The International Journal of Biochemistry & Cell Biology 56 (2014) 20–29

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Growing for different ends夽 Oron Catts, Ionat Zurr ∗ SymbioticA, School of Anatomy, Physiology and Human Biology, The University of Western Australia, Australia

a r t i c l e

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Article history: Received 3 June 2014 Received in revised form 24 September 2014 Accepted 25 September 2014 Available online 5 October 2014 Keywords: Semi Living In vitro meat In vitro leather Tissue engineered art Tissue engineered design

a b s t r a c t Tissue engineering and regenerative biology are usually discussed in relation to biomedical research and applications. However, hand in hand with developments of this field in the biomedical context, other approaches and uses for non-medical ends have been explored. There is a growing interest in exploring spin off tissue engineering and regenerative biology technologies in areas such as consumer products, art and design. This paper outlines developments regarding in vitro meat and leather, actuators and bio-mechanic interfaces, speculative design and contemporary artistic practices. The authors draw on their extensive experience of using tissue engineering for non-medical ends to speculate about what lead to these applications and their possible future development and uses. Avoiding utopian and dystopian postures and using the notion of the contestable, this paper also mentions some philosophical and ethical consideration stemming from the use of non-medical approaches to tissue constructs. This article is part of a directed issue entitled: Regenerative Medicine: the challenge of translation. © 2014 Published by Elsevier Ltd.

1. Introduction Tissue engineering and regenerative biology are usually discussed in relation to biomedical research and applications. However, alongside, some of the developments of this field are pursued outside to the biomedical context in areas such as consumer products, art and design (Reviewed in Tandon et al., 2014; Myers, 2012; Aldersey-Williams et al., 2008). This paper outlines developments regarding in vitro meat (food) and leather (fashion), actuators and bio machine interfaces, and provides an index of tissue engineered works in the growing areas of speculative design and contemporary artistic practices. Within the fields of design and engineering there is a growing interest in using biological processes and materials as a new manufacturing paradigm. This new paradigm goes beyond biomimicry, it represents a shift from the logic of building to that of growing. With the increased knowledge of biological processes and modes of manipulation of living systems and matter, the notion of highly controlled and engineered growth of biological products is ever so seductive. This new paradigm covers all aspects of the life sciences and all scales of biological complexity; with the bulk of attention given to the engineering of bacteria under the guise of synthetic

夽 This article is part of a directed issue entitled: Regenerative Medicine: the challenge of translation. ∗ Corresponding author. Tel.: +61 8421782739. E-mail addresses: [email protected], [email protected] (I. Zurr). http://dx.doi.org/10.1016/j.biocel.2014.09.025 1357-2725/© 2014 Published by Elsevier Ltd.

biology (Reviewed in Ginsberg et al., 2013). In addition the use of algae, fungi and plant material in less traditional ways is more established, probably due to the fact that these materials are considered less problematic from an ethical perspective and require quite different technical considerations (Reviewed in Myers, 2012; Aldersey-Williams et al., 2008). In the context of this article, we focus on the reappropriation of regenerative medicine technologies and hence concentrate mainly on the use of mammalian tissue and cells. There are numerous reasons for the use of tissue engineering and regenerative biology beyond the medical applications. We would like to indulge in speculating as to the main motivations for the use of this particular knowledge and know how:

• The collaborative and trans-disciplinary nature of tissue engineering: the field develops through mutual efforts and interests of disciplines such as biology, medicine, engineering, chemistry, material engineering and more. Therefore, by its nature this field is open for diverse frames of thoughts, methodologies and applications. • The field of tissue engineering and regenerative medicine has developed rapidly since the early nineties and led to the development of sophisticated and expensive tools and technologies. Due to economic interests (among others) there is a need to capitalise on these investments by diversifying the use of these tools to a wider range of end products that go beyond the original intent for which they were developed.

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• The realisation that tissue engineered constructs that are not intended to be (re)introduced in vivo, and can operate solely within in vitro environments reduces some of the complexities and problems involved with clinical and transplant research, making way for a new venue of research; tissue constructs that act as “tools” or grown for specific ends within an artificial, technological environment. • The abundance of tissue and its unique properties can lead to many unexpected outcomes. Also, concepts such as scaffolding, fluid dynamics, self-healing and generative materials, are prevalent in architecture, design and engineering. • Cheap tools and DIY approaches to tissue engineering become more available and are explored by hobbyists for different ends. For Example; the DIY Bioprinter that was developed last year by members of the biohacker movement in the Bay Area in California USA as an inexpensive device to print cells (Leber, 2013). • The rhetoric concerns sustainable modes of production and the promise of biological materials as efficient adaptations to problems of scarcity, makes tissue engineering a seductive material of fabrication. • The Authors’ work as The Tissue Culture & Art Project which led to the establishment of SymbioticA – The Centre of Excellence in Biological Arts, School of Anatomy, Physiology and Human Biology at The University of Western Australia may have played a pivotal role in the introduction of these technologies to artists and designers (Myers, 2012; Anotnelli, 2011; Stocker and Schopf, 2007). This will be discussed further in the article. Tissue – as a medium of manipulation – will always carry ethical and philosophical implications that bring into question deeper notions regarding life and bodies, and therefore every discussion about its use beyond the strictly medical is publically debated and culturally scrutinised. Tissue derived from complex organisms for purposes beyond the strictly biomedical raises numerous ontological, bioethical and biopolitical concerns ranging from the use of animals (whether human or/and non-human); the sacristy of life; the values in terms of agency and currency of different lives and/or gradients of life and more. We will touch on some of these issues in the concluding section. 2. Historical reflections 2.1. “Earmouse” Tissue engineering in many respects, co-evolved with the field of biofabrication (Mironov et al., 2009), both relying on the concept and actuality of the Bioreactor technology. The history and the name Bioreactor own roots are in agriculture and food production via fermentation which has been practiced for thousands of years. The development in tissue engineering came from the collaborative work of a surgeon, Dr Joseph P. Vacanti, and a material scientist, Dr Robert Langer, in the early 1990s. They developed a system that used specially designed degradable polymers that act as a scaffold for the developing tissue. Their research stemmed and aimed for biomedical purposes; although as will be illustrated, this was never a clear cut. One of the earliest “poster boys” for tissue engineering was the nude mouse with the human ear grown on its back (nicknamed “earmouse”), developed by Professor Vacanti and colleagues in the mid-nineties (Cao et al., 1997). However, once the image of the earmouse entered the public realm, it had a larger effect beyond the biomedical and became one of the symbols, in the public imagination, of the best and worst in biotechnology. The earmouse had also impressed upon the art world. It may be that the earmouse was a visceral realisation of the plasticity of the body and possibility of tissue to be used as something that may

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be shaped and altered in many “sculptural” forms which exceed the strictly biomedical realm. The image was inspirational to many artists (Piccinini et al., 1997; Rockman, 2000; Cadet, 2004; Stelarc, 2008; Strebe, 2014) including the authors of this paper (Catts et al., 2003) and was instrumental to our ongoing investigation into the use of tissue technologies as a medium for artistic expression. The survey presented in this article is not chronological, and not complete; rather it takes its starting point from the use of tissue engineered constructs for utilitarian uses such as consumer goods, to more symbolic and aesthetic examples of the use of tissue technologies for non-medical purposes. Furthermore, the scope of this paper will focus on the developments of tissue engineered consumer goods and will give some introductory notes and detailed index of the contemporary artistic work done with tissue engineering. Every project presented in the index deserves a full article outlining the technical, theoretical, conceptual and aesthetic aspects the project/developer presents, but this is outside to the scope of this paper. The authors hope that the limited information provided in this article will act as a guide for further research in this bourgeoning field. However, as will be illustrated, the history of the use of tissue engineering techniques for non-medical applications was influenced by artistic work throughout the years, and some of the most recent projects speculate about future utilitarian uses of tissue engineering, within a cultural and consumer context.

2.2. Semi-Living art & SymbioticA To start with the survey we would like to introduce another concept developed by the authors that will reappear through the article; a term used to define in vitro/tissue engineered constructs which are not intended to be implanted in a body – but rather exist and function as independent technological entities. While publishing our hypothesis for using tissue engineering for the creation of entities in the environment (Catts and Zurr, 2002) we referred to these tissue constructs as The Semi-Living – as these are living fragments of complex bodies which are dependent on non-living artificial support mechanism for their function and survival. The Semi-Living are a new class of objects/beings constructed of living and non-living materials; cells and/or tissues from a complex organism grown over/into synthetic scaffolds and kept alive with an artificial support. They are both similar and different from other human artefacts (homo-sapiens’ extended phenotype) such as constructed objects and selectively bred domestic plants and animals (both pets and husbandry). These entities consist of living biological systems that are artificially designed and need human and/or technological intervention in their construction, growth and maintenance (Catts and Zurr, 2013, 2010, 1998). Experiments with Semi-Living tissue constructs were and are conducted globally, though the focus for artistic explorations with regenerative biology stemmed from the work of the authors through their Tissue Culture & Art Project, initiated in 1996 as an open ended research project, exploring the use of tissue technologies as a medium for artistic expression, and later through the establishment in 2000 of the SymbioticA Laboratory. SymbioticA is the first research laboratory of its kind, enabling artists and researchers to engage in wet biology practices in a biomedical science department. SymbioticA is unique as it enables a creative biological research by non-biologists who are embedded within a scientific faculty at the University of Western Australia. SymbioticA encourages better understanding and articulation of cultural ideas around scientific knowledge and informed critique of the ethical and cultural issues of life manipulation. The Centre offers a new means of artistic inquiry where artists actively use the tools and technologies of science, not just to comment about them but also to explore their possibilities.

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Many of the examples surveyed and discussed in this paper were developed at SymbioticA. Furthermore, some of SymbioticA’s residents went on to develop their own laboratories in other parts of the world such as Canada, Portugal and the USA. 3. Food products: in vitro meat, Semi-Living Steak In 1932 Winston Churchill suggested that ‘We shall escape the absurdity of growing a whole chicken in order to eat the breast or wing, by growing these parts separately under suitable medium’ (Churchill, 1932). Churchill and many others were probably influenced by the developments in tissue culture in the early twentieth century, led by the surgeon Alexis Carrel. Twenty years after Churchill’s proposition, Fredrik Pohl wrote in his science fiction book Space Merchants about similar technology: Chicken Little is huge blob of cultured chicken breast that is growing and kept alive by algae skimmed by nearly-slave labour from multi-story towers of ponds surrounded by mirrors to focus the sunlight onto the ponds (Pohl and Kornbluth, 1952). The concepts of lab grown meat have appeared in numerous science fiction novels and stories; presenting a seductive promise of endless supply of victimless and environmentally sound animal protein for human consumption (i.e. Atwood et al., 2003). In 1995, The U.S. Food and Drug Administration approved NASA’s in vitro meat production techniques, which began as NASA’s attempts to create a means of providing food for long-term space travel (Catachem Inc., 1995). Four years later, in 1999 Willem van Eelen takes out U.S. and international patents for the Industrial Production of Meat Using Cell Culture Methods (Specter): Industrial production of meat from in vitro cell cultures (Patent: WO 1999031223 A1). The authors of the paper are familiar with the technicalities and discourse involved in the growth and construction of in vitro meat as they have been involved early on – and hands on – with this endeavour as part of their artistic inquiry into the Semi-Living. As was published in the Washington Post in 2000: ‘Now they [Catts and Zurr] want to grow quarter-size steaks using sheep muscle cells and are on the lookout for volunteers willing to eat them as part of a performance’ (Catts et al., 2000; Ferdinand, 2000). The Semi-Living Steak project was one of the outcomes of a yearlong research fellowship at the Tissue Engineering & Organ Fabrication Laboratory at MGH/Harvard Medical School in 2000. The first in vitro meat was grown from pre-natal sheep satellite cells, harvested as part of research into tissue engineering techniques in utero. The cells were seeded on a PGA polymer mesh, grown and matured into myoblast in a Synthecon rotary cell culture system. The “meat” was grown from an animal that was not yet born (Catts and Zurr, 2013) (Fig. 1). In the same year, the NSR/Touro Applied BioScience Research Consortium produce the first edible in vitro meat in the form of fish fillets made from growing goldfish cells (Benjaminson et al., 2002). 3.1. The first public eating of in vitro meat The first public eating of in vitro meat was staged by The Tissue Culture & Art Project as part of a complex artistic installation titled Disembodied Cuisine; this work was one of major pieces in the exhibition L’Art Biotech in Nantes, France 2003 (Solini et al., 2003). The exhibition was the largest European survey of artistic works dealing with biotechnology. The Disembodied Cuisine installation played on the notion of different cultural perceptions of what is edible and what is foul. Semi-Living frog steaks were grown, thus poking fun at French taste and their resentment towards engineered food, and the objection by other cultures of the consumption of frogs as food.

Fig. 1. The Semi Living Steak 2000, by the Tissue Culture & Art Project (Oron Catts and Ionat Zurr). Pre-natal sheep skeletal muscle and degradable PGA polymer scaffold. As part of the artists Research Fellowship in the Tissue Engineering and Organ Fabrication Laboratory, MGH, Harvard Medical School.

Frog skeletal muscle cells were grown over biopolymer for potential food consumption, while the healthy frogs lived alongside as part of the installation. In the last day of the show after three months of growth, the in vitro meat was cooked and eaten in a Nouvelle Cuisine style dinner, and the two frogs that were rescued from the local edible frog distributor were released to a beautiful pond in the local botanical gardens (Catts and Zurr, 2008) (Fig. 2). In 2004, a group of researchers started the non-profit organisation New Harvest, with the goal of promoting research into in vitro meat. Among the founders are Jason Matheny and Vladimir Mironov. In 2005, Henk Haagsman at the University of Amsterdam, the Eindhoven University of Technology and Utrecht University, in cooperation with sausage manufacturer Stegeman began a research into in vitro meat supported by a two million euro Dutch government subsidy. The first international In Vitro Meat Symposium was held in Norway in April 2008. At the same year, PETA (People for Ethical Treatment of Animals), an American animal rights organisation, announced a one-million dollar prize for the first group to successfully produce synthetic meat that is commercially viable comparable to naturally sourced meat products. In 2012 a company named Modern Meadow was established by a father and son team Gabor and Andras Forgacs. Peter Thiel’s philanthropic foundation gave US$350,000 to Modern Meadow, to use 3D bioprinting to create an “edible prototype” as a meat replacement. In August 2013 in vitro “burger” was cooked and eaten at a news conference in London. The news conference unveiled by Sergey Brin, Google co-founder (who funded the project for around D 250,000). Scientists from the Netherlands, led by Professor Mark Post, took cow’s stem cells and grew them into strips of muscle that they combined to make a burger. In vitro meat is promoted as an eco-friendly replacement to the meat industry; reducing animal suffering; and providing better controlled healthy meat. However, there are still many obstacles that are needed to be addressed before in vitro meat could (if ever) become a viable replacement to traditional meat. Some of these are indicated below: • There is still no effective replacement for the use of foetal calf serum in the context of high yield, fast metabolising satellite cells. Therefore any attempt to upscale production might still be partly dependent on animal derived nutrients.

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Fig. 2. Disembodied Cuisine Installation 2003, by the Tissue Culture & Art Project (Oron Catts, Ionat Zurr and Guy Ben Ary). Part of the L’Art Biotech Exhibiton curated by Jens Hauser, France 2003. Photography: Axel Heise.

• The potential risk of exposure to serum/growth factors to consumers from ingested in vitro meat. • The development of cost effective nutrients for large scale production. • In all likelihood antibiotics will still be required to be extensively used in a large scale commercial production of in vitro meat. • There are still environmental ‘costs’ concerned with the running of a laboratory/factory, i.e. fossil fuels burned, greenhouse gases produced, water and trees consumed, miles travelled and the waste created. • Size – the technology is still limited in the constructing/growing of thick constructs due to lack of artificial capillary system. • The skeletal muscle cells of in vitro meat have a consistency and texture very different to that of an exercised animal muscle. In order to achieve meat like texture the myotubes need (among other things) to align, there is a need to provide a form of exercise/stimulation regime. This is yet another possible up-scaling challenge. (see TEMA below). • The taste: a piece of meat taken directly from an animal consists of many tissue types (such as fat, bone, tendon, etc.). • Public acceptance is still quite slim and there is a need for a major shift in public attitudes towards the consumption of tissue engineered food. To summarise, the suggestion to use tissue engineering technologies for the production of food – in vitro or Semi Living meat, was developed by both scientists and artists. While the authors staged and performed the first public eating in 2003 as part of an artistic installation, the media blitz happened only ten years later in 2013 when scientist Mark Post, supported by Google’s funding and marketing services, grew an in vitro “burger”. However, there are still major problems with the up-scaling of in vitro meat, and at this stage, it seems that there is more publicity than substance.

4. Fashion: in vitro leather In 2004 the authors were commissioned to create an artwork for a fashion and textile exhibition. We developed the piece titled Victimless Leather – A Prototype of Stitch-less Jacket grown in a Technoscientific “Body”. The piece consisted of a custom made bioreactor circulating nutrient media drip fed to the tissue construct in the shape of a miniature jacket. This ironic piece was looking at the possibility of growing leather-like material using tissue engineering techniques. The research for the piece, conducted at SymbioticA at The University of Western Australia, also included a series of prototypes of tissue engineered leather grown on a range of scaffolds and ECMs. The piece was later shown at the Museum of Modern Art in New York as part of the 2008 Design and the elastic Mind Exhibition. While the authors were more concerned with the cultural and artistic aspects of the piece, this idea has moved into the realm of venture capital in later years. The earlier mentioned company Modern Meadow (that shares certain founders from the company Organovo which develops and manufactures 3D tissue printers and bioreactors since 2003) is proposing to develop and manufacture in vitro meat and leather: The Company’s CEO declared in 2012 that “Tissue-Engineered Leather could be Mass-Produced by 2017. . . [he] revealed the details of his company’s plan to 3D bioprint leather and ultimately meat, starting with punch biopsies of donor animals” (Keller, 2012). In June 2014 Horizons Ventures, the Hong Kong-based firm of billionaire investor Li Ka-shing, led a $10 million Series A investment in the company for this purpose: “The company aims to help fashion designers and makers of leather goods meet the increasing global demand for their wares without taking such a toll on animals and the environment” (Kolodny, 2014) (Fig. 3). The problems associated with the development of in vitro meat are similar to the hurdles concerned with the manufacturing of

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to a plastic “spine” with electrodes. The muscles were stimulated to produce a swimming motion. The “robotic fish” was placed in a tank of ringer solution designed to provide nutrients and keep the muscles alive. The robot could swim forward, backward, turn, and stop. They explain that their investigation concerns “the feasibility of using animal-derived muscle as an actuator for artificial devices” (Herr and Dennis, 2004). Here we see an example of using living tissue for robotics which is different to the more conventional approach of biomimicry, i.e. the attempt to mimic mechanisms of tissue out of non-living artificial materials.

5.2. Medusiod 2007–2012

Fig. 3. Victimless Leather – A Prototype of Stitch-less Jacket grown in a Technoscientific “Body” 2004, by The Tissue Culture & Art Project (Oron Catts and Ionat Zurr). Biodegradable polymer connective and chondrocytes cells, custom made bioreactor. Researched and developed in SymbioticA, School of Anatomy, Physiology and Human Biology, The University of Western Australia.

in vitro leather-like materials. However some of the hurdles are obviated as the product may be simpler to engineer: For example, the lack of need for co-culture of multiple cell types; no need for the biophysical cues to grow flat sheets of cells (differently to the techniques involved in muscle actuation); also as this product will not be consumed but rather used externally perhaps it more likely to be accepted by consumers. 5. Muscle actuation and biomachine interfaces This section concerns mainly with the use of tissue engineering in soft robotics and Artificial intelligence. However, these fields are still explained mostly in relations to the possible biomedical applications while the non-biomedical possibilities and speculations are usually played down as a secondary application. The examples listed below are chosen as they raise the possibility of non-medical applications and have been also pursued by artists. 5.1. A swimming robot actuated by living muscle tissue 2004 One of the earliest examples of the use of muscle tissue for the production of “soft robotics” is from 2004. Titled A swimming robot actuated by living muscle tissue, Hugh Herr and Robert G Dennis have created actuator made of frog muscles that are attached

The paper Muscular Thin Films for Building Actuators and Powering Devices (Feinberg et al., 2007) looked at the possibilities of the hybrid of cardiac cells with synthetic polymer thin films. These constructs, when taken out from the thermally sensitive polymer substrate, morphed into three-dimensional shapes. These shapes were designed to perform bio mimicry tasks resulting from their varying tissue architecture and assisted by electrical-pacing protocols. They were designed to perform tasks such as gripping, pumping, walking, and swimming. This research lead to a striking example published five years later of a cardiac muscle actuation which blurs the boundaries between the biomedical and other applications/possibilities and presents a somewhat an iconic image – similar to the earmouse – that was nicknamed by its creators as the Medusoid – an artificial jellyfish made of rat’s cardiac cells grown over silicone. “When placed in an electric field, it pulses and swims exactly like its living counterpart.” (Nawroth et al., 2012). Medusoid was created by a team from Harvard University and the California Institute of Technology (Caltech) and published in Nature in 2012. While the Medusoid may assist in understanding biomechanics and can be used as a platform for testing drugs, it is also designed and promoted in the media as an evocative object/entity which ignites public imagination.

5.3. Tissue engineered muscle actuator (TEMA) 2012 ongoing The authors’ (and additional collaborators from the University of Western Australia, Concordia University and University of Ottawa in Canada and Aalto University in Finland)i recent project, funded by the Australia Research Council, concerns the development of an artistic electro-mechanical device that will facilitate growth and formation of muscle fibres, thus enabling conditions (such as temperature, sterility, nutrient media, morphological and biomechanical elements) necessary for the fibres to maintain life and encourage growth. These specific cells have the potential to mechanically and chemically contract and expand if grown in specific conditions. The device thus has the primary function to organise and amplify the inherent movement behaviour of the muscle fibres, thus giving the cells the potential to become a moving Semi-Living machine. Our project has the potential to ‘exercise’ muscle cells grown in vitro if they will be aligned and electro-mechanically actuated to move. While there are possible practical uses for an in vitro skeletal muscle actuator (such as in the production of in vitro meat and soft robotics) we are more interested in the artistic/cultural possibilities of such an endeavour. The possibility of a Semi-Living kinetic sculpture may create effect and affect in the audience which will respond more to the ideas of life and vitality and further blur the perceptual boundaries between what is alive and what is artificial. TEMA work is based on previous research that looked at growing, aligning and measuring active tension Generated by C2C12

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Myotube (Akiyama et al., 2006; Lam et al., 2009; Fujita et al., 2010). 5.4. Three-dimensionally printed biological machines powered by skeletal muscle 2014 The field of muscle actuation for non-biomedical purposes is growing. One of the most recent examples to come out while writing this article was of 3D printed hydrogel “bio-bots” (Cvetkovic et al., 2014). These bio-bots printed with an asymmetric physical design, seeded with engineered mammalian skeletal muscle strip that its actuation resulted in the locomotion of the bio-bot. The authors explain the significance of such work in terms of machine design and environmental considerations: “cell-based soft robotic devices could have a transformative impact on our ability to design machines and systems that can dynamically sense and respond to a range of complex environmental signals”(Cvetkovic et al., 2014). Furthermore, the authors stress that the use of skeletal muscle rather than cardiac muscle (as in the case of the Medusoid described earlier in this section) gives the user better control and precision of use. 5.5. Biotic games In relation to bio-machine interfaces; more examples can be found in the field of “organs on chips” or cells on chips (Baker, 2011) as well as cells that are used as sensors (Reviewed Taniguchi, 2013). However, these examples are tightly related to the biomedical field and are out of the scope of this paper. A relevant example in relations to bio-machine interface for non-medical application, which is still in its infancy, is gaming. A prominent example is from Ingmar Riedel Kreuse’s Lab in the Department of Bioengineering, Stanford University, CA, USA. Although the examples used by the lab are of non-mammalian cells, we include this example as a possible use for mammalian cells in the context of entertainment and games. The example is of a “biotic” game made of a living paramecia contained inside a biotic game console. The human player interacts with these paramecia via traditional game controller and observes their responses on a video screen with a superimposed virtual game environment (Riedel-Kruse, 2011). Riedel-Kruse writes: “Here we propose the concept of ‘biotic games’, i.e. games that operate on biological processes. . . Analogous to video games, biotic games could have significant conceptual and cost-reducing effects on biotechnology and eventually healthcare; enable volunteers to participate in crowd-sourcing to support medical research; and educate society at large to support personal medical decisions and the public discourse on bio-related issues.” (Riedel-Kruse, 2011). However, at the same time the use of “real” biological materials for the purpose of entertainment may risk the abuse of biological matter and its exploitation for the entertainment business. By making biological matter a tool for entertainment we may affect its perception as a living, sentient being and reduce it into “object-toy”.

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of simulated animats or robotic creatures (Newman et al., 2012; Rolston et al., 2010). According to Potter, an animat is a computer simulated or robotic “animal” that is behaving in an environment (whether virtual or physical). The living cultured neuronal networks are interfacing with the animat via a multi electrode array, and the researchers are creating a method to study how information is processed and encoded in these cultures via a feedback loop with the animat (Bakkum et al., 2004; Potter, 2007; Rolston et al., 2009). Another project pursued in the Potter Neuroengineering lab is titled “EFRI-COPN: Neuroscience and Neural Networks for Engineering the Future Intelligent Electric Power Grid”. The overarching goal of this project is to explore the interfaces between neurobiology and control systems: “to make them more brain-like and be able to carry out real-time control of complex systems”. This project is based on an award from the Office of the Emerging Frontiers in Research and Innovation (EFRI), National Science Foundation, USA under the topic Cognitive Optimisation and Prediction: From Neural Systems to Neurotechnology (COPN) (Potter, 2010; Newman et al., 2013). 6. Semi Living art Moving from consumer goods and “utilitarian” examples of tissue constructs, this section will provide an index of the use of tissue technologies as arts. The in vitro constructs or as they referred to within the artistic field “Semi-Living entities” were produced for cultural and aesthetic purposes. Some of the works aim at looking critically at social, philosophical and ethical questions raised by the human made neo-life (aka neo-organs). As mentioned earlier, the survey below is more of an index or list of some of the most prominent artworks. We hope this section will act as a teaser for the reader to search further into the field and speculate about future developments in the field of tissue engineering and regenerative medicine as a medium for artistic expression. 6.1. MEART – the Semi Living Artist (SymbioticA Research Group 2002 in collaboration with Steve Potter Lab, Georgia Tech) MEART – The Semi Living Artist is a geographically detached, bio-cybernetic research and development project exploring aspects of creativity and artistry in the age of new biological technologies. It was developed and hosted by at SymbioticA, the University of Western Australia. MEART is an installation distributed between two (or more) locations in the world. Its “brain” consists of cultured nerve cells that grow and live in Steve Potter’s neuro-engineering laboratory, in Georgia institute of Technology, Atlanta, USA. Its “body” is a robotic drawing arm that is capable of producing twodimensional drawings. The “brain” and the “body” communicate, through electrical stimulations, in real time with each other for the duration of the exhibition (Potter, 2013). MEART – The Semi Living Artist was “drawing” audience portraits in real time at the gallery (Fig. 4).

5.6. Neurons and MEA technology In this section we use the Potter Laboratory for Neuroengineering in Georgia Tech as an example. Potter lab has worked closely with SymbioticA’s Research Group and some of SymbioticA’s core researchers (mainly Guy Ben-Ary) to foster art science collaborations through the technology of Multielectrode Arrays (MEAs). These are devices that contain multiple plates or shanks that obtain and deliver neural signals. Essentially they act as s neural interfaces that connect neurons to electronic circuitry. Potter’s lab cultured mammalian neurons on MEAs in order to achieve a long-term, twoway interface between the cultured neural networks and a computer: Potter explains that these systems “can serve as the ‘brain’

6.2. The Semi Living Worry Dolls (The Tissue Culture & Art Project – TC&A – 2000) This artistic piece was the first time that living tissue engineered constructs were presented within a cultural context (Catts and Zurr, 2002). Artistic expression has a long tradition in creating objects of symbolic meanings. The Semi-Living Worry Dolls are created as a symbolic gesture for the audience to care for and express their innermost worries and anxieties. In this project the authors handcrafted PGA, PLGA, P4HB and surgical sutures into the shapes of seven doll-like figurines and seeded them with living cells to create Semi-Living Worry Dolls. Alongside these growing dolls that

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Fig. 4. Meart: The Semi Living Artist, by SymbioticA Research group in collaboration with the Potter Lab. The robotic Arm, Australian Culture Now, 2004. Photography: Phil Gamblen.

were fed and cared for literally and performatively was positioned a ‘worry machine’ for people to express their worries and anxieties to the Semi-Living Worry Dolls. A computer station with the ‘worry machine’ application became an integral part of this installation and it remains a feature in the TC&A web site. This ever growing document of worries written to the Semi-Living Worry Dolls reveals a variety of cultural but mostly personal anxieties. One way the viewer/participant can observe and appreciate the aliveness of the Semi-Living is by revisiting them over an extended period of time in order to see, with human eyes, the phenotypic changes. For those who cannot do so the authors devised some artistic rituals, e.g. the Feeding and the Killing rituals: The rituals are performed for practical reasons – maintaining the life and growth of the Semi-Living sculptures – as well as for conceptual reasons; by celebrating and terminating SemiLiving art forms, the artists trouble the conventional art viewer’s autonomous reflective space (as does all performative art). The artistic installations involve performative elements that emphasise the responsibilities, as well as the intellectual and emotional impact, which results from manipulating and creating living systems as part of an artistic process. The Feeding Ritual – is performed routinely. The audience are invited to view the process of feeding which is done in a laboratory situated within the gallery as an integral part of the artistic experience. At the end of every installation, we are faced with the ultimate challenge of an artist – we had to literally kill our creations. The killing is done by taking the SemiLiving sculptures out of their sterile containment and letting the audience touch (and be touched by) the sculptures. The Killing Ritual enhances the idea of the temporality of life and living art, and our responsibility as manipulators of these new forms of life.

In a sense by employing the technology of tissue engineering to create a symbolic Semi-Living sculpture, the “liveliness” of the fragment of life growing in a techno-scientific body is enhanced. The audience are allowed a position of identification with the Semi-Living and have elevated it to place where relations with new technological entities can and should be negated (Fig. 5). 6.3. The Pig Wings (The Tissue Culture & Art Project – TC&A – 2000–2001) The Pig Wings project was developed in 2000–2001 during a research residency in Joseph Vacanti’s Tissue Engineering and Organ Fabrication Laboratory MGH/Harvard Medical School. Three sets of wings made out of pig mesenchymal cells (bone marrow stem cells) were grown over/into biodegradable/bioabsorbable polymers (PGA, P4HB). The wings size is 4 cm × 2 cm × 0.5 cm each, and they were grown for approximately nine months inside a rotary cell culture bioreactor. The original wings were fixed and preserved, coated with gold and kept in jewellery boxes. The Pig Wings Project is playing on the proverb “If pigs could fly”, critiquing some of the unfounded promises and hype concerning new technologies (which in return generate unrealistic public expectations as well as unrealistic fears of such developments). The authors presented the Semi-Living entities in their humble, somewhat technologically futile light: instead of flying pigs in a gallery they have hosted the winged shaped pig tissue miniature, floating in a bioreactor. Once the wings were taken away from their artificial life sustaining bioreactor, they died and are now positioned in cheap jewellery boxes. The Pig Wings deliberately adopted what

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6.6. Marsysus – Running out of Skin (Kira O’reilly 2004) Marsysus – Running out of Skin explored traditional lace making techniques interwoven with tissue culturing and engineering to develop an in vitro living lace of skin cultured from cells biopsied from the artist’s body. The project was funded by the Welcome Trust and conducted at SymbioticA, the University of Western Australia. 6.7. The Vision Splendid (Alicia King 2008) Using the artist’s own cells and co-culturing them with those of an anonymous 13 years old African-American girl that was isolated from a skin sample on January 31, 1969 (and purchased from the ATCC) over a form of a contemporary living reliquary. Grown inside a custom made DIY bioreactor, and travelling as in sideshows miracles, the piece is echoing religious artefacts and our changing relations with perceptions of engineered life. 6.8. The Immortalisation of Kira and Rama (Svenja Kratz 2010)

Fig. 5. Semi-Living Doll H 2000, by the Tissue Culture & Art Project (Oron Catts, Ionat Zurr and Guy Ben-Ary). McCoy Cell line, biodegradable/bioabsorbable polymers and surgical sutures. From The Tissue Culture & Art(ificial) Wombs Installation, Ars Electronica 2000.

we refer to as the Aesthetics of Disappointment: people, it was reasoned, would be drawn to see the piece because they believed that flying pigs and other biotechnological amazements will be presented to them. Instead they are confronted with tiny humble looking detached wings, made of tissue, which will never fly. The hype is a letdown. 6.4. Extra Ear – 1/4 Scale (the Tissue Culture & Art Project in collaboration with Stelarc 2003) In this collaboration, a quarter-scale replica of the left ear of the Australian artist Stelarc was grown using human and other animal cells. The ear was cultured in a rotating micro-gravity bioreactor which allows the cells to grow in three dimensions. Extra Ear – 1/4 Scale is about two collaborative concerns. The project represents a recognisable human part. However, it is being presented as partial life and brings into question the notions of the wholeness of the body. It is also confronts broader cultural perceptions of ‘life’ given our increasing ability to manipulate living systems. TC&A are dealing with the ethical and perceptual issues stemming from the realisation that living tissue can be sustained, grown, and is able to function outside the body. 6.5. Sugababe (Diemut Strebe 2014) The artist, together with scientists, has regrown “Vincent van Gogh’s ear”. According to the artist, cells from the great-great grandson of van Gogh’s brother, Theo, and other DNA used to construct a living replica of the ear. The ear is “identical” in shape to van Gogh’s ear by using computer imaging technology. The audience can talk to the ear as the input sound is processed by a computer using software that converts it to simulate nerve impulses in real time.

The Immortalisation of Kira and Rama is an ArtScience project that was researched and developed during a three month residency at SymbioticA. The project involved the isolation and display of living cells isolated from the skin of two foetal calves (named by the artist – Kira and Rama) in a custom ancient Egyptian-inspired bioreactor along with various relics from the calves’ bodies (teeth, hide, slides of organs, hearts). The project was inspired by the way in which contemporary technologies, such as cell and tissue culture, alter our perceptions of life and death, as viable cells can be obtained from bodies of organisms that have been dead for over a day. Maintained in the correct conditions, these cells can live for numerous months and even be frozen in liquid nitrogen to be revived months, or even years, later. Through further manipulation such as the introduction of viral DNA, or exposure to chemical agents, the cells can also be immortalised, enabling them to replicate potentially indefinitely. 6.9. In Potentia (Guy Ben-Ary, Kirsten Hudson, Mark Lawson, Stuart Hodgetts 2012) Pluripotent stem cell technology (iPS) used to reverse engineer foreskin cells purchased from an online catalogue into embryonic (like) stem cells, which the artists transformed into neurons. This resulted is a neural network or “biological brain” encased within a purpose built sculptural incubator, containing a purpose built bioreactor as well as a custom-made electrophysiological recording setup that converts neural activity into an unsettling soundscape. The piece has the potential to problematise the shifting forces that govern and determine life, death and personhood. 7. Speculative design and architecture Speculative Design explores design not just as a field to create tools, but rather as a place to create ideas and future speculations. It is important to note; that this area dwells on the possible rather than the actual (Reviewed in Dunne and Raby, 2013). Some of the works coming from speculative design and biology technology are outlined below: 7.1. Living Watch (Oliver Medvedik 2009) The prototype is made of primary chondrocytes grown around biodegradable polymers in a shape of a watch. A watch is a convenient, simple and familiar form that is imbued with deeper

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meanings concerning time. The researcher explains that “The history of design also reserves an important place for timepieces as symbols of the standardisation and mechanisation that were integral to the industrial revolution. . . Should as industrial–biological revolution come to pass – which some argue has already begun – the living watch may become ubiquitous”. 7.2. Half life Lamp (Joris Laarman 2010) This piece explores the idea of creating a lamp that incorporates bioluminescence cells as its lighting device. The same idea guides Symbiosis by Jelta Van Abbema, who suggests the use of bioluminescence cells as street signs. It suggested: “Living letters that grow, change colour, and eventually die. Could this herald a future of living graphic design?”

7.7. In vitro meat habitat (Mitchell Joachim–Terreform 2010) Terreform is a non-profit design group that promotes smart design in cities. Through creative projects and outreach efforts, they aim to bring into focus the environmental possibilities of urban environments around the world. In Vitro Meat Habitat is an architectural proposal for the fabrication of 3D printed extruded pig cells to form real organic dwellings. Sodium benzoate was used as a preservative to kill yeast, bacteria and fungi. Other materials in the model matrix are; collagen powder, xanthan gum, mannitol, cochineal, sodium pyrophosphate, and recycled PET plastic scaffold. As of now, the concept model consists of essentially very expensive fitted cured pork or articulated swine leather with an extensive shelf life. 8. Conclusions

7.3. Biological Atelier (Amy Congdon 2011) Congdon, from the Textile Futures Programme, Central Saint Martin College of the Art & Design, who did a residency in SymbioticA, is offering to grow objects from our own cells (or from other animals that are close to us) as personalised haute couture. She is using tissue engineering techniques to construct and grow accessories and jewellery. 7.4. Manufacturing Monroe (Emily Hayes 2011) The artist presents “A factory of the future” which exploits tissue engineering to grow and manufacture products that contain celebrity biopresence. These products can be then sold as desirable merchandise and paraphernalia for consumers who are who would like to get a real and living piece of their icon. The artist speculates on the ways and regulations of such a factory and offers these possible products: Product 1 – Marilyn Monroe pocket breast, grown from breast tissue from her stolen breast from her autopsy on August 5th, 1962. Product 2 – Michael Jackson brain slice, grown from his missing brain from his golden casket on the day of his funeral on July 7th 2009. Product 3 – John F Kennedy fabric, grown from his foreskin that was removed at the age of 21, in February 1938, due to irritation and tightness.” 7.5. Biojewellery (Tobie Kerridge and Nikki Stott 2005) A collaborative project involving design researchers at the Royal College of Art, and Ian Thompson, a bioengineer at Kings College London, with the aim is to bring the medical and technical processes of bioengineering out of the lab and into the public arena. The idea was to get about to wed couples to donate their own cells (mainly through the procedure of tooth extraction) to form, using tissue engineering techniques, wedding rings. 7.6. Bullet Proof Skin (Jalila Essaïdi 2012) The artist working with a team of scientists to create a new material: Genetically modified silkworms which produce spidersilk proteins have evolved into cocoons. Their cocoons were reeled into thread and woven into fabric. The modified silk was then wedged between bioengineered skin cells developed by biochemist Abdoelwaheb El Ghalbzouri at the Leiden University Medical Centre in the Netherlands and grown for five weeks. The artist then shot a half speed bullet through this bioengineered skin and photographed the process in very slow speed. The work concerns new materiality, hybridity of species, the history of warfare and the meaning of safety.

This is a partial survey of some of the works and suggested uses of tissue engineering technologies for purposes that goes beyond the strictly biomedical realm. What this survey does is to give the reader a glimpse into current and future uses of regenerative biology as a tool of cultural expression and production. While some of the suggestions are commercial in nature, others are symbolic, aesthetic and even critical of the use of tissue as a medium for manipulation. An important example outlined in this paper discusses the possibility of in vitro meat (or Semi-Living steak) that was grown and consumed first in an artistic context and then as a media publicity of a new techno-scientific product. While the artists emphasised the complications arising from the “victimless” meat endeavour, this was not the case when the idea was promoted as a product. The artists looked at this techno-scientific project with the criticality that it may create an illusion of technologically mediated victimless utopia. First, in order to grow in vitro meat, there is still the need for a serum extracted from animals’ blood. Although there is some research to find alternatives for this ingredient there is no solution in the near sight and animals (mainly foetal calves) are scarified for that ingredient. Second, all the “costs” concerned the running of a laboratory, i.e. fossil fuels burned, greenhouse gases produces, water and trees consumed, miles travelled and the waste created. Third there is a shift from ‘the red in tooth and claw’ of nature to a mediated nature. The victims are pushed farther away; they still exist, but are much more implicit. Hence, the animal is abstracted into fragments and mediated through technological apparatuses. When in vitro meat is promoted as a consumer product, all these aspects – which should be debated publically – tend to be hidden. There is an increase in the use of living matter as technology, and in treating life as a raw material that can be manipulated and engineered. Human relationship to life is increasingly confronted with our ability to intervene at all levels of the life processes. Just as engineers are entering the field of the life sciences to offer engineering solutions and utilitarian applications, so should artists, who offer non-utilitarian artefacts and gestures, participate in this field to problematise, provoke in order to create a cultural discussion and subvert some of the dominant understandings and uses of living material. One way to emphasise and attract attention to alternative frames of thought is to open up the very same tools and spaces that serve this future to other disciplines, including artistic. References Akiyama Y, Furukawa Y, Morishima K. Controllable bio-microactuator powered by muscle cells. Conf Proc IEEE Eng Med Biol Soc 2006;Suppl.:6565–8. Aldersey-Williams H, Hall P, Sargent T, Antonelli P. Design and the elastic mind. NY: MoMA Press; 2008. Anotnelli P. States of design 07: bio-design. Domus magazine. Rozzano, MI, Italy, vol. 952; 2011.

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Patents Patent: WO 1999031223 A1: Industrial production of meat from in vitro cell cultures http://www.google.com/ patents/WO1999031223A1?cl=en Retrieved 22/05/2014.

Growing for different ends.

Tissue engineering and regenerative biology are usually discussed in relation to biomedical research and applications. However, hand in hand with deve...
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