Saturday, December 05, 2009

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.

Friday, December 04, 2009

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.

Thursday, December 03, 2009

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.

Sunday, November 29, 2009

Many Cancer Treatments Not Cost Effective

There is an article in today's Washington Post with some information that I expect many people do not want to hear. The bottom line is that treatment for most cancers is ineffective and very expensive.
At the moment, there is a giant disconnect between patients, the cost of care and the clinical benefit of the treatment -- a disconnect that has caused us to lose perspective. When it comes to cancer care, we're not getting what we pay for.
But we are talking about someone's life! Yeah, well maybe spending thousands of dollars a month on ineffective cancer treatments might make you feel like you are doing something rather than nothing, but all that is really happening is....well, nothing.

How did we get to where we are in cancer treatment? In spite of the billions of dollars spent on the "war on cancer" we actually have no "evidence-based medicine" on which treatments are effective. Accepting this situation means, I guess, that maybe we will have "rationing" and "death panels" in some areas of medicine where treatments are just not effective. Maybe more time and money need to be put into counseling patients about their untreatable conditions rather than tens of thousands of dollars on the hope of a miracle cure.

Speaking of "death panels" read this. There is sometimes a limit on what an emergency room can do for you.