March 14

The Forgotten Cure Chapters 5-8

  1. The Soviet State healthcare system definitely hurt the spread of phage therapy and hindered the treatment of infectious diseases. For one, the resources were severely depleted in the country, along with a shortage of advanced medical knowledge. Penicillin and streptomycin seemed promising but it lacked momentum once it first hit Russia. Also, the fact that the public was urged to use herbs (because they were “ours” and promoted their political agenda) didn’t help prevent any contagious diseases. Perhaps the biggest obstacle to the treatment of infectious disease in Russia was, predictably, politics. The government already provided healthcare free of charge, which was already low quality, but the government also propagated the idea that Western medicine and technology was inherently evil, like the rest of the Western countries. This caused the aforementioned uprising in herbal treatments and “alternative medicine” that served as the main blockade to medical developments in Soviet Russia.
  2. Many different research centers sprouted across Europe as the drive to improve phage therapy swept the continent. The two institutes that are focused on are the Eliava Institute and the Hirszfeld Institute. First, the Hirszfeld Institute was created by Ludwik Hirszfeld in Wroclaw, Poland. Hirszfeld faced many run-ins with Russian officials during the Soviet era, who tried very hard to blockade his work. However, its birth and success are most directly credited to Stalin’s death. After Germany and Russia exchanged control of land during the war, the region containing Wroclaw eventually was filled with the Polish. However, Hirszfeld and his family faced oppression from anti-Semitic movements in Europe, and had to live in the Warsaw Ghetto. After his family’s escape to Wroclaw, he petitioned the local university to create an institute, probably to counteract the now widely accepted Lysenkoic view on biology (as all other views were not welcomed). This history is very similar to the Eliava Institute, where Eliava was forced to be a martyr for his work. Both men were persecuted by the Russian government for attempting to deviate from the norm and forced into unfavorable situations as a result. Although the outcomes were different, both men showed great resilience and did everything in their power to ensure that their scientific endeavors couldn’t be stopped. Their legacies live on in the form of their institutes.
  3. Merill made many great discoveries within the realm of phage therapy but faced one major issue: most, if not all, of the phage he would introduce into a system would be immediately filtered out by the spleen and liver, whose job is to filter out toxins in the body. Merill’s group selected the lambda phage, due to Delbruck’s extensive work with the phage, and injected a large volume into the stomachs of mice. After 7 hours, long enough for the spleen and liver to filter out phage, a blood sample was taken and the phage that resisted the filtration were isolated and reintroduced to the mouse’s system. After serial passaging the phage multiple times, 2 strains were isolated that could remain in the bloodstream much longer than previously believed. These phages were called Argo1 and Argo2. For the experiment, mice were injected with a lethal amount of E. coli bacteria. One mouse was left untreated as a control, one mouse was treated with wild-type phage, and the other two were treated with Argo1 and Argo2. The results showed not only that phage treatment worked on animals, but that the isolated phages were able to stay in circulation much longer due to the mice showing a milder illness at a quicker rate than the wild-type treated mouse. This process made sure that the phages that were able to withstand the filtration process in the animal’s body were selected for, and consequently showed more results when experimentally used.
  4. As time passes, more and more antibiotic-resistant bacteria are developing, meaning that antibiotics will son become less and less effective. Startup companies like GangaGen, mentioned in the book, are seeking to develop treatments and cures that focus on making bacteriophages its primary concern. While antibiotics are currently effective, these companies seek to prepare for when another strategy is needed, especially during a time when antibiotics are believed to be over-prescribed. Companies like GangaGen that possess a wide library of phages will have the resources needed to isolate phages that can potentially wipe out antibiotic-resistant strains of bacterial infections. Experiments like Merill’s need to be performed to prove the effectiveness of a potential phage treatment before it is released to be evaluated by the FDA and other departments or else phage therapy will likely never get it’s feet off of the ground. However, with an advancement in phage therapy, Western medicine will see an opportunity to customize treatments to complex bacterial infections, as well as see an avenue to spread the discoveries around the world to improve healthcare for the rest of the world’s population.
Category: Cooper Johnson, Uncategorized | 1 Comment on The Forgotten Cure Chapters 5-8
March 14

The Forgotten Cure (Chapters 5-8)

  1. In 1940s-50s Russia, phage therapy was more popular to use rather than antibiotics since it was cheaper to use. Due to state health system in Russia, this impacted on phage therapy. Most of the issues were due to lack of funding. Dr. Pokrovskaya’s reports hinted that phage therapy yielded such conflicting results was because it was hard to store and complex to use. Advanced technology wasn’t developed and needed funding for it, the lack of funding prevented that to happen.
  2. Hirszfeld Institute had gone through tragic events with the Russians. After Hirszfeld’s daughter passed away, he settled in Wroclaw and petitioned the Polish Academy of Sciences to set up an institute. However, the request was possibly slowed by a series of events taking place in the Soviet Union at the time. Hirszfeld fell victim to Lysenkoisa and he designated Milgrom as his successor of his institute. Throughout the years, his institute was involved in phage typing and other institutes came to be. Two of them are the Eliava institute and Phage therapy center. Eliava institute has goals that are more toward research of bacteriophages and their potential uses in therapy while Phage therapy center focuses more on the treatment of patients. Both institute have common goals, but do have their differences.
  3. Merril injected infected blood with bacteriophage, have it harvested in the mice for 7 hours, and repeated for a few times until a large amount of bacteriophage strains were present. The phages were named Argo1 and Argo2. Merril and his team found out that those strains could stay in the mices’ stomach at large amounts and rate than the control. According to PNAS, the control would go down by nearly half the amount as the staring titer. Argo1 and Argo2 only went down by a small amount. Through this, Merril and his team saw that the mice that were treated with phage therapy improved their conditions than mice without phage therapy.
  4. GangaGen was created by Ramachandran who decided to set it up in India due to advantage of cost and plenty of people to recruit. There were plenty of high tech companies around them to help them. He had the same mindset of to “follow D’Herelle’s principal that in a hospital there is always somebody natural recovering and therefore there is a chance they’ve been exposed to the phage in the environment. In fact, that proved to be true.” (pg 85) Nowadays, GangaGen is focused on developing novel therapeutic proteins targeting infectious diseases in areas of high unmet need such as MRSA and other drug resistant bacteria. Using a proprietary platform, GangaGen is developing highly-specific therapeutic proteins called ectolysins to target clinically meaningful types of bacteria. Ectolysins act very rapidly to lyse bacteria and therefore have low potential for developing resistance. Each ectolysin is specific to the type of bacteria for which it is developed and leaves other beneficial bacteria unaffected. This means that ectolysins can work on drug resistant bacteria or when the bacteria are not active, such as in hard-to-treat biofilms. It would be interesting to see experiments to how ectolysins can affect different strains of bacteriophages or strains that are not yet identified or annotated as well as the rate of the ectolysins activity.
Category: Soo-Un Jeong | 2 Comments on The Forgotten Cure (Chapters 5-8)
March 12

3.18.19 The Forgotten Cure Chapter 5-8

  1. 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.
  2. 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.
  3. 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.
  4. 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.
Category: Henry Burns | 4 Comments on 3.18.19 The Forgotten Cure Chapter 5-8
March 9

The Forgotten Cure 2

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

Category: Lucy Potts | 2 Comments on The Forgotten Cure 2
March 8

3-6-19 — Group Poster Comparison

Group Poster Comparison

Date: 3-6-19

  • Rational
    • The rational for this lab is to compare the four poster designs from each group to decide which features should be kept and which poster should be used as a base for the final poster.
  • Procedure
    1. All four final posters were presented to the class one by one.
    2. Likes and dislikes from each poster were recorded individually.
    3. A final poster was chosen to be the base for the final class poster.
    4. Additional features that the class thought should be added were recorded so that they can be integrated into the final poster design.
  • Results
    • A final poster draft was chosen to be edited and worked on as the final poster.

An image of the poster design chosen to be used for the final poster.

  • Future Plans
    • The next step is to finalize the chosen poster design, adding and removing liked and disliked features until a fully refined poster is created.
Category: Brandon Reider | LEAVE A COMMENT
March 8

3-4-19 — Final Group Rough Draft Poster Design

Final Group Rough Draft Poster Design

Date: 3-4-19

  • Rational
    • The rational for this lab is to continue working on the poster design from the previous lab on PowerPoint.
  • Procedure
    1. A second poster group was merged with ours in order to combine our work and finalize the first round of drafts.
    2. The PowerPoint presentation was shared with the new poster group.
    3. More diagrams and pictures explaining lab procedures were added to the poster. Formatting of the boxes, shapes, and colors were changed.
    4. A third, final rough draft of a poster created.
  • Results
    • A poster design was created on PowerPoint.

  • Future Plans
    • The next step is to compare this group’s poster with posters from other groups in order to decide which features from each should be included in the final poster.
Category: Brandon Reider | LEAVE A COMMENT
March 8

MARCH 4TH & 6TH

 MARCH 4TH, 2019

  • OBJECTIVE:
    • Work in large groups, to collaborate and make a combined poster idea 
  • PROCEDURE:
    • A powerpoint file was created and shared with all student in the group who then worked on the poster collectively 
  • END RESULT 
    • A poster using both teams ideas was created (see image below)
  • CONCLUSION:
    • Poster was completed and submitted as a QTM
  • FUTURE STEPS:
    • Get critiqued on poster, and continue edits 

MARCH 6, 2019

  • OBJECTIVE
    • To pick a poster design that will be used for the class poster
  • PROCEDURE:
    • All groups posters were presented using powerpoint, in front of the class 
    • Students then voted on which poster layout they liked the best 
  • END RESULT:
    • A poster design was chosen to work with 
  • CONCLUSION:
    • A poster deign was chosen, and will continue to be editing combining some elements from other posters 
  • FUTURE STEPS:
    • Determine issues with chosen poster and find way to fix those issues 

      The group created poster

Category: Lauren Foley | LEAVE A COMMENT
March 8

Class Poster Critique 3/6/19

Class Poster Critique 3/6/19

Rationale

The rationale behind these procedures is to ensure that poster creations for Scholar’s day follow the correct format and that basic poster requirements are understood. The procedures were also done to give practice for poster making and create a draft for the class to work on for Scholar’s Day.

Tools/Procedure

  1. Previously created large groups were each tasked with presenting their posters
  2. Each poster was critiqued and analyzed by the class
  3. The class voted on which poster to edit as the class final copy

Results

The above poster layout was the class winner. This poster will be edited by the class and will eventually be turned in for scholars day.

Conclusion

Lab period today was not used for any scientific research, but I can say that I demonstrated my understanding of poster making and the class is ready to move forward.

Future Plans

In the future, we will be working as a class to create a poster for Scholar’s day.

Category: Uncategorized | LEAVE A COMMENT
March 8

Large Group Poster Creation 3/4/19

Large Group Poster Creation 3/4/19

Rationale

The rationale behind these procedures is to ensure that poster creations for Scholar’s day follow the correct format and that basic poster requirements are understood. The procedures were also done to give practice for poster making and create a draft for Scholar’s Day.

Tools/Procedure

  1. Previously created groups were combined and worked together to create poster drafts based on previous instruction
    • Poster layout and design was created by blending the ideas of each group
    • Class data from last semester were examined and graphics were created based on these data
    • Methods were described in graphic format
    • Data from both semesters were compiled and results were reported
  2. The poster draft was submitted

Results

The above poster layout was designed by Rachel and I in conjunction with Cooper, Joseph, and Henry it is just a draft, but it demonstrates an understanding of scientific poster making and we did our best to include information that we would want to be included.

Conclusion

Lab period today was not used for any scientific research, but I can say that I demonstrated my understanding of poster making.

Future Plans

In the future, we will be working as a class to create a poster for Scholar’s day.

Category: Lucy FIsher | LEAVE A COMMENT
March 8

Poster Design 3/4/2019

Rationale: Continue creating poster on powerpoint

Steps:

  1. Joined groups with Copper, Josef, and Henry and added to the poster together

Result:

Final Draft of PowerPoint Poster

Next Steps:

Begin to create a poster as a class

Category: Rachel Melone | LEAVE A COMMENT