As a scientist, describe the main experiment you would like to see performed before phage therapy is approved for human use. What are the risks involved with using phage therapy?

As a scientist, two factors must be considered with each experiment that is used to prove the effectiveness/usefulness of a new treatment. Firstly, the scientist should consider whether or not the treatment is safe and ethical before beginning an experiment. A good experiment that features the testing of a new treatment should be safe and should also provide evidence to the FDA and public that the treatment is usable without substantial harm (if it is to be made public). Secondly, the experiment should be designed to determine the effectiveness of the treatment without skewing results in a direction to support or disprove a hypothesis. This increases the credibility of the work from a scientific standpoint and would also make the case presented to the FDA more convincing. If I were a scientist trying to determine if phage therapy should be approved for human use, I would like to do a direct comparison study between antibiotics and bacteriophage therapy. This study would be accomplished by first obtaining a constant bacteria strain that was antibiotic resistant. Next, a phage cocktail would be cultured (similar to those created at Phage Therapy Centers, such as those referenced by Kuchment in the text) to attack that specific strain of bacteria. This phage cocktail would be tested in conjunction with a control group with no treatment, an antibiotic treatment that contained a cocktail probable to have success against that particular resistant strain, and a general antibiotic such as penicillin. Results would include the success of the elimination of the resistant bacteria and the levels of endotoxins released by the bacteria that had died. This study would examine not only the effectiveness of phage therapy in relation to other modern treatments, but also the safety in relation to other modern treatments. If the results from this experiment returned favorably, they would play a large role in changing public perception of phage therapy (Kuchment discusses how western medicine has traditionally favored antibiotics while eastern medicine has traditionally favored phage therapy, which followed the political lines leading up to and during the Cold War) and could play a crucial role in getting the approval of the FDA.

A risk factor that would also be addressed by this experiment would be the release of endotoxins upon lysis of bacteria. This is a problem that is shared between bacteriophages and certain classes of antibiotics, so this experiment would be very useful in discerning the extent at which phages cause endotoxins to be released compared with the extent that antibiotics do. However, phages may have a unique property that could limit this risk factor. In addition to Kuchment’s description, Doss, Culbertson, Hahn, Camacho, and Barekzi describe a method that involves genetic engineering of bacteriophages to eliminate their major lysis proteins; these new phages kill bacteria by creating a hole in the inner membrane via the holin. The release of endotoxins could go from a potential problem with phage therapy to a very big advantage, as eliminating the risk of endotoxin release would reduce the worries of additional problems in the future with endotoxins causing more severe problems upon the death of bacteria. A second risk factor that would be addressed by this experiment would be the risk that the public would not have faith in the treatment. An approved treatment would remain relatively useless if the public did not trust it, so having evidence to substantiate the claims made by proponents of phage therapy before the treatment was approved could encourage the FDA to be more confident in approval of the topic, swaying public opinion in a favorable way. To summarize, this would eliminate the risk as a scientist of investing many resources into a treatment and experiments that would not be widely used. A final risk with phages is that the phage cocktails used in treatment that are designed for more breadth rather than one phage is that they can also cause bacterial resistance. Therefore, it would be important to use phages carefully and in a focused manner to ensure that bacterial resistance would be minimized.

Doss, J., Culbertson, K., Hahn, D., Camacho, J., & Barekzi, N. (2017). A Review of Phage Therapy against Bacterial Pathogens of Aquatic and Terrestrial Organisms. Viruses, 9(3), 50. doi:10.3390/v9030050