February 18

Checking LORF of Gene 50 2/18/19

Rationale: There were some calls that were a bit difficult so as a team we revised certain genes assigned to us.

Tools: DNAMaster, NCBI, Phamerator, GeneMark, PhagesDB

Procedure:

  1. Looked at gene 50’s reading frame to determine if I should elongate it to the LORF.
  2. Checked starterator, blasted both lengths of the gene, and checked the Coding Potential coverage to determine I shouldn’t bring it back.
  3. Also the better RBS score supported my call.

Results:

Conclusions and Future Work: The call was correct, there is no need to move the gene to its LORF. Next we will do a group-wide analysis of the entire annotation to make sure we don’t see any glaring issues. We will also begin the process of making a presentation of our findings.

February 18

Forgotten Cure Chapters 1-4

1. Dysentery was a major problem among troops during World War I. This need opened up the avenue for d’Herelle to make the discovery that some people were being miraculously cured of dysentery. Relating to locusts, d’Herelle was originally studying bacteria that killed locusts when he discovered that  there were some parts of his plate that had died for no explainable reason. What we now know as plaques. d’Herelle found the same clear spots on his plates when he examined the stools of some sick soldiers. These findings led to money being put into research for this microbial antagonist to  bacteria, as  dysentery was wounding military forces so greatly. This in turn led to the discovery of bacteriophages.

2. Like every great scientist d’Herelle was driven by his curiosity and could not let a question go unanswered. However, more than that he was extremely dedicated and passionate to science and treated it as more than a job. For example, when he took up an unpaid position. He was not dissuaded from continuing forward despite so many people doubting him. Eliava was similar in a sense, but he was described as more laid back, but both men were extremely dedicated to their craft. Eliava ended  up being executed due to the Soviet Regime.

3. Phage therapy wasn’t very well understood, so under normal circumstances it would’ve been extremely hard to get government  funding for research into  phage therapy. However, war pushes governments to move forward with risky moves in the hopes of getting the technological edge over their opponents. Since many people were dying of diseases such as dysentery, it was very important for governments to find a way to fix this problem before the enemy. This led to phage therapy research getting funded despite being such a new concept. Also, had the push for finding a cure for dysentery not occurred d’Herelle may have never made the connection between the spots on his plate in the locust killing bacteria and the dysentery patients.

4. A big reason phage therapy didn’t take off is because antibiotics seemed to be a better solution at the time. They were quick and very successful in treating bacterial infections. They also weren’t specific to certain bacteria. This wasn’t the problem alone, however, as there was the issue with scientists not fully understanding phage therapy yet and success rates of trials for phage therapy being pretty bad. Together this led to phage therapy being completely overtaken in functionality by antibiotics.

5. They were extremely curious on how bacteriophages replicated, which is how they joined the Phage Group. They discovered that it was DNA that was the genetic material for phages rather than proteins. Furthermore, they also discovered the replication mechanism for bacteriophages. Eventually they moved on to studying the reproduction of higher order life forms, which caused phage research to die out.

February 18

2-18-19 — The Forgotten Cure by Anna Kuchment

1. Describe the role that locusts, dysentery and war had in the discovery of bacteriophage.

While studying bacterial cultures from sick locusts, d’Herelle discovered clear spots in the bacterial lawns, later to be known as “plaques.” This was his first proof that there was something smaller than known microbes. This was later reinforced when, because of dysentery cases suffered during the war, some patients mysteriously and quickly recovered. d’Herelle recognized the same plaques in there cultures, and began experimenting with the application of this unknown microorganism in order to heal soldiers dying of this disease.

2. Discuss the characteristics of d’Herelle that led him to be a successful scientist. How did he compare to Georgi Eliava?  What happened to the Eliava’s?

d’Herelle had a uniquely selfless drive to study science. He was self-taught, having never attended university, and wasn’t interested in money as much as others. d’Herelle did, however, possess some unfortunate traits. His lack of formal education made him lacking in credibility among the scientific community, and he did make a few assertions that were false that he would’ve understood had he received a real science education. Eliava was born into privilege and became close friends with d’Herelle. They were both incredibly intelligent and had a drive to discover more in their field. Eliava was ultimately executed a few years after Stalin’s rise to power after an officer with a vendetta saw a chance to get back at the scientist for having the traits that he lacked.

3. Discuss the influence war and politics had on the spread of phage therapy.

War initially helped push for the spread of phage therapy, as the need for medicine for soldiers seemed to be solvable by phage usage; however, as the war heated up, more effective alternatives to phage therapy were discovered and popularized. Phage therapy was isolated to small lab groups here and there, but widespread application was halted.

4. What are some of the reasons that the spread of phage therapy failed?

Sulfa drugs were developed that were easy to produce and got consistent results. Using phage therapy, it was difficult to get consistent results. There was also ethical controversy involving control groups and whether it was acceptable to deny a group phage therapy for the sake of having a control group when there was a high likelihood the control group would have significantly more fatalities than the experimental group. Again, d’Herelle’s attitude didn’t gain him any respect in the scientific community, thus pushing readers to his competitors, even if they were incorrect in their assertions.

5. How did the physicists Delbruck and Luria end up as part of the Phage Group? What contributions did they make to phage biology?  Why did phage biology die out in the 70’s?

Both Delbruck and Luria were interested in combining physics and biology, and thus molecular biology was born. They began studying bacteriophages and were able to determine that genetic information was DNA and not proteins. The final nail was hit into phage therapy’s coffin when the rediscovery of penicillin brought a new, first-of-its-kind superdrug to the world. Penicillin wasn’t effective on every illness, some of which having been shown to be susceptible to phage therapy, but it was still preferred. The only places that held on to phage therapy were countries in the Caucasus.

February 18

The Forgotten Cure 1

The forgotten cure, written by Anna Kuchment, provided a detailed overview of the origin of phage therapy, developments, and future possibilities.

In chapter one,  one thing that was mentioned by the book was that the clearing effect of bacteriophage was actually observed by two scientists who weren’t in contact with, and one, Fredrick Twort went one with his research, classified the phenomenon as just a result of what the bacterium produced and was nothing of significance,  while the other, Felix d’Herelle, also observed the clearing, didn’t simply ascribed the phenomenon to just something the bacterium produced but later on remembered the findings several years later exterminating locust and inspecting the stools of soldiers infected with dysentery, which led him to the discovery of phage that cured dysentery and naming the type of organism “Bacteriophage”. It is truly intriguing when we look back in history and make comments about what certain historical figures should’ve done, such as some might argue that if Fredrick Twort went on and conjure up the concept of bacteriophages before d’Herelle he would’ve received credit for the discovery of phages, but to me that is exactly the point, sometimes making a major discovery is not because of one’s luck or intelligence but how careful they approach the problem and how much they respect the results. To be fair, d’Herelle indeed had impressive memories, but being observant must also played a significant role, the clearings couldn’t have only appeared in Twort’s and d’Herelle’s Petri dishes, but they were the ones who published some sort of recordings and only d’Herelle made a push, later on, to finally made the discovery of phages. And even though his self taught sciences led to his researched filled with lots of personal speculations and unproven assumptions, he had excellent instincts and great experimental techniques and for that d’Herelle had earned his respect today.

Chapter two talked about the remarkable partnership of two individuals, Felix d’Herelle and Georgi Eliava, the chapter depicted the culture of the science community through the encounters of the duo, factions of scientists with different beliefs arguing and presenting evidence to back up their theory and also counter-evidence to discredit their rivals, sometimes you can’t just do science experiments, rolling up your sleeves and defending what you believe in would also seem like an important and regular thing for scientists. While in the midst of trying to prove the phages are a viable and effective treatment against bacterial infections, Eliava battles with the changes around his home country, and ultimately he was set up and gave his life falling to the victim of the xenophobia and communism in pursuit of knowledge when he made enemies in the attempt to set up a research facility in the USSR. While the story was a tragic one and the field of science had lost one of its best, the tale showed that the war was the reason the bacteriophage was originally brought to d’Herelle’s attention and partially how he was motivated to study the organism in order to create a solution for the then-fatal bacterial diseases, it also became the reason why the USSR funded the research trying to liberate their own people from diseases, but ultimately the wars and conflicts around Europe led to our tragic end for Eliava. War seems to speed up science, however, usually at the cost of far more, and in the developments of phage therapy, the war both helped and hindered the progress of phage research, which will be elaborated more in chapter three.

Chapter three talked about the fade of phage therapy, with d’Herelle, the original founder reducing his defense on phage therapy and the poor quality of the phage therapy clinical treatments, more articles voicing against phage therapy were piling up, the invention of sulfa drugs along with the discovery of penicillin, but ultimately because of the general distrust of the potency of phage therapy. Some of the reasons phage therapy was doubted were that scientists couldn’t receive an experiment result that wasn’t affected by other factors, such as surgical interference, patient recovering from the disease without any treatment or maybe poor doctor’s reports, that last one, maybe was just the frustration of scientists trying to find someone to blame. Overall, due to the simple administration methods and the publicity gained by curing the president’s son sulfa drugs were considered as the new savior of mankind, especially when in a time that new effective treatment was needed since WWII was generating the need for emergency field treatments when injured, and sulfa drugs killed off bacteria like nothing they’ve ever seen before, it soon became the cure under the spotlight. Most labs studying phages were shut down during the war and the field mostly abandoned.

In chapter four, Physics crossed paths with biology, since the traditional observing method was no longer viable when the very things the scientists were trying to see are smaller than what the naked eye could capture, and in this chapter, bacteriophages were used to study genes. By the early 1950s, scientists knew phages had DNA stored in their heads, but they weren’t sure what were the genetic materials made up of, so with both of the candidates tagged with radioactive materials they found that DNA was indeed the genetic material for phages, furthermore they also found that the genetic material only entered the bacteria, and their findings paved the way for Watson and Crick’s breakthrough in the concept of DNA structure. However, with the study of human and animal cells becoming easier, lots of the researchers who used to study phages turned to other fields and phage biology died out again in the 1970s.

February 18

Forgotten Cure Part 1 2/18/19

The Forgotten Cure Part 1

In the first 4 chapters of The Forgotten Cure we learn about the early discoveries of phage, phage therapy, and phage biology.  Blog about which ideas or observations presented in the first 4 chapters surprised or shocked you concerning the process of scientific discovery? You may use these examples or comment on your own ideas.

  • Describe the role that locusts, dysentery and war had in the discovery of bacteriophage.
    • d’Herelle was studying sick locusts and by chance, also discovered bacteriophages in the form of clear circles on plates streaked with bacterial cultures. When WWI started  not long after, there was a pressing need for medicine to treat bacterial diseases such as dysentery. d’Herelle was tasked with analyzing dysentery outbreaks and begin examining stool samples. Again he witnessed the same clear spots on agar streaked with samples of recovering patients and this launched him into hos study of bacteriophages.

 

  • Discuss the characteristics of d’Herelle that led him to be a successful scientist. How did he compare to Georgi Eliava?  What happened to the Eliava’s?
    • d’Herelle was a stubborn, self-educated scientist who was known for being “self-confident, idealistic, outspoken and unafraid of controversy”. These personality traits helped phage therapy gain popular attention worldwide, but not in the scientific community. Georgia Eliava shared a similar privileged upbringing and was able to go to med school. Unlike d’Herelle, Eliava was charming and polished. d’Herelle became a mentor and friend to Eliava and the together they pushed the limits of phage therapy research. Eliava was later arrested and shot to death in the Republic of Georgia where he maintained a risky foreign and aristocrat status in a communist society paranoid of losing power to rebellion and resorting to using fear methods to control the population.

 

  • Discuss the influence war and politics had on the spread of phage therapy.
    • War provided a dire need for treatment against bacterial disease- both in troops and recovering countries. In the case of the Republic of Georgia, the soviet was far behind the leading countries in medicine and science and desperately wanted to catch up. This provided a perfect opportunity for Eliava and d’Herelle to gain support and funding to further study and advance phage therapy.

 

  • What are some of the reasons that the spread of phage therapy failed?
    • One of the main reasons phage therapy fizzled out was the lack of sound scientific testing. Scientists and physicians needed to produce double-bind tests with control groups to effectively demonstrate the capacities of phage therapy. However, it was difficult for doctors to leave out a control group when they wanted to an administer a promising drug to everyone who needed it. Other studies used multiple methods for treatment, leaving it unclear how much part of the recovery phage therapy held. Overall, there were too many conflicting reports on the topic and when antibiotics emerged, it quickly stole the spotlight from phage therapy.

 

  • How did the physicists Delbruck and Luria end up as part of the Phage Group? What contributions did they make to phage biology?  Why did phage biology die out in the 70’s?
    • Delbruck and Luria were both intrigued by the applications of physics in biology. Delbruck began by studying the effects of X-rays on DNA and published a paper that eventually reached Luria. Delbruck’s paper suggested that genes were tangible molecules and the “ultimate units of life”. Luria decided that the bacteriophage, the smallest presumably living thing would be the perfect specimen to test this on. After the two met at a conference, they shared ideas and began to work together. Together they founded a school to attract great scientists to study phage biology. It was the collaboration of this group that lead to the observation of the phage’s tadpole like structure with a head and a tail, and the very important scientific realization that genetic material is housed in DNA, not protein. In the 70’s, phage biology came to an end as antibiotics began to emerge. The phage group were more interested in studying phage to further understand DNA and not as a treatment for bacterial disease. With much stronger literary and scientific support for antibiotics on the rise, phage biology began to die out.
February 18

The Forgotten Cure Chapters 1-4

d’Herelle first discovered bacteriophages when he observed plaques in the bacterial cultures from sick locusts he had grown, however he was unable to reproduce this, and it was unpursued for a few years. He was able to eventually study bacteriophages when he was studying an outbreak of dysentery in the troops at Maisons-Laffitte. While studying the bacteria the clear spots or plaques once again appeared and d’Herelle was able to observe and study the cause. When he noticed that the plaques only appeared in the samples from patients that were recovering he started to study the possibility of using these bacteriophages as they would be called to help with the recovery of patients with dysentery and other bacterial infections or in other words phage therapy. d’Herelle’s discovery was aided not only by his initial observation when he was studying locusts, but also by the ability to study many samples brought by outbreaks of dysentery often found in troops at the time.

One of the major characteristics that lead to d’Herelle becoming a successful scientist were probably the fact that he was not afraid of criticism, his dedication to his discovery, and that he was outspoken when it came to his discovery. His discovery while accepted by some was challenged by others. If he had been afraid of controversy or had not been as outspoken and willing to defend his discovery when it was challenged, then then the study of phage therapy may not have gone as far or maybe not anywhere at all. He was also very dedicated to the idea of phage therapy and he performed many studies on the effectiveness of this procedure. If he had left more of this to other scientist, it’s likely that it would not have gone as far as the success of his studies are what help spark the interest of other scientists to also perform experiments on phage therapy.

One major way that politics influenced was in Russia. Lenin’s push for public health helped Eliava establish a lab where he could further study bacteriophages and phage therapy. d’Herelle on several occasions also traveled there to assist Eliava which further pushed the study of phage therapy. However, the politics in Russia also halted Eliava’s studies in Russia as well as his and d’Herells’ cooperation when those who had been educated before the revolution including Eliava began being arrested and executed by Stalin. I this way specifically using Russia as an example of how politics helped push the research of phage therapy as well as halted it in Russia.

I major reason was that the results of phage therapy were often inconclusive. This was because scientists often did not have a control to compare their results against. This cause them to be unable to tell the reason behind patients’ recovery especially when more than one procedure was used. One example that was mentioned was that patients with boils would often have them lacerated and cleaned before the phage were added. Without a control it was impossible for anyone to tell whether a patient’s recovery was the laceration of the boils, the phage therapy, or both. A major reason that control groups were neglected was because the scientists often did not wish to deny patients something that could help them of save their lives. This mindset is definitely understandable, however this prevented the successfulness of phage therapy from being confirmed and it was eventually abandoned.

February 18

The Forgotten Cure: ch 1-4

Overall

I was surprised that the person who discovered bacteriophages lacked a formal college education and discovered them through sheer curiosity and persistence.

  1. Describe the role that locusts, dysentery and war had in the discovery of bacteriophage.

D’Herelle first noticed bacteriophages in locusts that were suffering from a bacterial infection. The outbreak of World War I put a temporary pause on the research of the locusts, but d’Herelle’s research came full circle when he noticed the same phenomenon in the feces of patients infected with dysentery as a result of the war (close quarters and limited supplies/hygiene led to the spread of the infection). The clear spots d’Herelle noticed were plaques similar to those we experienced in lab; the bacteriophages present in the bacterial cultures would kill off the bacteria and leave clear spots, which intrigued d’Herelle. However, he only noticed these clear spots/tubes in locusts/patients that were in recovery, so this led him to believe that the things in the bacteria that appeared clear helped cure the infections.

  1. Discuss the characteristics of d’Herelle that led him to be a successful scientist. How did he compare to Georgi Eliava?  What happened to the Eliava’s?

D’Herelle didn’t give up—he was largely doubted by his colleagues, but he persisted nonetheless. Even with publications criticizing him, he remained steadfast in his discoveries from his experiments. His curiosity drove him to continue on in his research. Eliava was similar to d’Herelle in disposition, however Eliava completed a medical degree and formal laboratory training. They both came from wealthy backgrounds, however Eliava lived in Georgia, giving him connections to anti-Soviet people of power. This eventually led to his arrest by the secret police and to his and his wife’s murders when the Soviets purged the intellectual and rich.

  1. Discuss the influence war and politics had on the spread of phage therapy.

Like the Cold War generated competition for space travel, World War I created competition between the Soviet Union and the United States for scientific discovery and healthcare. The conditions brought about by the war led to outbreaks of disease from lack of food, close quarters, stress, etc. Thus, it was imperative for each nation to come up with a way to treat its people/troops. The aforementioned rivalry between the two nations led to each experimenting with phage therapy as an easy and cost-effective way to treat infections within their populations.

 

  1. What are some of the reasons that the spread of phage therapy failed?

The development of antibiotics overtook the usage of phage therapy; antibiotics were easier to reproduce positive results with, as their genomes did not change and were able to be mass-produced. Additionally, d’Herelle was arguably the largest proponent of phage therapy in the world at this time, and he removed himself from the limelight after the death of Eliava, thereby decreasing the spread of phage therapy because no one was actively promoting it.

  1. How did the physicists Delbruck and Luria end up as part of the Phage Group? What contributions did they make to phage biology?  Why did phage biology die out in the 70’s?

Delbruck and Luria created the Phage Group, which united scientists from different backgrounds and fields to come together and study the importance of phages and phage therapy. They generated more interest in the field for a short time and figured out how phage replicated. Unfortunately, they only researched 7 phages, so the spark of interest in the field degenerated fairly quickly.

February 18

Forgotten Cure Post Chapters 1-4

The Forgotten Cure, by Anna Kuchment, offers us insight into phage biology and therapy well beyond the textbooks, as well as offering us the story behind scientific discoveries such as phage biology. After reading the first four chapters of the book, here are my thoughts about what I have discovered about the process of scientific discovery:

The father of bacteriophages, and a pioneer for one of the most incredible advances in modern science, was self taught. How incredible is that? There are so many things that culminated into the discovery of the world of microbes, and more specifically, phages. All building off the knowledge and discoveries made by those prior. D’Herelle, of course, discovered bacteriophages purely by chance while plating bacterial cultures during his work with sick locust. The war brought forth new evidence for the plaques D’Herelle discovered on his agar plates as patients recovering from dysentery yielding plaques in the bacterial colonies taken from their stools, as he tested the introduction of phages to bacterial solutions. Of course, a discovery wouldn’t be complete without opposition right? The concept of bacteriophages contradicted many long-held beliefs in the world of microbes, but that did not stop D’Herelle from holding strong to his beliefs. He was able to successfully treat diseases such as the bubonic plague, a disease that had troubled mankind since the dark ages by using phage therapy 15 years before the discovery of penicillin. Also, to me it is incredible how fast D’Herelle was able to achieve legitimate results by jumping straight to human trials as there were no regulatory agencies in his way. I know that those agencies are put in place to ensure proper ethical and legitimate research is being conducted, but in the case of phage therapy, nothing screams legitimate results like human phage treatment.

It surprised me just how much human conflict drives scientific discovery, especially in the case of phage therapy. In times of war, countries will put forth their efforts into the sciences, in the hopes that something will turn up that will give them the edge on their competitors. That was the case of the USSR in the early to mid 30s, following World War I and leading up to the front of World War II. I was completely unaware of the “war on disease” Stalin had called upon the USSR, establishing institutions dedicated to acquiring knowledge of bacteriophages.

The biggest thing that frustrated me regarding the story of phages was the overwhelming amount of ignorance that impeded the process of scientific discovery. Despite physician experimentation occurring in the 1930s in the United States, they were incapable of producing legitimate results simply due to their inability to perform consistent experiments. In addition to this, many held fast to their beliefs that there existed no organism smaller than a bacterium, and those who held the correct viewpoint on phages were in the overwhelmingly small minority. Due to these failures in research, phage therapy results were few and underwhelming, leading bacteriophage results to be overshadowed by new drug advances in the form of sulfa pills and of course, penicillin. These two untimely discoveries helped solidify phage therapy’s fate in the early 1940s, as the people in the scientific community simply lost interest and moved on to the next thing that caught their eye. Despite experimentation continuing with scientist like Delbruck and Luria discovering that DNA was the genetic material and not protein through the use of bacteriophages, not much was done in terms of their use in medicine. Technology did not help push phage researcg forward as it allowed humans to work with larger animal cells, completely leaving bacteriophages behind in the 70s. If only American medicine had continued to keep phage therapy in their sights instead of sweeping it aside, the possible discoveries we could have made by now in 2019 after almost 80 years of research would be incredible.

In conclusion, the road to scientific discoveries is a long one, and this holds true in the case of phages. Initially deemed as agents of “immunity”, bacteriophages seemed to offer humanity the cure to bacterial infection, only to be forgotten after new discoveries pushed it away. Now, over 100 years after their initial discovery by D’Herelle, they have made their way back under the sights of scientists’ microscopes as they once again offer us a solution to the issue of super-bacterial infections, beginning the road to scientific discoveries for phages once again.

 

 

 

February 18

The Forgotten Cure 1

The Forgotten Cure 1 2/18/19

In the first 4 chapters of The Forgotten Cure we learn about the early discoveries of phage, phage therapy, and phage biology.  Blog about which ideas or observations presented in the first 4 chapters surprised or shocked you concerning the process of scientific discovery? You may use these examples or comment on your own ideas.

  1. Describe the role that locusts, dysentery and war had in the discovery of bacteriophage.
    • d’Herelle was very interested in infectious disease but he was poorly educated. As he began his research career one of his first few tasks was pest management and fermentation. As part of these tasks, d’Herelle experimented on locusts by infecting them with bacteria. From these experiments, d’Herelle made bacteria cultures, and it was there that he noticed that some cultures had clear circles in them. While d’Herelle did not investigate this phenomenon right away, it was one of the first recorded instances of bacteriophage plaques, and he would later return to continue his research. During the war research into how to control disease became more important because many soldiers were dying of disease, this meant d’Herelle had more support for his research and there was a greater sense of urgency.
    • Dysentery and war played a role in the discovery of bacteriophages because together they created a situation in which d’Herelle began to actually consider the plaques he had noticed before. During the war research into how to control disease became more important because many soldiers were dying of disease, this meant d’Herelle had more support for his research and there was a greater sense of urgency. When he was sent to study dysentery during the war, d’Herelle noticed the same clear areas as he had noticed when he studied locust. He then found that patients who were recovering seemed to show signs of these plaques while the ones who died did not. This led him to purify and research bacteriophage.
  2. Discuss the characteristics of d’Herelle that led him to be a successful scientist. How did he compare to Georgi Eliava?  What happened to the Eliava’s?
    • d’Herelle became a successful scientist because he was stubborn and had a genuine passion for what he did. While he was abrasive and argumentative, his being in the right place and the right time and being willing to really study his observations meant he was able to advance his scientific cause. Eliava, by contrast, was far more personable, while he was equally dedicated to scientific research, he was better educated and less abrasive, which allowed him to be successful in a different way.
    • However, because of Eliava’s connections to wealth and foreigners he and his wife faced trouble under communist rule. There were some ill feelings between Eliava and Beria and this eventually led to the Eliava’s being arrested by the Soviet secret police. They were shot at some point during the communist purge of intellectuals, wealthy people, and all other foreign interests. Meaning that d’Herelle outlived his student.
  3. Discuss the influence war and politics had on the spread of phage therapy.
    • War, helped spread phage therapy because it made new disease treatment methods a necessity. World War one in part helped spur on the discovery of bacteriophages, and their therapeutic uses made phage therapy research highly valuable, which allowed it to spread. Phages meant that soldiers could survive what they might not have otherwise, and because world wars one and two had massive body counts, ways to save lives became a huge priority.
    • In addition, political competition such as that, that existed between the USSR and the capitalist world meant that a large emphasis was placed on scientific advancement as a way to compete or catch up to other nations. For phage therapy, the soviet union was choosing to compete in many areas including phage research and d’Herelle was able to visit and continue his research there, after he left Yale.
  4. What are some of the reasons that the spread of phage therapy failed?
    • Phage therapy failed for a variety of reasons, but the first is that after Eliava dies, d’Herelle stopped promoting his work and stopped doing new research. He instead chose to live a more comfortable life and without his enthusiasm phage research lost a valuable advocate. In addition, there was a lot of conflicting information about phages in scientific research. Doctors weren’t doing double-blind trials or following other necessary scientific procedures so results from experiments with phage were often inconclusive or contradictory. Also, phage were a lot more temperamental and so it was harder to reproduce even positive results. This led to JAMA publishing increasingly less favorable reviews of phage therapy that began to dissuade physicians from using them. Finally, with the introduction of medicines like sulfa drugs, phage therapy became less popular as researchers began to focus on developing new antibiotics with less severe side effects. This research led to the discovering of penicillin which eventually became widely used. While there was still some phage research going on, it began to fizzle out and was eventually widely abandoned as a medical treatment.
  5. How did the physicists Delbruck and Luria end up as part of the Phage Group? What contributions did they make to phage biology?  Why did phage biology die out in the 70’s?
    • Both Delbruck and Luria ended up as part of the Phage Group by trying to find ways to combine physics and biology.  Luria was inspired by a paper Delbruck had coauthored, so he began to research bacteriophages. Delbruck also became interested in phages and when both of them chose to flee to America to escape Nazism they met and began to work together. They laid the foundation for Phage Group as a collection of researches using phage to study genes and their contributions grew from there. Phage group discovered that phage had complex structures including the phage tails that typify phage shape today. In addition, they proved that DNA was the genetic material when they showed that it was phage DNA and not proteins that entered the bacteria cell. Phage Group made the study of bacteriophage legitimate and cleared the way for many more scientific discoveries.
    • However, phage biology began to die out. In the 70s phage biology died out because many scientists were intrested in understanding functions and once the phage was understtod they felt there was little else to do. Also phage group had chosen to only research 7 phage species limitng the scope of research that could actually be done.
February 17

The Forgotten Cure ~ Chapters 1-4

  1. Describe the role that locusts, dysentery, and war had in the discovery of bacteriophage
  • Locusts, dysentery, and especially WWI played an essential role in the discovery of bacteriophage. Due to WWI, disease outbreaks and vaccines were among the most necessary problems that needed to be answered. Dysentery, an infection of the colon, was running rampant in the ranks of troops. Felix D’Herelle, a Montreal-born, Paris-raised scientist was asked to investigate the outbreak of dysentery and “fix” it if possible. Prior to the war, D’Herelle first discovered bacteriophage (meaning at the expense of bacteria) when studying sick locusts. There were clear plaques that appeared in his Petri dishes when growing bacteria, and then linked the same appearance of plaques when examining bacteria found in the feces of sick soldiers, D’Herelle then tested his hypothesis on a sick patient with dysentery by using the patient’s stool to extract the bacteria and bacteriophage from. The success of the experiment was applauded and D’Herelle published a paper on bacteriophages in 1917.

2. Discuss the characteristics of d’Herelle that led him to be a successful scientist. How did he compare to Georgi Eliava? What happened to the Eliava’s?

  • As a self-taught scientist, d’Herelle was passionate about the field of science and would not give up on any idea that he would think of. Any problem or obstacle that he encountered, d’Herelle countered with scientific reasoning and experimentation. These characteristics ended up helping d’Herelle by opening up research opportunities for him, such as in the Soviet Union (USSR). Georgi Eliava was a bacteriologist from the Soviet Republic of Georgia that did research alongside d’Herelle. Eliava was described as charming and laid back, while d’Herelle was prickly and businesslike, seemingly counters of each other. Both came from privileged backgrounds and both invested their entire lives to science and the expansion of the known frontier. Eventually, the Eliava’s were executed by Stalin in labor camps.

3. Discuss the influence war and politics had on the spread of phage therapy

  • War was one of the main driving forces that allowed for the discovery and usage of bacteriophage in medicine. If dysentery hadn’t run rampant during WWI, d’Herelle wouldn’t have been able to make the connection between his locus research and the plaques discovered when examining patients with dysentery. Due to this discovery, d’Herelle was able to publish papers and “start” the research on bacteriophage therapy (Not named that during the time period). Politics played a huge role in the spread of phage therapy in that the different countries all flocked to start research on bacteriophages, which resulted in the attraction and “migration” of many intellectual minds to different countries. In the specific example of the USSR, Stalin wanted to establish and accelerate the research of bacteriophage, which resulted in the establishment of the research facility in Georgia.

4. What are some of the reasons that the spread of phage therapy failed?

  • One of the major reasons why phage therapy failed was the development and research of antibiotics. Sulfa pills and Penicillium developed and instantly took over the scientific world heading as they were “more simple in administration” and had promising results. Bacteriophage research was commonly tested without control groups and were tested on self-limiting conditions, which resulted in mixed results or results that had no comparison to. There was further research on the use of bacteriophage with penicillin, but did not catch on. A lack on complete understanding of bacteriophages also contributed to the failure of phage research.

5. How did the physicists Delbruck and Luria end up as part of the Phage Group? What contributions did they make to phage biology? Why did phage biology die out in the 70’s?

  • Delbruck, an astronomy student living in Berlin, and Luria, an Italian-Jewish medical student living in Turin (At the time) were both scientists who ended up planting the seeds of what would become the Phage Group, which was a loose collection of scientists in diverse fields who believed that bacteriophages constituted he biological equivalent of hydrogen atoms; the smallest and simplest life forms. The group ended up finding the structure/physiology of bacteriophage, as well as determining it was DNA, not protein that was the genetic material. They also co-discovered the replication mechanism of bacteriophages. However in the 70’s, Phage Group and bacteriophage research died out due to research on human and animal cells that were easier to research (With the technology at that time).