Pathogens & People: Bacteriophage: The Invisible Microbe: by Edward Mcsweegan, For The Capital Published 07/05/09
Pathogens & People: Bacteriophage: The Invisible Microbe: by Edward Mcsweegan, For The Capital Published 07/05/09
microbe
If antibiotics disappeared tomorrow, would we be at the mercy of
every stray germ? Would every cut and scratch be a potential death
sentence? Would life become little more than survival of the
immunologically fittest? No, but life would be different, and perhaps
more complicated.
Decades before Alexander Fleming picked up a moldspeckled Petri
dish and discovered penicillin, other scientists had discovered a
mysterious entity that also could kill bacteria. In 1896, a man named
Hankin found that filtered, bacteriafree river water would kill Vibrio
cholerae, the agent of cholera. Two years later, another physician
named Gamaleya discovered a similar filtered water sample that
would kill Bacillus subtilis, a cousin of the anthrax bacillus. It wasn't
until 1917 that a FrenchCanadian microbiologist named Felix
d'Herelle systemically studied this bacteriakilling phenomenon and
put it to good use.
D'Herelle thought the mysterious bacteria killer was a virus: an
"invisible microbe" too small to be seen with the microscopes of the
day. He couldn't see these "bacteria eaters" or bacteriophage, but he
could grow them, study them, store them and test them. He thought if
they could kill bacteria in a test tube, maybe they could kill bacteria in
animals and people.
He was right, of course. His bacteriophages were viruses. Many of
them look like a cross between a lunar lander and a longnecked
spider. Yet, they act more like syringes; injecting their DNA into a
bacteria cell in order to take over the cell's genetic machinery and
massproduce more copies of themselves. The newly made viruses
eventually burst the cell to escape into the environment in search of
more hosts.
D'Herelle's first test subjects were chickens infected with a salmonella
species that caused typhoid, and rabbits infected with a shigella
species that caused dysentery. D'Herelle gave his test animals
injections or oral doses of his phages and then infected them with
bacteria. Most of the recipients of the phage therapy lived. He had
similar results treating a highly fatal bloodstream infection in water
buffalo. It seemed all he had to do was find a particular phage that
would lyse or break open a particular bacterial pathogen, and give it
to the infected animal.
He needed some human subjects to be sure. After drinking and
injecting various phage preparations and asking friends and family
members to do the same he decided the phages were safe for
human use.
In Alexandria, Egypt, he got a chance to test some antiplague
preparations on four people with bubonic plague. All four lived. That
caught the attention of the medical world, and d'Herelle was invited to
India to try phage therapy on cholera patients. It seemed to work
there too. (Fifty years later in Pakistan, a study of phages versus
tetracycline antibiotics showed the two treatments to be about equal
against cholera.)
D'Herelle's work with plague in Egypt would later become one of the
subplots in Sinclair Lewis' Pulitzer Prizewinning novel "Arrowsmith."
Yet even as phage therapy was making its way into hospital wards,
pharmaceutical companies and the popular culture, it was about to be
sidelined by two unexpected discoveries. The first was a simple
antibacterial chemical called sulfanilamide discovered in the 1930s.
The second was the discovery and mass production of penicillin in
the 1940s. Unlike the finicky, bacteriaspecific phages, penicillin and
sulfanilamide were two "generic" drugs that could kill a wide variety of
bacteria. Other such "broadspectrum" antibiotics were discovered
and commercialized in the '50s and '60s. It was the end of d'Herelle,
Arrowsmith and phagotherapy in the West.
But not in the East. In an obscure corner of the Caucasus, in Tbilisi,
Georgia, d'Herelle's work lived on. The George Eliava Institute of
Bacteriophage, Microbiology and Virology has been producing
phages and treating patients for decades. In 2005, the institute
created the Phage Therapy Center to commercialize its phage
therapies, and recently merged with the American company Phage
International.
After a long absence, phages may be creeping back into the U.S. In
2006, USA Today carried a story titled, "U.S. needs to open eyes to
'phage therapy.' " Maybe we have. Evergreen State College in
Washington is holding its 18th biennial International Phage Biology
meeting. Other American researchers are studying ways to reduce
bacterial contamination of beef and poultry products with phages.
Intralytix Inc. in Baltimore is developing commercial phage products
for use in food safety, environmental cleanup, and the treatment of
antibioticresistant infections.
D'Herelle would be pleased to know his invisible microbes continue to
intrigue scientists and save patients.
Dr. Edward McSweegan's column is on hiatus until November.