The NRP UEA iGEM team would like to thank the Biochemical Society for funding of our film, and Amy Congdon for direction and production of our film.

Quanticare & The Cura Tattoo

As part of our human practices we have produced a film in conjunction with our artist Amy Congdon which explores a futuristic world where synthetic biology is an aspect of everyday life. As we explored the idea of synthetic biology in the future we developed the idea of "Quanticare", a company created on the back of synthetic biology's rise to prominence. As the project within the labs continued and the idea of the Comparator Circuit and the Flexible Bacterial/Mammalian Hybrid Promoter came about we looked at how this new idea of cellular computing could be used within the Quanticare concept, leading to the idea of the living tattoo, Cura.

We wanted to produce something that would spark the imagination of the wider public and truly show the future power and potential of synthetic biology, and we believe that Cura and Quanticare have achieved those aims. With Cura we have developed an original idea of a tattoo not drawn with ink, but instead drawn with immortalised mammalian cells containing different BioBricks. The concept involves each shape of the tattoo containing cells with specific BioBricks that sense a particular chemical within the body, and report on any particular changes on that chemical's levels.

Figure 1. A graphic showing the result of the comparator circuit; mRNAs transcribed following activation of two promoters have cancelled one another out, leaving only the overhang representative to the imbalance in substrate chemicals to be translated and expressed.

The comparator circuit project involves multiple promoters that are sensitive to similar chemicals, a different reporter/effector enzyme for each promoter, and a range of specially designed DNA leaders that go between the promoter and reporter of each gene system. The idea involves the specially designed DNA leaders being complementary to one another and resulting in DNA annealing which covers the ribosome binding site; this means that mRNAs transcribed following activation of the promoters will cancel one another out and fail to be translated. If there is an imbalance of substrates one set of mRNAs would be produced in excess of the others as this set would not anneal to one another, therefore resulting in translation and expression of the associated protein. This is demonstrated in Figure 1. where two sets of mRNA have been produced, one with an RFP reporter and one with a CFP reporter; due to an imbalance in substrates four lots of the RFP-associated mRNA have been produced, while only two lots of the CFP-associated mRNAs have been produced. As the image shows the two CFP-associated mRNAs have annealed with two of the RFP-associated mRNAs, blocking the RBS and preventing translation, however due to the imbalance there are two RFP-associated mRNAs left to be translated and thus RFP would be expressed in this situation.

Similar comparator circuit set-ups would be used in the Cura tattoo. For instance in the case of Type I Diabetes one promoter would sense blood sugar while another would sense insulin; if the blood sugar outweighed the insulin, more of the mRNA with the blood sugar promoter would be produced and thus an effector enzyme for the production of insulin could be included in this mRNA in order to increase insulin production. If insulin production becomes too high the imbalance would shift so more of the mRNA with the insulin-sensing promoter was produced, and an effector enzyme to break down excess insulin could be translated from this mRNA strand in order to normalise insulin levels. A system such as this, as well as others (which simply report changes through fluorescent proteins), are explored in Figure 2.

Figure 2. Cura is Quanticare's revolutionary healthcare solution, a tattoo made of immortalised mammalian cells containing different BioBricks that have been specifically tailored to monitor and respond to changes in the body. Different areas of the tattoo correspond to different areas of the body, and using biological technology developed by the Norwich Research Park and University of East Anglia 2012 iGEM Team can react automatically to many unwanted changes, as well as fluorescing to alert the user of any problems.

We have also looked at therapeutic strategies within Quanticare and how the tattoo may be analysed. As part of the film we looked at the idea of a scanner to complement the Cura tattoo, which will scan the tattoo's fluorescence patterns and feed through to a specialised printer designed to produce a bacterial pill optimised to treat the conditions reported by the tattoo. These bacteria would contain BioBricks to produce drugs/enzymes as well as targeting mechanisms in order to find the site of a problem and correct mistakes being made; they could also be used to help swamp the likes of cancerous tumours and pump the tumour with drugs/apoptosis-inducing factors such as nitric oxide in order to help fight cancer; a mocked-up in vitro video of this occurring is included in the film.

As part of a marketing strategy to promote Quanticare and our film we have produced transferable tattoo versions of Cura which we will be handing out at the European Jamboree for other competitors, judges and interested parties to enjoy. We believe this will be an interactive and exciting approach to promoting our project and our ideas on the future of synthetic biology.

Some initial feedback, the Quanticare video was launched less than 24 before the wiki freeze:

. Blogged about on Biochemical Society blog

. On UEA news pages

. Mentioned in tweet from the BBSRC

. Many likes and tweets

. Some quotes;

"Inspiring and Innovative" Global Strategist and Author @DeanneLawrence

"Great project. Good luck!" @SocratesLogos Synthetic Biologist

"Sooooooo cool!" Kimberley Hirst Jones UEA-JIC_Norwich iGEM 2011 team member

Ethics of Quanticare and Cura

Through the film we have also explored the ethics of both synthetic biology healthcare solutions as well as synthetic biology as a whole. We have envisaged a world where public protests regarding synthetic biology have occurred, leading to companies such as Quanticare adopting stringent safety methods and testing in order to help calm public unease. We have also looked at the ethics of a tattoo and tattooing with immortalised cells, in particular the obvious risk of adding foreign cells to a body and public opinion on tattooing. We believe that while there is definite opposition, Cura is still a realistic future product provided the appropriate safety concerns are addressed.

As part of our human practices we ran a synthetic biology-based event at a local events centre, the Norwich Forum; at the event we debuted the video and looked to members of the public to give their opinions on the concept as well as a future involving synthetic biology. Many members of the public were extremely interested in the idea and some even asked if it was available for them to tattoo Cura onto themselves that day! However, there were also many concerns raised by members of the public which we were able to take on board and discuss with them. These concerns included:

. Whether the immortalised cells could result in a cancer forming

. Tattooing being frowned-upon by certain faiths and areas of society

. Harmful affects of the cells (e.g. over-production of insulin)

. Faults in the tattoo systems

. Encouraging members of the public to rely on the tattoo rather than using healthcare professionals such as doctors

We have recognised all of these concerns as valid and appropriate points, and have spoken with the members of the public raising them to discuss how they feel the points should be addressed. Solutions to some of the problems we have investigated include:

. Adding a suicide gene in all cells should they begin to divide uncontrollably

. Careful tuning and testing of all BioBrick systems to prevent over-production of certain products and to troubleshoot any faults

. In figure 2 some of the strands of the tattoo suggest consulting a doctor, and Cura is encouraged as both a healthcare solution and an aid to prevent reliance on Cura

Overall while there are many ethical issues to be addressed we feel that conversing with the public on these issues and gauging their thoughts is an integral part to moving forward with this concept movie and helping to bring synthetic biology to the forefront of society. We encourage any and all feedback on the film and Cura as a concept to help improve how synthetic biology is understood and presented.

We hope that Quanticare, Cura and our film are enjoyed by everyone who views them and that they provoke the debates and thoughts we designed the concept to.