turtles-own [ stem? ; a variable to keep track of whether a turtle represents a stem cell; T-stem cells,F-transitory cells age ; a variable to keep track of the age of each turtle/cell; age of cell. changes color with age metastatic? ; a variable to keep track of whether a turtle represents a metastasized cell; false for progeny of stem cell 0, true for progeny of stem cell 1 ] globals [ cell-count ; a variable to keep track of the number of cells mutation ; a variable to keep track of accumulated mutation (measured in % based on mutation frequency per Mb) ] ;-------------------------- SETUP --------------------------; to setup clear-all set-default-shape turtles "circle 3" ask patches [ set pcolor white ] ; coloring the patches set-stem ; creating the stem cells evaluate-params ; evaluating the parameters to stop the program if no cells are alive reset-ticks end to set-stem ; function to create two stem cells create-turtles 2 [ ; creating the turtles set size 2 ; setting turtle size setxy (min-pxcor / 2) 0 ; setting location set color blue ; setting color set stem? true ; setting these turtles as the stem cells set metastatic? false ; setting the turtles as non-metastatic in the beginning set age 0 ; setting starting age as 0 set mutation 0 ; setting starting mutation incidence as 0 ] ask turtle 1 [ ; the turtle/stem cell that will eventually metastasize set heading 90 ; stem cell 1 will move away ] set cell-count 2 ; set inital cell count end to evaluate-params ; function to evaluate parameters set cell-count count turtles ; storing cell count in a variable if (cell-count <= 0) [ stop ] ; stopping the entire program when there are no cells left end ;-------------------------- GO --------------------------; to go ask turtles [ ifelse leave-trail? ; a boolean switch to have each moving cell leave a trail [ pen-down ] [ pen-up ] if (who = 1) and (xcor < 30 ) and (metastatic? = true) ; movement of the metastic stem cell [ fd 8 ] set age age + 1 ; increase the age of all turtles/stem-cells by 1 with each tick accumulate-mutation ; calling the mutation accumulation function metastasis ; calling the metastasis function move-transitional-cells ; calling the function for the movement of the transitional cells mitosis ; calling the mitosis function death ; calling the death function ] tick evaluate-params end ;-------------------------- MUTATION ACCUMULATION --------------------------; to accumulate-mutation ; function to calculate mutation accumulation based on ; the number of new cells created and the smoking condition if cell-count mod 10 = 0 [ ; with every cell replication period that leads to 10 new cell ifelse smoker? ; a boolean switch to set whether the person is a smoker or no [ set mutation ( cell-count / 10 ) * 8.1 ] ; smokers have 8.1% increase in mutation incidence [ set mutation ( cell-count / 10 ) * 0.45 ] ; non-smokers have 0.45% increase in mutation incidence ] end ;-------------------------- METASTASIS --------------------------; to metastasis ; the 2nd stem cell set as metastatic once its mutation % goes above 30 ask turtle 1 [ if mutation >= 30 and (metastatic? = false) ; asking the metastatic-to-be stem cell if its mutation acc. is above 30% [ set metastatic? true ] ; setting the turtle as metastatic ] end to move-transitional-cells ; transitional cells move and hatch more if (not stem?) [ ; transitional cells are not stem-cells set color ( red + 0.25 * age ) fd 1 if age < 6 [ ; asking the cells to divide/hatch if they're over 6 yrs old hatch 1 [ rt random-float 360 fd 1 ] ] ] end to mitosis ; mitosis by the stem-cells if stem? [ ; asking if the turtles are stem-cells hatch 1 [ fd 1 set color red set stem? false ; need to set the newborn cells as non-stem cells ifelse (who = 1) [ set age 16 ] [ set age 0 ] ] ] end ;-------------------------- DEATH --------------------------; to death ; natural death of cells due to their age if (not stem?) and (not metastatic?) and (age > 10) ; asking non-stem and non-metastatic cells to die ; once they're over age 10 [ die ] if (not stem?) and metastatic? and (age > 8) ; asking non-stem but metastatic cells to die ; once they're over age 8 [ die ] end ;-------------------------- TREATMENT --------------------------; to thoracotomy ; lung surgery to remove the stem-cell that has not metastasized if turtle 0 != nobody ; if non-metastatic stem-cell has not died [ ask turtle 0 [ die ] ] ; ask it to die if [xcor] of turtle 1 < 30 ; asking all cells around the non-metastatic stem-cells to die [ask turtles [die]] end to radiation-treatment ask turtles with [ age < 10 and not stem? ] ; asking all non-stem cell turtles [ die ] ; younger than 10 yrs old to die end ; Copyright 1998 Uri Wilensky. ; See Info tab for full copyright and license. @#$#@#$#@ GRAPHICS-WINDOW 347 40 708 402 -1 -1 3.43 1 10 1 1 1 0 0 0 1 -51 51 -51 51 1 1 1 ticks 30.0 BUTTON 23 43 78 76 setup setup NIL 1 T OBSERVER NIL NIL NIL NIL 1 BUTTON 96 43 151 76 go go T 1 T OBSERVER NIL NIL NIL NIL 0 MONITOR 225 170 296 215 cell-count cell-count 0 1 11 BUTTON 13 115 161 148 thoracotomy thoracotomy NIL 1 T OBSERVER NIL NIL NIL NIL 0 SWITCH 185 73 304 106 leave-trail? leave-trail? 0 1 -1000 BUTTON 15 161 163 194 radiation treatment radiation-treatment NIL 1 T OBSERVER NIL NIL NIL NIL 0 PLOT 9 225 297 406 Living Cells Time Cells Alive 0.0 100.0 0.0 500.0 true false "" "" PENS "Cells Alive" 1.0 0 -16777216 true "" "plot cell-count" SWITCH 194 32 297 65 smoker? smoker? 0 1 -1000 @#$#@#$#@ ## WHAT IS IT? This model illustrates the growth of a tumor under two different conditions, smoking and not smoking. There are also medical methods such as thoracotomy and radiation included to showcase the resistance of tumors to treatment. A tumor consists of two kinds of cells: stem cells (blue turtles) and transitory cells (all other turtles). ## HOW IT WORKS During mitosis, a stem cell can divide either asymmetrically or symmetrically. In asymmetric mitosis, one of the two daughter cells remains a stem cell, replacing its parent. So a stem cell effectively never dies - it is quasi reincarnated after each division. The other daughter cell turns into a transitory cell that moves outward. Young transitory cells may divide, breeding other transitory cells. The transitory cells stop dividing at a certain age and change color from red to white, eventually dying. A stem cell may also divide symmetrically into two stem cells (blue turtles). In this example the original stem cell divides symmetrically only once. The first stem cell remains static, but the second stem cell moves to the right once the smoker switch is ON. This activity, in which the cell advances into distant sites and creates another tumor colony, is called metastasis. Notice that the metastasis is red. It is made of cells that die young. As the disease progresses, cells die younger and younger. ## HOW TO USE IT SETUP: Clears the world and creates two blue neoplastic (cancerous) stem cells. One cell stays put and the other moves to the right if the mutation accumulation incidence is passed. GO: Runs the simulation. THORACOTOMY: Kills the stem cell that has not metastasized. RADIATION TREATMENT: Kills all transitory cells but not the stem cells. SMOKER: If it's ON, means that the individual is a smoker and the mutation incidence is set to 8.1% increase with every new 10 cell. If OFF, means that the individual is a non-smoker and the mutation incidence is set to 0.45% increase with every new 10 cell. LEAVE-TRAIL: If it's ON, the cells trace their paths; if it's OFF, they do not. CELL-COUNT: Displays the total number of living cells. LIVING CELLS PLOT: plots the number of living cells. ## THINGS TO NOTICE First, notice the blue dot. It represents a normal stem cell that has been transformed into a tumor stem cell. Set the "leave-trail" switch to On, and click 'go'. A tumor is formed as the stem cell creates transitory cells, which reproduce themselves. It grows to a certain size. As it grows, a bulge appears on the right side once the smoker switch is turned on. This is a tumor outgrowth, caused by symmetric mitosis of the stem cell. The outgrowth will turn into a metastasis and grow into remote regions. After a while the tumor and metastasis appear to reach their ultimate size and nothing interesting seems to be happening. This illustrates how the tumor presents itself to the physician - as a solid cell mass. In reality, this seemingly solid mass conceals active cell turnover. To reveal it, set the leave-trail switch to Off, click on SETUP, and then click on GO to run the simulation again. Slow down the model so you can follow individual steps. Move the speed slider to the left, click on SETUP and GO, and observe the blue stem cell. It divides into two blue stem cells. One remains static, and the other moves to the right. Look at the static stem cell (blue). It breeds red cells which move outward and change their color as they age. When young, they are red and create more transitory cells. Then they turn white, and then they die. ## EXTENDING THE MODEL What alternative treatments would you suggest? How would you model them here? ## CREDITS AND REFERENCES The original StarLogoT Tumor model was contributed by Gershom Zajicek M.D., Professor of Experimental Medicine and Cancer Research at The Hebrew University-Hadassah Medical School, Jerusalem. Cancer literature: Tomasetti C, Vogelstein B. Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science. 2015 Jan 2;347(6217):78-81. doi: 10.1126/science.1260825. PMID: 25554788; PMCID: PMC4446723. ## HOW TO CITE If you mention this model or the NetLogo software in a publication, we ask that you include the citations below. For the model itself: * Wilensky, U. (1998). NetLogo Tumor model. http://ccl.northwestern.edu/netlogo/models/Tumor. Center for Connected Learning and Computer-Based Modeling, Northwestern University, Evanston, IL. Please cite the NetLogo software as: * Wilensky, U. (1999). NetLogo. http://ccl.northwestern.edu/netlogo/. Center for Connected Learning and Computer-Based Modeling, Northwestern University, Evanston, IL. ## COPYRIGHT AND LICENSE Copyright 1998 Uri Wilensky. ![CC BY-NC-SA 3.0](http://ccl.northwestern.edu/images/creativecommons/byncsa.png) This work is licensed under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License. To view a copy of this license, visit https://creativecommons.org/licenses/by-nc-sa/3.0/ or send a letter to Creative Commons, 559 Nathan Abbott Way, Stanford, California 94305, USA. Commercial licenses are also available. To inquire about commercial licenses, please contact Uri Wilensky at uri@northwestern.edu. This model was created as part of the project: CONNECTED MATHEMATICS: MAKING SENSE OF COMPLEX PHENOMENA THROUGH BUILDING OBJECT-BASED PARALLEL MODELS (OBPML). The project gratefully acknowledges the support of the National Science Foundation (Applications of Advanced Technologies Program) -- grant numbers RED #9552950 and REC #9632612. This model was converted to NetLogo as part of the projects: PARTICIPATORY SIMULATIONS: NETWORK-BASED DESIGN FOR SYSTEMS LEARNING IN CLASSROOMS and/or INTEGRATED SIMULATION AND MODELING ENVIRONMENT. The project gratefully acknowledges the support of the National Science Foundation (REPP & ROLE programs) -- grant numbers REC #9814682 and REC-0126227. Converted from StarLogoT to NetLogo, 2001. @#$#@#$#@ default true 0 Polygon -7500403 true true 150 5 40 250 150 205 260 250 airplane true 0 Polygon -7500403 true true 150 0 135 15 120 60 120 105 15 165 15 195 120 180 135 240 105 270 120 285 150 270 180 285 210 270 165 240 180 180 285 195 285 165 180 105 180 60 165 15 arrow true 0 Polygon -7500403 true true 150 0 0 150 105 150 105 293 195 293 195 150 300 150 box false 0 Polygon -7500403 true true 150 285 285 225 285 75 150 135 Polygon -7500403 true true 150 135 15 75 150 15 285 75 Polygon -7500403 true true 15 75 15 225 150 285 150 135 Line -16777216 false 150 285 150 135 Line -16777216 false 150 135 15 75 Line -16777216 false 150 135 285 75 bug true 0 Circle -7500403 true true 96 182 108 Circle -7500403 true true 110 127 80 Circle -7500403 true true 110 75 80 Line -7500403 true 150 100 80 30 Line -7500403 true 150 100 220 30 butterfly true 0 Polygon -7500403 true true 150 165 209 199 225 225 225 255 195 270 165 255 150 240 Polygon -7500403 true true 150 165 89 198 75 225 75 255 105 270 135 255 150 240 Polygon -7500403 true true 139 148 100 105 55 90 25 90 10 105 10 135 25 180 40 195 85 194 139 163 Polygon -7500403 true true 162 150 200 105 245 90 275 90 290 105 290 135 275 180 260 195 215 195 162 165 Polygon -16777216 true false 150 255 135 225 120 150 135 120 150 105 165 120 180 150 165 225 Circle -16777216 true false 135 90 30 Line -16777216 false 150 105 195 60 Line -16777216 false 150 105 105 60 car false 0 Polygon -7500403 true true 300 180 279 164 261 144 240 135 226 132 213 106 203 84 185 63 159 50 135 50 75 60 0 150 0 165 0 225 300 225 300 180 Circle -16777216 true false 180 180 90 Circle -16777216 true false 30 180 90 Polygon -16777216 true false 162 80 132 78 134 135 209 135 194 105 189 96 180 89 Circle -7500403 true true 47 195 58 Circle -7500403 true true 195 195 58 circle false 0 Circle -7500403 true true 0 0 300 circle 2 false 0 Circle -7500403 true true 0 0 300 Circle -16777216 true false 30 30 240 circle 3 false 0 Circle -7500403 true true 0 0 300 Circle -16777216 true false 105 105 90 cow false 0 Polygon -7500403 true true 200 193 197 249 179 249 177 196 166 187 140 189 93 191 78 179 72 211 49 209 48 181 37 149 25 120 25 89 45 72 103 84 179 75 198 76 252 64 272 81 293 103 285 121 255 121 242 118 224 167 Polygon -7500403 true true 73 210 86 251 62 249 48 208 Polygon -7500403 true true 25 114 16 195 9 204 23 213 25 200 39 123 cylinder false 0 Circle -7500403 true true 0 0 300 dot false 0 Circle -7500403 true true 90 90 120 face happy false 0 Circle -7500403 true true 8 8 285 Circle -16777216 true false 60 75 60 Circle -16777216 true false 180 75 60 Polygon -16777216 true false 150 255 90 239 62 213 47 191 67 179 90 203 109 218 150 225 192 218 210 203 227 181 251 194 236 217 212 240 face neutral false 0 Circle -7500403 true true 8 7 285 Circle -16777216 true false 60 75 60 Circle -16777216 true false 180 75 60 Rectangle -16777216 true false 60 195 240 225 face sad false 0 Circle -7500403 true true 8 8 285 Circle -16777216 true false 60 75 60 Circle -16777216 true false 180 75 60 Polygon -16777216 true false 150 168 90 184 62 210 47 232 67 244 90 220 109 205 150 198 192 205 210 220 227 242 251 229 236 206 212 183 fish false 0 Polygon -1 true false 44 131 21 87 15 86 0 120 15 150 0 180 13 214 20 212 45 166 Polygon -1 true false 135 195 119 235 95 218 76 210 46 204 60 165 Polygon -1 true false 75 45 83 77 71 103 86 114 166 78 135 60 Polygon -7500403 true true 30 136 151 77 226 81 280 119 292 146 292 160 287 170 270 195 195 210 151 212 30 166 Circle -16777216 true false 215 106 30 flag false 0 Rectangle -7500403 true true 60 15 75 300 Polygon -7500403 true true 90 150 270 90 90 30 Line -7500403 true 75 135 90 135 Line -7500403 true 75 45 90 45 flower false 0 Polygon -10899396 true false 135 120 165 165 180 210 180 240 150 300 165 300 195 240 195 195 165 135 Circle -7500403 true true 85 132 38 Circle -7500403 true true 130 147 38 Circle -7500403 true true 192 85 38 Circle -7500403 true true 85 40 38 Circle -7500403 true true 177 40 38 Circle -7500403 true true 177 132 38 Circle -7500403 true true 70 85 38 Circle -7500403 true true 130 25 38 Circle -7500403 true true 96 51 108 Circle -16777216 true false 113 68 74 Polygon -10899396 true false 189 233 219 188 249 173 279 188 234 218 Polygon -10899396 true false 180 255 150 210 105 210 75 240 135 240 house false 0 Rectangle -7500403 true true 45 120 255 285 Rectangle -16777216 true false 120 210 180 285 Polygon -7500403 true true 15 120 150 15 285 120 Line -16777216 false 30 120 270 120 leaf false 0 Polygon -7500403 true true 150 210 135 195 120 210 60 210 30 195 60 180 60 165 15 135 30 120 15 105 40 104 45 90 60 90 90 105 105 120 120 120 105 60 120 60 135 30 150 15 165 30 180 60 195 60 180 120 195 120 210 105 240 90 255 90 263 104 285 105 270 120 285 135 240 165 240 180 270 195 240 210 180 210 165 195 Polygon -7500403 true true 135 195 135 240 120 255 105 255 105 285 135 285 165 240 165 195 line true 0 Line -7500403 true 150 0 150 300 line half true 0 Line -7500403 true 150 0 150 150 pentagon false 0 Polygon -7500403 true true 150 15 15 120 60 285 240 285 285 120 person false 0 Circle -7500403 true true 110 5 80 Polygon -7500403 true true 105 90 120 195 90 285 105 300 135 300 150 225 165 300 195 300 210 285 180 195 195 90 Rectangle -7500403 true true 127 79 172 94 Polygon -7500403 true true 195 90 240 150 225 180 165 105 Polygon -7500403 true true 105 90 60 150 75 180 135 105 plant false 0 Rectangle -7500403 true true 135 90 165 300 Polygon -7500403 true true 135 255 90 210 45 195 75 255 135 285 Polygon -7500403 true true 165 255 210 210 255 195 225 255 165 285 Polygon -7500403 true true 135 180 90 135 45 120 75 180 135 210 Polygon -7500403 true true 165 180 165 210 225 180 255 120 210 135 Polygon -7500403 true true 135 105 90 60 45 45 75 105 135 135 Polygon -7500403 true true 165 105 165 135 225 105 255 45 210 60 Polygon -7500403 true true 135 90 120 45 150 15 180 45 165 90 square false 0 Rectangle -7500403 true true 30 30 270 270 square 2 false 0 Rectangle -7500403 true true 30 30 270 270 Rectangle -16777216 true false 60 60 240 240 star false 0 Polygon -7500403 true true 151 1 185 108 298 108 207 175 242 282 151 216 59 282 94 175 3 108 116 108 target false 0 Circle -7500403 true true 0 0 300 Circle -16777216 true false 30 30 240 Circle -7500403 true true 60 60 180 Circle -16777216 true false 90 90 120 Circle -7500403 true true 120 120 60 tree false 0 Circle -7500403 true true 118 3 94 Rectangle -6459832 true false 120 195 180 300 Circle -7500403 true true 65 21 108 Circle -7500403 true true 116 41 127 Circle -7500403 true true 45 90 120 Circle -7500403 true true 104 74 152 triangle false 0 Polygon -7500403 true true 150 30 15 255 285 255 triangle 2 false 0 Polygon -7500403 true true 150 30 15 255 285 255 Polygon -16777216 true false 151 99 225 223 75 224 truck false 0 Rectangle -7500403 true true 4 45 195 187 Polygon -7500403 true true 296 193 296 150 259 134 244 104 208 104 207 194 Rectangle -1 true false 195 60 195 105 Polygon -16777216 true false 238 112 252 141 219 141 218 112 Circle -16777216 true false 234 174 42 Rectangle -7500403 true true 181 185 214 194 Circle -16777216 true false 144 174 42 Circle -16777216 true false 24 174 42 Circle -7500403 false true 24 174 42 Circle -7500403 false true 144 174 42 Circle -7500403 false true 234 174 42 turtle true 0 Polygon -10899396 true false 215 204 240 233 246 254 228 266 215 252 193 210 Polygon -10899396 true false 195 90 225 75 245 75 260 89 269 108 261 124 240 105 225 105 210 105 Polygon -10899396 true false 105 90 75 75 55 75 40 89 31 108 39 124 60 105 75 105 90 105 Polygon -10899396 true false 132 85 134 64 107 51 108 17 150 2 192 18 192 52 169 65 172 87 Polygon -10899396 true false 85 204 60 233 54 254 72 266 85 252 107 210 Polygon -7500403 true true 119 75 179 75 209 101 224 135 220 225 175 261 128 261 81 224 74 135 88 99 wheel false 0 Circle -7500403 true true 3 3 294 Circle -16777216 true false 30 30 240 Line -7500403 true 150 285 150 15 Line -7500403 true 15 150 285 150 Circle -7500403 true true 120 120 60 Line -7500403 true 216 40 79 269 Line -7500403 true 40 84 269 221 Line -7500403 true 40 216 269 79 Line -7500403 true 84 40 221 269 x false 0 Polygon -7500403 true true 270 75 225 30 30 225 75 270 Polygon -7500403 true true 30 75 75 30 270 225 225 270 @#$#@#$#@ NetLogo 6.1.1 @#$#@#$#@ @#$#@#$#@ @#$#@#$#@ @#$#@#$#@ @#$#@#$#@ default 0.0 -0.2 0 0.0 1.0 0.0 1 1.0 0.0 0.2 0 0.0 1.0 link direction true 0 Line -7500403 true 150 150 90 180 Line -7500403 true 150 150 210 180 @#$#@#$#@ 0 @#$#@#$#@