1 00:00:05,943 --> 00:00:10,763 In 1884, a patient’s luck seemed to go from bad to worse. 2 00:00:10,763 --> 00:00:14,268 This patient had a rapidly growing cancer in his neck, 3 00:00:14,268 --> 00:00:18,909 and then came down with an unrelated bacterial skin infection. 4 00:00:18,909 --> 00:00:21,619 But soon, something unexpected happened: 5 00:00:21,619 --> 00:00:26,670 as he recovered from the infection, the cancer also began to recede. 6 00:00:26,670 --> 00:00:31,531 When a physician named William Coley tracked the patient down 7 years later, 7 00:00:31,531 --> 00:00:34,191 no visible signs of the cancer remained. 8 00:00:34,191 --> 00:00:37,162 Coley believed something remarkable was happening: 9 00:00:37,162 --> 00:00:41,472 that the bacterial infection had stimulated the patient’s immune system 10 00:00:41,472 --> 00:00:43,710 to fight off the cancer. 11 00:00:43,710 --> 00:00:46,504 Coley’s fortunate discovery led him to pioneer 12 00:00:46,504 --> 00:00:51,417 the intentional injection of bacteria to successfully treat cancer. 13 00:00:51,417 --> 00:00:55,867 Over a century later, synthetic biologists have found an even better way 14 00:00:55,867 --> 00:00:58,954 to use these once unlikely allies— 15 00:00:58,954 --> 00:01:04,040 by programming them to safely deliver drugs directly to tumors. 16 00:01:04,040 --> 00:01:07,670 Cancer occurs when normal functions of cells are altered, 17 00:01:07,670 --> 00:01:12,534 causing them to rapidly multiply and form growths called tumors. 18 00:01:12,534 --> 00:01:16,824 Treatments like radiation, chemotherapy, and immunotherapy 19 00:01:16,824 --> 00:01:20,459 attempt to kill malignant cells, but can affect the entire body 20 00:01:20,459 --> 00:01:23,457 and disrupt healthy tissues in the process. 21 00:01:23,457 --> 00:01:26,077 However, some bacteria like E. coli 22 00:01:26,077 --> 00:01:31,528 have the unique advantage of being able to selectively grow inside tumors. 23 00:01:31,528 --> 00:01:35,478 In fact, the core of a tumor forms an ideal environment 24 00:01:35,478 --> 00:01:39,367 where they can safely multiply, hidden from immune cells. 25 00:01:39,367 --> 00:01:41,068 Instead of causing infection, 26 00:01:41,068 --> 00:01:45,077 bacteria can be reprogrammed to carry cancer-fighting drugs, 27 00:01:45,077 --> 00:01:49,847 acting as Trojan Horses that target the tumor from within. 28 00:01:49,847 --> 00:01:54,794 This idea of programming bacteria to sense and respond in novel ways 29 00:01:54,794 --> 00:01:59,514 is a major focus of a field called Synthetic Biology. 30 00:01:59,514 --> 00:02:01,984 But how can bacteria be programmed? 31 00:02:01,984 --> 00:02:05,083 The key lies in manipulating their DNA. 32 00:02:05,083 --> 00:02:08,456 By inserting particular genetic sequences into bacteria, 33 00:02:08,456 --> 00:02:11,715 they can be instructed to synthesize different molecules, 34 00:02:11,715 --> 00:02:15,271 including those that disrupt cancer growth. 35 00:02:15,271 --> 00:02:18,332 They can also be made to behave in very specific ways 36 00:02:18,332 --> 00:02:20,866 with the help of biological circuits. 37 00:02:20,866 --> 00:02:25,075 These program different behaviors depending on the presence, absence, 38 00:02:25,075 --> 00:02:27,811 or combination of certain factors. 39 00:02:27,811 --> 00:02:31,557 For example, tumors have low oxygen and pH levels 40 00:02:31,557 --> 00:02:34,630 and over-produce specific molecules. 41 00:02:34,630 --> 00:02:39,369 Synthetic biologists can program bacteria to sense those conditions, 42 00:02:39,369 --> 00:02:44,012 and by doing so, respond to tumors while avoiding healthy tissue. 43 00:02:44,012 --> 00:02:46,377 One type of biological circuit, 44 00:02:46,377 --> 00:02:50,307 known as a synchronized lysis circuit, or SLC, 45 00:02:50,307 --> 00:02:53,079 allows bacteria to not only deliver medicine, 46 00:02:53,079 --> 00:02:55,769 but to do so on a set schedule. 47 00:02:55,769 --> 00:02:58,009 First, to avoid harming healthy tissue, 48 00:02:58,009 --> 00:03:02,242 production of anti-cancer drugs begins as bacteria grow, 49 00:03:02,242 --> 00:03:05,324 which only happens within the tumor itself. 50 00:03:05,324 --> 00:03:07,671 Next, after they’ve produced the drugs, 51 00:03:07,671 --> 00:03:10,840 a kill-switch causes the bacteria to burst 52 00:03:10,840 --> 00:03:14,000 when they reach a critical population threshold. 53 00:03:14,000 --> 00:03:18,497 This both releases the medicine and decreases the bacteria’s population. 54 00:03:18,497 --> 00:03:22,549 However, a certain percentage of the bacteria remain alive 55 00:03:22,549 --> 00:03:24,537 to replenish the colony. 56 00:03:24,537 --> 00:03:28,518 Eventually their numbers grow large enough to trigger the kill switch again, 57 00:03:28,518 --> 00:03:30,568 and the cycle continues. 58 00:03:30,568 --> 00:03:33,618 This circuit can be fine-tuned to deliver drugs 59 00:03:33,618 --> 00:03:37,858 on whatever periodic schedule is best to fight the cancer. 60 00:03:37,858 --> 00:03:42,288 This approach has proven promising in scientific trials using mice. 61 00:03:42,288 --> 00:03:46,534 Not only were scientists able to successfully eliminate lymphoma tumors 62 00:03:46,534 --> 00:03:48,124 injected with bacteria, 63 00:03:48,124 --> 00:03:51,294 but the injection also stimulated the immune system, 64 00:03:51,294 --> 00:03:55,832 priming immune cells to identify and attack untreated lymphomas 65 00:03:55,832 --> 00:03:57,592 elsewhere in the mouse. 66 00:03:57,592 --> 00:03:59,468 Unlike many other therapies, 67 00:03:59,468 --> 00:04:02,478 bacteria don’t target a specific type of cancer, 68 00:04:02,478 --> 00:04:07,789 but rather the general characteristics shared by all solid tumors. 69 00:04:07,789 --> 00:04:12,169 Nor are programmable bacteria limited to simply fighting cancer. 70 00:04:12,169 --> 00:04:14,970 Instead, they can serve as sophisticated sensors 71 00:04:14,970 --> 00:04:17,939 that monitor sites of future disease. 72 00:04:17,939 --> 00:04:22,198 Safe probiotic bacteria could perhaps lie dormant within our guts, 73 00:04:22,198 --> 00:04:25,098 where they’d detect, prevent, and treat disorders 74 00:04:25,098 --> 00:04:28,042 before they have the chance to cause symptoms. 75 00:04:28,042 --> 00:04:31,617 Advances in technology have created excitement around a future 76 00:04:31,617 --> 00:04:35,610 of personalized medicine driven by mechanical nanobots. 77 00:04:35,610 --> 00:04:38,224 But thanks to billions of years of evolution 78 00:04:38,224 --> 00:04:40,084 we may already have a starting point 79 00:04:40,084 --> 00:04:44,343 in the unexpectedly biological form of bacteria. 80 00:04:44,343 --> 00:04:46,620 Add synthetic biology to the mix, 81 00:04:46,620 --> 00:04:49,637 and who knows what might soon be possible.