Recently this article was published in The Adelaide Advertiser (30-3-2010). I wanted to re-post it here with some extra bits and pieces because it generated some very nice feedback from people looking for more information. I think it’s a really interesting idea that deserves more research but at the same time I do not want to come off as peddling a new ‘miracle cure’. If you are interested I have included some references at the end where you can find and read the info yourself. Finally, while Thomas and I do sometimes carry around stethoscopes and I have a manual Sphygmomanometer, we are not doctors or medical experts. We are just biology nerds with an internet connection.
Bacteria possess many properties that make them fantastic candidates for cancer treatments.
Potential benefits include cheaper production costs, more targeted activity and their ability to be genetically engineered to be as safe as possible.
As well, many micro-organisms have developed ways of accessing specific areas of the body that can be difficult for conventional drugs to reach.
Research into the potential uses of microorganisms as cancer therapeutics has produced a range of organisms capable of being manipulated into anti-cancer therapies.
But why should we look for new drugs?
Current cancer therapies can be horrible experiences for the patient and involve injections of dangerous chemicals into the body as well as repeated doses of radiation.
Side-effects can range from mild discomfort to long-term damage but these techniques are designed to kill cancer cells and are only used when the benefits outweigh the costs. Despite the intervening pain the cost is your life, so the benefits are always worth it.
Cancer cells have a number of distinguishing characteristics, one of which is an increased cell division rate. Cells around the body have differing rates of division depending on function. Hair follicles divide rapidly, as do epidermal cells that become your skin whereas ‘Memory cells’ of the immune system may not divide for years, unless they are met with an appropriate stimulus, the correct foreign invader.
Cells that divide rapidly use up the resources in their environment, starving other cells and making them more likely to either die or mutate and potentially become cancerous themselves. But as these cells are so resource dependent we have targeted therapies such as chemo and radiotherapy to hit these cells hard and deplete resources resulting in cancer cell death and, with a bit of luck, the survival of the healthy, normal tissue around it. But cancer cells are not the only cells that divide rapidly.
Chemo and radiotherapy cause the death of immune system cells, hair follicles and sperm which can damage the patient more – both immunologically and psychologically.
The advantage of using a bacterium to specifically attack tumor cells is that only the cells that need attacking are killed leaving healthy cells alone.
This can sometimes reduce the need for large amounts of chemo and radio-therapeutic treatments.
One of the most striking observations about tumors is that they often grow rapidly in all directions to a certain size, and often into a sphere, until the cells in the middle of the tumor mass start to die because they are too far away from the blood to receive oxygen.
The tumor continues to grow and the dead area in the middle gets larger while the area of living tumor tissue always remains the same width.
At the border between the living and dead cells are cells called ‘quiescent cells’ or cells that are not dead but have slowed down metabolically to try to prevent their own death. Chemo and radiotherapy are less effective against these cells as they are not dividing rapidly and have stunted their metabolic demands. Once the living tumor has been destroyed, these slow cells are now close to the blood supply again and can then reactivate, growing into another tumor. The bacterial therapies that have been devised are, in some cases, able to kill these quiescent cells.
An enormous amount of research has shown that the species Clostridia can be safely injected directly into the tumor or taken as a pill by a patient with large established tumours (both living and dead cells).
The bacteria will then move throughout the body before finding the tumor and destroying it. Clostridia can do this is because it is introduced in spore form. As a spore the micro-organism often passes straight through people who do not have tumors.
Clostridia spores specifically migrate into the center of tumors and work from the inside out, killing cancerous cells as they go, until they reach high levels of oxygen where the bacteria die or turn back into spores. Using this idea researchers have been able to achieve the holy grail of cancer research, complete remission with no re-activation, but only in research models.
There is resistance to this sort of idea that comes from the long association of bacteria, Clostridia especially, with human disease. Among the sub-species of Clostridia are the causative agents for gangrene and botulism, not the most welcoming of company. Other bacteria that have been used in this work include Listeria and Salmonella, yeah, those two.
The important thing here is control. We can genetically engineer these bacteria to be safe by removing toxins and placing tighter restrictions on their growth to ensure they can only thrive in low/no oxygen environments.
This idea has interested me for a very long time not because it results in ‘cure’ of cancers in models but because of the way in which the ‘cure’ is achieved. Thinking about bacteria in this way represents a shift in the way biomedical researchers view the world around them. No longer are bacteria always the bad guys. Recent developments using bacteria as ‘toxin sinks’, bio-fuel manufacturers and, as in this case, novel vehicles for pharmaceutical delivery show that by applying our understanding of the microbial world we can modify it to become useful, as opposed to harmful, to us.
Barbe, S., et al. (2004). “Clostridium-mediated transfer system of therapeutic proteins to solid tumors: increased heterologous protein production.” Commun Agric Appl Biol Sci 69(2): 49-52.
Nuyts, S., et al. (2002). “Clostridium spores for tumor-specific drug delivery.” Anticancer Drugs 13(2): 115-25.
Pan, Z. K., et al. (1995a). “A recombinant Listeria monocytogenes vaccine expressing a model tumour antigen protects mice against lethal tumour cell challenge and causes regression of established tumours.” Nat Med 1(5): 471-7.
Pan, Z. K., et al. (1995b). “Regression of established tumors in mice mediated by the oral administration of a recombinant Listeria monocytogenes vaccine.” Cancer Res 55(21): 4776-9.
Rosenberg, S. A., et al. (2002). “Antitumor effects in mice of the intravenous injection of attenuated Salmonella typhimurium.” J Immunother25(3): 218-25.
Theys, J., et al. (2001a). “Clostridium as a tumor-specific delivery system of therapeutic proteins.” Cancer Detect Prev 25(6): 548-57.
Theys, J., et al. (2001b). “Improvement of Clostridium tumour targeting vectors evaluated in rat rhabdomyosarcomas.” FEMS Immunol Med Microbiol 30(1): 37-41.
Toso, J. F., et al. (2002). “Phase I study of the intravenous administration of attenuated Salmonella typhimurium to patients with metastatic melanoma.” J Clin Oncol 20(1): 142-52.
Van Mellaert, L., et al. (2006). “Clostridium spores as anti-tumour agents.” Trends Microbiol 14(4): 190-6.