Bacteriophage Therapy History (Part 3)

Use of phage therapy in the USA declined drastically with the advent of antibiotic therapy. But this was not the case in Eastern Europe. The Eliava Institute, founded in 1923 in Tbilisi, Georgia, by Giorgi Eliava, continues to this day to research phage therapy. In fact, there is a Phage Therapy Center to this day in the Republic of Georgia that takes patients for phage therapy treatment.

There are hundreds of published research reports on phage therapy. A large number of these are to be found in non-English journals published in the former Soviet Union and Poland. Stefan Slopek, of the Laboratory of Bacteriophages, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, published a series of papers in the 1980's, on the effectiveness of phage therapy against infection with several different bacterial pathogens including multi-drug resistant bacteria. A review of the work was published by Slopek in 1987. Slopek reported that of 550 patients treated with phage therapy, "positive results were found in 508 cases (92.4%)". Most of these cases were infections with drug resistant bacteria.

More recently, at the same Institute in Poland, Gorski reported that "1307 patients with suppurative bacterial infections caused by multidrug-resistant bacteria of different species were treated with specific bacteriophages (BP)". And that, "BP therapy was highly effective; full recovery was noted in 1123 cases (85.9%)".

Reports concerning phage therapy of staphylococcal infections of the lung, sepsis in newborns, urinary tract infections, infections of surgical wounds, and eye infections have been published. Unfortunately, in many cases the trials were not completed in a manner to allow rigorous evaluation of the results.

Research on phage therapy does continue in the USA. In fact, rather than using the whole phage virus which can be attacked by the human immune system and in some cases by the bacteria themselves, a phage lysin can be used to attack the bacterial cell wall.

More information about phage therapy can be found at this Evergreen International Phage Biology Meeting website. An extensive list of the phage therapy literature can be found here.

Bacteriophage - Therapy History (Part 2)

Bacteriophages are viruses that can infect and destroy bacteria. This fact was actually used, prior to the discovery and widespread use of antibiotics, to treat certain infections.

Who discovered bacteriophages is the subject of debate. Most credit Frederick Twort (1915), an English bacteriologist, and Felix d'Herelle (1917), a French-Canadian microbiologist with the independent discovery of bacteriophages.

Frederick Twort
Felix D'Herelle

But in 1896 another British bacteriologist, Ernest Hankin, observed that water from the Ganges river in India had a marked inhibitory effect against Vibrio cholerae. Furthermore, he observed that the substance was susceptible to heat and could pass through a fine porcelain filter. The first phage was not visualized until 1939 by Helmut Ruska using an electron microscope.

D'Herelle used phages to treat dysentary and was probably the first to use phages therapeutically. In one experiment, he purified a phage preparation and ingested it himself to insure its safety. The next day he gave the preparation to a 12 year old boy suffering from severe dysentary. The boy's symptoms ceased after a single dose of the phage and he fully recovered from the dysentary.

The first published report of using phage as a therapeutic treatment was in 1921 by Bruynoghe and Maisin who used phage therapy to treat staphylococcal skin disease. Felix D'Herelle eventually started a commercial laboratory in Paris to produce phage preparation marketed to treat 5 different bacterial infections. The company later became L'Oreal.

In the USA in the 1940's the Eli Lilly Company manufactured phage preparations for human use. These preparations were specific for staphylococci, streptococci, E. coli and several other bacteria. It was a subject of debate of how effective these phage preparations were in treating infections.

Unfortunately (and fortunately) the large scale production of penicillin also occurred in the 1940's and commercial production of phages ceased in most of the world.

Bacteriophage (Part 1)

What are bacteriophage? Bacteriophages (or phages) are viruses that infect bacteria rather than eukaryotic cells. The word bacteriophage comes from "bacteria" and "to eat" because many phages literally destroy the bacteria they infect.

Bacteriophage T4 is a classic example of phage virus. It infects the E. coli bacterium. Below is a diagram of a T4 phage and an actual electron micrograph of the phage.
The T4 phage looks alot like the lunar lander doesn't it? The "legs" of the T4 phage allow for attachment to the E. coli host bacterium and the phage "tail" is hollow to allow for the injection of the phage DNA into the bacterium. You can see an animation of the T4 phage infecting a bacterium here.

Viruses have two different types of life cycles called lytic and lysogenic. The lytic life cycle is the more common type of life cycle used by viruses and it results in the destruction of the bacterium or cell. The below excellent diagram, from the U. of Delaware, shows the lytic life cycle of a T4 phage.
Basically, the bacterium is infected, the phage takes over the metabolic machinery of the bacterium, reproduces itself and destroys the bacterial host cell thus releasing more virus available to infect new host cells.

The lysogenic cycle is different and is pictured below.
In this phage "life style", the phage DNA is actually incorporated into the bacterial genome. This newly integrated phage DNA is referred to as a prophage. The advantage of this life cycle is that every time the bacterium divides, the DNA of the prophage is replicated along with the bacterial genome. At some time in the future, the prophage can be induced to enter the lytic phase where new phages are reproduced and the bacterial cell is destroyed, releasing the phage virions.

So phages are good because they infect and destroy bacteria. Well not so fast. Phages are also known to increase the disease-causing capability (virulence) of some bacteria. For instance, the toxin produce by Vibrio cholerae bacterium diarrhea and rapid dehydration of the infected person, is due to infection of the bacterium with CTX phage. The toxin which causes cholera is actually encoded by the phage genome and not the bacterial genome. It is possible that phage infection of bacteria could be responsible for the evolution of more virulent bacteria. Other toxins reported to be encoded by phages include shigalike toxin in some pathogenic E. coli strains, botulinum toxin, diptheria toxin and erythrogenic toxin. This is serious business because it may be possible for phage to transfer virulence genes from disease-causing bacteria to unrelated bacteria which normally do not cause disease. You can read more about this phenomenon here.

On Homosexuality, Civil Rights and Christian Judgement

It all started a few weeks ago with a letter to the editor of the Adirondack Daily Enterprise written by a very brave soul. The letter concerned gay marriage as a civil right. The letter generated 85 comments on the ADK website. What is surprising to me is the number of comments supporting the letter writer. I was not so surprised by the comments made by local homophobes.

A few days ago another letter to the editor was published in the ADK. This letter was written by a local bible-thumper and stated that homosexuals are sinners. As you might imagine (or maybe not) the letter has so far generated over 140 comments. The discussion rapidly devolved into whether what the bible says is worth the paper it is printed on. Interesting reading.