WEBVTT 00:00:05.943 --> 00:00:10.763 In 1884, a patient’s luck seemed to go from bad to worse. 00:00:10.763 --> 00:00:14.268 This patient had a rapidly growing cancer in his neck, 00:00:14.268 --> 00:00:18.909 and then came down with an unrelated bacterial skin infection. 00:00:18.909 --> 00:00:21.619 But soon, something unexpected happened: 00:00:21.619 --> 00:00:26.670 as he recovered from the infection, the cancer also began to recede. 00:00:26.670 --> 00:00:31.531 When a physician named William Coley tracked the patient down 7 years later, 00:00:31.531 --> 00:00:34.191 no visible signs of the cancer remained. 00:00:34.191 --> 00:00:37.162 Coley believed something remarkable was happening: 00:00:37.162 --> 00:00:41.472 that the bacterial infection had stimulated the patient’s immune system 00:00:41.472 --> 00:00:43.710 to fight off the cancer. NOTE Paragraph 00:00:43.710 --> 00:00:46.504 Coley’s fortunate discovery led him to pioneer 00:00:46.504 --> 00:00:51.417 the intentional injection of bacteria to successfully treat cancer. 00:00:51.417 --> 00:00:55.867 Over a century later, synthetic biologists have found an even better way 00:00:55.867 --> 00:00:58.954 to use these once unlikely allies— 00:00:58.954 --> 00:01:04.040 by programming them to safely deliver drugs directly to tumors. NOTE Paragraph 00:01:04.040 --> 00:01:07.670 Cancer occurs when normal functions of cells are altered, 00:01:07.670 --> 00:01:12.534 causing them to rapidly multiply and form growths called tumors. 00:01:12.534 --> 00:01:16.824 Treatments like radiation, chemotherapy, and immunotherapy 00:01:16.824 --> 00:01:20.459 attempt to kill malignant cells, but can affect the entire body 00:01:20.459 --> 00:01:23.457 and disrupt healthy tissues in the process. NOTE Paragraph 00:01:23.457 --> 00:01:26.077 However, some bacteria like E. coli 00:01:26.077 --> 00:01:31.528 have the unique advantage of being able to selectively grow inside tumors. 00:01:31.528 --> 00:01:35.478 In fact, the core of a tumor forms an ideal environment 00:01:35.478 --> 00:01:39.367 where they can safely multiply, hidden from immune cells. 00:01:39.367 --> 00:01:41.068 Instead of causing infection, 00:01:41.068 --> 00:01:45.077 bacteria can be reprogrammed to carry cancer-fighting drugs, 00:01:45.077 --> 00:01:49.847 acting as Trojan Horses that target the tumor from within. 00:01:49.847 --> 00:01:54.794 This idea of programming bacteria to sense and respond in novel ways 00:01:54.794 --> 00:01:59.514 is a major focus of a field called Synthetic Biology. NOTE Paragraph 00:01:59.514 --> 00:02:01.984 But how can bacteria be programmed? 00:02:01.984 --> 00:02:05.083 The key lies in manipulating their DNA. 00:02:05.083 --> 00:02:08.456 By inserting particular genetic sequences into bacteria, 00:02:08.456 --> 00:02:11.715 they can be instructed to synthesize different molecules, 00:02:11.715 --> 00:02:15.271 including those that disrupt cancer growth. 00:02:15.271 --> 00:02:18.332 They can also be made to behave in very specific ways 00:02:18.332 --> 00:02:20.866 with the help of biological circuits. 00:02:20.866 --> 00:02:25.075 These program different behaviors depending on the presence, absence, 00:02:25.075 --> 00:02:27.811 or combination of certain factors. 00:02:27.811 --> 00:02:31.557 For example, tumors have low oxygen and pH levels 00:02:31.557 --> 00:02:34.630 and over-produce specific molecules. 00:02:34.630 --> 00:02:39.369 Synthetic biologists can program bacteria to sense those conditions, 00:02:39.369 --> 00:02:44.012 and by doing so, respond to tumors while avoiding healthy tissue. NOTE Paragraph 00:02:44.012 --> 00:02:46.377 One type of biological circuit, 00:02:46.377 --> 00:02:50.307 known as a synchronized lysis circuit, or SLC, 00:02:50.307 --> 00:02:53.079 allows bacteria to not only deliver medicine, 00:02:53.079 --> 00:02:55.769 but to do so on a set schedule. 00:02:55.769 --> 00:02:58.009 First, to avoid harming healthy tissue, 00:02:58.009 --> 00:03:02.242 production of anti-cancer drugs begins as bacteria grow, 00:03:02.242 --> 00:03:05.324 which only happens within the tumor itself. 00:03:05.324 --> 00:03:07.671 Next, after they’ve produced the drugs, 00:03:07.671 --> 00:03:10.840 a kill-switch causes the bacteria to burst 00:03:10.840 --> 00:03:14.000 when they reach a critical population threshold. 00:03:14.000 --> 00:03:18.497 This both releases the medicine and decreases the bacteria’s population. 00:03:18.497 --> 00:03:22.549 However, a certain percentage of the bacteria remain alive 00:03:22.549 --> 00:03:24.537 to replenish the colony. 00:03:24.537 --> 00:03:28.518 Eventually their numbers grow large enough to trigger the kill switch again, 00:03:28.518 --> 00:03:30.568 and the cycle continues. 00:03:30.568 --> 00:03:33.618 This circuit can be fine-tuned to deliver drugs 00:03:33.618 --> 00:03:37.858 on whatever periodic schedule is best to fight the cancer. NOTE Paragraph 00:03:37.858 --> 00:03:42.288 This approach has proven promising in scientific trials using mice. 00:03:42.288 --> 00:03:46.534 Not only were scientists able to successfully eliminate lymphoma tumors 00:03:46.534 --> 00:03:48.124 injected with bacteria, 00:03:48.124 --> 00:03:51.294 but the injection also stimulated the immune system, 00:03:51.294 --> 00:03:55.832 priming immune cells to identify and attack untreated lymphomas 00:03:55.832 --> 00:03:57.592 elsewhere in the mouse. NOTE Paragraph 00:03:57.592 --> 00:03:59.468 Unlike many other therapies, 00:03:59.468 --> 00:04:02.478 bacteria don’t target a specific type of cancer, 00:04:02.478 --> 00:04:07.789 but rather the general characteristics shared by all solid tumors. 00:04:07.789 --> 00:04:12.169 Nor are programmable bacteria limited to simply fighting cancer. 00:04:12.169 --> 00:04:14.970 Instead, they can serve as sophisticated sensors 00:04:14.970 --> 00:04:17.939 that monitor sites of future disease. 00:04:17.939 --> 00:04:22.198 Safe probiotic bacteria could perhaps lie dormant within our guts, 00:04:22.198 --> 00:04:25.098 where they’d detect, prevent, and treat disorders 00:04:25.098 --> 00:04:28.042 before they have the chance to cause symptoms. NOTE Paragraph 00:04:28.042 --> 00:04:31.617 Advances in technology have created excitement around a future 00:04:31.617 --> 00:04:35.610 of personalized medicine driven by mechanical nanobots. 00:04:35.610 --> 00:04:38.224 But thanks to billions of years of evolution 00:04:38.224 --> 00:04:40.084 we may already have a starting point 00:04:40.084 --> 00:04:44.343 in the unexpectedly biological form of bacteria. 00:04:44.343 --> 00:04:46.620 Add synthetic biology to the mix, 00:04:46.620 --> 00:04:49.637 and who knows what might soon be possible.