Teacher Guide Reinventing the dodo synthetic biology in the future Colophon This teaching module was developed by the Freudenthal Institute for Science and Mathematics Education, within the framework of the European SYNENERGENE project. Authors Dirk Jan Boerwinkel, Miranda Overbeek, Marie-Christine Knippels Illustrations Jenty Heijstek Design Miranda Overbeek The Creative Commons Naamsvermelding Niet-commercieel Gelijk delen 3.0 Nederland License applies to this teaching module (http://creativecommons.org/licenses/by-nc-sa/3.0/nl). Please contact the Freudenthal Institute at [email protected] if you have any questions or comments. This lesson module was developed with a grant from the ‘European Union’s Seventh Framework Programme for research, technological development and demonstration’ (grant agreement number: 321488). 2 Content Level and learning goals Introduction Background information for the teacher Structure of the module Instructions per lesson Appendix 1: Alternative techno-moral vignettes Appendix 2: Basic information for students on synthetic biology Appendix 3: Teacher tool for holding a whole-class dialogue 4 4 5 6 7 13 17 21 3 Level and learning goals Level Subject Upper secondary Havo/Vwo [pre-academic] Biology Required prior knowledge Before this lesson module pupils should have completed the following themes: Learning goals After completing the module, pupils should be able to: End terms Reflect on and discuss arguments relating to bringing back extinct animals Describe current and possible future techniques with their obstacles in bringing back extinct animals. Give their considered opinion about synbio (applications). Explain and apply gene expression and regulation within the context of synbio This module supports among others the following (sub)domains of the biology exam program: Duration Genetics DNA Bio technology (pupils should be familiar with techniques such as recombinant DNA technology) A1 Informatievaardigheden gebruiken [Using information skills] A2 Communiceren [Communication] A9 Waarderen en oordelen [Value and evaluate] A14 Systeemdenken [Systemic thinking] B1 Eiwitsynthese [Protein synthesis] C1 Zelforganisatie van cellen [Self organization of cells] C3 Zelforganisatie van ecosystemen [Self organization of eco systems] D1 Moleculaire interactie [Molecular interaction] D2 Cellulaire interactie [Cellular interaction] E2 Levenscyclus van de cel [Cell lifecycle] 3 x 50 minutes Introduction Synthetic biology (synbio) is a new interdisciplinary field that is experiencing rapid growth. Synbio has a lot of potential to solve problems that relate for example to health, food and energy, but there are also potential risks. In this module pupils are confronted with a possible future scenario in which a specific application of synbio technology, bringing back an extinct animal, is imagined with the consequences this may have. This scenario (called a ‘vignette’) stimulates students in formulating emotions, arguments and questions. By researching these question students learn about the specifics of this application, and in the third lesson, comparisons are made with other applications. 4 Background information for the teacher The interdisciplinary scientific field of synbio has emerged over the last ten years or so, through cooperation between biologists, engineers and information scientists. Synbio further develops existing techniques from bio technology, such as recombinant DNA technology and DNA sequencing, so that existing and new biological systems can be adapted, designed and constructed. This is also referred to as engineering biological systems. While in classic recombinant DNA technology the necessary DNA sequence had to be cut from existing DNA, now DNA sequences can be synthetized, and DNA can be ordered online. The DNA can be selected from a database, or be designed. Another option is BioBricks, standardized DNA parts with a specific function. These allow adapting existing systems as well as creating new ones. To learn more about synbio, you can follow the following links: The virtual learning platform about synthetic biology of the Freudenthal Institute, containing among other things background information and materials: http://www.fisme.science.uu.nl/experimenteel/synenergene/ There is a theme page about synbio on Kennislink with background information, applications and interviews: http://www.kennislink.nl/thema/synthetische-biologie The magazine of the Stichting Biowetenschappen en Maatschappij [Foundation for Bio Sciences and Society] offers extensive (background) information about synbio: http://assets.kennislink.nl/system/files/000/230/891/original/Synthetische_bi ologie.pdf A social reflection on the rise of synthetic biology by the Rathenau Institute: http://depot.knaw.nl/4934/1/Rathenau_Instituut_-_W98_Leven_Maken.pdf What are technomoral vignettes ? This lesson starts with a ‘technomoral vignette’ in the form of an animated future scenario. Technomoral vignettes are short stories, informed by recent scientific publications, in which possible futures and moral dilemmas are being introduced. Techno‐moral vignettes can help in imagining SynBio‐related futures and starting up the SSI (SocioScientific Issues)‐based learning process in secondary biology education. The vignettes were originally developed to invite politicians to debate and have proven to have educational potential1. http://www.rathenau.nl/themas/thema/project/synthetische-biologie/what-aretech-moral-vignettes.html 1 Ruijter, C. de (2013). Techno-moral vignettes: A useful tool to introduce synthetic biology related socio-scientific issues? Faculty of Science Utrecht University Master Thesis http://dspace.library.uu.nl/handle/1874/278453 5 Structure of the module Lesson 1 1 Introduction 2 video: 5 min 10-15 min topic and purpose of the lesson animation on reinventing the dodo. Students note feelings and questions 3 4 taking stock of feelings taking stock of questions 20-25 min 10 min 5 dividing tasks and reflection 5 min exchange of feelings in duo and class distinguishing two types of questions; what is already possible/ what should (not) be done? homework; read appendix 2 and find information on the question of your group. https://www.youtube.com/watch?v =0laHb6cl6PQ Les 2 1 preparing the presentation/ exchange 2 presentation/exchange 3 reflection 15 min students prepare oral or written texts 25 min students give oral presentations or exchange their results in groups teacher summarizes with the students what was 10 min Les 3 1 introduction 2 discourse 5 min 20 min 3 broadening the scope 15 min 4 closure 10 min students discuss arguments related to the case the case is compared with other SynBio applications 6 Instructions per lesson Lesson 1 1 2 3 4 5 introduction video taking stock of feelings taking stock of questions dividing tasks and reflection 5 min 10 min 15 min 15 min 5 min Needed Digital video, two flip over boards or a smartboard on which summaries can be written 1. Introduction (5 min) The teacher informs the students that they will watch a video which tells a story that could happen in a near future, based on current technological developments. the technological developments are examples of synthetic biology. Synthetic biology studies the possibilities of creating or adapting new forms of life. An existing example is modifying bacteria into producing anti-malaria medicine. A special application of synthetic biology, studied in these lessons, is to bring extinct animals back to life. These lessons are meant to prepare students for a future in which these developments become more common, in order to discuss which developments are desirable. In these lessons this is done by studying different kinds of arguments and information on synthetic biology that supports or discredits these arguments. 2. Video (10 min) Students watch the video ‘reinventing the dodo’. https://www.youtube.com/watch?v=0laHb6cl6PQ They are asked to write down their feelings on reinventing extinct animals with synthetic biology, and questions they have about this case Feelings can include emotions such as curiosity, fear, anger, enthousiasm, but can also contain arguments. * Appendix 1 contains other examples of vignettes which can be chosen with descriptions of the issues involved 3. Taking stock of feelings (15 min) Students are asked to exchange their feelings and ideas in duos, and to clarify to each other their initial thought about bringing back extinct animals. After that, the teacher asks several students to share their ideas with the class, and notes the different viewpoints on the flip-over chart or the smartboard. Discussions are kept short and at this point only used to refine the viewpoints. Students are told that later a discussion will be held based on more information on the case. When questions arise, they are noted on the second flip-over chart paper which is used in the next part. 4. Taking stock of questions (10 min) The teacher makes two lists of questions (as questions will already arise in part 3, it is advisable to have the paper or screen in which the questions will be noted 7 already available at the start of the lesson). Students can be asked to participate in classifying and noting the questions. The first kind of questions can be indicated as “What is already possible?”. These are questions about the technology, for which objective answers can be found in the literature. Examples are; a. how does it work? b. Is this possible already? c. Are there real examples like this case? d. Can it be done with humans? The second kind of questions can be described as “What is desirable?”. These are questions on Ethical, Legal or Societal Aspects (ELSA). They are mostly openended questions which cannot be answered definitely. However, information can help to find arguments related to these questions. Examples are; a. What use could this technology have (for instance for agriculture or health care)? b. Who profits from this technology? c. What risks can this technology bring about? (distinguish between the risk of unexpected and undesired side effects and the risk of abuse of the technologies for dangerous purposes) d. Can anybody just change organisms? How is this regulated? e. Should we change organisms at all (‘playing God’)? f. Which rights do the created and altered organisms have? g. How will this technological innovation change behavior of people? Not all questions mentioned above will arise with this case. Different vignettes will evoke different questions, both because the technologies differ and because the moral questions differ. Therefore it might be useful to study more than one vignette. Appendix 1 indicates for each case the technologies and the main questions involved. 5. Dividing tasks and reflection (10 min) The questions that arose in part 4 are divided between groups of students, preferably based on their choice. The students have the task to find answers and to report to the others. Next to this, they have to study the basic text on synthetic biology (Appendix 2), in order to acquire also a general view on synthetic biology technologies. The task to find answers to the questions and preparing the presentation can be done in school or as homework. In this module, students search for information between lessons and prepare the presentation in lesson 2. The teacher keeps contact with the groups in order to assist in formulating more specific questions and finding sources. At the end of the lesson, the teacher reflects with the students on what is learned in this lesson, for instance by asking two students what they found the most interesting fact or question. Sources Some sources of information about bringing back extinct animals can be found below, with an indication of techniques or arguments are given. Students can be given these sources next to the handout in Appendix 2. 1. https://en.wikipedia.org/wiki/De-extinction 2. http://www.nationalgeographic.com/deextinction/ (pro and con) 3. http://www.smithsonianmag.com/ist/?next=/science-nature/these-areextinct-animals-we-can-should-resurrect-180954955/ (pro) 8 4. http://www.dailymail.co.uk/sciencetech/article-2997433/Could-soonCLONE-woolly-mammoth-Scientists-extract-DNA-extinct-creature-bringspecies-dead.html (mammoth) 5. http://www.sciencetimes.com/articles/4932/20150327/bringing-extinctanimals-back-life-longer-part-movies.htm (short article on techniques) 6. http://news.stanford.edu/news/2013/april/greely-species-deextinction040413.html (pro and con) 7. https://www.youtube.com/watch?v=6vqCCI1ZF7o (video Tasmanian Tiger) 8. http://ww2.kqed.org/quest/2013/03/25/resurrection-biology-the-realityof-bringing-back-extinct-species/ (con and techniques) 9. http://blogs.discovermagazine.com/d-brief/2013/04/04/5-reasons-tobring-back-extinct-animals-and-5-reasons-not-to/#.Vg5TN_mqpBc (pro and con) 10. http://bioscience.oxfordjournals.org/content/64/6/469.short (techniques, pro and con) Background information on bringing back extinct animals In order to bring back extinct animals it is not sufficient to reconstruct the genome of an extinct animal (which would already pose great problems with animals extinct in much earlier ages). DNA in a nucleus is extremely organized, and during embryonic development, DNA has to change according to the stage of development. Current attempts include 1. Using cells taken from animals before their extinction (such as the Pyrenean Ibex) and fusing these cells with a denucleated egg cell of a related animal. If this succeeds, the embryo can be implanted in the uterus of a related animal. This can be seen as a form of cloning. 2. Using genes from DNA recovered from an extinct animal to insert in the genome of a related animal, thereby creating a hybrid. For example, mammoth genes could be introduced in an elephant’s genome. Techniques such as CRISPR are used here. CRISPR is a technique by which very specific cuts can be made in the DNA, making insertion of newly inserted DNA more effective. (http://www.nature.com/news/crispr-the-disruptor1.17673) 3. Breeding back existing animals to forms that resemble extinct animals such as in the Tauros project (www.taurosproject.com) In order to conclude which of these methods can be called synthetic biology, the synthetic biology definition has to be used which entails the synthesis of new genetic structures. The first method mixes genes from one organism with cell material from another. Although this means creating a new life form, it is not synthetic biology in the strict sense, as no new genetic components are developed. The second method mixes genes from one organism with genes from another. Here a new gene product is made, and in order to regulate the expression of the inserted genes, other genetic elements will have to be introduced. This method can thus be considered as a special form of synthetic biology. The third method is of course not synthetic biology at all, as this is based on classical breeding techniques. Bringing back extinct animals is therefore a scenario on which scientists are already working, but which still has many problems to solve. In plants, it has proved possible in some cases to revive old seeds, and it is generally more easy to grow plants from stem cells. 9 Lesson 2 1 2 3 preparing the presentation presentations reflection 15 min 25 min 10 min 1. preparing the presentation (15 min) The teacher asks how the research has proceeded and instructs the students to prepare their presentations. Students can be given a format to present. A format can be a list such as: The question they started with The answers they found New questions that arose Sources of information and their reliability Depending on what students can do and should learn in presentation skills, different forms can be chosen such as: a. an oral presentation by each group of the results (this has the risk of becoming boring, and information is difficult to remember. On the other hand, oral presentations can attract attention when well presented) b. a handout of the results, to be read and discussed (this has the advantage that the teacher can check the handouts in an earlier stage, and students have the information on paper) c. a combination of a and b, in which handouts are made and shortly presented by each group. d. an ‘expert method’, in which new groups are formed, consisting of one student from each earlier group. In these new mixed groups, each student has the task to present the results his/her group found. Handouts as in b. are also useful here to support the exchange. 2. presentations/exchange (25 min) Students present and listen/read each other’s answers. Students ask each other clarifying questions, and new questions may arise which are noted. Questions may also arise on the general information on Synthetic biology, as in Appendix 2. It is important in this phase that the teacher explains that examples of bringing back extinct animals can use different methods, not all of which are synthetic biology. Here can be reminded of the text students have studied (Appendix 2) in which is made clear that synthetic biology entails using or creating new genetic structures. 3. reflection (10 min) The teacher discusses with the class to what extent the questions have been answered, and whether the students feel sufficiently prepared to start an informed discussion on whether to bring back extinct animals or not. Again, a short reflection on what is learned is advisable. 10 Lesson 3 1 2 3 4 introduction discourse broadening the scope closure 5 min 20 min 15 min 10 min 1. Introduction (5 min) The teacher reminds explains the rules of the discussion. 2. Discourse; Should we bring extinct animals back to life? (20 min) Different strategies can be used in this phase. Not recommended is a debate, as students tend to view this as a competition in which the arguments of the adversary should be undermined or neglected. More useful are forms in which students learn to understand that several viewpoints are possible, based on different sets of values or different weighing of advantages and disadvantages (see also Appendix 3 for suggestions). Strategy 1. ‘what moves you?’ Students are asked to position themselves on a line in the classroom, where one end of the line represents for example ‘bringing back extinct animals should never be done’ and the other end ‘bringing back extinct animals should be encouraged’. Students can be asked to explain their position (literally). They can also indicate whether their choice is made based on rational arguments, emotions or ‘gut feelings’. After exchanging arguments, students can decide to take a new position or stay in the same spot. Again, it can be asked why they have or have not changed position. A variant is that a central statement is used (such as ‘bringing back extinct animals should be encouraged’) which after each positioning of the students is gradually changed, for example ‘bringing back extinct PLANTS should be encouraged’ or ‘DNA of animals in danger of extinction should be stored’. After each change, students can position themselves again and explain their position. Strategy 2. React to the reactions Students are placed in groups of 4-6. Each student is given a A4 paper, on which she/he writes a statement on using SynBio to bring back extinct organisms. The students hand their paper to the student on their left. They read the statement and react to it on a post-it which they attach to the backside of the paper. This is repeated until each student has her/his own paper back. Students then read the reactions of the others and reflect whether these reactions influence their reasoning. In a discussion, students exchange on what they have read. Strategy 3. Finding the hidden values Students are asked to formulate their opinion on the statement ‘Using synthetic biology to bring back extinct animals should be encouraged’ They answer this in one of the following ways 1. Yes, because…. 2. Yes, but under certain conditions, because… 3. No, because… 4. No, unless under certain conditions, because… 5. I am not sure, because…. Students are placed in groups of 4-6, and exchange their answers. Next, students are given a list of values related to this question (in this case, the values are formulated as norms): - we should prevent harm being done to humans or animals 11 - we we we we we should should should should should use our resources to help nature and mankind do things according to natural processes be careful with new technologies of which results cannot be predicted take care that resources and power are distributed equally encourage technological innovation Students within a group try to link the different answers with one or more of these values. They may add other values when they miss one. In this way they may conclude that differences are due to a different weighing of the values involved. A variant is a ‘place-mat discussion’ in which a large chart is put on the table on which every student writes her/his statement. The values are written in the middle, and in the discussion they are linked with the statements by drawing a line between the value and the statement. Some arguments used in the discussion in the literature: Benefits: Scientific knowledge: De-extinction could offer insights into evolution and natural resources that are currently unavailable to us. Technological advancement: De-extinction could be a big step forward for genetic engineering. Environmental benefits: Threatened or damaged ecosystems could be restored with the help of certain now-extinct species. Justice: If people pushed plant and animals species into extinction, perhaps we owe it to these species to try and bring them back. Wonder: How cool would it be to see extinct species alive and kicking again? Objections: Animal welfare: People could be exploiting animals for solely human purposes, and may cause individuals of the de-extinct species harm. Health: Species could carry retroviruses or pathogens when brought back to life. Environment: De-extinct species would be alien and potentially invasive; their habitats and food sources have changed, so their roles in these changed ecosystems could be too. Political: De-extinction may change priorities in other fields of science, such as medical research and the conservation of currently endangered species. Moral: Is de-extinction playing god, or just plain wrong? It may also have unforeseen consequences. 3. Broadening the scope (15 min) Based on the general information on synthetic biology that the students have read in Appendix 2, the teacher compares the specific application of synthetic biology in bringing back animals to more common and already existing applications. Although there are similarities in that all methods produce an organism with new properties, there are also differences such as indicated below. bringing back extinct animals animals in some cases whole genomes no synthetic genetic elements the result is a whole animal most other synthetic biology mostly bacteria and yeasts genes newly created genetic elements the result is mostly a bacterium or yeast that responds to certain signals and subsequently produces substances 12 Students can be asked to what extent the arguments and opinions exchanged in the former part apply as well to other applications of synthetic biology, such as creating a bacterium with new genes that can produce specific antibiotics. 4. Closure; what have we learned? (10 min) At the end, students are asked to write down their most important learning results. Some students are asked whether they want to share this with the class. The teacher can also formulate her/his learning effects. 13 Appendix 1 Alternative technomoral vignettes A vignette can be situated in time in different ways: a. An already existing application (such as the production of Artemisinine) b. An application that is not yet realized but is already realizable (such as the iGEM proposals, see the other SynBio lesson for examples) c. An application further in the future with technologies not yet possible but plausible Vignettes further in the future are less realistic, with the risk that students consider these as irrelevant science fiction. On the other hand, these vignettes further in the future offer more possibilities to illustrate techno-moral change, because you can picture a situation in which a technological development has become normal and widespread. Existing applications often are still limited and are normally for purposes for which there is a general consensus such as the production of medicine. Other aspects in which vignettes differ are the technologies used and the type of questions they evoke. Some techniques used in Synthetic Biology: a. Combining biochemical modules (‘Biobricks’) from different organisms such as inducible promotors, genes coding for desired proteins, and genes coding for colors that indicate successful transfer b. Transferring gene-constructs via plasmids into bacteria or yeast, often combined with technologies to select bacteria with the plasmid such as genes for antibiotic resistance and mechanisms to prevent transformed bacteria to spread. c. Transferring gene-constructs into plants in tissue culture, thereby creating plants with new properties d. Transferring gene-constructs into animals by removing the nucleus from an egg cell and inserting a nucleus with the desired genes, or fusing an animal cell with the egg cell. e. Extracting stem cells, introducing genetic changes and placing these cells back in the organism In the lesson example the vignette ‘Reinventing the dodo’ has been chosen Available materials Animation: https://www.youtube.com/watch?v=0laHb6cl6PQ Text: http://www.rathenau.nl/fileadmin/user_upload/rathenau/Projecten/Synthetische_ biologie/Vignetten/Reinventing_the_dodo_2.pdf The resurrection of extinct species, especially the large creatures of the past, has appeared as a popular theme in works of fiction. With fast and cheap technologies to ‘read’ (sequence) and ‘write’ (synthesize) DNA currently available, it also becomes the objective of some researchers in synthetic biology. Thus we have seen the resurrection in the laboratory of the extinct virus which caused the deadly 1918 flu pandemic. Most researchers may not be primarily interested in the resurrection of a living animal, but hope to find new ways to understand disease or evolution. But a few, perhaps, would like to bring back one of our lost species in a zoo, or in the wild. 14 Situation in time: further in the future ( it is not yet possible to reconstruct a whole extinct animal from DNA) Technologies: Reconstructing the genome of an extinct animal and injecting this into a fertilized egg of which the nucleus has been removed Questions: - Are we allowed to produce new life forms even when these are animals that once lived? - Which responsibilities do we have towards life forms we created ourselves and which are dependent on us (this question is also relevant for life forms that we created through more classical methods of breeding). - what other applications could this technology have? Alternative vignettes are: A. Mother’s day Available material: Animation: https://youtu.be/bPlkeIRmqY0 Text: http://www.rathenau.nl/fileadmin/user_upload/rathenau/Projecten/Synthetische_ biologie/Vignetten/Mother_s_day.pdf Synthetic biology may contribute to healthier and longer lives by facilitating early diagnosis and prevention of cancer, improving our intestinal flora, but also by countering the ageing process more directly. Telomeres (structures at the end of our chromosomes involved in cell division) have been known for some time to be related to ageing. With each cell division, the telomeres become shorter, ultimately leading to inhibition of the capacity for replicating, and thus to cell death. The enzyme telomerase is known to counteract this shortening of telomeres. Several companies are now constructing synthetic molecules able to increase telomerase production in cells. How effective this will be in countering the ageing process is still being contested. http://www.sierrasci.com/proof/index.html Situation in time: A bit further in the future (repairing telomeres is not yet fully possible) Technologies; using a telomere-repairing enzyme as a means to prevent aging Questions: - should research be directed to elongation of life? - what other effects might repairing telomeres have on health - what other applications could this technology have? B. MYSSN pill (Make your stool smell nice) Available material: Text: http://www.rathenau.nl/fileadmin/user_upload/rathenau/Projecten/Synthetische_ biologie/Vignetten/MYSSN_pill.pdf Synthetic biology has been used by researchers to change the smells and/or colors of bacteria. For example, students from an MIT iGEM team managed to 15 change the awful smell of Escherichia coli into a minty one. Another iGEM team engineered bacteria in such a way that they indicate the presence of a specific substance by emitting a specific color (visible to the naked eye). This technology can be useful for all kinds of sensing and warning systems (it could for example warn that drinking water contains toxins by turning it red), but it might be used for more frivolous purposes as well. http://openwetware.org/wiki/IGEM:MIT/2006/Blurb http://www.echromi.com/ Situation in time: Realizable, the base of this vignette is an existing iGEM project Technologies Creating and introducing a gene construct which reacts on substances in the gut by inducing a promotor which activates genes that code for other substances Questions: - what effects could the introduction of such an innovation have on what is considered normal and healthy? - what other applications could this technology have? C. Bioluminescent street lamps Available material: Animation https://www.youtube.com/watch?v=xGQ6Cp1dC4c Text: http://www.rathenau.nl/fileadmin/user_upload/rathenau/Projecten/Synthetische_ biologie/Vignetten/Bioluminescent_street_lamps.pdf Given the energy crisis facing our planet, synthetic biology could contribute by developing alternative ways of lighting, which currently accounts for 8% of our use of electricity. In order to provide any solution to the problem, a biological solution must tap into a currently unused energy resource. For this reason we decided to consider the use of bioluminescent trees to replace conventional street lamps. A tree in this position would be able to photosynthesize during the day, building up reserves of energy. We then imagined it emitting light by night, using the bacterial luciferase system. We placed genes from fireflies and bioluminescent bacteria into E.coli. Codon optimization and single amino acid mutagenesis allowed us to generate bright light output in a range of different colors. We built a set of Bricks to allow bioluminescence in a wide range of colors which have applications as natural light sources. http://2010.igem.org/Team:Cambridge Situation in time: Realizable, the base of this vignette is and iGEM project (introduction of gene for fluorescent substances has already been realized) Technologies: creating a gene-construct containing a gene for an enzyme (luciferase) producing a fluorescent substance and introducing this gene in plants using tissue culture. Questions: - what are the risks of (accidentally) introducing modified organism in nature? - what other applications could this technology have? - how do we decide which innovations are desirable, especially when the consequences affect everyone? 16 D. Technomoral vignettes have also been developed by iGEM teams, teams that participate in a competition to design new SynBio applications. They can be found at http://www.rathenau.nl/themas/thema/project/synthetische-biologie/synbiofutures.html for example ‘Tomato guard or chemicals?’ http://2014.igem.org/wiki/images/0/0c/Wageningen_UR_synenergene_techno_sc enario_1.pdf 17 Appendix 2 Basic information on synthetic biology What is it and what can you do with it? The following video gives a short introduction to the topic https://youtu.be/ocWxetewIyg History When biologists started working with physicists, chemists and technologists around the start of the twentieth century this led to great developments. For example the development of biotechnology and of new techniques such as recombinant DNA technology and DNA sequencing. When biologists also began to cooperate with information scientists and engineers, this led to the rise of synthetic biology (see figure 1). So synthetic biology (synbio) is a scientific field in which various specialisms cooperate. Synbio works on further developing existing techniques such as recombinant DNA technology and DNA sequencing. Researchers can use these improved techniques to design and build new biological systems. They can for instance insert new functions into an existing cell, tissue or organism, or create new cells themselves with synbio. To better understand what synbio is, we compare it to a computer: in synbio, the software (DNA) is designed and inserted into the hardware (the cell). Different software provides different programs (processes in a cell). By cutting, pasting and combining parts of the software many programs, with different functions, can be designed. You can also develop software that normally doesn’t occur in your hardware. Synbio also lets you build your own hardware. Figure 1:History of synthetic biology 18 Techniques Synthetic biology is based on recombinant DNA technology. In figure 2 you can take another look at how this works. Figure 2: Recombinant DNA technology In synthetic biology researchers no longer have to cut the desired bits of DNA from existing DNA: they can design the desired DNA themselves and order it online. The DNA is then produced synthetically by a machine, using sugar as a source material. Researchers can also order BioBricks from an online database. These are bits of DNA with a specific function (for instance, they code for a particular protein) that have been designed to be combined easily. BioBricks are therefore also called ‘plug-and-play DNA’. There are several types of BioBricks, for example: BioBricks with only a coding gene or a part of the DNA that can regulate a gene. 19 BioBricks that contain the coding gene as well as all parts that regulate this gene. BioBricks consisting of multiple genes that together perform a function. Researchers can use BioBricks to change an existing organism, for example a yeast cell. This works as follows (figure 3): Figure 3: Changing a host with synthetic biology techniques. In this case the host is a yeast cell. Researchers also try to create minimal cells. These are cells that only need the genes that are necessary to survive. In future, researchers might be able to add BioBricks to these minimal cells, to have the cells perform specific functions, such as manufacturing a drug. Minimal cells can be made in two ways: top-down and bottom-up. Top-down means that a researcher adapts an existing cell. To make a minimal cell, a researcher would remove as many genes as possible from the cell, until only the genes that are necessary for the cell to survive and divide are left behind (figure 4). Bottom-up means that the researcher builds a cell from scratch. The researcher writes the DNA, or makes use of BioBricks. By only selecting the genes the cell needs to survive and divide, you end up with a minimal cell (figure 5). Figure 5: Minimal cell made bottom-up Figure 4: Minimal cell made top-down 20 Applications Synthetic biology has only been used for about ten years, but already an impressive number of applications has been developed. Cheap anti-malaria drug The malaria drug artemisinin was originally obtained from a plant, sweet wormwood (artemisia annua). This is expensive and there wasn’t always enough of the drug available. By synthesizing the genes for the production of artemisinin with synthetic biology and insert them in yeast (figure 6), yeasts can now produce the drug quickly and cheaply in a reactor vessel. A pharmaceutical company is using this method to produce artemisinin, resulting in about a 100 million malarial treatments a year. Sweet wormwood Figure 6: The synthesized genes for the production of artemisinin are inserted in the yeast DNA. The yeast can now produce artemisinin. Sustainable fuel Bio-ethanol is an alcohol that can be used as sustainable fuel. Bio-ethanol is made using baking yeast that can convert sugars in corn into bio-ethanol. This can result in corn becoming too expensive as a food crop. Synthetic biology makes it possible to use agricultural waste products such as straw and corn foliage as raw materials for bio-ethanol. This has been realized by adding genes to baking yeast that can convert the sugars in waste products into bio-ethanol. The first factory producing bio-ethanol in this way opened in 2014. Lab with yeasts converting waste-sugars into bio-ethanol. Synthetic Biology and the dodo The applications shown so far concern mainly bacteria and yeast in which individual genes are inserted. In the case of ‘reinventing the dodo’ synthetic biology techniques are applied to animals instead of unicellular organisms, which makes both the techniques and the ethical discussion much more complicated. Also, reinventing extinct animals may concern the whole genome instead of a few genes. This brings many other problems because the genome is constantly in interaction with the cellular environment and cannot easily be transplanted with success. But although this technology is not yet fully developed, there are no principle reasons that it would remain impossible. 21 Appendix 3 Teacher tool for classroom discussions To be added 22
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