Fighting cancer with bacteria
I just got back from the annual American Society of Microbiology Conference on Undergraduate Education, which ended with a fascinating plenary talk given by Bert Vogelstein, of Johns Hopkins University. Prof. Vogelstein has received many academic honors over his career, and currently has the distinction of being the most highly cited scientist in the life sciences today. That is, the scientific papers on which he is an author have been cited by other researchers in their papers more than any other scientist.
The talk detailed recent work on the use of Clostridium novyi, an organism associated with infrequent human infections, but unlike other Clostridium species, has an extremely strict anaerobic growth requirement. The growth of solid mass tumors is promoted by the development of blood vessels, which enable the delivery of nutrients and oxygen to the tumor mass. The new blood vessels, however, supply the exterior of the tumor, and the interior of the tumor frequently has very little blood supply, and consequently very low to non-existent oxygen levels.
This observation offers a novel way to approach tumor therapy. Most standard methods of cancer treatment are via surgical resection of the tumor, or radiation/chemical treatments to inhibit or kill the fast growing cancer cells. Some new methods (for example, Avastin) work instead to inhibit the development of new blood vessels, in essence starving the tumor cells. The drawbacks of all of these methods is that they will significantly affect the normal cells of the body, and consequently cancer treatment is typically a harsh process on the patient.
With Clostridium novyi, we have an organism that grows only in anaerobic conditions, such as those in the interior of a solid mass tumor. The premise is this: a patient is purposefully infected with endospores from C. novyi, which unlike the vegetative cells, are able to tolerate oxygen. When the endospores get to an environment appropriate for growth (for example, in the interior of a tumor,) the endospores germinate and begin to grow. Many species of Clostridium also produce a variety of toxins that can damage and destroy human cells, and the administration of C. novyi in combination with other antitumor compounds, causes the rapid destruction of the tumor as the tumor is destroyed from within.
The main complication here is sepsis, or infection of the blood as growth of the bacterium spreads throughout the body. The clever bit here is that C. novyi is exquisitely sensitive to penicillin, so that once the patient begins to show the signs and symptoms of sepsis such as spiking fever, the patient can be treated with common antibiotics to bring the infection under control.