Can we program bacteria to fight cancer?

Cancer occurs when normal functions of cells are altered, causing them to rapidly multiply and form growths called tumours. Treatments like radiation, chemotherapy, and immunotherapy attempt to kill malignant cells, but can affect the entire body and disrupt healthy tissues in the process. In 1884 a patient had a rapidly growing cancer in his neck, it grew larger and larger. The patient then came down with an unrelated bacterial skin infection. Surprisingly as he recovered from the infection, cancer also began to recede. When a physician named William Coley tracked the patient down 7 years later, no visible signs of cancer remained. Coley believed that the bacterial infection had stimulated the patient’s immune system to fight off cancer, hence decreasing the size of the tumour. This lead to the discovery of the intentional injection of bacteria to successfully treat cancer, which was pioneered by Coley.

Synthetic biologists have found a way to use disease-causing creatures by programming them to safely deliver drugs directly to tumours. Some bacteria like E. coli have the unique advantage of being able to selectively grow inside tumours. In fact, the core of a tumour 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, targeting the tumour from within. This idea of programming bacteria to sense and respond in novel ways is a major focus of a field called Synthetic Biology. The key to doing this 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 specific ways with the help of biological circuits. These program different behaviours depending on the presence, absence, a or combination of certain factors. Tumours have low oxygen and pH levels and over-produce certain molecules. So synthetic biologists will program bacteria to sense those conditions, so that the bacteria, respond only to tumours while avoiding healthy tissue.

One type of biological circuit, known as a synchronized lysis circuit (SLC) allows bacteria to not only deliver medicine, but it can do so on a set schedule. To avoid harming healthy tissue, the production of anti-cancer drugs begins as bacteria grow, which only happens within the tumour itself. After they’ve produced the drugs, a kill-switch causes the bacteria to burst when they reach a critical population within the tumour, so that the bacteria can cause no other infection. This releases the medicine and decreases the bacteria’s population. However, a certain percentage of the bacteria remain alive, these again 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 cancer. This approach has proven promising in scientific trials using mice. Scientists were able to eliminate lymphoma tumours injected with bacteria The injection also stimulated the immune system, helping immune cells to identify and attack untreated lymphomas elsewhere in the mice.

Unlike many other therapies, bacteria don’t target a specific type of cancer, but rather the general characteristics shared by all solid tumours. Programmable bacteria are not 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 bacteria. Thanks to evolution we already have a starting point but with synthetic biology, we may be able to achieve what seemed impossible.

References 

Matheson, Rob, and MIT News Office. "Reprogramming Gut Bacteria as "living Therapeutics"." MIT News. N.p., 05 Apr. 2016. Web. 19 Apr. 2020.
https://www.youtube.com/watch?v=_3guktHJNPM