My OperaDo-it-yourself Multicellular Organism
Sunday, March 27, 2011 9:58:00 PM
I'll try to describe an idea for a computer game that I've had for a while, although the idea is very raw, and only numerous prototyping cycles can answer the question of whether it can be made playable.
The game models the development of a multicellular organism from a single fertilized egg (zygote). The modern science has more questions than answers about how the same genetic information that's copied to every cell in the organism determines the development of a complete organism with complex structure and more than 200 types of specialized cells from a single cell. However, we do know some basic facts.
Cells that have particular functions in the organism are called specialized. Such are, for example, myocytes (muscle cells), neurons (nerve cells), erythrocytes (red blood cells) and many other types. On the other hand, the so-called stem cells do not have a particular function, but they can divide. The zygote is the most universal (totipotent) stem cell which gives rise to all cells of the organism. The first several cell generations after the division of the zygote are also totipotent, but after a few days after fertilization some cells become different from the others — they differentiate. After the first differentiation, the cells are still stem cells, but they are not totipotent anymore. Rather, they are multipotent: they can give rise to many, but not all types of cells in the organism. As the number of cells in the organism grows, their differentiation continues. After a number of such steps, the stem cell finally transforms into a specialized cell of one or another type. The reverse — transformation of a specialized cell back into a stem cell — is impossible in most organisms. An adult organism always contains stem cells in different stages of differentiation. They divide periodically to maintain their own population as well as specialize to replace worn or lost tissue cells, such as in regeneration.
But how does a stem cell “know” what it should turn into? Why don't we end up with heart cells in the brain and nerve cells in the liver? How do the cells making up tissues stick together, and why do organs grow to be certain shapes and sizes? The development potential in a stem cell is regulated by receptor proteins that “monitor” the situation around the cell. At the same time, the cell produces signal substances — ligands — to let others know about its presence. Each receptor is activated by a certain type of ligand and stimulates or inhibits specific processes in the cell, such as production of a particular protein. As a result, the presence or absence of particular types of cells at short or long distances determines the fate of the stem cell: passivity, division without differentiation, differentiation into a certain other type of stem cell, final specialization or even self-destruction (apoptosis). Cells of some types tend to group together with other cells of the same or related type. Special binding proteins (cell adhesion molecules) allows cells to stick to their neighbors and form tissues.
This is an extremely simplified and imprecise description of the development of a multicellular organism, but it's good enough for our purposes, especially because we'll have to simplify it further for the game.
The player's goal is to program the development of a multicellular organism with desired properties by editing the genetic code in the single cell — the zygote. The game does resemble programming, but it's programming with pictures and arrows rather than with lines of code.
The player has access to several types of specialized cells complete with pictures and descriptions of their functions. I'm thinking about flat pictures from the biology textbook, with different types of cells painted in different colors. To get the cell to specialize into one of these types, one needs to start production of a particular substance called a growth factor. The player can create as many other proteins as needed, such as receptors, cell adhesion molecules, enzymes, transcription factors. The proteins get funny names like “tralalase”. By having these proteins activate each other's production, one can in fact program the cell's behavior. For example, for a membrane receptor: “If no doodle ligands are around, trigger production of the munchmunch factor”.
Having specified the set of proteins encoded in the genetic information, the player clicks the start button and watches the organism develop. The protein molecules synthesized in the cells can be seen at a sufficient zoom level. The simulation can be paused, rewound and fast forwarded. To make things simpler, everything happens in two dimensions. By changing the set of proteins and restarting the simulation, the player tries to produce an organism with the desired properties.
Every level has its own requirements to the organism. For example, on the first level the player is to build a semblance of volvox: a ring with a particular diameter made of flagellate cells. The player gets only one type of specialized cells at this level, and has to use cell adhesion molecules to bind the cells together in a ring and receptors to control its size.
The requirements get more complex on subsequent levels, such as to produce a coelenterate with two layers of cells, to create a creature that moves from the darkness towards the light, or to provide for regeneration after minor damage to the body. The number of available specialized cells grows. Because any complex enough structure of the body would require immensely complex cell signaling, the player gets readily available proteins activating increasingly complex development processes, such as a “heart forming factor”. Also, a free modeling mode is available where the player has access to all growth factors and specialized cell types that exist in the game. In this mode, the player can use their imagination to build an organism without particular prerequisites. Players can share genetic codes for interesting organisms in an online community.
I'm not sure such a game is possible to implement. In case it can be implemented, I'm not sure it will be playable. Finally, in case it's playable, I'm not sure anybody will want to play that. In this sense, the idea is even more raw and controversial than my previous idea for a computer game, “Full Speed Astern!” — because here we're trying to model something extremely complex and not completely understood for entertainment purposes. But there is a rather playable game about star formation, why can't there be one about morphogenesis, too?
По-русски: Многоклеточный организм своими руками
The game models the development of a multicellular organism from a single fertilized egg (zygote). The modern science has more questions than answers about how the same genetic information that's copied to every cell in the organism determines the development of a complete organism with complex structure and more than 200 types of specialized cells from a single cell. However, we do know some basic facts.
Cells that have particular functions in the organism are called specialized. Such are, for example, myocytes (muscle cells), neurons (nerve cells), erythrocytes (red blood cells) and many other types. On the other hand, the so-called stem cells do not have a particular function, but they can divide. The zygote is the most universal (totipotent) stem cell which gives rise to all cells of the organism. The first several cell generations after the division of the zygote are also totipotent, but after a few days after fertilization some cells become different from the others — they differentiate. After the first differentiation, the cells are still stem cells, but they are not totipotent anymore. Rather, they are multipotent: they can give rise to many, but not all types of cells in the organism. As the number of cells in the organism grows, their differentiation continues. After a number of such steps, the stem cell finally transforms into a specialized cell of one or another type. The reverse — transformation of a specialized cell back into a stem cell — is impossible in most organisms. An adult organism always contains stem cells in different stages of differentiation. They divide periodically to maintain their own population as well as specialize to replace worn or lost tissue cells, such as in regeneration.
But how does a stem cell “know” what it should turn into? Why don't we end up with heart cells in the brain and nerve cells in the liver? How do the cells making up tissues stick together, and why do organs grow to be certain shapes and sizes? The development potential in a stem cell is regulated by receptor proteins that “monitor” the situation around the cell. At the same time, the cell produces signal substances — ligands — to let others know about its presence. Each receptor is activated by a certain type of ligand and stimulates or inhibits specific processes in the cell, such as production of a particular protein. As a result, the presence or absence of particular types of cells at short or long distances determines the fate of the stem cell: passivity, division without differentiation, differentiation into a certain other type of stem cell, final specialization or even self-destruction (apoptosis). Cells of some types tend to group together with other cells of the same or related type. Special binding proteins (cell adhesion molecules) allows cells to stick to their neighbors and form tissues.
This is an extremely simplified and imprecise description of the development of a multicellular organism, but it's good enough for our purposes, especially because we'll have to simplify it further for the game.
The player's goal is to program the development of a multicellular organism with desired properties by editing the genetic code in the single cell — the zygote. The game does resemble programming, but it's programming with pictures and arrows rather than with lines of code.
The player has access to several types of specialized cells complete with pictures and descriptions of their functions. I'm thinking about flat pictures from the biology textbook, with different types of cells painted in different colors. To get the cell to specialize into one of these types, one needs to start production of a particular substance called a growth factor. The player can create as many other proteins as needed, such as receptors, cell adhesion molecules, enzymes, transcription factors. The proteins get funny names like “tralalase”. By having these proteins activate each other's production, one can in fact program the cell's behavior. For example, for a membrane receptor: “If no doodle ligands are around, trigger production of the munchmunch factor”.
Having specified the set of proteins encoded in the genetic information, the player clicks the start button and watches the organism develop. The protein molecules synthesized in the cells can be seen at a sufficient zoom level. The simulation can be paused, rewound and fast forwarded. To make things simpler, everything happens in two dimensions. By changing the set of proteins and restarting the simulation, the player tries to produce an organism with the desired properties.
Every level has its own requirements to the organism. For example, on the first level the player is to build a semblance of volvox: a ring with a particular diameter made of flagellate cells. The player gets only one type of specialized cells at this level, and has to use cell adhesion molecules to bind the cells together in a ring and receptors to control its size.
The requirements get more complex on subsequent levels, such as to produce a coelenterate with two layers of cells, to create a creature that moves from the darkness towards the light, or to provide for regeneration after minor damage to the body. The number of available specialized cells grows. Because any complex enough structure of the body would require immensely complex cell signaling, the player gets readily available proteins activating increasingly complex development processes, such as a “heart forming factor”. Also, a free modeling mode is available where the player has access to all growth factors and specialized cell types that exist in the game. In this mode, the player can use their imagination to build an organism without particular prerequisites. Players can share genetic codes for interesting organisms in an online community.
I'm not sure such a game is possible to implement. In case it can be implemented, I'm not sure it will be playable. Finally, in case it's playable, I'm not sure anybody will want to play that. In this sense, the idea is even more raw and controversial than my previous idea for a computer game, “Full Speed Astern!” — because here we're trying to model something extremely complex and not completely understood for entertainment purposes. But there is a rather playable game about star formation, why can't there be one about morphogenesis, too?
По-русски: Многоклеточный организм своими руками
