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Synthetic Life

Alex: Hi my name’s Alex Grigg, and this is my teammate Dev Vyas. And we would like to welcome you to the first episode of Synthetic Ethics. So Dev, I’m sure your familiar with synthetic biology, but what about our listeners who still don’t quite get what synthetic biology is?

Dev: Well synthetic biology is an emerging science with vast potential and opportunity. It can be described as the combination of science and engineering. What synthetic biologists do is create new organic systems operating within living organisms. It even has the potential to create life from scratch.

Alex: I’m going to stop you right there, because today we are discussing the ethics of synthetic life, a topic which draws some of the most excitement, and controversy to our field. So, if I were to tell you that a colossal achievement that has been compared to other scientific milestones such as the sequencing of the human genome, and the cloning of the sheep Dolly happened just a few months ago, what would you think I was talking about?

Dev: Does it have anything to do with Bald Bearded scientists?

Alex: Good guess Dev! Although I think every scientific milestone can be somehow attributed to the Bald and Bearded. The particular accomplishment to which I’m referring is the creation of synthia, the first synthetic, self-replicating life.

Dev: That’s right, in 2008 a team of scientists at the J. Craig Venter Institute headed up by Drs. Craig Venter, our bald and bearded scientist, Hamilton Smith, and Clyde Hutchison were able to create a small bacterial genome, and by May 2010 it was announced that they had successfully used a synthetic genome of the bacterium mycroplasma mycocides to create a bacteria that could sustain, and replicate itself.

Alex: Alright, lets take a step back and talk about how such an achievement was attained. It all started with the chemical synthesis of DNA fragments of 1078 base pairs. These cassettes each had overlaps of 80 base pairs, which allowed them to be recombined in yeast. 10 of these cassettes were recombined into 10kb cassettes of DNA, which were then recombined again into 100kb pieces that could be used to create the final synthetic genome of mycroplasma myocides which is 1.08 million basepairs long. Venter and his team also included what are called “watermarks” in the genome which are sequences that allow us to differentiate this synthetic genome, from the naturally occurring genome. But what’d they do next with the genome?

Dev: Well, M. mycoide genomes were transplanted into restriction-minus Mycoplasma capricolum recipient cells. These cells, containing only the synthetic genome that they had created, were able to self-replicate.

Alex: This Sounds like great news! Craig Venter and his team has proven that we are able to create life, Imagine the possibilities. We could potentially create organisms which we have never before observed.

Dev: Well I for one think “We're all doomed! Doooooooooooommmmmmmmmmmmeeeeeeeeeddd!!!”

Alex: Wow Really? Why?

Dev: To be honest I don’t really think we’re all doomed, but that is a comment taken from a story in the guardian in which many of the reader’s voice concerns about synthetic life, and show that there is a lot of fear taken from news of this achievement. Another commenter, posting under the name CruyffTurn had a concern when he read that the synthetic organism had included watermarks so that we can keep track of it. He said: “So, what you really mean if the organism somehow manages to escape in to the environment, subsequently mutating in to some evil virulent pathogen, killing billions, we can be safe in the knowledge that we will know where it came from. Amazing piece of scientific work though.”

Alex: Well do you think that there’s a possibility that this synthetic mycroplasma myocide will mutate into a some sort of superbug that will kill billions?

Dev: I’m actually not that concerned. What people need to understand is that the bug that Craig Venter synthesized is essentially the same as a bug that came to us naturally, through Darwinian evolution. The DNA is fully synthetic, but the sequence itself is natural, and so is the cell in which they inserted the genome so that it can replicate and carry out protein synthesis.

Alex: Well it seems to me that we aren’t doomed at all, all they made was an naturally occurring germ. But, another commenter said “I want to be excited by this news, but it scares the bejeezus out of me...”

Dev: So what else are they scared of?

Alex: Well I know a lot of fear stems from the possibility of synthesizing organisms which would be extremely harmful to humans if they were released.

Dev: Ok, I think that is a legitimate concern. So what kind of organisms would that be?

Alex: Well one example of a synthetic organism that could cause massive casualties is smallpox. Digital genomes of smallpox are present online, and could potentially be created chemically using a similar process that Craig Venter used. In June 2006 a reporter for the guardian obtained a small sequence of smallpox DNA delivered to his home from a gene synthesis company. Now that sounds scary.

Dev: Well what kind of company would send the smallpox genome to a residential address? Even if it is piece by piece.

Alex: This reporter was able to achieve this from a major gene synthesis company through the lack of screening technology and safeguards that are present at these gene synthesis companies. As the price of synthesizing genes gets more and more affordable, efficient safeguards which screen both the content being ordered, and who is ordering them needs to be put in place in order to ensure that gene sequencing isn’t used by would-be terrorists.

Dev: Why isn’t there anything already in place to help gene synthesis companies from sending out sequences that contain harmful genes?

Alex: Actually there is. The International Gene Synthesis Consortium is an organization consisting of 5 major gene synthesis companies, and makes up over 80% of commercial gene synthesis capacity world-wide. These companies have agreed to screen synthetic gene orders to identify pathogen sequences and other potentially dangerous sequences, screen customers by requiring identification, and keep records for at least 8 years of customers, sequences, and delivery information. They also do not send to post office boxes, which seems like a no brainer to me.

Dev: Ok, so we can all feel a little safer knowing that random people can’t just order sequences containing harmful genes, but the idea that some disgruntled scientist can synthesize killer bugs in his basement is a little far-fetched.

Alex: Yeah people need to understand that this kind of work requires more than a few test tubes. What kind of things would a disgruntled scientists need if he wanted to synthesize an evil organism?

Dev: Well besides the need for precise chemical synthesis of gene fragments from somewhere such as a gene synthesis company, synthesizing self-replicating life requires high-throughput sequencing facilities so that you can be sure you have the right sequence, sophisticated designing strategy, and multiple steps of quality control. Among other things.

Alex: So this sort of thing couldn’t be done alone in your garage.

Dev: Assuming your garage isn’t extremely well equipped.

Alex: But people aren’t just worried about their safety in the sense that harmful organisms could be created, there is also a lot of concern revolving around the ethical implications of our newfound capacity to chemically create life. There’s a lot of use of the phrase “playing god”.

Dev: But is this a real worry? I mean it’s not like we can now create new organisms or animals.

Alex: Well there is a concern that as we further this technology, we will be able to create organisms that did not come to us through natural Darwinian evolution, and even gain the ability to use this technology to genetically design humans.

Dev: That sounds almost like something out of science fiction.

Alex: At this stage in the game, it sort of is, but that doesn’t mean that we shouldn’t be aware of the ethical risks associated with the advancement of our capability to synthesize life. The Vatican’s response to the creation of replicating synthetic life by Craig Venter and his team was actually fairly positive. “If it is used toward the good, to treat pathologies, we can only be positive” the Vatican’s top bioethics official, Monsignor Rino Fisichella, told Italian state-run television news programme TG Uno. The head of the Italian Catholic bishop’s conference Cardinal Angelo Bagnasco said that “intelligence can never be without responsibility”

Dev: Well I think that that properly sums up the attitude that we should have towards instances like this. The advent of synthetic life represents a momentous step forward in mankind’s ability to combat many of the problems facing us, but we need to ensure that those tools are not abused so as to cause harmful results.

OUTRO

Alex: Well thanks for joining us while we explore the ethical issues associated with synthetic biology. If your looking for more news and exciting stories within synthetic biology, check out our blog at http://igemcalgary2010.blogspot.com, or if you want to learn more about our team and the work we are doing check out our wiki at https://2010.igem.org/Team:Calgary

Open Source Biology

Introduction: Welcome to Synthetic Ethics from the University of Calgary’s iGEM team.

Alex: Hello and welcome to synthetic ethics from the University of Calgary’s iGEM team. My name is Alex Grigg, and this is my iGEM teammate Dev Vyas. Let’s give out listeners a little information on what iGEM is all about.

Dev: Sure Alex, iGEM is an undergraduate synthetic biology competition in which undergraduate students like ourselves work over the summer to design and develop a project. This year 128 teams from all over the globe are participating.

Alex: Yes, and the project is pretty much completely open ended, past project have ranged from detecting arsenic in drinking water, to beer that fights cancer, to bacterial art using fluorescence proteins.

Dev: There’s a number of streams that you can choose to work in, including Food or Energy, Environment, Health or medicine, manufacturing, new application, foundational advance, and information processing.

Alex: So should we let the listeners hear a little about what we were working on in the wet-lab?

Dev: Yeah sure, this year we were constructing a biological toolkit that can detect problems with protein expression within E. Coli. Our vision for our circuit is a kit on two plasmids, which researchers could implant a gene of interest coding for the protein they want to be expressed in E. Coli, and determine where problems are occurring.

Alex: Yep, One circuit we built would confirm that the protein is being translated and transcribed, and the other circuit could tell if a protein is being mislfolded. It detects protein misfolding in the periplasm, and cytoplasm, and will give us a simple visual output of fluorescence proteins.

Dev: At the end of all this work the teams all meet at M.I.T to present their projects, and judges determine which teams deserve medals.

Alex: So what kind of criteria do we need to meet in order to achieve one of these medals?

Dev: Well the criteria are rather extensive, and you don’t need to meet all this criteria in order to achieve a bronze or silver medal. For one, your team needs to describe your project on your team wiki, you can view ours at https://2010.igem.org/Team:Calgary. Both Calgary and Team needs to be capitalized. We also need to present a poster, and talk at the jamboree, and we need to submit a new bio brick to the Registry of Parts.

Alex: Yeah that’s right, all the genetic sequences that code for the parts that we create our projects with have been standardized into something we call a biobrick. Every biobrick has the same prefix and suffix made of restriction sites. This allows every biobrick to be put together into a “circuit” that we can then transform into a host such as e coli, which will then use those sequences to carry out their function.

Dev: O.K. so every bio brick can be cut, and then put together using the same enzymes and sites?

Alex: Yep, Biobricks have been likened to lego bricks, every piece has the same sized holes on the bottom and top so that you can easily put them together and build whatever you and your team have dreamt up.

Dev: Well that makes it sound pretty easy to create these biological circuits; it wouldn’t be very hard to teach anyone how to put these systems together.

Alex: iGEM is making synthetic biology much easier to access, opening it to thousands of undergraduate students. And the creation of standardized biobricks isn’t the only aspect of iGEM that is making synthetic biology easier and more accessible; it also has created the Registry of Standard Biological Parts.

Dev: Yeah the Registry of Standard Biological Parts is a collection of these interchangeable biobrick parts that are made available to iGEM teams and certain academic labs. It runs on a “get some, give some” basis, meaning that everyone who benefits from being able to access this collection of parts to create integrated biological systems, will also then contribute to the registry by providing information on the parts they use, and submit new parts which contain the biobrick prefix and suffix.

Alex: So how many parts does this registry have?

Dev: Well the registry was created in 2003 at M.I.T, by 2004 it had accumulated about 100 parts such as protein coding sequences, and devices built from these parts. This is because assembly of parts into devices and systems can then be put back into the registry so that others can use it to improve their own projects. Now with the growth of iGEM, the registry contains 2000 defined parts, 700 of which can be ordered.

Alex: So what kind of parts does it contain now?

Dev: Well the fact that people can now access the registry, and be completely creative with their projects has given the registry a vast array of parts with many different functions. You can affect the motility of a bacteria, use sequences that can use cell-cell signaling and quorum sensing so that cells can talk to each other, and there are many others even including sequences that makes bacteria produce scents such as banana. The best part of the registry is that each contributor can build on the work of others. If you go to http://partsregistry.org you can browse every part for yourself.

Alex: Yeah, and although most parts are made for use within e. coli, the registry is also growing in the types of organismal hosts that parts are made for. Bacillus subtilis, bacteriophage T7, and even yeast which is a eukaryote have parts made for them within the registry. But Dev this is the synthetic ethics podcast, and I can already see the concerns that are associated with making synthetic biological systems.

Dev: Yep the registry would be an example of what is known as “open source biology”. This is a term coined by one of iGEM’s founders, Drew Endy. This is the idea that biology can be developed using open intellectual property models just like open source software, like the firefox browser, or linux.

Alex: Well I think the benefits of open source biology in this context are very apparent. It supports the belief the idea that biology develops best when ideas, data, and resources are shared openly.

Dev: But I think to many of our listeners, the dangers of making synthetic biology not only easier to access, but also creating a large collection of easily accessed parts is also very apparent.

Alex: Making biology convenient and available to more and more people, and inviting the general public to start coming up with ideas not only maximizes the amount of creativity and cooperation within synthetic biology. There is the risk that people accessing this technology such as hackers, amateurs, and even terrorists could develop malicious systems.

Dev: Yeah our iGEM team went on a visit to DRDC Suffield. Which stands for Defence Research and Development Canada. DRDC Suffield specializes in chemical and biological threats. When we were there we explained the iGEM philosophy of standardization and the cooperation of teams through the registry of parts. In a round table discussion with experts we got to hear their concerns having to do with iGEM.

Alex: I remember that they expressed concern with making synthetic biology easier to access. Some of their largest concerns with that is someone could potentially either on purpose or on accident release antibiotic resistant bacteria into the environment causing an epidemic. Other concerns had to do with the potential to engineer a host that will more efficiently create biotoxin, which a terrorist or disgruntled scientist could use in an attack. So the threat of a bioweapon that can’t be found in nature is real.

Dev: But does that mean that open-source biology is contributing to that danger? Drew Endy seems to believe that keeping synthetic biology transparent and open is the best way for us to monitor labs for malicious activity. He said “The only way the (expletive deleted) doesn't hit the fan is if everybody engineering biology does so in the open. We're co-opting the idea from open-source software that 'many eyes lead to few bugs.' In other words, I don't trust you not to make any mistakes the next time you program a piece of DNA. You shouldn't trust me."

Alex: Alright, so I guess the argument can be made that open source science allows science to self-monitor for unethical or dangerous practices. But this system wouldn’t work for do-it-yourself biologists who work with no federal funding. Synthetic biology may therefore necessitate a new model for addressing ethical and policy issues because of the complexity of the biological systems being manipulated.

Outro: Well thanks for joining us while we explore the ethical issues associated with synthetic biology. If your looking for more news and exciting stories within synthetic biology, check out our blog at igemcalgary2010.blogspot.com or if you want to learn more about our team and the work we are doing check out our wiki at https://2010.igem.org/Team:Calgary.

Genetically Modified Foods

Alex: Hi my name is Alex Grigg, and I’m here with my teammate Dev Vyas, and this is the third of our synthetic biology ethics podcast. Today we’re talking about a heavily debated topic within synthetic biology, which is genetically modified foods.

Dev: "There will be a significant challenge for agriculture and the science that will be required to provide a healthy, nutritious and adequate food supply in coming decades for a rapidly growing population,"

Alex: Wow Dev that’s pretty profound, did you come up with that?

Dev: No that’s actually a quote from University of Idaho animal scientist Rod Hill in an article in science daily. But it’s a popular opinion that as our population and demand for food rises, we’ll need to find new ways to increase our food production using technologies such as those present within synthetic biology.

Alex: Yeah although synthetic biology is still in its infancy as a science; genetically modified foods have been around on the market for human consumption since 1994. A genetically modified food is any food that comes from an organism that has had genes either inserted into it’s nucleus, or deleted from it’s genome. Techniques used in synthetic biology such as gene synthesis have the potential to have a drastic effect on the foods that we consume.

Dev: Yeah, genetically modified food most commonly refers to crops created for human or animal consumption using the latest molecular biology techniques. New methods of farming, as well as manipulating current food sources to be grown more efficiently are both possible approaches that could solve the growing demand for food.

Alex: Genetically modified food can be modified to have an array of advantages of over naturally occurring sources such as herbicide tolerance, pest resistance, disease resistance, drought tolerance, and increased nutrition.

Dev: And these foods are already available on the market. The first commercially available food that was available is the flavr savr tomato. This tomato was modified so that the ripening process was slowed down, and therefore it would have a long shelf life. This was achieved by the introduction of an antisense gene that interfered with an enzyme that accelerated the ripening process.

Alex: One of the most common examples of using genetically modified food is the use of Bacillus thuringiensis, or B.T, genes in corn and other crops. As of 2003, 62 million hectares of B.T gene containing crops were planted worldwide. These genes produce the Cry toxin, which binds to the cell membrane of insect cells within its gut. This causes the cells to lyse, and kills the insect.

Alex: So it’s great that the tomatoes can last longer, and corn can produce it’s own pesticides, but is it safe to eat? I mean can we have unintended effects when modifying the genetic make up of these foods?

Dev: Well the FDA approved the consumption of the Flavr Savr tomato in 1994 stating that it is as safe as tomatoes bred by conventional means, but production ceased in 1997 due to production costs. But there are a lot of concerns about the safety of genetically modified food.

Alex: Yeah these foods have sometimes been referred to as “Franeknstein foods”, A major concern about modifying food is inadvertently triggering an allergic reaction. Specific proteins in milk, eggs, wheat, fish, tree nuts, peanuts, soybeans, and shellfish cause over 90% of food allergies, and if one of these proteins was used in a genetically modified food it could unknowingly trigger an allergic reaction.

Dev: This scenario is unlikely though because of safeguards that are already in place from organizations such as the FDA. Producers of genetically modified food must prove that they have not incorporated any allergenic substance into their product. If they are unable to prove this, a label will be put on the product to alert consumers of the risk.

Alex: But governmental organizations aren’t always successful in properly managing genetically modified organisms. There was an example of this in genetically modified trees in China. China has planted over one million genetically modified trees that were designed to contain genes that would make the trees resistant to insects and pests. Because the trees are not classified as crops, China's Ministry of Agriculture has no control over genetically modified trees and they are allowed to plant without having to meet the same standards as food. It was then determined that the trees "are so widely planted in northern China that pollen and seed dispersal cannot be prevented".

Dev: So what other dangers are there if this were to happen to a genetically modified crop?

Alex: One of the dangers that I’ve heard about is the potential for genes to be “leaked” to the naturally occurring form of organism, or even genes being transferred into bacteria in the human gut.

Dev: And there is some legitimacy in this concern. Researchers from the University of Newcastle upon Tyne proved that in an experiment on intestinal bacteria that DNA plasmids can be taken up by these gut cells. This only happened in one in every 300 cells though, and another experiment confirmed that some transgenes in GM foods might survive passage through the small intestine. In this experiment, 19 volunteers ate a burger and milkshake containing genetically modified soya. 7 of the volunteers have had their colons previously removed, which allowed them to examine ileostomoy bags to look for gene transfer in the gut. It was found that 3.7% of the DNA had survived, and some of it had been transferred to bacteria in the gut.

Alex: Yeah that’s true, but they were unable to isolate the precise bacteria that had taken up the DNA because of the small amount that was transferred. Also, when they examined the stools of the volunteers, no evidence of the DNA was found, showing that although it may be capable of surviving the small intestine, it was completely destroyed in the large intestine. The fact that the DNA survived shouldn’t be very unsettling either, unmodified DNA from soya is degraded exactly the same as the DNA from the modified strain.

Dev: Well it’s good to know that if we consume anything that has been genetically modified, it is unlikely that genes that, for example contain antibiotic resistance, are very unlikely to be transferred to bacteria within the gut. But in April 2001, a poll conducted by PBS with over 21,000 respondents indicated that 65% of those polled said that we should not grow genetically modified food. So there is still a lot of controversy involved in consuming genetically modified products.

Alex: Yeah, there is also a worry that genetically modified foods are worse for the environment. In 2003 there was a trial which used three modified types of crops, and compared it to its effect on wildlife with the naturally occurring type of crop. In order to test the effect on wildlife on this farm, researchers monitored weeds, weed seeds, and collected beetles and other insects in traps.

Dev: The results of this study found that in two of three plots, weeds didn’t grow near as well. When comparing the genetically modified corn with the natural type, it was actually found that there were more weeds growing, and that it actually had the potential to increase the biodiversity on farms.

Alex: So what are governments doing about controlling genetically modified foods? If people think that it somehow harmful to either them, or a risk to the environment can they avoid it?

Dev: Well in Canada, if the nutritional value or composition of the food has been changed, or if there is an allergen present in the food, the food must be labeled to indicate this. Though it doesn’t have to indicate if the food has been genetically modified, because we have adopted a standard for voluntary labeling of genetically modified products.

Alex: Yeah, but this isn’t the case for all countries, the U.K takes a much more stringent approach. Since September 1998, U.K all foods, additives, and flavorings that contain more than 1% GM content have to be labeled. In April 2000, the new UK Food Safety Agency extended that provision to all GM foods, additives, and flavorings, including those on the market before 1998. The UK also requires that all restaurant meals with GM foods be labeled.

Dev: Synthetic biology may have the potential to help make these products, and even help relieve some of the controversy surrounding the use of genetically modified foods. The use of transgenes, which is DNA from another organism introduced in a crop causes a lot of concerns because of fears that it could be leaked.

Alex: Yeah, but new technology is already helping this field become less controversial. Marker assisted selection is an example of this. This allows us to use genetic markers to locate genes affecting traits such as meat quality, or disease resistance. Because this involves the use of existing DNA within the organism, and not transgenic DNA, there is the possibility that this will created modified food that will be less controversial. The public's acceptance or rejection of new technologies that could determine future food supplies will be crucial for the direction of synthetic biology.

Dev: Well thanks for joining us while we explore the ethical issues associated with synthetic biology. If your looking for more news and exciting stories within synthetic biology, check out our blog at igemcalgary2010.blogspot.com, or if you want to learn more about our team and the work we are doing check out our wiki at https://2010.igem.org/Team:Calgary,