0:00:05.943,0:00:10.763
In 1884, a patient’s luck seemed [br]to go from bad to worse.

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This patient had a rapidly growing [br]cancer in his neck,

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and then came down with an unrelated [br]bacterial skin infection.

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But soon, something unexpected happened:

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as he recovered from the infection, [br]the cancer also began to recede.

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When a physician named William Coley [br]tracked the patient down 7 years later,

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no visible signs of the cancer remained.

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Coley believed something remarkable [br]was happening:

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that the bacterial infection [br]had stimulated the patient’s immune system

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to fight off the cancer.

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Coley’s fortunate discovery [br]led him to pioneer

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the intentional injection of bacteria [br]to successfully treat cancer.

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Over a century later, synthetic biologists[br]have found an even better way

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to use these once unlikely allies—

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by programming them to safely [br]deliver drugs directly to tumors.

0:01:04.040,0:01:07.670
Cancer occurs when normal functions [br]of cells are altered,

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causing them to rapidly multiply [br]and form growths called tumors.

0:01:12.534,0:01:16.824
Treatments like radiation, chemotherapy, [br]and immunotherapy

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attempt to kill malignant cells, [br]but can affect the entire body

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and disrupt healthy tissues [br]in the process.

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However, some bacteria like E. coli

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have the unique advantage of being able [br]to selectively grow inside tumors.

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In fact, the core of a tumor forms [br]an ideal environment

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where they can safely multiply, [br]hidden from immune cells.

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Instead of causing infection,

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bacteria can be reprogrammed [br]to carry cancer-fighting drugs,

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acting as Trojan Horses [br]that target the tumor from within.

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This idea of programming bacteria [br]to sense and respond in novel ways

0:01:54.794,0:01:59.514
is a major focus of a field called [br]Synthetic Biology.

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But how can bacteria be programmed?

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The key lies in manipulating their DNA.

0:02:05.083,0:02:08.456
By inserting particular genetic sequences [br]into bacteria,

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they can be instructed [br]to synthesize different molecules,

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including those [br]that disrupt cancer growth.

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They can also be made [br]to behave in very specific ways

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with the help of biological circuits.

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These program different behaviors [br]depending on the presence, absence,

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or combination of certain factors.

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For example, tumors have low oxygen [br]and pH levels

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and over-produce specific molecules.

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Synthetic biologists can program bacteria [br]to sense those conditions,

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and by doing so, respond to tumors [br]while avoiding healthy tissue.

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One type of biological circuit,

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known as a synchronized lysis circuit, [br]or SLC,

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allows bacteria [br]to not only deliver medicine,

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but to do so on a set schedule.

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First, to avoid harming healthy tissue,

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production of anti-cancer drugs [br]begins as bacteria grow,

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which only happens [br]within the tumor itself.

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Next, after they’ve produced the drugs,

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a kill-switch causes [br]the bacteria to burst

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when they reach a critical population [br]threshold.

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This both releases the medicine [br]and decreases the bacteria’s population.

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However, a certain percentage [br]of the bacteria remain alive

0:03:22.549,0:03:24.537
to replenish the colony.

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Eventually their numbers grow large enough[br]to trigger the kill switch again,

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and the cycle continues.

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This circuit can be fine-tuned [br]to deliver drugs

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on whatever periodic schedule[br]is best to fight the cancer.

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This approach has proven promising [br]in scientific trials using mice.

0:03:42.288,0:03:46.534
Not only were scientists able [br]to successfully eliminate lymphoma tumors

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injected with bacteria,

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but the injection also stimulated [br]the immune system,

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priming immune cells [br]to identify and attack untreated lymphomas

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elsewhere in the mouse.

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Unlike many other therapies,

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bacteria don’t target a specific type [br]of cancer,

0:04:02.478,0:04:07.789
but rather the general characteristics [br]shared by all solid tumors.

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Nor are programmable bacteria [br]limited to simply fighting cancer.

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Instead, they can serve [br]as sophisticated sensors

0:04:14.970,0:04:17.939
that monitor sites of future disease.

0:04:17.939,0:04:22.198
Safe probiotic bacteria could perhaps [br]lie dormant within our guts,

0:04:22.198,0:04:25.098
where they’d detect, prevent, [br]and treat disorders

0:04:25.098,0:04:28.042
before they have the chance [br]to cause symptoms.

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Advances in technology [br]have created excitement around a future

0:04:31.617,0:04:35.610
of personalized medicine [br]driven by mechanical nanobots.

0:04:35.610,0:04:38.224
But thanks to billions of years [br]of evolution

0:04:38.224,0:04:40.084
we may already have a starting point

0:04:40.084,0:04:44.343
in the unexpectedly biological [br]form of bacteria.

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Add synthetic biology to the mix,

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and who knows what might soon be possible.