March
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3.18.19 The Forgotten Cure Chapter 5-8
- Having a state health system was particularly damaging to the consistent treatment of infectious diseases in Russia. Since the state was liable for paying for care of patients, both economic and political factors became important when determining the course of care a patient would receive. During World War II, antibiotics were presented from western countries to the Soviet Union for the first time. Their success stories were very compelling to citizens and doctors, but their high cost proved to be an issue for the Soviet Government. This led to hospitals operating with only a small portion of antibiotics that were created, and of that portion they consistently were out of types of antibiotic. This economic shortage implicated politics, as the Russian government did not want to appear weak or unable to care for their own citizens. Therefore, they created propaganda that favored alternative, or home-grown, remedies in order to encourage more citizens to use methods that did not include antibiotics. This also allowed bacteriophage therapy to coexist with the limited antibiotics that were being used, as they were less expensive to produce.
- Across Europe, many institutes were created to further investigate bacteriophages and phage therapy. Interest with these organization lies mainly within three highlighted groups: Eliava Institute, Hirszfeld Institute, and Phage Therapy Center. The Hirszfeld and Eliava Institutes share similar struggles with Russian authorities. As examined in the first discussion, the Eliava Institute struggled with Russian politics, as Eliava himself petitioned the wrong individuals for permissions, and the politicians that were snubbed worked against him and eventually led to his arrest and execution. The Hirszfeld Institute also struggled with Russian rule in its developmental stages. Ludwik Hirszfeld constantly battled against Lysenkoism, which was staunchly supported by Stalin. Any other theory on biology was greatly discouraged by Russian authorities, and holding the beliefs that Hirszfeld did about biology was considered dangerous and a slight against authority. Therefore, Hirszfeld was not able to freely publish his work, which slowed the development of his petitions for an institute. His petitions were further damaged after a group of mainly Jewish scientists and doctors were convicted for a plot to poison government officials. Due to the Jewish linage present in Hirszfeld and his associates, there was fear that they would be soon persecuted as well. Again, this worked against the creation of a Hirszfeld institute. Thus, the Eliava and Hirszfeld Institutes both struggled under Russian rule. The third institute examined was the Phage Therapy Center. When compared with the Eliava Institute Today, it becomes apparent that while they overlap on ideas and missions, their core goals differ. In other words, the Eliava Institute contributes more towards the research and understanding of bacteriophages and their potential use in phage therapy while the Phage Therapy Center is mostly concerned with treating individuals who have conditions that are better treated by phage therapy (stated on their website as conditions localized to specific areas of lower blood flow, acute or chronic bacterial infections, or cases that implicate bacteria resistant to antibiotics). Historically, however, the Eliava Institute was very involved with the treatment of bacterial infections and diseases with bacteriophages.
- A large challenge that Merril had when he attempted to use phage therapy as a treatment was that the majority of the bacteriophages used were instantly filtered out as by the liver and spleen. This led to the development of the serial passage technique. First, Merril and his team chose lambda phage, a very well-known and understood bacteriophage because of the work by Delbruck, for the experiment. This allowed them to control for variables that would otherwise have been unknown. Next, the group injected infected blood with a large amount of bacteriophage. The bacteriophage that made it through the mice was harvested seven hours later, and the process was repeated many times until a large amount of bacteriophage that was viable could be used to combat the disease in the organism. The comparison between bacteriophages that had undergone serial passage and those that had not was clearly shown in a figure of the PNAS paper to have approximately twice the concentration after 25 hours of being in the infected mouse. This portion proved that a phage resistant to being filtered out by internal organs could be obtained. The next step was to prove that mice with E. coli could actually be saved by the phage treatment. Therefore, they created an experiment where some mice with E. coli received phage treatment and others did not. When the phage treatment worked, they concluded that the newly passaged phages were effective in treating a relatively straightforward disease. These results were displayed in the PNAS paper in a line graph that compared symptoms to time; mice that received phage treatment with passaged phages Argo1 and Argo2 were healed within 100 hours, and those that were not died due to the infection. To continue to investigate the magnitude of the discovery, they investigated how phages could combat a more dangerous type of bacteria (VRE). The group proved that the phages were capable of treating this strain of more severe bacterial infection. Lastly, and of perhaps greater concern to critics of phage therapy and the FDA, the group managed to show that bacteriophage, not the immune system, was the agent that was causing the results by introducing heat-killed bacteriophages that would stimulate the immune response, but not kill any of the bacterial cells. When the same effectiveness was not shown with the heat-killed phages, it was concluded that the phages had some effect in combating the infections.
- GangaGen was described in the text as a company originating in India due to the finding of bacteriophages in the Ganges River (which resulted in the name of the company). Due to the attractiveness of phages, the company attracted investors before any real ideas had been developed. The other companies, like GangaGen, are focused on developing products that can help to treat disorders with phages rather than other treatments and changing bacteriophages from an alternative treatment to a tool that can be used to combat modern medical problems. These treatments could be particularly useful, as antibiotic-resistant strains of bacteria are becoming more prevalent and cannot be easily solved with current technologies. Experiments proving bacteriophage effectiveness in combatting modern antibiotic-resistant strains along with other conditions where bacteriophages would be less expensive than antibiotics would allow doctors and individuals being treated to have more options, which can often lead to better care. The additional options would be achieved by the specificity of bacteriophages, as doctors or patients would not need to rely on extrapolating an antibiotic to try to combat an evolved strain of bacteria.
Henry, I think it is important that companies like GangaGen are exploring bacteriophage therapy for bacterial infections, especially for bacteria that are becoming resistant to antibiotics. However, as fast as bacteria are able to evolve, they will become resistant to the phages as well. Using a combination of phage and antibiotics will create the best results, as it will be harder for the bacteria to become resistant to both.
Lucy, that’s a really good point. It might be interesting to do an observational study of phage therapy, antibiotics, and cases where both were used to see a percentage difference on the rate at which the new antibiotic resistant strains developed. This point could help solidify the relevance of bacteriophages if it was drastically lower!
Sounds like a good research project!
A good example of the ongoing “arms race” between predator and prey.