Phage Therapy

Thomas Kalinoski

Submitted to Dale Sullivan, April 9, 2010

Abstract

Phage therapy is the application of bacteriophages to therapeutic effect in the body to control pathogenic bacteria. The use of phages has many potential applications for treating bacterial infections, especially infections that do not respond to conventional antibiotic treatment. Although the use of phages to control bacteria has been proposed decades ago, phage therapy use for human medicine has not yet been approved in most of the world and continues to undergo extensive research. The proposed review examines various research literatures involving the use of phages in human medicine. Included background information features some of the basic information already known about the bacteriophages and their potential applications. The study’s review method, parameters, and time frame are summarized in the following paragraphs.

Introduction

Even from the start of widespread antibiotic use in the 1940’s, it has been known that resistance strains of bacteria would become a problem in treatment. Today, there are a diminishing number of antibiotics that can be used in many cases, and highly resistant strains are becoming more and more of a problem to health care professionals. In addition to education of correct antibiotic use and the continual discovery of new antibiotics, use of bacteriophages to treat infections stands out as a promising alternative. Research on bacteriophages to treat specific diseases is widespread. In an effort to amass this research and analyze its significance, I am proposing to construct a research review essay for English 324 as a part of a class assignment. The study will bring together a variety of different research literature in order to review the critical points of current knowledge on phage therapy. This proposal will include background information on phage therapy, a description of the research review project, the method that will be used to conduct the review, and a predicted schedule.

Background

Bacteriophages have been studied for many decades, resulting in a wealth of information on the topic. Bacteriophages, or simply phages, are viruses that exclusively infect bacterial cells. Bacteriophages were discovered in the early 20^th century, and not long after their discovery, they were already being tested therapeutically to fight against infections. The first study was conducted by Felix d'Hérelle at the Hôpital des Enfants-Malades in Paris in 1919 on a 12 year old boy with dysentery. According to the report, the boy’s symptoms ceased after a single administration (Sulakvelidze, 2001). In 1923, George Eliava founded the Eliava Institute in Georgia, devoted to the development of phage therapy. Research and commercialization of phages soon began in Russia and the United States in the 1940’s, at the same time that antibiotics were taking off. The fact that early use of phage therapy was largely unreliable, and that the newly discovered antibiotics were seen as “wonder drugs”, ensured a loss of interest from most of the scientific community. Research into phage therapy continued in the Soviet Union, where it was isolated due to the cold war. Phage therapy continues to this day exclusively in Georgia at the Eliava Institute (population, 2004). A renewed interest to find alternative methods of treating bacteria due to increasing antibiotic resistance has increased the amount of recent research on the subject in the west. The fact that bacteriophages are much more specific agents than antibiotics, have few side effects, do not stress the liver, and are self-replicating, make phage therapy an attractive option (Abhilash, 2009). The proposed study will examine the new research on phage therapy, as well as address the issues and obstacles that have prevented this technology from taking hold in western medicine.

Project

The intent of this review is to bring together the wealth of current literature out there on bacteriophages and phage therapy, in order to bring the reader up to date on the critical points of the current knowledge on the topic. This is intended as an unbiased and comprehensive review of the topic, and allows the reader information to come to their own conclusions about the use of phage therapy as an alternative medical treatment. As a junior biochemistry major, I have gained strong background in biology and microbiology. I feel that I have the required background knowledge to take on the task of reviewing scientific articles related to this subject. This review will be targeted at people within the scientific community, as well as anyone with a general interest in science and healthcare with some prior knowledge on the subject. The review will include a general overview of bacteriophages in order to give the reader some kind of basic background before reading the rest of the review. The issue of phage therapy will be introduced, and the objectives of the review will be addressed. The studies will then be described in detail. In the next section, the studies will be compared and evaluated. Finally, the implications of the studies will be addressed, as well as conclusions as to which pieces are best considered and convincing in their argument and make the greatest contribution to the understanding of the research in the review.

Method

In this literature review, 7-15 research articles that relate to phage therapy will be selected to analyze. The search for relevant articles will be conducted using scientific search engines such as Web of science, SciFinder Scholar, and ScienceDirect. The preliminary search will include most relevant articles, which will then be assessed later on to find ones suitable for review. The assessment will be done based on author credentials, sufficient evidence, objectivity of the experiment at hand, and overall value and contribution to the understanding of phage therapy. Also, care will be taken to choose articles that are most representing of phage therapy in their research. The selected articles will then be read, and key points will be taken from them, such as the precise methods used and theories tested. This will be essential for comparing the different research articles. The review paper will then be written. The articles will be evaluated and compared, and a conclusion will be drawn.

Schedule

The project will begin September 29th, 2010 and conclude December 3, 2010. The first week of the project will be spent searching form articles to review. I will be searching for anything related to bacteriophage studies. In the following week, I will narrow down my selected articles to assess which ones that I will base the review on. The next few weeks will be spent reading and taking notes on the literature, then comparing and evaluating each of them. In the final week of the project, a conclusion will be made and references will be cited. Other documents will be prepared along with the research review itself. These include a research analysis due October 8^th and an annotated bibliography due October 29^th. A final portfolio consisting of all of these documents will be submitted by December 13^th.

Conclusion

Infections with multiple resistant strains of bacteria are becoming a common occurrence. In order to keep up the fight against these pathogenic bacteria, new research in areas such as phage therapy continues. The proposed review will examine many articles in the scientific literature about phage therapy in order to bring the reader up to date with the newest findings in this exciting area of research.

References

Sulakvelidze, A., Alavidze, Z., Morris, J. (2001). Bacteriophage Therapy.

American Society for Microbiology. 45 (3), 649-659.

Abhilash, M., Vidya, A.G., Jagadevi, T. (2009). Bacteriophage Therapy: A War Against Antibiotic

Resistant Bacteria. The Internet Journal of Alternative Medicine. 7 (1).

Levin, B., Bull, J. (2004). Population and Evolutionary Dynamics of Phage Therapy. Nature Review: Microbiology. (2), 166-173.