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The Teaching of Immunology Using Educational Gaming Paradigms Patrick Clements Jeremy Pesner University of South Carolina Columbia, SC Dickinson College Carlisle, PA [email protected] [email protected] ABSTRACT Educational gaming is an exciting genre of computer programming that attempts to find interesting and compelling ways to teach while also being fun. Research has been conducted to determine what aspects make certain educational games effective, but there have been no conclusive findings. Combining information about successful educational gaming elements from these studies with our own knowledge, we created an educational game that simulates the processes of human immune systems by using a “Tower defense”-type game. of one type of game over another, and how the game could be innovative, educational, and fun given our development time and skills. 2. EDUCATIONAL GAMES 2.1. Educational games in the past Educational Gaming, immune system. Since computer games were first developed, there has been a significant market for educational games, largely aimed at younger children. Ideas were developed when educators noticed what a magnetic pull Pacman had on gamers. Malone stated that the goals for educational games should be [2]: 1) Clear goals that students find meaningful; 2) Multiple goal structures and scoring to give students feedback on their progress; 3) Multiple difficulty levels to adjust the game difficulty to learner skill; 4) Random elements of surprise; 5) An emotionally appealing fantasy and metaphor that is related to game skills. Many educational games released in the early 90s such as Reader Rabbit (The Learning Company), Math Blaster (Knowledge Adventure), The Oregon Trail (Broderbund Software), Number/Word Munchers (Minnesota Educational Computing Consortium), and Math Rescue (Apogee Software) appear to roughly follow this form. 1. INTRODUCTION 2.2. Educational games today Categories and Subject Descriptors K.8.0 [Personal Computing]: General – Games. J.3 [Life and Medical Sciences]: Biology and genetics. General Terms Design Keywords In 2005, Jim Zheng and Daniel Shegogue coauthored a paper entitled “Object-Oriented Biological System Integration: a SARS Coronavirus Example” which described a parallelism between object-oriented (OO) programming and biological systems. For example, a hierarchical relationship is characterized by inheritance in OO, and characterizing an enzyme as a type of protein in biological systems, while multifunctionality is represented by polymorphism in OO, and enzymes catalyzing different substrates in biological systems. Zheng then wanted to use an educational video game in order to teach interested students about the workings of the immune system. The task of our project was to develop and program a game for the task, using Zheng and Shegogue’s framework as a basis. As frequent gamers ourselves, we were able to bring a lot of informal knowledge to the table, but our project required research into the workings of the immune system, the programmatic practicalities As the sophistication of these games has increased, they have found currency not only with improved games for younger children, but for middle school, high school and even college students. Despite these advances, games have been slow to find favor with most educators. This can be attributed to a general trepidation around new media and methods, along with pundits who claim that games encourage violent behavior, stifle creativity, and/or reduce intelligence. However, in summarizing the many studies done, Kirkegaard found these correlations to be inconclusive at best, and some have claimed that in some cases the experiments themselves were biased [1]. Considerable research has been done into the quantitative effectiveness of games as an educational tool with mixed results. It turns out that no one game experience captures everyone’s attention, thereby preventing games from being a universal instruction method [4]. 2.3. Our educational game To develop our game, we first examined those which came before ours. Most notable is a game called Immune Attack, developed by the Federation of American Scientists. It employs both 3D graphics and voiceovers to present a polished, professionallooking game. The basic story is that a student with a nonfunctioning immune system injects a nanobot into her body. The player then takes control of the device, which is charged with stimulating her immune system to fight off various diseases. The gameplay is reminiscent of other 3D spaceship pilot games (in order to appeal to a genre many gamers are familiar with), but portrays the various cells and pathogens in an accurate fashion. The biological information dispensed during the gameplay is both correct and useful for the player to achieve the stated goals, which are usually tasks related or complementary to those of the cells the player is learning about. produce antibodies if a pathogen with those antigens enters the body again (this leads to “immunity”) [3]. With all this information in mind, we began to devise our game. We wanted to ensure that our game was distinct from Immune Attack, and we came up with several differences: for one, Immune Attack focuses on the innate immune system, while our goal was to teach the adaptive immune system, which will react differently to different antigens. In addition, the complexity of Immune Attack has a steep learning curve to effectively control the nanobot, especially if the player has never played a “space combat” game before. Finally, there is little incentive to play Immune Attack again once it has been completed, as the level designs and objectives do not change. While this game appeared to fulfill most of the qualities Malone laid out, it did not contain an adjustable difficulty level, nor were most elements of the game random (which could lead to players quickly becoming bored with repetition). 3. IMMUNE SYSTEM The immune system includes many interdependent systems of the body, which act to stop invasions by pathogens. Pathogens are any object that causes disease and include bacteria and viruses. When a pathogen enters the bloodstream either through a cut or the mucous membranes in the nose and mouth, it is first recognized by phagocytic cells like macrophages (“big eaters”) (Figure 1 step 1). Phagocytes recognize objects as being either “self” or “non-self” through a protein complex on the surface of all vertebrate cells called the Major Histocompatibility Complex (MHC). After partially digesting any “non-self” cells the phagocyte will present portions of the cell called antigens on its surface using MHC (Figure 1 step 2). Helper T cells then use this information to direct the immune responses of the body [3]. The immune system acts to remove pathogens from the body by two methods called the cell mediated response and the humoral response. Both responses are triggered by Helper T cells. A macrophage that has digested a “non-self” body will then secrete chemicals called cytokines (regulatory molecules that activate cells of the immune system). Specifically, the cytokine secreted by macrophages is called Interleukin-1 (IL-1) (Figure 1 step 3). IL-1 signals Helper T cells to bind to the macrophages presenting the antigen-MHC of pathogens. The Helper T then releases more cytokines, this time Interleukin-2 (IL-2) (Figure 1 step 4). IL-2 triggers both the humoral (B Cells) and cell-mediated (Cytotoxic T Cells) responses of the immune system. For the humoral response IL-2 stimulates B Cells, but for the cell-mediated response it stimulates Cytotoxic T cells [3]. B Cells bind to antigen presenting cells (ATCs) and remember the specific antigen for targeting. Once activated by IL-2 (Figure 1 step 5), B cells respond by developing into either Plasma cells (Figure 1 step 7) or Memory cells (Figure 1 step 8). Plasma cells produce Antibodies (Figure 1 step 9), which bind to the specific pathogens and infected cells that contain the antigen from the ATC (Figure 1 step 10), marking them for destruction by macrophages (Figure 1 step 11). Memory cells “remember” the specific antigen that they were signaled for and immediately Figure 1. Immune Response Process [3]. Cytotoxic T cells also bind to ATCs and remember a specific antigen. They respond to IL-2 by dividing into more Cytotoxic T cells [3]. Cytotoxic T cells are responsible for destroying cells that are infected by pathogens with the antigens from the ATC in order to stop the multiplication of pathogens (Figure 1 step 6). Another type of cell that aids the immune system is the Natural Killer (NK) cell, which acts much like a Cytotoxic T cell, destroying cells that do not have “self” MHC presentations or have damaged MHC presentations (such as cancerous cells) [3]. 4. SOFTWARE PROCESS We knew from the start that our game would not be able to match Immune Attack in terms of technical prowess, but could appeal to a more “lighthearted” gamer. We envisioned a game with two dimensional graphics, controls that were very simple to learn, constantly-updating circumstances, a difficulty setting, a list of high scores, and randomly generated levels to move about in. This would satisfy all of Malone’s points except for the fantasy element. While Immune Attack dispensed the biological facts around a fantasy story, we wanted to keep non-realism to a minimum so that the biological processes and facts would remain the focus of the game. When devising the actual gameplay, we considered the idea of a Real-Time Strategy Game (in which the different cells were directed around in turn-based combat), a shooter (in which a single white blood cell would move around and shoot down antigens), and a Tower of Defense type game (in which the player could supply a number of units to automatically fend off attackers and, depending on how well they do, add more as the game moves on). Eventually, we settled on the third exclusively, as it had the most potential to simulate the biological system as accurately as possible. In our game, the player essentially controls an immune system, which is responsible for creating and sending the correct cells to the pathogens’ locations. Depending on how many pathogens the player is able to help defeat, s/he will have the option to send more help. Our idea adapted a traditional “tower-defense” game into a novel cell-based approach with immune system cells taking the place of towers. One of our main concerns with this idea though was maintaining a fun and involved game that was also educational. The automated, strategic nature of this game could bore players if they were not interacting enough or did not feel their actions made a difference in game play. To counter this we made a few additions that increased user input, which will be discussed in more detail later. Normally in a Tower Defense game, a player must defend a castle with citizens inside it by strategically placing different types of defensive towers along the path of the incoming attackers. The towers automatically shoot at attackers in their vicinity and the player receives points for destroying attackers. After each “wave” of attackers the player can purchase more advanced towers or upgrade existing towers with the points they have earned. Players can save up points over several waves to buy more advanced towers. An attacker that makes it all the way to the castle kills one citizen. The game is over when all of the player’s citizens have been destroyed. In our adaptation, the player has immune system cells to defeat attacking pathogens in the bloodstream. The pathogens enter the bloodstream at random positions and search for cells to infect. The cells available for the player are macrophages, Cytotoxic T cells, Helper T cells, and B Cells (B Cells are capable of developing into Plasma and Memory Cells). These cells act as the “towers” only instead of being stationary they move about in the bloodstream and automatically interact with any pathogens in their vicinity. Also floating in the blood stream are generic cells that act as the “citizens.” Once a pathogen binds to a cell however, it multiplies into several more pathogens. After a wave of pathogens is defeated by the immune system cells, the player can add more cells choosing from those listed above by using points received. In each successive stage, the user’s “citizen” cells regenerate and the number of pathogens increases. Additionally, more user control during each stage has been included to increase both the interaction and interest level of the player as previously mentioned. These additions allow the player to select an immune system cell and direct it towards a pathogen or other cell. When the user selects a target for a cell, it overrides any automatic movements that the cell would normally make. Because the cells cannot “see” other cells outside their range, it is critical that the user directs them at times. The user may also use this feature to protect “citizen” cells from coming into contact with pathogens as they float around in the bloodstream. In order to code these ideas, we organized our thoughts into usecase scenarios, and a state diagram for the overall game. For all of the actors in the game, we had a base class containing information about their position, velocity, their primary target, and data pertaining to cells they had bound with. In addition to this base class, we used two interfaces to consolidate functions that many of the cells would have in common such as the capability to divide. Each of the specific cells were then derived from combinations of these three items and extended to contain all of the specific movements and interactions that each cell undergoes with the others. During game play, all of the cells are placed in a list and looped through, first updating their positions and then checking their interactions with other cells. Cells can react to other cells by either colliding (“binding”) or by being within a certain distance of another cell. The player earns points for buying cells based on the number of “citizen” cells remaining at the end of each wave of pathogens. The player’s score is calculated by adding 20 points every time a pathogen is destroyed, and giving a 221 point bonus for each “citizen” cell that remains at the end of a stage. 5. FUTURE WORKS After playing the game, we found many ways in which it could be improved upon in future versions. With more time, the game could be expanded to include features such as randomly generated levels, different difficulty levels, and several different types of pathogens. Randomly generated levels would allow for both increased size (levels could be partially out of view) and make each game experience unique. Some time was spent with this idea, but we were unable to be complete it in the time we had available. The levels would be similar to a vein network generated from nodes. The nodes would generate branches based on a probability and have a maximum number of branches allowed for each node. Around each line connecting nodes, a box would be created in which the cells float around inside these connected boxes in a network of nodes. With the addition of several different types of pathogens, the game would gain biological accuracy by including immunity as well as an extra fun factor to gameplay. This system would work by making it so that immune responses by the immune cells target specific antigens on the surface of pathogens and pass on these antigens as targets for the Cytotoxic T Cells and B Cells. In this way, each different pathogen would require a separate immune response. Varying degrees of difficulty could use the different types of pathogens to make sure the game fits the abilities of more users. If several types of pathogens were introduced to the game, the difficulty level could increase or decrease the number of types of pathogens that would attack (it would be more difficult to defend against several types of pathogens). The difficulty could also be adjusted by raising or increasing the threshold distance of activation for cells. Separate from the game itself, a framework could be created that would use scripting to allow the user to extend the game by modeling any similar cellular system of the body in a very short period of time. 6. CONCLUSION The effectiveness of our immune defense game could be most definitively measured through actual human testing of what players learned by playing the game, but due to restraints on project time and the availability of testers this was not possible. Therefore we have evaluated our game by comparing it to Malone’s observed components of effective educational games [2]: 1) Clear goals that students find meaningful. The immune defense game has a clear goal of defending cells from infection. Students can relate to this because everyone has been sick and realizes the importance of eliminating viruses and bacteria. There is also a high scores list that encourages students to try for the highest score. This is one of the most basic elements of motivation in a game and helps create competitiveness among peers. 2) Multiple goal structures and scoring to give students feedback on their progress. As previously noted the students' highest scores are tracked. At the end of each stage the student receives immediate point feedback based on how well they defended their cells during that wave. They receive more or less depending on their performance. 3) Multiple difficulty levels to adjust the game difficulty to learner skill. Unfortunately we did not have time to add multiple difficulty levels, so our game runs the risk of being too hard for some and too easy for others. Neither of these scenarios is acceptable as the student will quickly become either frustrated or bored and be hindered in their learning. 4) Random elements of surprise. Although the random elements in the game are not full of surprises, the game plays differently every time because of the random placement and movement of cells. This area could be improved with added plot details such as having multiple pathogens that enter perhaps in later stages. The result of upgrades in this area could allow the game to be fun for multiple sittings rather than a few. 5) An emotionally appealing fantasy and metaphor that is related to game skills. Our game is based very strongly in reality, so the most fantastic element is the appearance of the cells. Though they are in some ways true to the real appearance, they are cartoon-like and twodimensional. However this does not preclude the game from having emotional appeal, because most students wish that they could help their immune system so they can get better quicker. Our immune attack game matches at least three of the five elements outlined by Malone and partially fits the others. As much as these elements of good educational games are believable, there are many types of games which can be successful with little use of these components. For example simulation games are educational but lack many fantasy elements. They are made successful by their detail and ability to customize several different aspects of a player's game. Games can be successful as long as they are engaging and allow players to learn something during their play. In light of this, our immune defense game is actually a fairly close simulation of the immune system's processes. Our game's ability to educate students on the processes of the immune system depends heavily on how engaging and entertaining the game is for actual students; many studies have shown that different types of games can be entertaining. However, entertainment is not our main goal and therefore the real value of the game will only be assessed after testing its ability to teach students. 7. ACKNOWLEDGEMENTS This work was done at the University of South Carolina as part of the Research Experiences for Undergraduates in Multidisciplinary Computing project and supported in part by the National Science Foundation (Award #0649105). We would also like to thank Dr. Jijun Tang, Dr. John Bowles, Dr. Caroline Eastman, Jeremiah Shepherd, Matt Mitman, Mike McLaughlin, and Kimberly Yonce for their help and guidance with this project. 8. REFERENCES [1] KIERKEGAARD, P. 2008. Video Games and Aggression. International Journal of Liability and Scientific Inquiry, 411417. [2] MALONE, T. W. 1981. Toward a Theory of Intrinsically Motivating Instruction. Cognitive Science: A Multidisciplinary Journal, 333-369. [3] RAVEN, P. H., AND JOHNSON, G. B. 2002. Biology, 6th ed. McGraw-Hill, New York, NY. [4] SQUIRE, K. 2003. Video Games in Education. International Journal of Intelligent Simulations and Gaming, 49-62.