Human Practices

Topics

1. Cooperation is Lacking.

2. Safety Concerns.

.3. Intimidating Skills Required

4. An Underengaged Public.

5. Conclusion.

What is “human practices”?

As a team we wanted to analyse and address the society’s relationship with science, and more specifically, synthetic biology.

After researching society’s views on synthetic biology we perceived four important problems that we could solve:

1. Cooperation between scientists is lacking.

2. The public does not perceive synthetic biology to be safe.

.3. The key skills required for synthetic biology can be intimidating.

4. The general public are not as engaged as they should be.

We believe that cooperation and collaboration are two of the fundamental principles behind the success of synthetic biology. By always keeping these themes at the forefront of our thinking, we could allow them to permeate through our entire project whether it was working directly with another team to reach a common goal, or just making software on multiple platforms to allow more people to use it.

Tayside iGEM

We were delighted to be able to work closely with the St Andrews iGEM team, who are based just across the Tay Bridge, about 40 minutes away from Dundee. It was really useful to meet with them and share our experiences. As described later in this section, we worked with them to put on a discussion on the pros and cons of synthetic biology’s place in society to coincide with the world schools debating competition.

Towards the end of the project we found out that the St Andrews team were having troubles cloning their antimicrobial peptide generator part into the psb1c3 plasmid. We were pleased to be able to help them troubleshoot their experiments and by working together we were able to successfully clone the part.

The main problem St Andrews were having seemed to be related to the production of new plasmid backbone via PCR with the iGEM specified primer design and specified RFP part. We were able to overcome this problem by carrying out some of their cloning in our lab using their AMP generator and our plasmid backbone which we made by restriction digest of uncut plasmid followed by gel cleanup. While we were doing this St Andrews carried out the same cloning cycle in paralell but using backbone they had generated by PCR. This confirmed that the source of the odd behaviour shown by the St Andrews ligation reactions and by their transformants was likely due to the method of backbone production.

Our troubleshooting experiments led to us being able to provide the St Andrews team with a plate of bacteria containing their part on the desired backbone. Further cooperation between the teams will take place over the coming weeks in order to determine why the PCR based backbone amplification procedure was not working as it should. It was really great to share our time and resources with them, and we hope there will be a good relationship between the two teams in future iGEM competitions. We wish them the best of luck for the Jamboree.

Software Advice

Our computer scientists were able to help the TUM iGEM team by offering software advice. Having had difficulties to embed Javascript on their wiki, the TUM team tweeted for assistance. The computer scientists on the Dundee University iGEM team were very happy to help. They tweeted back giving a detailed explanation of what needed to be done. Having followed our advice they tweeted back stating that it was successful. It was interesting to interact with another iGem team we hadn’t met, following the iGEM spirit. We’re excited to meet the team in Amsterdam.

Submitting Our Parts

When submitting our biobrick parts, we took care to make the parts easily accessible to teams of the future. With new research still carried out into the way the BMC is expressed, and which features are required to form a fully functioning BMC. We hope that by submitting the structural components separately we can encourage other teams to experiment further, for example with the order and composition of the operon.

Safety Concerns

SynBin

We felt the best way to address safety concerns was to evaluate our behaviour in the laboratory, ask ourselves whether it would be acceptable to the general public, and if not, how can we make it more acceptable.

This evaluation inspired the “SynBin”, a tool to help future teams share and discuss their accidents (“Syns”). Whether it’s an embarrassing slip or a more serious “Rachelle’s set the lab on fire… again!” all incidents can be posted anonymously in the SynBin’s database. This will allow fellow synthetic biologists to learn from each other’s mistakes and adapt the way they work, creating a safer lab environment for everyone.

By demonstrating how seriously we take health and safety, we can show the public that synthetic biology is being carried out in a safe and controlled environment. We feel that practical solutions like this are the best way forward to a more engaged and accepting public.

The SynBin is in late stages of development and we hope for it to go live in the next few weeks.

Intimidating skills required

Software

One of the first problems any scientist will have on joining the world of synthetic biology is gene cloning. Gene cloning is the method by which DNA molecules can be assembled in vitro, taken up by host cells, and then replicated with the cells as they divide. By speaking with scientists within our building and by noting the problems we encountered while working, we realised that cloning can be quite intimidating!

Two problems we encountered, by no means all, with cloning were as follows:

• Different organisms use codons differently.

• Making PCR primers is confusing.

Gene Synthesiser

Many synthetic biology projects involve the heterologous expression of foreign genes in a host such as E. coli/S. cerevisiae etc. For successful and efficient translation, the codon usage of the newly introduced gene must be optimised to match the tRNA pool of the host organism. However, if one simply picked the most common codon for each amino acid, the rate of translation would be extremely fast across the entire gene. This may lead to subtle characteristics of translation being lost. For example, it has been suggested that in certain regions of the gene, the source organism may ‘choose’ a short run of rare codons, in order to slow down translation in that region. This slowing of the emerging polypeptide from the ribosome has been suggested to facilitate the correct folding of the heterologous protein and/or allow time for the insertion of essential co-factors [19]. These regions of "slow" translation, may occur in loops between different domains of the protein. It may be therefore important for certain genes, to maintain this pattern of fast to slow translation in the target organism.

“Gene Synthesiser” is a java application that makes this possible by enabling codon usage pattern matching. The application analyses the patterns of codon usage of the gene that one wants to express, in its native organism and generates new synthetic DNA sequence, optimised for the codon usage of the new target organism, yet matching any patterns of rare to common codons. Gene Synthesiser utilises codon usage data for over 35000 organisms. [20]

We also designed a number of mobile applications (Apps). With the development of smart phones, there is now a demand for simple efficient programs that can aid carrying out everyday tasks.

The Lazy scientist

The Lazy Scientist is a translation tool. The app has a number of functions including DNA to amino acid translation, back translation, reverse, complement and reverse complement. The app also contains a genetic codon lookup table allowing all corresponding codons for an amino acid to be looked up. The app is available for free in both the iPhone App Store and the Android Market.

Gene Slicer/Gene cutter

The Gene Cutter (iPhone app) and The Gene Slicer (Android app) are gene cutting tools. The apps have two functions to help restriction mapping of nucleotide sequences. The apps are able to search a sequence for a specific enzyme and can also return a list of enzymes not present in the sequence. The app is available for free in both the iPhone App Store and the Android Market.

To date there have been over 1200 downloads from all over the world. Making apps will increase the accessibility of synthetic biology, allowing scientists to have portable tools to aid them in synthetic biology wherever they are.

An Unengaged Public

The Panel Discussion

To try and engage members of the public, we collaborated with St Andrews iGEM to organise a debate/discussion to coincide with the world school debating championships. The World School Debating Championships (WSDC) is an annual global event with high school students from different cultures and backgrounds, competing and debating on current issues. The WSDC has been an annual competition since 1988 and has been hosted in exotic locations around the world such as Sydney, Lima and Singapore. This year it was held in Dundee. In the past, the Championships have had Nelson Mandela and Tony Blair participating as patrons.

We felt that the aims and objectives of the WSDC which focus on international understanding would be a good incentive for us to introduce and encourage interest in the relatively controversial field of synthetic biology. Many of the participating WSDC students are potential leaders. The knowledge of Synthetic Biology would be advantageous to future global decisions. By being able to link politics and Synthetic Biology, political promotion of the subject can greatly be enhanced and Synthetic Biology can have a larger beneficial role.

After having decided to collaborate with the iGEM team of St Andrews, we set up a meeting where both teams and Jon Urch, of Revealing Research Dundee, brainstormed ideas for the event. Our first plan was a panel debate, where we would first give a short introduction on synthetic biology (giving a description of synthetic biology and discussing its benefits and limitations) and then allow the students to perform a debate. After lots of discussion we chose to give a longer presentation and then have an open discussion where both the St Andrews and Dundee team form a panel where the audience could direct questions and/or discuss among themselves. In the meetings prior to the discussion, we chose to divide the presentation into two parts: the positive and the negative aspects of Synthetic Biology. The responsibility of the negative aspects was held by the St Andrews team while we prepared for the introduction and discussing the benefits of Synthetic Biology.

On the 21st of August we held the discussion on Synthetic Biology at The Union in The University of Dundee. At the beginning of our presentation, the audience was asked if they knew anything about synthetic biology and what their opinion regarding it was. Only one person in the audience said that they were opposed to Synthetic Biology.

The Arguments

Synthetic Biology is hard to define, even scientist struggle with the definition. We thus began our presentation by showing what synthetic biology may be defined as. The following definition was used: “ (a) the design and fabrication of biological components and systems that do not already exist in the natural world (b) the re-design and fabrication of existing biological systems” (source: http://syntheticbiology.org/FAQ.html).

Though to describe Synthetic Biology as engineering is a controversial matter, as Simon Munnery says “The engineering equivalent of genetic engineering is to get a bunch of concrete and steel, throw it into a river, and if you can walk across, call it a bridge”. We also thought we would briefly explain in our introduction, how the concept of Synthetic Biology worked; explaining how we use bacterial DNA to give a different function to yeast, and the basic concept of biobricks. We introduced what iGEM was, its goals and past projects, such as the arsenic biosensor. We proceeded to discuss the influence of media and public perception in Synthetic Biology. Breakthroughs such as the organism designed from scratch by Craig Venter has lead to a lot of worry in the general public that scientists are tampering with life. It is mostly fear and lack of understanding, which will slow down the development of useful products through Synthetic Biology.

The rest of the presentation was used to explain the benefits of Synthetic Biology in more detail. Synthetic Biology is unique in it being able to design and create a product which can suit a specific need. There are many areas in which this would be useful. Synthetic Biology is applicable in renewable energy where research into bio alcohols, photosynthetic algae and hydrogen fuel is looking to solve the global dependence on fossil fuels and reducing damaging emissions. Synthetic Biology has in the past been used to create effective medicines, such recombinant DNA technology to produce human insulin from bacteria. Cheaper pharmaceuticals to treat malaria are also being designed and tested by the use of Synthetic Biology. In the future synthetic biology might be able to produce personalized medicine. The use of Synthetic Biology extends even further. Agriculture and environment protection can be substantially improved.

Synthetic biologists are testing disease resistant and high yield plants. These can be complemented with environmentally friendly and safe micro-organism which can reduce water dependence and eliminate chemical fertilizers. They are using experiments that entail combining metabolic components from different organism to improve nutritional components in plants, like increased amounts of food grade protein. This could be a great and efficient way to help famine stricken areas. In addition, Scientists are also looking into naturally occurring oil-devouring micro-organisms which can help in developing new methods to reduce pollution. Natural occurring and environmentally friendly “Wetting agents” or biosurfactant’s produced by bacteria, yeasts or fungi, are potential solutions to damage from pollutants. Synthetic Biologists may be able to isolate the constituent of biosurfactants produced from a microbe and design them to clean up precise locations of a spill or polluted area.

Another relevant example is the use of synthetic bio-films to be used as environmental biosensors. These could be beneficial for sensing nutrient quality or areas of environmental degradation in the soil.

The presentation ended with a quote from Alistair Elfick of the University of Edinburgh:

“It is envisaged that synthetic biology may be able to contribute to resolving many of the challenges facing us in the 21st Century. The potential applications are immense. We can make devices to produce fuel or animal food from our waste; we can make devices to soak up carbon from the atmosphere and lock it away; we can make devices to synthesise plastics without the need to use oil; we can make devices to sense pollutants; we can make devices to create new drugs. Indeed, synthetic biology holds huge potential to impact positively on our daily lives.” (source: http://www.synbiostandards.co.uk/about_synbio.php)

The second part of the presentation was handed over to the St Andrews team who outlined and discussed the negative aspects and limitations of synthetic biology. St Andrews began by discussing the role of bioterrorism within synthetic biology. Explaining that since the open source approach used in Synthetic Biology can be used by anyone, it is possible to create a virulent strain of bacteria/virus. The example used here was the assembly of Polio from mail order oligonucleotides. Other potential harmful effects include any organism that escapes the lab into the environment. The consequences of this are potentially dangerous. The bacteria could either colonize people causing harmful effects or even be lethal. In addition, the bacteria could potentially out compete other natural flora. This danger stresses the need for scientists to test their synthetic bacteria in the open environment. For example, the arsenic sensor that was produced by an iGEM team needs to be used in an open environment in order to fulfill its use. There is a possibility here that the bacteria becomes endemic in the environment during the test, causing lethal or severe damage to animals, plants or humans before one could destroy the bacteria. The St Andrews team then proceeded to discuss the ethical duty and responsibility of GEMs. Questions such as who defines what life is, and whether scientists alone should define life, were discussed by St Andrews. The controversial concept of scientist playing god through synthetic biology was discussed, emphasizing the issue that scientist might end up modifying biological systems before they properly understand them. Dual-use dilemma was discussed in which the nuclear fission experiments in 20th Century was used as an example.

St Andrews used the last part of their presentation to explain that though these issues are pressing there are many ways that they can be prevented. It is foremost, for scientist worldwide to be primarily concerned with the protection of the public. In actual fact Bioterrorism is realistically not a big threat because there are large amounts of resources required to synthesize and produce a virulent strain of bacteria/virus. In addition, the risk of colonization of synthetic bacteria is also very small, as they would most likely be out competed by their naturally occurring counterparts in an open environment. Using the kill switch (which the St Andrews iGEM team 2011 has built) as an example, cell level safeguards, along with laboratory protocols and transportation procedures can be tailored to substantially eliminate any big threat in Synthetic Biology.

The Response

A lot of interesting questions were raised after the presentations. Among them where issues on patenting, and someone had read an inaccurate representation of a scientific discovery/breakthrough in the press. The Dundee team emphasized the danger of incorrect coverage of science in the media. There was a suggestion that Synthetic Biology could have a fact check website, like politics have, where journalists could evaluate the credibility of media’s coverage on a topic.

View Debate Information

University of Dundee Open Day 12th November 2011

To conclude our human practices project the team will take part in a university wide open day in November. We will use an iGEM stand to explain the vision of synthetic biology and clarify any myths surrounding the area. A short demonstration will be used to explain our project and the potential of the Sphereactor. Using the concerns and questions that were raised during the discussion portion of the debate. The stand will be present throughout the whole of the open day providing an opportunity to speak to a large number of people with an active interest in science. The open day is more than just an opportunity to educate people about synthetic biology. We feel that it fits into our program of offering solutions rather than just philosophically wondering about the state of synthetic biology. By using university open days, we will target a group of inquisitive and interested people. We believe this will be a more effective marketing campaign than wider focus events that broadly target the community in a context were people are not specifically interested in the subject. The solution of working with an engaged public and then further using this to spread information is a valuable bridging system between the scientific community and the general public.

Conclusion

Our main aim was to address problems in a practical manner while laying groundwork for future iGEM teams to develop on. Only by understanding and embracing these associated problems can we come up with long-term solutions. We feel that the Dundee University iGEM team has made a number of novel steps in the right direction, better defining the purpose of human practices while solidifying the its place within all aspects of synthetic biology.