From tending to a virtual farm to embarking on a gun-slinging treasure hunt, video games transport players to new realities, offering them reprieve after a long day. For Onur Özer, a geneticist at University Hospital Schleswig-Holstein, the game isn’t just virtual—it’s happening inside the human body. “If you think about the competition between the host and the pathogen itself, this can easily be considered a game.”
Players must formulate a strategy to fend off pathogens. Each pathogen has a specific set of tags.
HLA Defense
Özer studies human leukocyte antigen (HLA) gene diversity through ancient and modern genomes. HLA genes encode for cell surface proteins that help the immune system distinguish the cells that do and do not belong in the body. He thought that developing a video game could be an engaging way to introduce high school and college-level players to the complex scenarios that unfold between pathogens and the immune system. Over the course of six months, Özer developed HLA Defense, a single-player online game that turns the interaction between HLA alleles and pathogens into a strategic battle.
When designing the game, one of Özer’s main inspirations was Munchkin, a dungeon-crawling card game in which players battle monsters, collect loot, and race to reach level 10. Players can work together to defeat monsters—or turn on one another to prevent an opponent from winning. “Games also allow you to think about scenarios you cannot really come across in real life. [It makes you] develop strategies in your mind to defeat the opponent.” Özer wanted to capture that same sense of competition and strategy while creating a game that could introduce to concepts in immunology and genetics.
The game begins with four HLA alleles (two per gene) and 20 health points. Each allele has tags that identify pathogen aspects: DNA or RNA virus, parasite, bacterial toxin, and more. Then, the round begins with a detected pathogen, with its own power level and feature tags.
A player’s combat power is determined by how well the pathogen’s tags match those of the player’s HLA alleles. If the player’s power score meets or exceeds that of the pathogen, they win the encounter and earn credits. A defeat, meanwhile, results in damage and a loss of health points. When the health points reach zero, it’s game over.
Players must fight, collect 40 credits, and survive a never-ending onslaught of pathogens in HLA Defense.
HLA Defense
Players need 40 credits to win the game, but the credits can also be spent in the Market to purchase modifiers. For example, antiparasitic therapy can reduce the power of pathogens carrying a parasite tag. However, repeatedly relying on the same modifier can cause its effectiveness to decrease, much like drug resistance in real life. Players can also exchange their original alleles for ones with different tags. While this ability isn’t possible in real life, Özer likens it to an imagined, highly advanced form of CRISPR-Cas9 technology.
“One of the most important features that make a game enjoyable are trade-offs. It’s not fun if you do one thing and then just win the game. You need to have different strategies to be able to deal with different kinds of threats,” explained Özer.
These trade-offs reflect a biological reality. A diverse HLA repertoire can help the immune system recognize and respond to a wider range of pathogens, but greater HLA diversity may also be associated with an increased risk of autoimmune disease.
As players battle through waves of pathogens, random events can also alter the course of the game. In some cases, the player’s body adapts to a challenge, resulting in an immune boost. A repeat encounter with a pathogen can also trigger “immune memory,” producing a stronger protective response and increasing the player’s power. Other events represent the consequences of an overstressed immune system. These complications can make pathogens more powerful, forcing players to adjust their strategies.
Özer believes HLA Defense could eventually become a broader educational tool. Future updates could include informational sections that explain concepts such as allele divergence and provide opportunities for players to explore related research papers. Ultimately, Özer hopes HLA Defense will inspire more science-based games that make complex scientific concepts more engaging and accessible.