Hacking bacteria to fight cancer - Tal Danino

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In 1884, an unlucky patient who had a rapidly growing cancer in his neck came down with an unrelated bacterial skin infection. As he recovered from the infection, the cancer surprisingly began to recede. The infection had stimulated the patient’s immune system. Today, synthetic biologists program bacteria to safely deliver drugs directly to tumors. How is this possible? Tal Danino investigates.

Lesson by Tal Danino, directed by Chris Bishop.

In 1884, a patient’s luck seemed
to go from bad to worse.

This patient had a rapidly
growing cancer in his neck,

and then came down with an unrelated
bacterial skin infection.

But soon, something unexpected happened:

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

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

no visible signs of the cancer remained.

Coley believed something
remarkable was happening:

that the bacterial infection had
stimulated the patient’s immune system

to fight off the cancer.

Coley’s fortunate discovery
led him to pioneer

the intentional injection of bacteria
to successfully treat cancer.

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

to use these once unlikely allies—

by programming them to safely
deliver drugs directly to tumors.

Cancer occurs when normal functions
of cells are altered,

causing them to rapidly multiply
and form growths called tumors.

Treatments like radiation, chemotherapy,
and immunotherapy

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

and disrupt healthy tissues
in the process.

However, some bacteria like E. coli

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

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

where they can safely multiply,
hidden from immune cells.

Instead of causing infection,

bacteria can be reprogrammed
to carry cancer-fighting drugs,

acting as Trojan Horses that target
the tumor from within.

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

is a major focus of a field
called Synthetic Biology.

But how can bacteria be programmed?

The key lies in manipulating their DNA.

By inserting particular genetic
sequences into bacteria,

they can be instructed to
synthesize different molecules,

including those that disrupt
cancer growth.

They can also be made to
behave in very specific ways

with the help of biological circuits.

These program different behaviors
depending on the presence, absence,

or combination of certain factors.

For example, tumors have low
oxygen and pH levels

and over-produce specific molecules.

Synthetic biologists can program
bacteria to sense those conditions,

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

One type of biological circuit, known
as a synchronized lysis circuit, or SLC,

allows bacteria to not only deliver
medicine, but to do so on a set schedule.

First, to avoid harming healthy tissue,

production of anti-cancer drugs
begins as bacteria grow,

which only happens within
the tumor itself.

Next, after they’ve produced the drugs,

a kill-switch causes the
bacteria to burst

when they reach a critical
population threshold.

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

However, a certain percentage of
the bacteria remain alive

to replenish the colony.

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

and the cycle continues.

This circuit can be fine-tuned to deliver
drugs on whatever periodic schedule

is best to fight the cancer.

This approach has proven promising
in scientific trials using mice.

Not only were scientists able to
successfully eliminate lymphoma tumors

injected with bacteria, but the injection
also stimulated the immune system,

priming immune cells to identify
and attack untreated lymphomas

elsewhere in the mouse.

Unlike many other therapies, bacteria
don’t target a specific type of cancer,

but rather the general characteristics
shared by all solid tumors.

Nor are programmable bacteria
limited to simply fighting cancer.

Instead, they can serve as
sophisticated sensors

that monitor sites of future disease.

Safe probiotic bacteria could
perhaps lie dormant within our guts,

where they’d detect, prevent,
and treat disorders

before they have the chance
to cause symptoms.

Advances in technology have
created excitement around a future

of personalized medicine driven
by mechanical nanobots.

But thanks to billions of years
of evolution

we may already have a starting point

in the unexpectedly biological
form of bacteria.

Add synthetic biology to the mix,

and who knows what might soon be possible.