[Script Info] Title: [Events] Format: Layer, Start, End, Style, Name, MarginL, MarginR, MarginV, Effect, Text Dialogue: 0,0:00:05.94,0:00:10.76,Default,,0000,0000,0000,,In 1884, a patient’s luck seemed \Nto go from bad to worse. Dialogue: 0,0:00:10.76,0:00:14.27,Default,,0000,0000,0000,,This patient had a rapidly growing \Ncancer in his neck, Dialogue: 0,0:00:14.27,0:00:18.91,Default,,0000,0000,0000,,and then came down with an unrelated \Nbacterial skin infection. Dialogue: 0,0:00:18.91,0:00:21.62,Default,,0000,0000,0000,,But soon, something unexpected happened: Dialogue: 0,0:00:21.62,0:00:26.67,Default,,0000,0000,0000,,as he recovered from the infection, \Nthe cancer also began to recede. Dialogue: 0,0:00:26.67,0:00:31.53,Default,,0000,0000,0000,,When a physician named William Coley \Ntracked the patient down 7 years later, Dialogue: 0,0:00:31.53,0:00:34.19,Default,,0000,0000,0000,,no visible signs of the cancer remained. Dialogue: 0,0:00:34.19,0:00:37.16,Default,,0000,0000,0000,,Coley believed something remarkable \Nwas happening: Dialogue: 0,0:00:37.16,0:00:41.47,Default,,0000,0000,0000,,that the bacterial infection \Nhad stimulated the patient’s immune system Dialogue: 0,0:00:41.47,0:00:43.71,Default,,0000,0000,0000,,to fight off the cancer. Dialogue: 0,0:00:43.71,0:00:46.50,Default,,0000,0000,0000,,Coley’s fortunate discovery \Nled him to pioneer Dialogue: 0,0:00:46.50,0:00:51.42,Default,,0000,0000,0000,,the intentional injection of bacteria \Nto successfully treat cancer. Dialogue: 0,0:00:51.42,0:00:55.87,Default,,0000,0000,0000,,Over a century later, synthetic biologists\Nhave found an even better way Dialogue: 0,0:00:55.87,0:00:58.95,Default,,0000,0000,0000,,to use these once unlikely allies— Dialogue: 0,0:00:58.95,0:01:04.04,Default,,0000,0000,0000,,by programming them to safely \Ndeliver drugs directly to tumors. Dialogue: 0,0:01:04.04,0:01:07.67,Default,,0000,0000,0000,,Cancer occurs when normal functions \Nof cells are altered, Dialogue: 0,0:01:07.67,0:01:12.53,Default,,0000,0000,0000,,causing them to rapidly multiply \Nand form growths called tumors. Dialogue: 0,0:01:12.53,0:01:16.82,Default,,0000,0000,0000,,Treatments like radiation, chemotherapy, \Nand immunotherapy Dialogue: 0,0:01:16.82,0:01:20.46,Default,,0000,0000,0000,,attempt to kill malignant cells, \Nbut can affect the entire body Dialogue: 0,0:01:20.46,0:01:23.46,Default,,0000,0000,0000,,and disrupt healthy tissues \Nin the process. Dialogue: 0,0:01:23.46,0:01:26.08,Default,,0000,0000,0000,,However, some bacteria like E. coli Dialogue: 0,0:01:26.08,0:01:31.53,Default,,0000,0000,0000,,have the unique advantage of being able \Nto selectively grow inside tumors. Dialogue: 0,0:01:31.53,0:01:35.48,Default,,0000,0000,0000,,In fact, the core of a tumor forms \Nan ideal environment Dialogue: 0,0:01:35.48,0:01:39.37,Default,,0000,0000,0000,,where they can safely multiply, \Nhidden from immune cells. Dialogue: 0,0:01:39.37,0:01:41.07,Default,,0000,0000,0000,,Instead of causing infection, Dialogue: 0,0:01:41.07,0:01:45.08,Default,,0000,0000,0000,,bacteria can be reprogrammed \Nto carry cancer-fighting drugs, Dialogue: 0,0:01:45.08,0:01:49.85,Default,,0000,0000,0000,,acting as Trojan Horses \Nthat target the tumor from within. Dialogue: 0,0:01:49.85,0:01:54.79,Default,,0000,0000,0000,,This idea of programming bacteria \Nto sense and respond in novel ways Dialogue: 0,0:01:54.79,0:01:59.51,Default,,0000,0000,0000,,is a major focus of a field called \NSynthetic Biology. Dialogue: 0,0:01:59.51,0:02:01.98,Default,,0000,0000,0000,,But how can bacteria be programmed? Dialogue: 0,0:02:01.98,0:02:05.08,Default,,0000,0000,0000,,The key lies in manipulating their DNA. Dialogue: 0,0:02:05.08,0:02:08.46,Default,,0000,0000,0000,,By inserting particular genetic sequences \Ninto bacteria, Dialogue: 0,0:02:08.46,0:02:11.72,Default,,0000,0000,0000,,they can be instructed \Nto synthesize different molecules, Dialogue: 0,0:02:11.72,0:02:15.27,Default,,0000,0000,0000,,including those \Nthat disrupt cancer growth. Dialogue: 0,0:02:15.27,0:02:18.33,Default,,0000,0000,0000,,They can also be made \Nto behave in very specific ways Dialogue: 0,0:02:18.33,0:02:20.87,Default,,0000,0000,0000,,with the help of biological circuits. Dialogue: 0,0:02:20.87,0:02:25.08,Default,,0000,0000,0000,,These program different behaviors \Ndepending on the presence, absence, Dialogue: 0,0:02:25.08,0:02:27.81,Default,,0000,0000,0000,,or combination of certain factors. Dialogue: 0,0:02:27.81,0:02:31.56,Default,,0000,0000,0000,,For example, tumors have low oxygen \Nand pH levels Dialogue: 0,0:02:31.56,0:02:34.63,Default,,0000,0000,0000,,and over-produce specific molecules. Dialogue: 0,0:02:34.63,0:02:39.37,Default,,0000,0000,0000,,Synthetic biologists can program bacteria \Nto sense those conditions, Dialogue: 0,0:02:39.37,0:02:44.01,Default,,0000,0000,0000,,and by doing so, respond to tumors \Nwhile avoiding healthy tissue. Dialogue: 0,0:02:44.01,0:02:46.38,Default,,0000,0000,0000,,One type of biological circuit, Dialogue: 0,0:02:46.38,0:02:50.31,Default,,0000,0000,0000,,known as a synchronized lysis circuit, \Nor SLC, Dialogue: 0,0:02:50.31,0:02:53.08,Default,,0000,0000,0000,,allows bacteria \Nto not only deliver medicine, Dialogue: 0,0:02:53.08,0:02:55.77,Default,,0000,0000,0000,,but to do so on a set schedule. Dialogue: 0,0:02:55.77,0:02:58.01,Default,,0000,0000,0000,,First, to avoid harming healthy tissue, Dialogue: 0,0:02:58.01,0:03:02.24,Default,,0000,0000,0000,,production of anti-cancer drugs \Nbegins as bacteria grow, Dialogue: 0,0:03:02.24,0:03:05.32,Default,,0000,0000,0000,,which only happens \Nwithin the tumor itself. Dialogue: 0,0:03:05.32,0:03:07.67,Default,,0000,0000,0000,,Next, after they’ve produced the drugs, Dialogue: 0,0:03:07.67,0:03:10.84,Default,,0000,0000,0000,,a kill-switch causes \Nthe bacteria to burst Dialogue: 0,0:03:10.84,0:03:14.00,Default,,0000,0000,0000,,when they reach a critical population \Nthreshold. Dialogue: 0,0:03:14.00,0:03:18.50,Default,,0000,0000,0000,,This both releases the medicine \Nand decreases the bacteria’s population. Dialogue: 0,0:03:18.50,0:03:22.55,Default,,0000,0000,0000,,However, a certain percentage \Nof the bacteria remain alive Dialogue: 0,0:03:22.55,0:03:24.54,Default,,0000,0000,0000,,to replenish the colony. Dialogue: 0,0:03:24.54,0:03:28.52,Default,,0000,0000,0000,,Eventually their numbers grow large enough\Nto trigger the kill switch again, Dialogue: 0,0:03:28.52,0:03:30.57,Default,,0000,0000,0000,,and the cycle continues. Dialogue: 0,0:03:30.57,0:03:33.62,Default,,0000,0000,0000,,This circuit can be fine-tuned \Nto deliver drugs Dialogue: 0,0:03:33.62,0:03:37.86,Default,,0000,0000,0000,,on whatever periodic schedule\Nis best to fight the cancer. Dialogue: 0,0:03:37.86,0:03:42.29,Default,,0000,0000,0000,,This approach has proven promising \Nin scientific trials using mice. Dialogue: 0,0:03:42.29,0:03:46.53,Default,,0000,0000,0000,,Not only were scientists able \Nto successfully eliminate lymphoma tumors Dialogue: 0,0:03:46.53,0:03:48.12,Default,,0000,0000,0000,,injected with bacteria, Dialogue: 0,0:03:48.12,0:03:51.29,Default,,0000,0000,0000,,but the injection also stimulated \Nthe immune system, Dialogue: 0,0:03:51.29,0:03:55.83,Default,,0000,0000,0000,,priming immune cells \Nto identify and attack untreated lymphomas Dialogue: 0,0:03:55.83,0:03:57.59,Default,,0000,0000,0000,,elsewhere in the mouse. Dialogue: 0,0:03:57.59,0:03:59.47,Default,,0000,0000,0000,,Unlike many other therapies, Dialogue: 0,0:03:59.47,0:04:02.48,Default,,0000,0000,0000,,bacteria don’t target a specific type \Nof cancer, Dialogue: 0,0:04:02.48,0:04:07.79,Default,,0000,0000,0000,,but rather the general characteristics \Nshared by all solid tumors. Dialogue: 0,0:04:07.79,0:04:12.17,Default,,0000,0000,0000,,Nor are programmable bacteria \Nlimited to simply fighting cancer. Dialogue: 0,0:04:12.17,0:04:14.97,Default,,0000,0000,0000,,Instead, they can serve \Nas sophisticated sensors Dialogue: 0,0:04:14.97,0:04:17.94,Default,,0000,0000,0000,,that monitor sites of future disease. Dialogue: 0,0:04:17.94,0:04:22.20,Default,,0000,0000,0000,,Safe probiotic bacteria could perhaps \Nlie dormant within our guts, Dialogue: 0,0:04:22.20,0:04:25.10,Default,,0000,0000,0000,,where they’d detect, prevent, \Nand treat disorders Dialogue: 0,0:04:25.10,0:04:28.04,Default,,0000,0000,0000,,before they have the chance \Nto cause symptoms. Dialogue: 0,0:04:28.04,0:04:31.62,Default,,0000,0000,0000,,Advances in technology \Nhave created excitement around a future Dialogue: 0,0:04:31.62,0:04:35.61,Default,,0000,0000,0000,,of personalized medicine \Ndriven by mechanical nanobots. Dialogue: 0,0:04:35.61,0:04:38.22,Default,,0000,0000,0000,,But thanks to billions of years \Nof evolution Dialogue: 0,0:04:38.22,0:04:40.08,Default,,0000,0000,0000,,we may already have a starting point Dialogue: 0,0:04:40.08,0:04:44.34,Default,,0000,0000,0000,,in the unexpectedly biological \Nform of bacteria. Dialogue: 0,0:04:44.34,0:04:46.62,Default,,0000,0000,0000,,Add synthetic biology to the mix, Dialogue: 0,0:04:46.62,0:04:49.64,Default,,0000,0000,0000,,and who knows what might soon be possible.