Drug-Resistant Bacteria: Part I

For this week’s column, I am going to presume some knowledge on the reader’s part regarding the growing problem of antibiotic-resistant bacteria. If you are not familiar with this issue, let me recommend that you open a new browser window, do a Google search on “drug-resistant bacteria,” and then come back. If you are not inclined, a brief summary follows:

More and more bacteria are developing resistance to more and more antibiotics. Of particular concern are drug-resistant strains of E. coli which contaminate food, and staphylococcus (staph) which cause skin infections in hospitals. There are also ongoing global outbreaks of drug-resistant gonorrhea and tuberculosis. The rate at which bacteria are developing drug resistance far exceeds the rate of development of new antibiotics. There is a serious and realistic concern that humanity is on the path to return to a pre-antibiotic era in which people die from simple infections.

In what I find to be an interesting bit of irony, it seems to be increasingly plausible that the solution to the challenges posed by antibiotic-resistant bacteria may come from the work of some long-forgotten doctors of the pre-antibiotic era. It’s a story filled with drama, famous historical figures, and conspiracy theories. So let’s get to it.

Our story begins with an outbreak of cholera, a bacterial disease, in London in 1854. A local physician, Dr. John Snow, meticulously tracked all of the cases and was able to determine that a single contaminated water source, the Broad Street Pump, was responsible for the epidemic. Dr. Snow’s discovery led to the development of germ theory, the concept that disease could be caused by very small organisms. The logic followed that if germs were alive, we should be able to kill them before they kill us.

Now let’s move forward to 1896, when British bacteriologist Ernest Hankin was studying a cholera outbreak in India along the Ganges River. Dr. Hankin had heard reports that people drinking water from some sections of the river were being cured. He collected some of this water, ran it through a porcelain filter, which he knew would remove cholera bacteria, and gave the filtered water to cholera patients, with good results. He surmised that some sort of unidentified substance which passed through the filter was responsible. As we will explore more below, he was correct.

Our story now moves to World War I, when a garrison of French troops was struck by an outbreak of hemorrhagic dysentery, which (like cholera) is a bacterial infection. The French army summoned Dr. Felix d’Herelle. D’Herelle isolated some of the bacteria from the soldiers’ feces and, in a similar manner to Hankin, collected some bacteria-free filtrate. He let the bacteria grow in several Petri dishes and then treated some of them with the filtrate. When he saw that the treated bacteria died, he gave some of the soldiers the filtrate and they were cured. D’Herelle correctly surmised that the filtrate contained viruses that killed the bacteria. He named these viruses bacteriophages, a combination of the words “bacteria” and “phagein,” which means “to eat” in Greek.

Viruses that infect bacteria function exactly like those that infect humans. They latch on to the outside of the bacteria cell and wait for the cell’s own mechanisms to transport them to the interior. Once inside, the virus hijacks the functioning of the cell such that new copies of the virus are made – a lot of them. Eventually the cell becomes filled with virus particles, ruptures, and dies. This allows the new copies of the virus to escape and infect new cells.

Let’s consider how the infection cycle may have created the healing waters in the Ganges. At some point along the river, people suffering from cholera were having diarrhea, and bacteria from their feces was contaminating the water. It is extremely likely that some of the bacteria in the water was infected with bacteriophages. These infected bacteria then generated millions of additional bacteriophages and released them into the water where they infected and killed more of the bacteria. Meanwhile, they created even more copies of themselves. Given the right conditions, the bacteriophages would have eliminated cholera bacteria in the river water but still have been floating along. If a cholera patient were to drink some of the water with the bacteriophages in it, they could be cured. Fascinating, eh?

After World War I ended, d’Herelle opened a lab in Paris to make bacteriophage preparations to treat staph infections, strep infections, E. coli, cholera and bubonic plague. The company that marketed these preparations grew into L’Oreal, which still exists today as a cosmetics manufacturer. In 1923, d’Herelle along with Giorgi Eliava co-founded an institute to study and develop bacteriophages (or phages, for short) in the Soviet Republic of Georgia, called the Eliava Institiute. The Eliava Institute was the world leader in both phage research and production. Sadly, Josef Stalin, in one of his many rounds of attacks against intellectuals, declared Eliava to be an “enemy of the people” and had him executed in 1937.

At the same time that Giorgi Eliava was falling out of favor in the USSR, development of phage therapy in the U.S. experienced a major setback. By the 1930s, while there were some companies in the U.S. trying to develop bacteriophage preparations, most of the best work was being done by our “enemies” in the USSR, and the United States antibiotics industry – the competitor to phages – was just getting off the ground. So when the American Medical Association (AMA) commissioned a review of bacteriophages in 1934, are you surprised to learn that the review was negative? Not only did the authors state that phages were ineffective, they also claimed, despite overwhelming evidence, that phages were not in fact viruses. The negative review published by the AMA effectively stopped all research and development of bacteriophages in the United States. This was a clear case of the established medical-pharmaceutical power structure using its influence to prevent a potentially effective alternative medical treatment from getting a fair chance. Many proponents of alternative medicine allege that similar suppression continues even today.

Now, 100 years after d’Herelle’s work with the French soldiers, the news is filled with reports of infections from drug-resistant superbugs and food contamination with pathogenic bacteria. Scientists are now trying to determine if d’Herelle’s “bacteria eating” viruses may be the solution to both of these problems. Next week in Part II, I will discuss why that is.

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