March 18

Forgotten Cure Part Two

Forgotten Cure Part Two

1. How did having a state health system influence the treatment of infectious disease in 1940s-50s Russia?

The state health system was underfunded, so while it tried to provide health care for all, it was often short on resources (like money and antibiotics). This was an embarrassment to the Soviet Union, so it relied on propaganda to discourage the use of antibiotics to treat infectious disease. This propaganda encouraged citizens to rely on alternative medicines like herbs, and because phage therapy was also considered alternative medicine, it became more popular as a treatment for infectious disease during that time.

2. The Hirszfeld Institute is also intertwined with Russian history. A tragic quote is given on page 66 by Hirszfeld about the death of his daughter. Even so, the outcome of these 2 centers has been very different. Discuss why you think this is so. Contrast the Phage Therapy Center in Wroclaw with the Eliava Institute in Tbilisis.

The Phage Therapy Center might have succeeded where the Eliava Institute did not because of the differences in their founding, focus, and support. The Phage Therapy Center was supported by the Polish government after the end of World War 2 and became better established afterward. The Eliava Institute, by contrast, lost funding towards the end of world war 2 and focused more on phage. The two different political climates surrounding these institutions can account for the differences in what happened to them.

3. Research in the USA often differs from other countries because of regulations by the FDA and private investments. Describe the experimental design that Merril used to determine how to select for phages that were not removed by the liver and spleen. Review the Merril, Carlton, and Adhya PNAS paper, focusing on interpreting their figures.

For his experimental design, Merril injected lambda phage into mice and tested for the presence of phage in the blood after 7 hours. He then selected the remaining phage from the parent testing and used serial-passage techniques to select the phages Argo 1 and Argo 2 that survived longer than the original parent lambda phage (around 18 hours). This was done by selecting the remaining phage and reinjecting the mice 8 times. As can be seen in the figures below, Argo 1 and Argo 2 persisted in the blood longer that the wild type at high concentrations.

These passaged phages were then used in another experiment to demonstrate their effectiveness against E. coli. Four groups of mice were infected with a lethal dose of the bacteria and three were treated with phage (Argo 1, Argo 2, or wild-type phage) and one was left as a control. The ones treated with phage were more likely to survive, and Argo 1 and Argo 2 phage treatments seemed to lessen the disease severity.

4. The most convincing argument for using phage is tied to the increasing problem of antibiotic resistance. Even so, many still consider phage therapy an alternative therapy. Chapter 8 describes several start-up companies: Phage Therapy, Phage Biotics, GangaGen, Exponential Biotherapies. Research these companies and discuss the potential for phage therapy in modern Western medicine. What experiments need to be done?

Personally, I think that for phage therapy to lose the label of alternative medicine and be fully embraced by Western Medicine science alone will not be sufficient. I think that Phage Therapy in the west has been hurt by associations with eastern medicine and the soviet union. I think that double-blind experiments do need to be done and continued, but I also think prominent western scientists will need to lend their support to phage therapy. In addition to a bit of a PR campaign, more experimental data showing the use of phage and antibiotics together to combat antibiotic resistance would be beneficial. Finally, what I found to be most intriguing was mention in the book, the author said that many bacteria that developed a resistance to phage seemed to mutate into a harmless, avirulent form of the bacteria. If there could be experiments done that showed that bacteria tended to become avirulent when becoming resistant to phage not only would that revolutionize how we treat disease, but it would also help phage therapy.

Category: Lucy FIsher | 3 Comments on Forgotten Cure Part Two
March 17

Forgotten Cure 2

Forgotten Cure

 

  1. How did having a state health system influence the treatment of infectious disease in 1940s-50s Russia?

The state health care system created by the USSR during wartime created many issues in the treatment of infectious disease. The conditions created by World War II spurred many outbreaks of bacterial infections. Then, non-traditional medicine became more popularized and this sparked an increased interest in phage therapy because it was viewed as natural or non-traditional. The government was communist at this time and thus people were distrusting of the government as a general rule. The government had interfered with antibiotic development and inserted itself into personal healthcare, so trust of the government wasn’t common. Antibiotic use in Russia was difficult to obtain at first, but then it turned to being available on shelves without prescriptions and this contributed to the growing number of antibiotic resistant bacterial strains and thus increased use of phage therapy.

  1. The Hirszfeld Institute is also intertwined with Russian history. A tragic quote is given on page 66 by Hirszfeld about the death of his daughter.  Even so, the outcome of these 2 centers has been very different.  Discuss why you think this is so.

Contrast the Phage Therapy Center in Wroclaw with the Eliava Institute in Tbilisis.

Both the Hirszfeld Institute and the Eliava Institute came about because of oppressive regimes in eastern Europe and both had to overcome differing ideologies in regards to phage therapy. The Hirszfeld Institute found more success in its longevity because the Eliava Institute had only a short period of popularity and scientific discovery. Unfortunately, in order for institutes such as these to exist and experiment, they need funding and support. The geographical locations of the two made this immensely difficult when compared to similar places in countries like the United States; the Eliava Institute is located in Georgia, which is small and fell under Soviet rule in the days the institute was established. Thus, the Phage Therapy Center, located in Poland, has found more success than the Eliava institute because being rooted in Poland gives it more connection to the western world and thus more opportunity to receive funding from more developed countries and the donors that reside in them.

 

  1. Research in the USA often differs from other countries because of regulations by the FDA and private investments. Describe the experimental design that Merril used to determine how to select for phages that were not removed by the liver and spleen.

Review the Merril, Carlton, and Adhya PNAS paper, focusing on interpreting their figures.

Mice were injected with phage and a bacteria and the blood was tested after several hours and the phages that survived were isolated and propagated in order to increase the number of them. This was repeated 8 times until the remaining phages were able to survive for 18 hours within the mouse. The figures in the paper reflect the strength of the symptoms associated with the bacterial infection relative to the dose and type of phage used to treat the mouse. Mice treated with only antibiotic had reduced symptom presence, but mice treated with phage had the least symptoms.

  1. The most convincing argument for using phage is tied to the increasing problem of antibiotic resistance. Even so, many still consider phage therapy an alternative therapy.  Chapter 8 describes several start-up companies:

Phage Therapy, Phage Biotics, GangaGen, Exponential Biotherapies.  Research these companies and discuss the potential for phage therapy in modern Western medicine. What experiments need to be done?

First of all, many of the phage therapy studies mentioned in the book were completed in European countries and did not follow typical protocol for studies to be completely accepted, such as using double-blind experiments. Experiments proving again the effectiveness of combining phage therapy with antibiotics but following guidelines for research that will make it more widely accepted in western medicine. Because the currently published studies were not conducted in such a manner, there is doubt from western doctors and thus doubt in the usage of phages to treat bacterial infections.

Category: Lily Goodman | LEAVE A COMMENT
March 17

The Forgotten Cure Part 2

Phage therapy has been subjected to the influences of several varying cultures and political climates in countries such as Russia, India, Poland, and the United States. Each country viewed phage therapy differently than the other, ushering in a wide array of uses for phage in some countries such as Russia and Poland, while also being completely reduced to nothing in the others such as the United States.

During the 1940s-50s, Russia’s state health system influenced the treatment of infectious diseases greatly as the country could not rely on the use of “superdrugs” such as antibiotics to fight off infectious diseases. The country’s healthcare was supplemented purely by the government, and due to lack of funding and resources, the Russian people had to turn to alternative treatments to prevent infectious disease. With the withdrawal of financial support from the West after the end of World War II, the Russian government turned to propaganda to turn the citizens away from the “foreign Western antibiotics” urging them to use herbal remedies that were considered more patriotic and just. This turn away from traditional Western medicine allowed alternative treatments such as phage therapy to flourish in the Soviet Union as it was cost-effective and supported by the government’s propaganda.

Despite both the Phage Therapy Center and the Eliava Institute being under the rule of the Soviet Union, both institutions had vastly different outcomes regarding their phage research. The Eliava Institute, unfortunately, gained its peak during World War II at the height of Stalin’s reign of terror. During the war, it was primarily used to further bacteriophage research so that they could control the spread of infectious diseases on the battlefield, but once the war ended so did their usefulness. The institute’s leader, George Eliava, fell victim to Stalin’s reign of terror and was executed by the regime. Many did not return to the institute and it began to fall into disarray, but the institute is now running once again trying to further bacteriophage research. Unlike the Eliava Institute, The Phage Therapy Center in Wroclaw did not share the same fate and once the USSR fell, the Polish government continued to fund the institution’s research with phages. The center focuses now more on the use of bacteriophages to treat antibiotic resistant diseases, and even has received support from the European Union.

In the early 1990s, Carl Merril, Richard Carlton, and Sankar Adhya performed a revolutionary experiment that allowed them to select for phages that could evade the liver and spleen in their host organisms. This experiment was brought about as many attempts of phage therapy in animals seemed to fail as the phages would disappear in their host way too early to fight off any infection. To perform the experiment, the team first injected a phage they called “lambda” into the stomachs of mice. They waited for 7 hours, removed blood samples from the mice, isolated phages from the blood, and reinfected the mice with the isolated phage samples. They performed this task 8 times to isolate a phage that could remain in the bloodstream for at least 18 hours. The new phage that they isolated (Argo1 and Argo2) had a survival rate thousands of times higher than their parent lambda and proved they were still capable of curing mice from lethal doses of E. coli.

As the risk of antibiotic resistant bacteria continues to rise as more and more physicians rely on treating bacterial infections with antibiotics, several companies have begun to focus on alternative solutions to superbugs. One of which, GangaGen, focuses on developing therapeutic proteins that target drug resistant bacteria. GangaGen’s leading ectolysin P128 is one of those proteins, and it focuses on antibiotic resistant strains of Staphylococcus. Its incredible effectiveness comes from its ability to only attack its specific strain and leaves the rest of the beneficial bacterial flora intact. Most of these companies are trying to eliminate the incoming threat of antibiotic resistant strains of bacteria by furthering the practice of phage therapy and are utilizing their natural ability to attack bacterial cells. Still, it is a long road ahead, and many more experiments, phages, and proteins need to be derived, isolated, and tested.

Category: Gabriel Andino | 1 Comment on The Forgotten Cure Part 2
March 17

The Forgotten Cure 2

  1. Having a state health system in the USSR during the 1940’s -1950’s caused the USSR physicians and researchers to research other alternatives of treatments rather than rely on antibiotics. During World War II, through Western funding and support, the USSR was able to rely on the United States and Great Britain for aid in advancements in antibiotics. However, with the end of World War II, the USSR was left alone with little resources to continue antibiotic research. Alternative medicine has always been an essential part of treatment in the USSR, so phage therapy was able to take root more easily in that culture than in others. In a culture where natural substances were trusted, phage therapy was readily accepted and used to treat infectious diseases.
  2. The Hirszfeld Institute in Wroclaw and Eliava Institute in Tbilisis were two medical institutes established near/during the 2nd World War. However, only the Hirszfeld Institute found lasting support and success. I believe this is mostly credited to the strict emphasis placed on bacteriophage research and immunology at the institution. Such an example is in 1952, when Hirszfeld petitioned to devote an institution only to immunology within the Medical School’s Department of Microbiology, as well as the continued emphasis and research in phage typing throughout the years of 1950-1960. I also believe that the Hirszfeld Institute was able to flourish because of their joining of the EU in 2005, which connected them to other Western countries. The Eliava Institute was prosperous for a while, but lost most of it’s market after the dissociation of the USSR.
  3. Merril and his team took blood samples from animals and isolated the phages present and re-injected them into the mice. This process was repeated multiple times to isolate lambda phages that were able to remain in the bloodstream for as long as 18 hours (Named Argo1 and Argo2). These phages, along with wild-type phages were used to treat mice injected with lethal doses of bacteria. Argo1 and Argo2 phage-treated mice had a milder illness before recuperating than those treated with the wild-type phage, showing results that supported Merril’s hypothesis.
  4. Phage Therapy has immense potential in Western Medicine but in may cases, are stopped by government regulations and approvals that can only be given through studies which yield safe results. Particularly in the United States, the FDA has since recently allowed the establishment of the first phage therapy center at University of California, San Diego; however, phage companies yet have to conduct large studies with control groups to ensure credible results for approval. Companies, such as GangaGen, have devoted their resources and research towards discovering and developing ectolysins (high-specific therapeutic proteins) to target meaningful types of bacteria. Although first founded in India in 2000, it was incorporated into the US in 2001. Experiments run by phage companies should show the effectiveness of phage in treating infections, but also should emphasize the safety of the phages. One large misconception of phage therapy may be the notion perceived when individuals are told that scientists are using viruses to infect bacteria. The use of terms such as viruses may immediately be a red flag to patients or individuals. This misconception needs to be addressed and changed so we are more accepting of discoveries which are different from what we are used to.
Category: Justin Yu | 3 Comments on The Forgotten Cure 2
March 17

Forgotten Cure 2

  1. In Russia, phage therapy was used readily rather than antibiotics since it was cheaper to use. The USSR control of the health system caused doctors to seek other methods of treatment. Doctors would look at phage therapy for answers since it was cheaper, and the USSR used its money for weapons for the Cold War rather than medicine for its people and soldiers. Since antibiotics were used more in the western world, Russia placed a negative conation towards antibiotics since they were at “war” with western countries powerhouses. This led Russia to focus on treating diseases via phage therapy and the forgotten cure was born in the west.
  2. After the death of Hirszfeld’s daughter, he founded Hirrszfeld Institute after many battles with the Soviet Union. The institute had gone through many events with the Soviet Union, and later Hirszfeld would ultimately give the institute to Milgrom. The institute focuses on phage typing. Other institutes such as Eliava institute and Phage therapy center came to do the same thing and helped in different ways to help cure diseases. Eliava institutes research bacteriophages and their potential use as phage therapy to cure diseases, and the Phage therapy center treat the patients.
  3. Merril and his team worked on breeding a phage that could evade the liver and spleen. The team injected phage active against a specific strain of coli into stomachs of mice. They chose a specific phage, called lambda since it was a phage that was studied thoroughly by Delbruck. After seven hours of injection, the team took blood samples from animals, isolated the phages, and serial passaged the phage eight times. The survival rate of these new phages was a thousand times higher than phage lambda, and the team called the phages Argo1 and Argo 2. The team then had to see if the Argo1 and Argo2 could actually save mice infected with E. coli. They took four mice, and all injected with a lethal dose of bacteria. Three of the mice were treated with phage and the last one was used as the control of the experiment. The results showed that untreated mice died in two days, those treated with phage survived, and Argo1 and Argo2 had a milder illness compared to the non-passaged strain of lambda.
  4. 1 shows the development and partial characterization of long-circulating bacteriophage. Bacteriophages the could avoid entrapment by the RES were developed by selecting phage strains that could remain in the circulatory system of mice for progressively longer periods. The serial-passage experiment’s goal was to increase the incidence of mutation in phage lambda, so as to enhance the probability that one or more of the phages offspring would have properties that permit evasion of the RES. Both Argo 1 and Argo 2 displayed a similar enhanced capacity to avoid RES entrapment. Fig. 2 shows the comparison of long-circulation Argo phage versus wild-type phage as antibacterial agents in an animal model. All the mice were scored based if they showed signs of illness. Mice treated with W60 showed signs of severe illness before recovering, and both Argo1/Argo2 showed signs of minor signs of illness. Mice that were treated with phage all survived. Fig. 3 shows the ability of the phage to influence bacterial infections is dose-dependent. Animals showed signs of illness with a minimum dose of phage and increases in phage doses showed lower signs of illness. Fig. 4 shows the characterization of Argo 1 and Argo 2. The images compare the lambda phage capsid E protein versus the W60 capsid E protein and show an alkaline shift in the Argo 1 E protein capsid.
  5. Many companies discussed inThe Forgotten Cure research on how phage therapy is the alternative to antibiotics. Many companies were discussed in inThe Forgotten Cure such as Phage Therapy, Phage Biotics, GangaGen, Exponential Biotherapies. GangaGen is a company where it has done research to show that phage therapy is the alternative to antibiotics. Since phage therapy was the forgotten cure in the western world, many experiments are needed to be done in order to spread phage therapy in the U.S. Phage therapy must be approved by the Food and Drug Administration (FDA). New methods and therapies would have to go through a series of tests set by the FDA, such as the therapy need to be tested on animals before tested on humans. These advancements will help cure the forgotten cure. Companies are looking to find which treatment via phage therapy is the best to cure many diseases. Companies like the Exponential Biotherapies are working towards phage cocktails, to cure acute kidney injury and irradiation damage from cancer therapies.
Category: Michael Lum | 1 Comment on Forgotten Cure 2
March 17

The Forgotten Cure Chapters 5-8

  1. Antibiotics were introduced to the Soviet Union through the Western culture and was funded by Great Britain, and therefore Russia started to produce antibiotics. Due to World War II occurring during the 1940’s-50’s, the Soviet Union’s funding for antibiotics, which was used for funding of the war weapons, were decreased and the Russians had to rely on their scarce supplies. They did not have equipment or the people to support the production and use of antibiotics as well. The main issue that arose from this was the lack of funding. The way that the USSR’s health care system was operating did was inefficient due to the issue The USSR health care system provided all medical care for free for the patients but charge to the state. Without the adequate funding for antibiotics the USSR encouraged alternative medicines such as anise seeds, dill seeds, chamomile tea, and phage therapy to treat diseases. Phage therapy, due to its inexpensive nature of production, became a popular alternative for antibiotics.  
  2. The Hirszfeld Institute located in Poland was founded by Ludwik Hirszfeld. He faced oppression from Stalin due to being e a Jew and forced to endure harsh living situations and face the death of his daughter as well. Due to being Jewish, the “Doctor’s Plot” incident where doctors who were prominently Jewish had been accused of trying to poison army members, did not help in the advancement of the Hirszfeld Institute. The Eliava Institute located in Tbilsis faced similar consequences as did Hirszfeld Institute. They faced oppression from Stalin, and the family was executed as well. The Eliava Institution in 2001 operates without heat and electricity leading to the members of the lab taking the phages home to keep refrigerated which led to the loss of many phages. The Eliava Institute focusses mainly on the research of bacteriophages and practical applications of phages, while Phage Therapy Center created by Gorski in Wroclaw focusses on treatment of patients and clinical uses.  
  3. Merril was interested about the use if phages to treat diseases. He inserted phages into mice and observed the amount of time the phages were present in the body. He observed that the phages were removed by the spleen and liver. In order to obtain a phage that could invade the spleen and liver, Merril and his team performed a procedure called serial passage using phage lambda with E coli. A lambda phage was inserted into an E coli strain which was then inserted into the mice’s stomach. When observing the blood samples of the mice seven hours later the research team isolated phage which could invade the spleen and liver and was present even eighteen hours later. This phage was called Argo1 and Argo2. Three groups of mice were treated with the phage, and the fourth group, was left untreated. After a few days the untreated mice had died, showing that the phages could help the mice survive. When observing the figures of the PNAS paper, when injected with more phage the mice recovered faster and didn’t have prolonged symptoms of the disease.  
  4. Phage therapy is becoming an increasing interest for the alternative of antibiotics. GangaGen is a company based in India, inspired by the phages discovered near the Ganges and Jamuna River. The company focusses on alternative ways of treatment such as the use of bacteriophages rather than antibiotics. The company focusses on ectolysins which lyses the bacteria quickly. Ectolysins are also created to target one type of bacteria and therefore does not destroy other bacteria in the process. This company focusses on drug resistant bacteria which create diseases in humans. Companies have done some experiments to focus effectiveness of the phage therapy on specific strands of bacteria. More analysis needs to be done on the experiments and results of these companies. Clinical trials, both positive and negative, should be conducted under differing conditions to check the validity of the findings of these companies. Also, effectiveness of phage therapy on situations of antibiotic resistance should be done to see if this can be an alternative to antibiotics. Legal compliance including FDA should be completed before approving the therapy for public use. Extreme cautiousness and a most conservative approach should be adopted to ensure safety of the patients, and not rush with introduction of the phage therapy. Where applicable, a combination of both antibiotics and phage therapy may be applied, if that can produce better results.  
Category: Sona Subramanian | 1 Comment on The Forgotten Cure Chapters 5-8
March 16

The Forgotten Cure: Chapters 5-8

  1. Having a state health system in Russia during the 1940s-1950s led Russia to experience less freedom in the healthcare system. Due to the heavily controlled access to medicine that the people of the USSR faced, antibiotics were hard to come by during the time period. There was a considerably less amount of antibiotics available in the USSR in comparison to the United States. While the West did aid in the introduction of antibiotics to the USSR during World War II, their contributions were halted after the end of the war. This greatly slowed the strides that the USSR was making towards manufacturing proper antibiotics for consumption by the population. The state health system led to a lack of resources being allocated to the study of antibiotics during the time, which reduced the number of antibiotics available to the common population. Instead, herbs and more natural remedies were offered, and the absence of antibiotics paved the way for bacteriophage therapy to be more commonly used in the USSR.
  2. Out of the three main organizations discussed in the novel, the Eliava Institute, the Phage Therapy Center, and the Hirszfeld Institute, there are somewhat different outcomes of each organization that have allowed for the differentiation between them. The Eliava Institute and the Hirszfeld Institute were both organizations that were impacted by the Russian government. The quote provided by Hirszfeld was given as a result of the struggles and tragedy that the family had to endure as a result of World War II and their struggles in Poland. The two organizations are similar in their struggles but greatly differ from the Phage Therapy Center. The Phage Therapy Center did not endure obstacles to the same degree as the Eliava Institute or the Hirszfeld Institute and it focused more on the treatment of patients. The Eliava Institute focused more on the research behind bacteriophages and their use.
  3. Merril’s experiment utilized lambda phage and infected the blood of mice with it. After seven hours of infection, the surviving bacteriophage was isolated and reinjected into the bloodstream. This process was repeated eight times to allow for phages that lasted longer to be present in the bloodstream. Two phages called Argo1 and Argo2 were deemed to be the two phages present at the end of the rounds of serial passaging. Mice with E. coli were treated with Argo1 and Argo2, as well as W60, or lambda phage, in the experiment. The results were compared against a control group that received no phage therapy. The control group had a lower survival rate than those treated with phage therapy. The figures in the article showed that those treated with Argo1 and Argo2 showed significantly fewer symptoms of disease in comparison to the W60 group or the control group.
  4. Despite the promising results that phage therapy has brought, antibiotics still seem to be the prevalent use of treatment today. More experimentation must be done on phage therapy before it can be widely accepted for use by others and the FDA. It appears as if phage therapy has been tested on a smaller scale, but few experiments have occurred on a large scale, which is needed in order to make strides towards more frequent use. In order to ensure safety for the public, more clinical trials must be performed as well as experimenting on what mixtures of phages are best for use for the differing diseases. There are undoubtedly unique circumstances that occur where one specific phage is needed, however developing a mixture of phages to combat the more common diseases would be beneficial for the general public. The company GangaGen recognizes the need for increased use in phage therapy and is working to treat infectious diseases that have a high level of antibiotic resistance. GangaGen is looking into combating multiple species of bacteria that are harmful to humans, and with enough published and accepted experimentation, the company, as well as others, may change the public outlook on phage therapy in the future.
Category: Emily Gaw | 2 Comments on The Forgotten Cure: Chapters 5-8
March 15

The Forgotten Cure Second Response

1.

As a result of the USSR controlling the health system, doctors and patients were forced to seek alternative forms of treatment rather than antibiotics due to Russia spending its money on weapons for the Cold War rather than medicine and the health system. Since Russia was unable to afford the production and supply of antibiotics like the west they encouraged natural remedies/alternative medicine, including such things as phages. Additionally, the government branded antibiotics as foreign and linked to the Western enemy through the use of propaganda, increasing the suspicion of them amongst the population. Ultimately, the state health system in Russia resulted in a far greater focus on treating infectious diseases with natural remedies/medicine compared to Western linked and relatively expensive antibiotics.

2.

Even though both centers developed in the USSR under oppressive and scientifically strangling ideologies like Lysenkoism the Hirszfeld Institute was able to endure and flourish, while the Eliava Institute saw its glory days come and go. I ultimately believe the differences in outcome between the Phage Therapy Center (Hirszfeld Institute) and the Eliava Institute results from the location of both. Since the Phage Therapy Center (PTC) is in Poland, they are a part of the EU and thus much more closely tied to the west. The Eliava Institute, however, is in Georgia, considered by many in the west to be backwater former Soviet state, additionally, they are lacking in the economic development that countries like Poland are experiencing. This results in them having less access to funding due to more wariness on the part of investors, especially those from the west. However, the PTC has experienced far more support from the west due to it actually being in the west and under the western style of control and regulation scientifically. In the end, the PTC has been able to receive adequate external support in comparison to the Eliava Institute where its location in Georgia has even driven away external support despite its history and successes.

3.

Merril injected lambda phage into mice and after seven hours took blood samples and isolated the phage that survived. They proceeded to grown and propagate that phage and repeat this serial passage method for a total of eight times. By the end of the serial passages, they had phages that were isolated were able to last up to 18 hours in the blood. These phages where then able to be injected into mice infected with E. Coli and survive the liver and spleen, allowing them to kill the bacteria. The figures of the paper show that the mice treated with Argo1 and Argo2 had dramatic symptom reduction over the course of several hours as compared to the wild type lambda phage.

4.

Phage therapy has great potential in modern Western medicine, especially in the face of increasing reliance on and subsequent bacterial resistance to antibiotics. But in order for it to be widely accepted FDA approved studies need to be conducted and the results published in order to begin swaying the opinions of Western medicine regarding phage therapy. Specifically, they need to be double-blind studies in order for there to be no chance for bias. Companies like GangaGen, for instance, have made an active effort to bring phage therapy into the mainstream of modern medicine, in an effort to do so they began collecting a library of phages to work with. They soon attracted investors who have and continue to provide the necessary resources to develop the company and bring phage therapy to prominence in Western medicine. According to their website, they are currently in the midst of conducting clinical trials and preclinical trials for a variety of phage-based drugs in an effort to have them approved by the FDA.

Category: Nathan Newton | 1 Comment on The Forgotten Cure Second Response
March 15

The Forgotten Cure Part 2

Phage therapy’s influence has varied over time and across different countries such as Russia, Poland, India, and the United States. Politics and culture have both contributed to increases and limitations of the use of phage therapy.

In the 1940s–50s Russia, the state health system controlled the treatment of diseases due to its limited supplies. During World War II, Soviets received Western support and funding which allowed for antibiotic production. This support was removed after the war. Since Russia provided universal health care without charge, the Soviets did not have the resources to continue antibiotic production or buy from American pharmaceutical companies. The lack of resources caused phage therapy to regain popularity through government-supported propaganda which promoted patriotism.

World War II had differing influences on the phage research institutions including the Ludwik Hirszfeld Institute of Immunology and Experimental Therapy in Wroclaw and the Eliava Institute in Tbilisis. In Wroclaw, Poland, the Hirszfeld Institute was in fear of Stalin’s Lysenkoism since “more than 90% of Wroclaw’s Jewish population was killed” and both the founder, Ludwik Hirszfeld, and many staff members had Jewish heritage (Kuchment 65). After Stalin’s death, the Polish government provided support to the Hirszfeld institute. In contrast, the Eliava Institute had its peak during World War II since they received support from other countries to create phages to use for soldiers. After the war their funding was eliminated, they started to focus more on research than the production of phages. In 2003, two Eliava Institute scientists created the Phage Therapy Center in Tbilisi with goals of making phages more available for use. The outcomes of these centers can be contributed to political influences and differing priorities.

During the 1990s in the United States, an antibiotic resistance article led to a phage experiment performed by Merril, Carlton, and Adhya. Although other phage studies had already been performed in Russia and Poland, many Western scientists remained skeptical of how reliable the outcomes of these experiments were due to their poor study designs. In Merril’s experiment, the design considers various variables including: phage’s narrow host range, possible presence of phage lysate toxins, and the patient’s immune defense system. Mice were divided into four groups: a control group, a W60 (the “parent” lambda phage) treated group, an Argo1 treated group, and Argo2 treated group. Through serial-passage techniques, they were successfully able to isolate phages (Argo1 and Argo2) that could survive longer than the original lambda phage and eradicate the target bacteria.

With concerns for the antibiotic resistance problem, many companies are still looking into phage therapy as a possible alternative. In 1993 in the United States, Exponential Biotherapies emerged to commercialize phages to specifically target inflammatory responses. In 2000 in India, Dr. J Ramachandran founded GangaGen Inc. In recent publications, GangaGen has looked into using phage-derived lysins to break down biofilms which have high resistance to antibiotics. They are also working on a phage to target antibiotic resistant MRSA and VRSA infections.  Although more research is being performed, there are still some holes that research should fill before phage therapy can be applied to modern Western medicine. More experiments should use a design that considers variables and uses controls in order to show that phages are safe and beneficial. For instance, would the use of phages to treat minor infections significantly more beneficial or even necessary? Most doctors believe “draining puss from an infection is often enough to cure it – even without phages or antibiotics” (Kuchment 69). If phage therapy becomes approved in the United States for patients, it most likely will be used with antibiotics and probably will not replace them since it would be extremely rare for a bacterium to develop resistance to both phages and antibiotics.

By time traveling through different stages of phage therapy history, one can grasp a greater understanding of how the various political climates and cultural mindsets shaped the spread of phage therapy across different countries.

Category: Kathryn Adkins | 2 Comments on The Forgotten Cure Part 2
March 14

Forgotten Cure Ch5-8

  1. In the 1940s-50s, Russia had scant resources and knowledge when it came antibiotics. Even though there was collaboration with the western allies, the lack of proper funding held back the production and use of antibiotics in the USSR. The USSR attempted to implement a state healthcare system that provided treatment without cost with inadequate funding, which is why it failed to be effective. So, alternative medicine was promoted by the state. this is the biggest influence for the use of phage therapy at the time as it was considered as alternative medicine. It gained widespread use due to the influence of the state health system and became the primary way to treat infectious diseases at the time.
  2. The two institutes and their founders suffered similar setbacks in terms of persecution and lack of cooperation of with leadership. But they both had different outcomes. The Eliva institute did not reap the same success as the phage therapy center. This is mainly due to how the death of Stalin favored the fate of the Phage Therapy Center in Wroclaw.  Both institutes suffered due to persecution from leadership but when Stalin died, the individual who was the main driving force for this persecution, the institute was revived with passing of the petition for the Institute of Immunology and Experimental Therapy, which helped it gain global connections and flourish in the scientific community whereas the Eliva Institute struggled.
  3. The biggest challenge faced by phage therapy, which is what made many doctors skeptical of its effect, was to find phages that would not be immediately removed by the liver and the spleen. Merril accomplished this by using a phage called lambda. 7 hours after infecting the mice with phages , the surviving phages were extracted and reinjected into the mice. this process was called serial passage. After repeating the process was repeated eight times, the team acquired phages that lasted up to 18 hours in the bloodstream. the mice were also infected with multiple phages, which increased its effectiveness. the phages, named Argo 1 and Argo 2 were then used in another experiment to prove their effectiveness. four groups of mice were infected with a lethal dose of E.coli. three of the groups were treated, leaving one group as a control group. the untreated died but the treated survived. the phages also remained in circulatory system of the mice after recuperation, proving the effectiveness of the therapy.
  4. Antibiotics have been the spearhead for the treatment of infectious diseases for the past few decade. It continues to be our primary tool for fighting against infections but its effectiveness continues to wane. Resistance to antibiotics increases among bacteria. Companies like Phage Biotics, GangaGen and Exponential Biotherapies offer another possible tool for fighting against bacterial infections. their research into phage therapy holds the potential to defeat the rising tide of resistance in bacteria. More experimentation is required in the effectiveness of antibiotics and phage therapy together. together, they may poses a greater threat to bacteria and may be a possible way improve the effectiveness of treatment for infectious diseases. But a better understanding of the dynamics of the two together is required to properly apply them for treatment.
Category: Aman Patel, Dr. Adair | 1 Comment on Forgotten Cure Ch5-8