remark the importance of the Goethe's dream [13] and discrete and stochastic predictability and reliability of the system. As cells mutate approaches have been proposed as much more suitable and die, these two parameters should be achieved by tools than ordinary differential, traditionally and more either the use of a large number of cells or by commonly used equations. synchronization through cell-communication [11]. 8
  4. 4. Applications of Synthetic Biology Synthetic Biology Which have been the highlights of Synthetic Biology? 4 areas of research in What new applications has this field made possible? Are Design and redesign of cellular networks. these new applications really new? Genetic circuit engineering. One of the best known applications of SB is the production of artemisinin, a drug against malaria that Synthesis of biomaterials. only the plant Artemisia annua can make, by a genetically modified organism. In 2006, Dae-Kyun Ro Quest for the minimal organism. managed to genetically engineer yeasts to produce the Fu, P.[21] precursor of artemisinin [15] reducing the cost of cultivating the plants to obtain the drug. But is this amazing achievement really an application of Synthetic Most of the research on Synthetic Biology has focused Biology? This particular work is far from the engineering on designing this kind of device, but it is not hard to principles discussed above, like standardization. Parts realize that although these are incredibly interesting they taken from different organisms were far from being have little practical application (unlike the work of Dae- "plugged and played"[16] and this case is not an Kyun Ro with artemisinin). They are, instead, basic exception. One may think that in the future, as the science, which might be the basis for tomorrow's real discipline grows, standardization and other engineering synthetic biological applications. principles will become more and more common, A new chemistry for a new biology revealing, without any doubt, a challenging scenario for Several attempts have been made to synthesize new the development of new biotechnology. molecules able to substitute those found in organisms. Designing artificial networks has also yielded some very In this chapter, we will describe such research and interesting results like switches[17], [18], which are devices discuss its ethical implications as well. that allow the cell to adopt one of two possible states; Instead of using DNA or RNA as information-carrying oscillators[19] which produce regular fluctuations in the molecules, Piet Herdewijn and Philippe Marlière[22] have part of networks that allow different cells to designed new nucleic acids differing only in the sugar communicate and synchronize between each other[20]. present in the backbone of the structure, that is, instead 9
  5. 5. THE REVIEW Synthetic Biology... aims at making the pr design and constructi ocess of of having ribose or deoxyribose, these new models have on of many-componen engineered biologica t, threose (TNA), glycerol (GNA), hexitol (HNA) or l systems easier. cyclohexenyl (CeNA). These new structures do not Shetty RP, Endy D, Kn ight TF Jr.[25] essentially differ from the double helix described by Watson & Crick[23]. This new approach could prevent contamination first sight, does not differ from the ethical questions between genetically modified and natural organisms as discussed more than thirty years ago when the first their genetic information would not be compatible. This recombinant DNA techniques were born. So, what's would make biological devices safer. different now? The minimal genome project[24] poses new ethical questions, which need to be discussed. The creation of a brand-new organism with the only purpose of using them as a chassis for further genetic implementation has very different ethical implications than the idea of modifying naturally occurring organisms. In the latter case, Synthetic Biologists would be creating new life forms instead of modifying them and this is indeed an entirely new way of looking at nature. The ability DNA to create life will certainly lead us to a discussion on the definition of life. From Asilomar to Synthetic Biology Ethical questions in Synthetic Biology mostly focus on risks, paying special attention to the need of controlling self-replicating machines that could genetically pollute the environment. This, at RNA Piet Herdewijn and Philippe Marlière[22] 10
  6. 6. In 1975, Paul Berg organized a conference to propose weaknesses into our designed organisms) is not as an ethical code for genetically engineering living important as intentional harm. Nevertheless, using organisms in Asilomar, California. The chance to obtain Synthetic Biology for the purposes of Bio-Terrorism is, at genetic hybrid between an Escherichia coli (a bacterium) least currently, impractical since it is easier and cheaper and SV40 (a virus that can produce cancer in monkeys) to manage other tools like chemicals or natural non- raised the alarm of new potential bio-risks (for more engineered organisms[28]. information you can check: Summary Statement of the Scientists’ actions may also be driven by their dedication Asilomar Conference on Recombinant DNA to their work and publications, as Antoine Danchin Molecules[26]). Certain principles and ground rules for the comments in the fascinating paper 'Not every truth is emerging field were announced, but as years passed, good'[29]. He recounts how the smallpox virus, which experts started to realize that the technique was not as only affects humans, was sequenced instead of being powerful as first thought. Today all the considerations totally destroyed when it was possible. Now, due to that discussed at the conference have become obsolete. negligence, its sequence is freely available on the Web However, Synthetic Biology, which is a more effective and thanks to the new, and increasingly cheaper, DNA- way to engineer organisms, may need new regulations synthesis techniques, it is an even greater threat than as strict as those proposed in Asilomar in 1975. ever. In fact, proposals to regulate the DNA-synthesis Although designing and creating new biological industry have been made by experts[31], their plan machines have become much easier and cheaper with serving three purposes: Promoting biological safety and the rise of Synthetic Biology, this scenario can also have negative consequences. For instance, the possibility of non-biotechnologists entering the field “SB's vocabuary identifie s organisms wiht artifa and starting to make their own experiments is an identification that, given cts, an the connection between evident bio-safety risk. New concepts like bio-hackery 'value', may in the (very) 'life' and long run lead to a weak (designing and manufacturing biological systems society's respect for hig ening of her forms of life that are without any kind of regulatory oversight) or Do-It- regarded as worthy of pro usually tection.” Yourself biology should be closely watched [27]. Experts usually agree that the risk of accidental harm Boldt, J. & Müller, O.[30] (which can easily be prevented by introducing 11
  7. 7. THE REVIEW Synthetic Biology... involves the creation ar tificial gene and me of program new cell an tabolic networks to d organism behaviors. Gerchman Y, Weiss [33] R. security, encouraging the further development of synthetic biological technologies and the wide-world Different worlds application of these regulations. Europe and America are, in fact, two very different Many groups are now working on establishing some places to practice Synthetic Biology. Just a quick ground rules for the practice of Synthetic Biology as a comparison shows us that 64% of the publications in central initiative, like Synbiosafe in Europe, SynBERC in the field came from US laboratories[8]. The European the USA, or the BBSRC (Biotechnology and Biological Union has already started some initiatives to change this Sciences Research Council) in the UK. We are at the situation by creating a regulatory and scientific beginning of a new field and now the right moment infrastructure to support research in this direction, but as seems to have come to start considering all these Mark Greener[32] points out: "they need to avoid an ethical and risk-related issues seriously. overly restrictive framework that stifles research". ‘Synbiosafe. Synthetic Biology and its safety and ethical aspects’ is a documentary film where a lot of experts (including Drew Endy, George Church, Gautam Mukunda or Victor de Lorenzo) are interviewed by Markus Schmidt and express their opinions in all the topics related to Synthetic Biology. http://www.synbiosafe.eu/DVD/Synbiosafe.html 12
  8. 8. Excuse me, where can I learn helping to enlarge the Registry of some SB? Standard Biological Parts, Synthetic Biology, like every new field in adding new and characterized science, is hard to teach and to learn in the gene sequences to the biobrick usual way for two basic reasons. First, it is database. hard to define the subject of study because it is being constantly reanalyzed and redefined. And second, the interdisciplinary nature of the field makes it hard to gather and teach to REFERENCES: two different kinds of students (basically biologists and engineers) that have such different backgrounds. Instead of typical instruction, Natalie Kuldell[34] describes the possible core structure of studies in Synthetic Biology. [1]: Leduc, S., (1912) La Biologie Synthétique. Paris, This would include (but not be limited to) the following: France: Poinat. 1. Students will design biological systems in skillful and responsible ways; 2. Students will design, specify and [2]: Szybalski, W., Skalka, A., (1978) Nobel prizes and whenever possible implement their design; 3. Students restriction enzymes. Gene. 4, 181-182. will conscientiously use materials and 4. Students will [3]: de Lorenzo V., Serrano L., Valencia A., (2006) define the values, culture, safety practices, and Synthetic biology: challenges ahead. Bioinformatics. 22 organizational community of the field. (2), 127–128. The iGEM is also aimed at young undergraduate [4]: Pereto J., Catala J., (2007) The Renaissance of students who want to know more about Synthetic synthetic biology. Biological Theory. 2 (2), 128–130. Biology. In the summer months, they propose and [5]: Deamer D., (2009) On the origin of systems. design a project that will be presented in early Systems biology, synthetic biology and the origin of life.. November. This is a great first step for people who lack EMBO Rep.. 10. the opportunity to study this subject at their own universities. As they present their project, they are also 13
  9. 9. THE REVIEW Synthetic Biology... is a ‘field in the makin combines the experti g’ that se and knowledge of biologists and enginee rs. Calvert J, Mar tin P.[35] [6]: Purnick PE., Weiss R., (2009) The [12]: Heinemann M., Panke S., (2006) [16]: Karig DK., Simpson ML., (2008) second wave of synthetic biology: Synthetic biology: putting engineering Tying new knots in synthetic biology. from modules to systems. Nat Rev into biology.. Bioinformatics.. 22 (22), HFSP J. 2 (3), 124-8 Mol Cell Biol. 10, 410–422. 2790-2799 [17]: Gardner TS., Cantor CR., Collins [7]: Endy, D., (2005) Foundations for [13]: Moya A., Krasnogor N., Peretó JJ., (2000) Construction of a genetic engineering biology.. Nature. 438, J., Latorre A., (2009) Goethe's toggle switch in Escherichia coli. 449-453. dream. Challenges and opportunities Nature. 403 (6767), 339-342 for synthetic biology. EMBO Rep. 10, [8]: Deplazes, A., (2009) Piecing [18]: Atkinson MR., Savageau MA., S28-S32 together a puzzle. An exposition of Myers JT., Ninfa AJ., (2003) synthetic biology . EMBO Rep. 10 (2), [14]: de Lorenzo V., Danchin A., Development of genetic circuitry 428-432. (2008) Synthetic biology: discovering exhibiting toogle switch or oscillatory new worlds and new words.. EMBO behavior in E. coli. Cell. 13 (5), [9]: Serrano, L., (2007) Synthetic Rep. 9, 822-827 597-607 biology: promises and challenges. Mol Syst Biol.. 3:158. [15]: Ro DK., Paradise EM., Ouellet [19]: Elowitz MB., Leibler S., (2000) A M., Fisher KJ., Newman KL., Ndungu synthetic oscillatory network of [10]: http://parts.mit.edu. JM., Ho KA., Eachus RA., Ham TS, transcriptional regulators. Nature. 403 [11]: Andrianantoandro E, Basu S, Kirby J., Chang MC., Withers ST., (6767), 335-338 Karig DK, Weiss R., (2006) Synthetic Shiba Y., Sarpong R., Keasling JD., [20]: Bulter T., Lee SG., Wong WW., biology: new engineering rules for an (2006) Production of the antimalarial Fung E., Connor MR., Liao JC., emerging discipline. Mol Syst Biol. 2. drug precursor artemisinic acid in (2004) Design of artificial cell-cell engineered yeast. Nature. 440 communication using gene and (7086), 940-943 14
  10. 10. metabolic networks. Proc Natl Acad [25]: Shetty RP., Endy D., Knight TF [30]: Boldt J., Müllert O., (2008) Sci U S A. 101 (8), 2299-2304 Jr., (2008) Engineering BioBrick Newtons of the leaves of grass. Nat vectors from BioBrick parts. J Biol Biotechnol.. 26 (4), 387-389 [21]: Fu P., (2006) A perspective of Eng. 2:5 synthetic biology: assembling building [31]: Bügl H, Danner JP, Molinari RJ, blocks for novel functions. Biotechnol [26]: Berg P., Baltimore D., Brenner Mulligan JT, Park HO, Reichert B, J.. 1 (6), 690-699 S., Roblin RO., Singer MF., (1975) Roth DA, Wagner R, Budowle B, Summary statement of the Asilomar Scripp RM, Smith JA, Steele SJ, [22]: Herdewijn P, Marlière P., (2009) conference on recombinant DNA Church G, Endy D., (2007) DNA Toward safe genetically modified molecules. Proc Natl Acad Sci U S synthesis and biological security. Nat organisms through the chemical A.. 72 (6), 1981-1984 Biotechnol. 25 (6), 627-629 diversification of nucleic acids. Chem Biodivers. 6 (6), 791-808 [27]: Schmidt, M., (2008) Difussion of [32]: Greener M., (2008) Is the grass Synthetic Biology: a challenge to greener on the other side? [23]: Watson JD., Crick FH., (1953) biosafety. Syst Synth Biol.. 2 Encouraging the development of Molecular structure of nucleic acids; a synthetic biology in Europe. Gene. 4, structure for deoxyribose nucleic [28]: Russ ZN., (2008) Synthetic 181-182 acid. Nature. 171 (4356), 737-738 biology: enormous possibility, exaggerated perils. J Biol Eng.. 4, [33]: Gerchman Y., Weiss R., (2004) [24]: Gibson DG, Benders GA, 181-182 Teaching bacteria a new language. Andrews-Pfannkoch C, Denisova EA, Proc Natl Acad Sci U S A. 101 (8), Baden-Tillson H, Zaveri J, Stockwell [28]: Szybalski, W., Skalka, A., (1978) 2221-2222 TB, Brownley A, Thomas DW, Algire Nobel prizes and restriction enzymes. MA, Merryman C, Young L, Noskov Gene. 2:7 [34]: Kuldell N., (2007) Authentic VN, Glass JI, Venter JC, Hutchison teaching and learning through [29]: Danchin A., (2002) Not every CA 3rd, Smith HO., (2008) Complete synthetic biology.. J Biol Eng.. 1:8 truth is good. The dangers of chemical synthesis, assembly, and publishing knowledge about potential [35]: Calvert J., Martin P., (2009) The cloning of a Mycoplasma genitalium bioweapons. EMBO Rep. 3(2), role of social scientists in synthetic genome. Science. 319 (5867), 102-104 biology. Science & Society Series on 1215-20 Convergence Research. EMBO Rep. 10 (3), 201-204 15

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