Bacteriophage research, like all research, relies on interested scientists and funding for its success. Not only does it rely on this, but also the state of the government and the government systems. In Russia, phage therapy was cheaper than antibiotics and because of this, was more prominent during the 1940s-50s. The phage came from the environment and did not cost the government like antibiotics did. Also, the Russians liked to use non-conventional medicines and treatments like herbs. Bacteriophage were not considered standard medications, and because of this, the Russians naturally fell to using phages in place of antibiotics when possible. However, one difficulty in the spreading of phage research in the 1940s and 1950s in Russia was the state health system. Because of lack of funding, scientists were not paid well. Institutes like Eliava did not always have electricity, which made keeping phages alive difficult with no refrigeration. Some doctors even took their phage home with them. So while the Russian systems influenced the spread of phage, other areas of the government kept them from becoming more widespread.
Many different phage institutes in Russia made discoveries in bacteriophage research. The institutes all had their own difficulties, and many of them fought against wars such as World War II. Hirszfeld and his family suffered from the war and Stalin’s reign in Russia. Because of the wars and other difficulties, many of the phage institutes struggled to continue. The Eliava Institute is still functioning today and has grown much larger, expanding to include many spin-off companies. The Phage Therapy Center in Wroclaw focuses more on providing therapies and treatments to patients than new research like the Eliava Institute does. They treat many different infections such as acne, colitis, laryngitis, and burns. The different institutes all play an important role in the spread of bacteriophage research and therapy.
When bacteriophage research spread to the US, many changes had to be made to accommodate the regulations in the US. For instance, scientists and the FDA wanted proof that the phage actually helped in the healing process and did not just activate the immune response. Carl Merril and his team helped to prove this by using heat-killed phages to show that while they did activate the immune response, the phages would do more by lysing the bacterial cells. Merril, Carlton, and Adhya, in their PNAS paper, provided a way to select for bacteriophages that would stay in their patient longer and therefore help in the immune response. Using lambda phage and E. coli, Merril and his team created the passaging technique to select for phages that could survive longer in the stomachs of their patients. They would isolate phages still present in the stomach of their mice patients 7 hours after infection, propagate them, and then reinject the phages into the mice. The scientists would do this multiple times, and in the end, they created strains of lambda phage that could survive in the stomach conditions for longer than the wild types. The phages, names Argo1 and Argo2, were able to stay in the stomach in much higher amounts than the wild type. In their PNAS paper, the figures show how at 24 hours, the titers of the wild type would have been reduced by about half of their original titer, while Argo1 and Argo2 would have only gone down a small amount. Also, the scientists were able to see that mice treated with the phage improved much more than mice without treatment and that those treated with Argo1 had fewer symptoms than those treated with the wild type lambda phage.
While many still consider phage therapy an alternative to other treatments like antibiotics, there are many companies discussed in The Forgotten Cure that are researching to change this and make phage as prominent as antibiotics in bacterial treatments. GangaGen is one company that is attempting to make bacteriophage an alternative treatment to antibiotic-resistant bacteria. There are many experiments that need to be done in order to spread phage therapy in the US. Phage therapy has to go through clinical trials in order to be approved by the FDA and given as treatment to patients. Experiments need to be done to test more bacteriophage and find more that match specific bacterial strains in order to best fight these diseases. Also, experiments need to be done to test the best phage cocktails for different diseases, as well as the effect of combining them with different antibiotics. One example is the experiments at Exponential Biotherapies. They are working on phage therapy for acute kidney injury and irradiation damage from cancer therapies. Because of the FDA and other regulations, any new possible therapies will need to be tested with animals and then undergo strict human clinical trials. While each of these experiments will take time, it could lead to a new era of treatment in bacterial infections
