Immune Attack present the cellular and molecular worldin an accurate and engaging video game.

Immune Attack: A Video Game in the Molecular World
Melanie A. Stegman and Michelle L. Fox
Learning Technologies Program, Federation of American Scientists
Washington, DC 20036

FAS!

Immune Attack increases students’ confidence
regarding cellular and molecular biology.
Immune Attack teaches students core
concepts of Cellular and Molecular Biology.
100%

80%
70%
60%

I would be able to understand this diagram if I read it andthink about it.
1 Disagree definitely

50%
CORE CONCEPTS
1. Cells can respond to their environment quickly, altering
their activities, and often sending out signals to which
other cells respond.
2. Some cellular responses alter the complement ofproteins the cell has inside and on its surface.
3. The ability of several cell types to respond to, and emit
specific signals (molecules) produces a cellular network,or an organ system.
4. The response of a cell to a given signal can vary,
however, depending on the other types of molecules
present within it.
5. The molecules a cell contains (proteins, lipids,metabolites, etc.) are a function of which genes areactive, which proteins/RNA accumulate, and the activity
levels of the proteins of the cell.
6. Cellular responses can include directed migration,specific adhesion, and the generation and secretion ofspecific molecules.
7. Molecules and cells generally move in random ways,
and their binding to specific sites occurs because arandom bounce happens to bring the two sites closeenough together that their specific interactions comeinto play.

Figure 1. This is a view of how Micro and Nano scale objects and action will
be presented in Immune Attack 2.0. The player is manipulating the Nanobot
on the surface of the vein endothelial cell, while the change in behavior ofcells can be observed in the Microbot‘s camera.

Control Students n = 21
Test Students n = 1690%

8. Under some conditions cells can move in directed ways
(chemotaxis) by responding to gradients in specificmolecules. This process can lead cells to migrate
toward the source of the molecule.

Introduction
Molecular science is not introduced to American students until advanced high school classes or college. This means that most of thegeneral public do not understand the molecular aspects of environmental or health issues. For example, the debate about flu vaccination
policy cannot be informed by a straightforward explanation of the genes that H and N stand for. If the average person understood thecentral dogma we would at least be debating the flu vaccination based on facts and not trying to come up with metaphors that leave
everyone annoyed and possibly suspicious at the vagary of the whole debate. How to teach intuitively? As Jerome Bruner points out,
make it a game. Players can learn the rules of a game and apply them to new scenarios without being aware of or even being able tocomprehend the implications or the formal science learning behind the game. As Mihaly Csikzentmihalyi has pointed out, people stay intask and enjoy what appears to be hard work requiring intense attention when they are in a state of “Flow.” Flow is the state of being
challenged but still close to our level of competence. As Bowman points out that video game, such as Pacman and Donkey Kong are sopopular because they meet the requirements for Flow. Finally, Kurt Squire has demonstrated that video games like Civilization can takeadvantage of the state of Flow to teach and to inspire interest in history. Additionally, James Paul Gee has pointed out that games canteach players how to think like an expert, which would be the end goal for a Cell Biology game, but we must first introduce the molecularand cellular world before we can train students to design experiments in it.
Making a video game to introduce cells and proteins and the entire molecular world requires us to first make a list of the concepts we wish
to teach, take advantage of modern game engines and graphics to create an accurate Micro world and an accurate Nano world, recruit
many scientists in fields such as immunology, chemical engineering, cell biology, organic chemistry, etc. in order for the game to be “peerreviewed,” and then finally to design an evaluation method that allows us to determine whether the core concepts are learned by players.
Preliminary data presented here demonstrate that our goals can likely be met. Immune Attack successfully integrate accurate object
presentation with engaging game play. Scientists in many fields have volunteered their time and expertise not only to reviewing the game,
but to making the game play more intricate. And finally, preliminary studies demonstrate that learning occurs and that players gain
confidence with cellular and molecular diagrams, which may extend beyond the topics directly portrayed in Immune Attack.

2 Disagree somewhat
3 Neutral
4 Agree somewhat
5 Agree definitely

40%
30%
20%
10%
0%

12345678910Figure 2. Some results of our current evaluation. Each class is randomly
divided into two groups. One group plays Immune Attack for two 40-minutesessions, separated by 1 week, while the control group plays an unrelated
computer game. 1 or 2 days after the second session, all students take an
online survey. The questions are designed to determine whether players
comprehend the core concepts, see below.
1. What does the word “macrophage” mean?
Big eater.
Big antibody.

2. The walls of veins are made of what?
MuscleCollagen(Vocabulary)

Big cell.
Big killer.

4. How do cells of the immune system get to the site of an infection?
They exit the blood vessel through spaces in the vessel wall.
(Concepts 2 and 3)
They diffuse to the site of the invading bacteria.
They accumulate due to swelling at the site of infection.
They travel from lymph nodes to the infected tissue.

5. Which cells are the first to respond to a bacterial infection?
Red Blood Cells
Monocytes(Concepts 2 and 3)
T-Cells

A video game may be used to create an understanding of the Core
Concepts of Cell biology.

1Disagree

2(Concepts 1 and 6)

Cough.

Nature Reviews Immunology, 2007. 7:678.

Conclusions
A video game can teach basic facts and vocabulary about Cellular andMolecular Biology.

FibersCells

3. What is the first line of defenses the body employs against potentialpathogens?
Antibodies.
White Blood(Concepts 1 and 4)
Cells.
Red Blood Cells.

Percent of students who responded

2356/B733
ABSTRACT: Jerome Bruner proposed the Spiral Curriculum as a method for
creating deep understanding of scientific concepts. Bruner writes that five year olds
intuitively create grammatically correct sentences and are therefore prepared tounderstand sentence structure more deeply when it is formally introduced in school.
Immune Attack is a three-dimensional video game that provides a place to gain an
intuitive understanding of cellular biology and molecular science. Proteins, moleculesand cells behave in Immune Attack as they do in nature. Objects in the game, suchas white blood cells, are drawn to look like the schematics that scientists use in theirown models. Game actions, such as the capture of white blood cells by proteins onblood vessel walls, mimic actions that occur in nature, and are described using
vocabulary similar to that of scientific literature. Our Scientific Advisory Group of 20
active scientists reviews our game outline and contributes to the faithful and excitingpresentation of molecular science. We have successfully developed a method ofcommunication, a guided wiki-like document, that allows these scientists tocontribute meaningful information in a time efficient manner. We collaborate directlywith teachers to conduct controlled evaluations, using the Medical Mysteries Series(MedMyst, which covers non-molecular aspects of infectious disease) as a negativecontrol. We tested students’ knowledge, comprehension of game dynamics andconfidence with the material (n = 180 Immune Attack, n = 142 MedMyst). We foundhighly significant gains in confidence with molecular science related materials andsignificant gains in knowledge of the cell biology and molecular science presented, inthe groups that played Immune Attack as compared to the control game. We arebuilding on the results of these studies to create an evaluation tool for the Fall of2009. Additionally, we have used Immune Attack to inspire high school computer
programming classes to create their own new videos games based on Immune
Attack. Immune Attack provides an intuitive introduction to molecular and cellularbiology for 7th grade students, thus significantly lengthening the “Spiral Curriculum.”

2.77
12

3

5
AgreeImmune Attack players
Control Game players

3.25

3Neutral

44

5
Agree

Results are significant
T-Test, 2 sided,
p value of 0.00`012

Figure 3. To determine whether Immune Attack provides intuitive
learning, we designed a test for feelings rather than actual
knowledge. The TOP figure demonstrates an increase inconfidence due to playing Immune Attack. This figure, despite its
complexity, contains many IA related aspects. The BOTTOM
figure is preliminary data that indicates that the confidence gain
may not be limited to topics in the game, but may also betransferred to any three dimensional depiction of molecularstructures. We will follow up on these results.

Infected Cells

6. How do Macrophages summon other cells to help fight an infection?
They divide into specialized cells that recruit other cells.
They convey a message through red blood cells.
They send a special chemical signal to the lymph nodes.
They send a special chemical signal that other cells follow.

7. What changes happen to the cells of the vein when there is an infection
nearby?
The cells start making...
... a protein that sticks to white blood cells.
... a chemical signal that attracts white blood cells.
... new antibodies.
... a chemical signal that attracts red blood cells.

8. What is the name of the protein that will make a slowed Monocyte cometo a stop?
PeptinPseudomonas

ICAMSelectin

9. When a white blood cell exits the blood stream what is the process
called?
Transmigration.
Trasportation.

Transvessel movement.
Transferrance.

2.71
1Disagree

2Immune Attack players N = 16
Control Game players N = 21

3.38

3Neutral

45Agree

T-Test, 2 sided,
p value of 0.04

A video game about this complex topic can make students more confident intheir ability to understand the topic.
Future Goals
1. To build more levels of Immune Attack that more explicitly require theplayer to understand and employ the core concepts of Cellular andMolecular science.
2. To demonstrate that Immune Attack provides a deep understanding ofcellular biology and molecular biology. We will continue to develop ourevaluation, focusing on whether Immune Attack conveys a deeper
understanding of the core concepts. We are recruiting 7th – 12th gradeteachers now. We plan a large scale evaluation in 2013-2014 and 2014
and 2015.
3. To create a online database that mirrors the in-game “Mission IntelligenceDatabase” that will serve as an place where students and scientists
submit “datacards” on the topics of molecular chemistry, cellular biology,chemical engineering, etc. This database will be part of IA2.0… coming in2010.
References
1. Bruner, J. S., The Process of Education, Harvard University Press,
Cambridge MA. 1960, p12.
2. Csikszentmihalyi, M., Beyond Boredom and Anxiety. Jossey-Bass
Publishers, San Francisco, 1975.
3. Squire, K. (2003). Video games in education. International Journal ofIntelligent Simulations and Gaming (2) 1.
4. The Entertainment Software Association (ESA), 2008 Essential Facts
About the Computer and Video Game Industry. July, 2008. By IpsosMediaCT for the ESA, self published at
www.theesa.com/facts/pdfs/ESA_EF_2008.pdf
5. Leshner, A. Outreach Training Needed. Science, 12 January 2007.
www.sciencemag.org/cgi/reprint/315/5809/161.pdf
6. Papert. S. Mindstorms: Children, computers, and powerful ideas. New
York: Basic Books, 1980.
Development of Immune Attack is funded by NIAID grant 1R25AI084848-0110
to M.S. with support from the Entertainment Software Association Foundation.