Playable Virus: HIV Molecular Aesthetics in Science and Popular Culture

Playing microbiology: molecular space goes public

Although it had been attempted many times before, the puzzle was considered more intractable than impossible. Video game players, twisting a ribbon into complex and delicate shapes while avoiding overlaps and other problems represented by small, red, spiked orbs, worked toward a high score. After 10 days of play, undertaken by hundreds of gamers from around the globe, one user was able to fold the ribbon in such a way that it avoided errors or spiky interferences. Her score rushed up the leader board, her teammates sent congratulations, and her process for discovering the pattern immediately interested a number of players. Gaming is, after all, competitive, and scores are kept. Not all interested parties, though, were gamers. They were computational and experimental biologists, reporters, the public. In finding the perfect arrangement of folds and twists, the player mimi had indeed achieved a high score and notoriety. She had, as well, discovered the shape of an important and long-researched protease. The game is Foldit, and in just over a week players had folded a solution describing a structure, representing a protein important to Mason-Pfizer Monkey Virus (M-PMV). For 15 years, all manner of other attempts, by humans and by complex computer programs, had been made to solve this puzzle using physical models, simulations, and algorithms. It was in the game that the pieces were shaped into alignment. A high score, yes. But also: a scientific discovery of immediate experimental importance.

This article argues that Foldit offers a means of animating molecular space that allows players to participate in advanced research, producing a mobile vision of molecular material in which proteins are folded, played, and collaborated with in order to develop new understandings, and new images, of how life functions at the level of molecules. ¹ Moreover, the specific cultural moment of Foldit, as much as the material practices of protein analysis built into the game, determine the way molecular space is publicly animated. While it is not the only or the most scientifically productive mode of scalar travel, the game illustrates the profound ways that cultural practices shape and are shaped by molecular thinking.

Developed at the University of Washington, Foldit is a protein folding game that converts the rules of molecular structure into game parameters, allowing non-scientists to conduct research, especially pattern recognition. ² Because the rules of folding are well known, ³ advanced processing power enabling molecular model simulation is readily available, and online networking provides the game to an unlimited number of players, Foldit neatly integrates the culture of gaming into the culture of research. As players interact with the game’s rules and models, they score points. But they also create animated structures that interact with the simulated molecular environment. Through play, then, a moving vision of molecular space is animated. Other non-gaming experiments enlist the public in scientific work. A precursor to Foldit, Rosetta@home, for example, creates a screen where individuals see their spare processor power being used by lab-based researchers. ⁴ SETI@home, too, allows users to offer processing power to search for signs of life in otherwise chaotic galactic radio noise. ⁵ Do-it-yourself (DIY) molecular biology, in which untrained individuals purchase and perform biological experiments, has begun to occur in garages and kitchens. ⁶ Everywhere, molecular biology is going public. But with Foldit, the quick successful solution to a longstanding problem highlighted the importance not just of computer processors and hobbyists, but also of non-expert skills, including game-play and the capacity to imagine and mentally rotate structures.

Players may work on puzzles individually or in groups. Groups are collectively scored and have a team ranking. Currently ranked second, the Contenders group describes itself as ‘sociable but dedicated’ and claims to ‘work differently’; players are ‘free to express themselves’ once they join the Contenders, which they do by application. ⁷ Members of team Contenders were included as co-authors reporting the M-PMV protease solution, published in 2011 in the journal Nature Structural & Molecular Biology (Khatib et al., 2011). Because M-PMV is a retrovirus, potential treatment involves antiretroviral medications, as noted in the paper:

Following the failure of a wide range of attempts to solve the crystal structure of M-PMV retroviral protease by molecular replacement, we challenged players … to produce accurate models … Remarkably, Foldit players were able to generate models … that provide[d] new insights for the design of antiretroviral drugs. (p. 1175) ⁸

Their success was in part due to the game’s design. Foldit ‘leverage[s] human three-dimensional problem-solving skills to interact with protein structures using direct manipulation tools and algorithms’ (p. 1175). Scientists developed visual representations of molecular parts, including amino acids, connection bonds, and spatial limitations. Given these conditions, players work with teammates in a competition against other teams to get the highest score, which correlates to the lowest-energy (or most likely) structure for a given protein.

In part they do this by moving the simulation around, rotating models, resetting problems, and noting partial solutions using an in-game tool bar. Players can click the model and move its orientation, for example, giving themselves a unique perspective not governed by the game itself. In short: players animate the model in a search for a 3D pattern that meets the structural requirements of a protein’s function, determined by how it is folded. The Nature report includes a time-line graph showing the series of steps undertaken by a number of players. Starting with a structure reminiscent of tangled yarn, users swapped various models, threading together pieces of the protein in three dimensions, and sharing their steps with other players. After over 60,000 models, each representing a different possible molecular shape for the M-PMV protease, ‘Foldit player mimi made additional improvements … and generated a model … of sufficient accuracy to provide an unambiguous molecular replacement solution’ (p. 1176). The protease mimi was working on, part of M-PMV, is crucial in the viral infection cycle, which is immunosuppressive.

Gathering up both gaming and molecular research, the report concludes that the player-generated model might be used to develop ‘anti-retroviral drugs, including anti-HIV drugs’ and that ‘although much attention has recently been given to … game playing, this is the first instance that we are aware of in which online gamers solved a longstanding scientific problem’ (p. 1177). The solution did not come from better data processing, nor did it arise from the sheer computational power of users. Rather, players are given a system in which their work animates the theory of protein folding, represented on screens as ribbons. ⁹ While a computer might algorithmically match protein structures based on data, players use a graphical interface, in which molecular space is enlarged and through which their intuitions about structures and patterns are given life in the playable environment. The findings of the Nature paper structured the popular and academic interest in the relationship between gaming and scientific research. Reporters noted that gamers’ competitiveness proved that humans had skills such as spatial pattern recognition that could not be simulated by machines (for example, see Coren and Fast Company, 2011; Praetorius, 2011). For instance, computers have difficulty seeing the molecular model as a shape that moves in three dimensions in an environment. The visibility of the animated simulation thus plays to the spatial and pattern recognition skills of human players. Other reporters noted that, given the crucial role of the protease, the newfound structural understanding could help drug development. Widely celebrated was the novelty of coupling advanced scientific simulation with leaderboards and team competitions. Quoting Seth Cooper, Foldit’s developer, one reporter agreed that ‘games provide a framework for bringing together the strengths of computers and humans’ (Boyle, 2011: np). ¹⁰ Dozens of web-videos use animated Foldit models, images of players at their computers, and interviews to illustrate the fun, importance, and complexity of the game; indeed, an entire YouTube channel is devoted to videos about Foldit. Academic researchers, too, studied how players used gaming as a form of good citizenship, the unique basis of human pattern-recognition skills, and the use of gaming to teach molecular biology to non-scientists. ¹¹

Certainly, this is an important framework for understanding games like Foldit. After all, most popular coverage of gaming involves the potential risks play poses to society, including violence and negative gender stereotypes. Representations of gaming in films, from War Games (John Badham, 1983) to The Lawnmower Man (Brett Leonard, 1992) and Gamer (Mark Neveldine and Brian Taylor, 2009) implicate games in destroying human life, emotionally and physically. Insofar as it reverses this trend, celebratory coverage of Foldit as in the HuffingtonPost, Arstechnica and Time is an important reminder that gaming is a complex phenomenon with no single social effect (Horn, 2011; Praetorius, 2011; Timmer, 2010). Moreover, in evoking a relationship to HIV, this coverage couples molecular point of view to the public mission of curing disease. In part, this explains why cultural commentary on Foldit associated this single protease to longstanding AIDS research, a connection that was not the direct scientific context of mimi’s M-PMV solution.

The protease, in fact, was only one of a number of proteins of M-PMV, which by mass is 60 per cent protein. Still, in many popular accounts, this solution was taken up as a potentially important step on the way to creating new treatments, including new antiretroviral medicines for HIV. Moreover, this solution was thought of by the players themselves as embedded within the tradition of AIDS research. The chasm between what was actually represented and a cure for HIV suggests a continuing interface problem between advanced research and public understanding, between the power of imagery to suggest great and sweeping change and the incremental work of science. In addition to specific proteins, Foldit animates the tensions that structure this ongoing conversation. Even though widespread reporting suggested a clear link between the M-PMV and HIV, what, indeed, did the Foldit solution actually illustrate?

M-PMV was initially observed in 1970, and was long thought to induce simian AIDS. However, while both M-PMV and SIV promote, like HIV, immunodeficiency, the latter is more akin to HIV, while the former is a different type of retrovirus altogether. Still, M-PMV has been used in research on HIV, including the fusing of M-PMV and HIV to study viral assembly. One article suggests that the relationship between viral proteins is strong enough that they can be fused together into a chimera for comparative research (Sakalian et al. 2002). However, Foldit players were not presented with an entire virus; rather, they were given a model of a protein-cutting enzyme, the M-PMV retroviral protease. Importantly, this model refers to protein active in a monkey virus. Why, then, did popular coverage of a protein folding game suggest repeatedly that, ‘the cracking of the M-PMV retroviral protease is the biggest success to date not only because the enzyme is important in the study of AIDS, cancer and Alzheimer[’]s, but also because the problem had proved so intractable?’ (Heaven, 2011). Perhaps, in part, members of the public need to be enrolled in solving research problems without any scientific knowledge, driven by a desire to help people, rather than the desire to produce scientific knowledge. The repeated references to AIDS suggest that this particular Foldit puzzle attracted attention because of the social and cultural context justifying player interest, given they have no specific research context for understanding what Foldit represents (Moskvitch, 2011). In interviews, mimi regularly noted the desire to help others. While this is certainly no substitute for advanced scientific knowledge and ongoing AIDS research, expert discourse is immaterial to the work of Foldit players, who employ spatial reasoning – and not the logic and information inherent to complex understandings of molecular biology – in their puzzle solutions.

In part, the original Nature article makes the connection, though the suggestion does not imply direct application or immediate benefit to drug development or even increased knowledge about HIV. Still, the popular press amplified this connection beyond what was originally reported. But it cannot be denied that for players, the Foldit M-PMV puzzle was played and solved in the name of AIDS science, establishing a strong visual link between the iconography of Foldit and HIV research. Hundreds of other Foldit puzzles refer to proteins that have nothing to do with HIV, at all. But the extent to which Foldit imagery is represented in public culture is largely defined by its connection to this experimentally important achievement. Thus, the translation of the M-PMV solution from a strictly scientific to a popular context – a process that underwrites the very effectiveness of the game, and one that is fraught with inaccuracies and misunderstandings – enabled a collective rejuvenation of public discourse aimed at participating in ‘AIDS science’.

Thirty years before Foldit, molecular perspective was achieved most notably in the form of electron microscopy, which produced powerful and politicized images, including extreme close-ups of HIV. In molecular visualizations, material objects such as viruses and proteins are assumed to be naturally and truthfully uncovered through dispassionate research, often using advanced technologies. However, in the history of HIV research, molecular imaging is not disconnected from the broader public discourse of HIV/AIDS. Molecular points of view give visual form and material structure to cultural debates, uniting the work of imaging with practices of managing HIV/AIDS. Prior efforts to image molecular space largely resulted in photorealistic, color-contrasted images that evoked a concept of molecular life as full of frightful foreign matter. Now, through animation, molecular parts are understood as malleable, constantly in flux, diverse, plural. In coverage of Foldit’s successful description of M-PMV retroviral protease, the relation of this achievement to the history of the public interest and involvement in HIV research was reactivated, energizing a dimension of public health activism largely divorced from high-technology, capital-dependent HIV research. Coupled to the speed of sharing enabled by video sites such as YouTube, interest in molecular aesthetics has increased, carrying the animated model of molecular objects into a variety of non-laboratory contexts. The example of Foldit, then, shows that molecular practices are forms of cultural politics that are enabled and limited iconographically and ideologically.

Molecular aesthetics in popular culture: Impure science and expert images

HIV/AIDS science has been marked by long periods of difficult basic research, with infrequent excitement at the hope of a new cure, vaccine, or treatment. Much of the knowledge generated by HIV research has been converted into breakthroughs in treatment, reducing the mortality rate and extending life for many people living with AIDS. These breakthroughs include developing antiretroviral medicines such as AZT and newer medications such as once-a-day Atripla, efficient and cheap screening methods, protocols for health workers, safe sex practices and public awareness. Representational techniques have been crucial to a number of these advances. This section traces the particular importance of molecular animations via image making that has, in part, marked HIV as a particularly visual disease. Travel to the molecular scale of microbiology, including HIV/AIDS research, has undergone many changes since the 1980s, when the use of scanning electron microscopy made possible viral magnification many millions of times, exposing structures that standard microscopes cannot. ¹² Genetic mapping, visualized on computer monitors in blocks of color, is a common technique. Linking advanced computation to microscopy, data about magnified structures can be recorded, enabling video animations. ¹³ Foldit, then, is part of a long tradition of experimentation generating novel ways to achieve molecular perspective. This section will focus on two moments in a longer history of AIDS imagery, important in that they illustrate the various ways aesthetics is central to cultural debates about the relationship between the body and its microscopic parts.

While many types of representation are used in medical research, in the 30-year history of biomedical visualizations of HIV, the image of the ‘viral other’ has received particular public attention. Represented as a menacing foreign object, this imagery suggests a relation of threat and containment with strong ties to Cold War ideology. ¹⁴ As Sander Gilman (1987: 88) noted:

Disease is thus restricted to a specific set of images, thereby forming a visual boundary, a limit to the idea (or fear) of disease. The creation of the image of AIDS must be understood as part of this ongoing attempt to isolate and control disease.

As the visible manifestation of this control, the typical image shows a T-cell under siege. The images are often enlarged, colour contrasted to indicate human and foreign matter, and set against non-biological backgrounds (see Figure 1). In one image, for example, a T-cell is shown infected with HIV. The green-blue sweeps of the human cell are near rupturing, as HIV has replicated inside the cell and will spread upon release. Extracted from the body, the infected cell is set against a solid black background. As if seen from outer space, the virus explodes the sanctity of molecular identity; the human body needs protection, even at the molecular scale. Even 20 years after the end of the Cold War, images showing the distribution of spikes on the virus’s outer surface have come to signify the need for HIV containment and eradication, and are often presented in purely visual space, extracted from the body (Zhu et al., 2006). In 2006 and 2007, two advances in HIV imaging – one that allows scientists to see receptors on the surface of the cell, and another that illustrates the initial interaction of HIV with a white blood cell – returned media focus to the importance of molecular AIDS imagery to ongoing research (Zhu et al., 2006). As the chemist Tami Spector (2003) has noted, in biomedical science,

in contrast to the disease’s grotesque physical effects depicted in medical and media images, AIDS is encapsulated by images of [HIV] and computer renderings of the structure of HIV protease. Thus, scientists are compelled not only by their desire to understand the pathologic mechanisms of AIDS, but also by a fascination fostered by the aesthetics of their models of HIV and its molecular components. (p. 62)

Moreover,

for molecular scientists, HIV protease transforms disorder into order by refracting its exquisite form into a scientific object with a concise molecular structure that can be catalogued, refined, and transmuted; a medicinal object that can be pharmacologically exploited; and, a cultural object that absents the human form and psychologically mollifies the chaos of the disease represented by the person with AIDS. (p. 67, emphasis added)

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Figure 1.

Colorized image of HIV-infected H9 T-cell. © National Institute of Allergy and Infectious Diseases. Image in the public domain.

Indeed, controlling the virus through graphics and animation has been crucial to establishing human control over the molecular barbarism and chaos of viral others; as Deborah Lupton (2007: 560) has noted as well, the relation of control and chaos is the conduit through which metaphors of viral contagion have been mapped onto computer culture more generally, converting particularly molecular concerns into cultural worries about the structural integrity and stability of digital machines. While magnification, graphical isolation, and chemical abstraction divorce the molecular from the human, processes like those employed in Foldit, using simulation and animation, networking, and gamification, show that the effect of molecular modelling need not decouple molecular perspective from human concerns. ¹⁵ In molecular representations, viewers are given a visual syntax through which to think about life at a different scale, but also about what it means to be human or not, to be isolated or a member of a community, an expert or an onlooker. More generally, molecular images disseminate particular ways of biomedical thinking about infection and illness within popular culture, becoming public biomedical artifacts that are not always and perfectly legible in terms of what they represent, but rather as an experience of scale shifting. These artifacts are at once didactic and pleasurable; they are boundary objects in which technology and culture meet and take shape.

In terms of scale, Nikolas Rose (2006: 12) has argued that molecular biology, along with other techniques, uses imagery to locate questions of human life in molecular space. This molecular focus is contrasted, in spatial and scalar terms, to what Rose calls a ‘molar self’. Fluids such as blood, and tissues such as organs make up the biological matter of a molar self. ‘This is the visible, tangible body’, he states, ‘as pictured in the cinema or on the TV screen … Today, however’, Rose argues, ‘biomedicine visualizes life at another level – the molecular level’ (p. 12). Further, he shows that, ‘the laboratory has become a kind of factory for the creation of new forms of molecular life. And in so doing, it is fabricating a new way of understanding life itself’ (p. 13). Central to this process is access to the molecular scale, often gained through imaging. In redefining what life is in molecular terms, scientists hope to provide individualized molecular medicine that treats ‘biologically risky or at risk individuals … by medical intervention at the molecular level’ (p. 40). ¹⁶ Moreover, molecular imaging asserts the need for advanced technology, skilled experts, and free enterprise to guide our understanding of life itself. While many interventions into the lives of PWA have been molar – calls for quarantine, safe sex protocols – others, such as AZT treatment regimens, work at the molecular level. Both suggest the continued importance of both science and culture in managing HIV.

HIV science, including imaging practices, emerged as the ‘epidemic’ spread to thousands of individuals in the early 1980s. Because gay men were the first visible population to experience high rates of infection, and because of widespread cultural homophobia, not only were gay men blamed as the cause of HIV, but ‘solutions’ ranged from quarantine to incarceration. It is within this cultural climate that the virus replicated, biologically and visually. Simon Watney argued in 1987 that the standard visual structure of HIV’s public image takes the form of a diptych that is at once molar and molecular. Homosexuality is the virus, and the reality of its deadly nature is disclosed in the molecular aesthetics of the asteroid. He shows that this relation can only be accomplished through the isolation and iconographic display of the deadly cause and effect (homosexuality/illness) of the virus.

We may glimpse something of the political unconscious of the visual register of AIDS commentary, which assumes the form of a diptych. On one panel we are shown the HIV retrovirus … made to appear, by means of electron microscopy or reconstructive computer graphics, like a huge Technicolor asteroid. On the other panel we witness the ‘AIDS victim,’ usually hospitalized … This is the spectacle of AIDS. (p. 78, emphasis in original)

Of course, many means of molecular representation have been developed since 1987; however, it was the political response to the representational economy that embedded scientific image-making practices into the larger discussion of HIV/AIDS. Especially in the early years of viral imaging, laboratory-based scientists produced molecular images of HIV. In part, this was because they had access to the equipment necessary to magnify and image the virus. While today many of the static images are produced using computation, including image combination, that produces animations, the aesthetics of HIV are largely contained by laboratory practices due to the continued need for high-powered tools. Because the process requires the technical training, a biological model with which to look for the virus (and not, for example, accidentally image something else), and equipment and space, these pictures are ‘expert images’. By this, I mean to suggest that molecular visions of HIV have traditionally been represented through scientific means, which are then apprehended in popular culture as aesthetic objects, medical and ideological simultaneously, subject to interpretive practices by which the public addresses medical imagery (often as foreign, dangerous matter), and the political and institutional frameworks that enable and constrain these interpretations. And yet, as the inaccurate uptake of Foldit as ‘AIDS science’ indicates, there is a powerful ‘interface problem’ between AIDS research and popular culture that is in part a product of scale and in part the result of a lack of public access to tools used to produce molecular images. Importantly, games such as Foldit trouble the producer/consumer divide, activating democratic access to the protocols of making scientific knowledge through practices of visualization, animating a theory of life in the play of users. As media attention focuses increasingly on the technical wonder of advanced imaging, including digital fly-through and extreme sub-visible ‘close-up’, the role of cultural practices risks obscurity. Scientific work, though, is certainly concerned with human health and meaningful disease prevention and treatment. Still, in molecular aesthetics, this concern is difficult to discern, as the images are themselves abstract and easily misunderstood.

As historian of science Steven Epstein shows, the status of the scientific expert was contested during the early years of the HIV/AIDS crisis. The ‘impure science’ of AIDS research is partially related to the historical timing of its emergence in the early 1980s, in which activists demanded epistemic parity with and participation in biomedicine. Epstein (1996: 3) suggests that:

From a scientific standpoint, the sheer complexity of AIDS has ensured the participation of scientists from a range of disciplines, all of them bringing their particular, often competing, claims to credibility. But AIDS has also been a politicised epidemic.

Because of how those with HIV were treated in the early years of the epidemic, non-scientist activists made a set of moral demands on state-funded and private research that allowed them to intervene in the production of scientific knowledge about HIV, including development of treatment regimens, hospital protocols, antibody test development, education, and condom access. AIDS research is thus a form of impure science, in which basic research is conducted, in part, as public discourse. The Aids Coalition to Unleash Power (ACT UP) was an early and important community response to HIV/AIDS, whose work crucially highlighted the role of imagery and representation. As TV Reed (2005: 180) has noted, ‘part of the genius of ACT UP … has been the group’s amazing creativity, particularly through the use of the visual and performing arts.’ The work of ACT UP was not only to critique the packaging of HIV discourse by the media; the coalition made its own visual matter – videos, posters, performance art, television – through which it could disseminate a different view about HIV. Moreover, ACT UP demanded that the scientific perspective – including scientific images – move outside of the context of the laboratory and become a topic that activists could contest.

Again, Foldit is a protein folding game that offers puzzles that come from many areas of molecular biology; it is not a game designed to ‘solve AIDS’. The connection was, though, widely reported and repeated in media including popular and specialist journalism, incorporated into the vocabulary players used to describe their own efforts and desires, and provided a context used in podcasts and educational video to illustrate the powerful possibilities enabled by enlisting thousands of researchers in solving complex molecular problems. In one podcast, for example, a 13-year-old describes getting first place in many puzzle competitions, suggesting the import of expanding access to the means of producing molecular representation (Lilley, 2011). The transformation of scale enabled by Foldit, from the everyday point of view to the molecular, is abrupt. It is matched by a corresponding enlargement of the imagined role players take for themselves, working on a single retroviral protease in the hopes of finding a ‘cure for AIDS’. Of course, the invocation of a potential cure is part of scientific discourse itself, and recent efforts to map the HIV genome and develop a vaccine, plus the discovery of ‘super controllers’ who have natural immunities to HIV infection, have increased hope for new avenues to a cure (Virgin and Walker, 2010; Walker et al., 2011). Scale thus works in both directions, animating molecular space and also the desire to participate in transnational attempts to advance scientific research – and win games.

Certainly, 1980s electron microscopy and protein folding are not the only ways of imaging molecular space, much less the only visualization techniques used in AIDS science. What makes Foldit interesting, I argue, is that the game activates the political claims made by ACT UP as practices of medical visualization through the use of networked gaming, providing a form of what Lucas Hilderbrand (2006) calls, in particular reference to ACT UP, retroactivism, with an emphasis on community and innovative politics. Taking seriously the possibility that the public can be producers of scientific reality at the molecular scale, Foldit might be understood as a form of molecular retroactivism. In the next section, I will describe the cultural and visual economies enabling a shift in how molecular space is imagined, and how this shift alters where scientific knowledge might come from in the 21st century. While rightly understood as a wondrous achievement in coupling gaming to research, Foldit is equally a shift in the moral imaginary of what counts as life. The look of the virus – magnified, isolated, color-contrasted – has managed continually to remind us of its laboratory origins, linking the metaphors of contagion and containment to the supposedly realist space of the photograph, uniting the reality-effect of photography to the real consequences of disease. High-power photorealism is an important, but not exclusive, means of creating molecular knowledge.

You are not alone: Collaborative animations of molecular space

In Foldit, simulation, aesthetic simplification, and game scoring offer a molecular scale that is clearly a game, part of a cultural process of encoding microbiological thinking into everyday life (see Figure 2). Changing from ‘the real’ of microscopy to ‘the simulated’ of computational biology, the photograph to the animated model, Foldit introduces both a means of collaborative, community-based scientific visualization, and a relation of play to techniques of scalar travel. In Foldit, viral proteins become problems collectively twisted into more elegant and elaborate shapes, solutions for science but also for fun. This aesthetic shift is not simply about techniques of viewing, but also about the political and cultural stakes that animate the ongoing attempt to graphically and socially manage disease, including HIV.

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Figure 2.

Foldit protein showing base nucleotides (ribbons) twisted in a molecular environment. Team scores are listed upper right, and individual player scores above the molecule. © Center for Game Science, University of Washington. Reproduced with permission of the Center for Game Science at the University of Washington.

If it is the case that Foldit provides a new means of addressing molecular space, then under what conditions is an altered perspective possible, and with what potential consequences? In addition to data collection regarding molecular protein structures, many crucial developments in infrastructure, gaming industry and player maturation, and popular culture were necessary to make Foldit’s molecular point of view possible; in this way, the game is not solely a product of scientific expertise but more accurately an impure science. The conditions of possibility enabling the molecular retroactivism enabled by Foldit include increased prominence of gaming in daily life, especially the integration of game play as a form of social engagement, computer simulation and modelling using consumer electronics, and the diversification of narrative and visualization strategies within game production that have led to the rise of ‘bio-games’, or games that ‘jump scale’ and are centrally concerned not with bodies, but with how narratives of biological processes, at once didactic and pleasurable, are created (Cohen, 2011).

Early video games were crafted to allow users to move through a world created by designers. Game play in Megaman (1987) and Metroid (1986) included solving simple puzzles, finishing levels and beating a clock. While some early games, such as Habitat (1986), were networked, most were played locally. And while many games were strongly influenced by science fiction, including technologies produced by war, none could claim to be essentially scientific. Contemporary bio-games, though, using advanced processors, high-definition screens, and networks, design spaces and narratives that allow users to engage laboratories, and in some cases, molecular perspective suggested by high-tech microbiology. In 1997’s Fallout, for example, players navigate a post-apocalyptic planet scorched by nuclear conflict. The game, which forces players to explore a biologically mutated Earth, suggests a sense of doom and military science run amok. Ten years later, Bioshock, which again asks players to explore a world riddled by conflict and experimentation gone awry, cemented the role of scientific spaces and topics – the laboratory, the ethical responsibilities of researchers, the role of corporations and ideology in shaping the use of technology – as central to the development of video games.

In 2011, users could play Child of Eden on Microsoft’s Kinect. In this game system, interaction is achieved through body movements, rather than a controller. The plot, which involves attempting to give a personality to the archive of human thought (rendering the collective archive as a living, individual being, shown to players as a number of levels and moving organisms), is relatively simple, as is the exhausting gameplay. A virus threatens the archive, and must be eliminated. While the hand and arm motions are repetitive, the explosive animated environments are full of molecules that the player eliminates by moving their body. Engaged in a battle with viral matter to save human hope, the user is asked to take on a molecular point of view, and to eliminate the foreign matter whose threat is viral. Occupying the scalar space of molecular life, the player’s thoughts and movements are staged as a simulation of the body’s immune system, enrolling the molar body in the defense of its microscopic parts. Here, then, the player literally embodies the Cold War mentality that structured immunological representations of the body’s ‘defense system’ that formed the foundation of early molecular HIV representations (Haraway, 1990).

Games such as these accomplish two related tasks as part of popular culture. First, in asking players to consider biological narratives as essential to the survival of both the body and the species, they train players to think from the point of view of biomedicine. Second, they present players with an animated iconography and aesthetic apparatus with which to think about molecular objects. By integrating laboratory spaces and equipment, tasks such as research and development, and imagery such as body scans and molecular models into their narrative space, games such as Fallout and Child of Eden incorporate the discovery of knowledge about molecular biology, among other topics, into the spaces of visual pleasure. Thus, these games – like the commercials, medical dramas, and films with which they share these concerns and visual techniques – animate the advanced optics necessary for the success of molecular biology as a particular way of knowing what constitutes life, but as entertainment.

Given the shared need for visualization, microscopic point of view, 3D rendering, mobile perspective, and visual and tactile interfaces to achieve molecular access, it is not surprising that the relationship between gaming and medical research has become productive. Scholars have documented experiments in the use of gaming as a scientific and medical tool. In addition, they have pointed to the creation of games as a pedagogical apparatus for training health professionals and teaching students. These games, which treat social issues as problems that can be solved using gameplay, are forms of gamification. As discussed by Nick Pelling (2004), who coined the term ‘gamification’, Jane McGonigal (2011) and others, this concept stands for the use of gameplay and game mechanics in non-game contexts. Players might, for example, be charged with establishing strategies for environmental cleanup by playing through a number of scenarios. In this context, medicine or physics students might work through a curriculum, or gain badges and rewards for key achievements. Foldit, using crowdsourcing, networking and points scoring, treats protein structuring as a game, allowing individuals or teams to animate microbiological theories as play.

Media theorist Elizabeth Losh (2007) has argued that some serious games, as part of their rhetorical structure, make available to users a kind of expertise that acts as a professional training ground. In part, learning is achieved by creating a porous membrane between the user’s point of view and the sub-visible spaces of microbiology. She notes that in these games, ‘if constraints on what is revealed and concealed from the learner can be read as making manifest a spatial representation of the rituals and rules of medical knowledge’, then they are serious not just in their content, but also as a form of cultural politics (p. 103). She describes Immune Attack, a supplement to a high school biology textbook that ‘takes place from the perspective of a fluid-borne nanobot for which the vessels of the human body serve as a combination of exploratory classroom and chaotic war-zone’ (p. 103). This game, importantly, can be downloaded; however, play is educational, rather than research-oriented.

Other games, such as Primary Care of the HIV-AIDS Patient, locate the user/student in a virtual clinic. Highlighting the roles of spatial access in accruing medical knowledge, the game’s spaces are ‘demarcated by computer-generated graphics that depict floor plans, cutaways, hallways, and closed doors’ (Losh, 2007: 110). As the protagonist, users explore both the topography of the clinic and that of the patient’s body, gaining access to both through the privileged point of view of medical expertise and, as well, through the privileged access to advanced computer simulation technologies. In another game, players act as an HIV prevention counsellor. Uniting playability with the concerns of medical professionals and researchers, these games provide and secure privileged epistemological and visual access to medical knowledge. When they take up the microscopic point of view in this kind of travel through the membrane of the visible world, experts are invested with the power to know molecular life. The assumed authority over the matter under examination granted by visualization is linked, then, to the ability to meaningfully access the image-making practices essential to medical and scientific research.

While many of these games are made available to students, instructors, and researchers with affiliations to specific institutions, which invest millions of dollars producing, licensing, and securing software and hardware, Foldit harnesses the power of networks to provide, analyze, and use game play as a public research tool. With a user account, players download Foldit software for free. After initial training puzzles, high scores are reported to researchers. Scores and outcomes become not simple puzzles that are solved, but potential protein structures that can add important information to other types of research and attempts to discover possible treatments or cures. While playing, the user has control over the point of view from which the ribbon is seen, granting them authority over the molecular space itself, as well as the target protein/ribbon. They move the ribbon into different shapes, watching their score increase or decrease based on the relative conformity of the protein to the chemical rules of folding. A twist that decreases the score can be undone, registered as an unsuccessful attempt, and the puzzle can be reset. Some puzzles, such as the M-PMV protease problem solved by mimi, have tens of thousands of attempts before being solved; the Foldit puzzle list currently shows 778 total puzzles, including many that remain unsolved, provoking players to derive more ingenious twists and folds. By working and reworking structures, manipulating the point of view, and logging successes and failures, users become producers of molecular knowledge as gamers, and not as pseudo-experts or armchair scientists. Using the cultural work of gaming to produce molecular knowledge, players of Foldit, then, activate the political claims of ACT UP but within the context of molecular research and imaging itself, rather than as an exterior social critique of patterns of medical practice. Especially as scientists actively seek out this participation, the oppositional discourse of ACT UP, necessary given the political climate of the 1980s and 1990s, is itself shifted to one of cooperation and collaboration between advanced research and widespread interest in an ‘AIDS cure’. In short, by occupying the point of view of a molecular subject, whose field of vision is defined as animated molecular space, players embody a point of view that is impure, at once part of the special realm of expert knowledge and the animated worlds of computer games. In democratizing who has visual access to and control over molecular space, these games enlist a new set of metaphors in molecular imaging. Of course, there are other practices in AIDS research that produce important results, and other images directly connected to HIV research. However, as a means of democratic knowledge production, Foldit stands as a good example of the potential benefits arising from treating some scientific work as culturally achievable.

Conclusion: Scalar travel in the 21st-century molecular body

As part of the GE Focus Forward Films competition, in 2013 filmmaker Lucy Walker created a short film, The Contenders, which documents Foldit, and the unification of video game play, distributed communities, and scientific research. ¹⁷ At just over three minutes long, the film employs cartoon-style animation, Foldit models, sound effects, and audio recordings of members of the Contenders team to illustrate the history and stakes of the M-PMV solution. At one point, players are drawn sitting at their computers, connected by dashed lines. At another, a Foldit ribbon is shown on a screen integrated into an upright arcade console, highlighting that, while the graphics are part of a piece of scientific research, they are just as at home in the visual spaces of gaming culture. Yet another shows newspaper clippings while an animated version of mimi, the player who made the final M-PMV model, narrates the explosion of interest in Foldit and her motivations for participation. Her cartoon body lies on the ground looking into the sky; mimi’s voice is heard:

Humans will always see faces in clouds; don’t think you can teach a computer to do that. And that’s maybe why the scientists haven’t achieved finding what the shape was in all these years that they’ve been looking at it.

Playful, idle dreaming is thus coupled to specific problems in molecular biology as a new mode of scalar perception that takes the visual culture of research and animates it as a gaming system, defining a new potential mode of knowledge. The short then cuts to one of mimi’s teammates, Renton. Drawn at a coffee shop, he ponders the importance of Foldit:

We’ve given our little input so that people can use it with AIDS-related disease. So Foldit is a game of life. Just have a look at yourself.

As he says this, the animated body is split slightly above the waist. Cut in two and separated, he continues talking. In the gap between his upper and lower halves, a swirling mixture of proteins, which have been grabbed from the virtual space of Foldit and integrated into the animated space of the film, sparkles. He says:

Like, you’re built up of all these proteins and you’re a beautiful person. And I hope that one day all these beautiful things that I can see and the way that I can fold will be able to help someone.

Everyday vernacular and playful animation bring together the molecular point of view (the ‘beautiful things’) with the molar body (the ‘way that I can fold’) into a unified perspective that is at once molecular and cultural.

Electron microscopy and game simulation, along with many other means of visualization not discussed in this article, produce important and necessary molecular visions. Each has allowed researchers to better understand the mechanics of viral replication, enabling a host of techniques for managing the disease, from antibody tests to pharmaceuticals. However, as I have shown, the specific technological and historical contexts of molecular travel are as important as the scientific knowledge these images enable and illustrate. For microscopy, the isolation of viral matter and the stabilization of graphical space combined with the high-technology mode of production in a cultural climate already resistant to gay people and sexual practices to create a refined image of menace that united sexuality to disease. Today, still, this idea endures, even in games such as Child of Eden or Immune Attack, which ask players to defend the sanctity of human life at the level of its molecular parts. But Foldit and other biogames can also enable modes of molecular travel that forward different cultural meanings, including the one produced by the Contenders group, namely that animating molecular perspective within culture is an attempt to help people suffering from disease, even if the direct results are only tangentially related. In this case, I have shown how gamification enabled players to understand themselves as the animating subject uniting molecular and molar selves. Rotating molecules in three dimensions, sharing work with teammates, and treating molecular space as malleable and playable rather than stable and permanent, players were able to unite their spatial and cultural perspectives at the molecular scale as a way of understanding themselves, rather than as an expert displacing the myths of culture with the truths of molecular structure. This strategy is made operable by contemporary techniques of molecular science, which treat protein folding, genetic signals, and other processes as the material substance of life itself. This substance, appropriately known, might yield chemical interventions that are molecularly targeted, enabling not only individualized medicine but molecular refinement. But in their strategies of play, users show that the atomization and individualization of molecular life are coupled to the practices of human interaction and communication, play, pattern recognition, and the drive to make social and cultural improvements for others. Multiple visions of the relation between molecular and molar life are possible, and the contemporary coexistence of microscopy and Foldit suggests that the scalar relations between life and culture are not only structured by biology, but also by the modes of knowledge established in relation to specific historical contexts. If I might fold Donna Haraway’s famous conclusion to Simians, Cyborgs, and Women (1990): in molecular space, culture animates science.