65
billion years ago, but only in recent years has science begun to understand the genetic
mechanisms behind that evolution and the role they play in the evolution of their bacterial
hosts. It also has become clear that not only are tailed phages remarkably abundant in the
environment, but that they probably constitute a numerical majority of organisms on the
planet.8 Estimates of the total population are on the order of 1031 total viral particles, an
astronomical number, in that 1031 tailed phages laid end to end, would extend into space
to a distance of 200 million light years. Estimates of the longevity of phages in the environ-
ment suggests that the entire population turns over every few days.9
Phages can assume many different lifestyles—lytic or temperate. “Lytic” phages infect
a bacterium and immediately begin replicating, disintegrating the cell a short time later.10
“Temperate” phages can arm a bacterium with an additional poisonous gene and turn it
into a lethal weapon.11 They also integrate their DNA into the bacterial chromosome, lead-
ing to a state of lysogeny. (A phage in the lysogenic state is called a “prophage.”) Certain
prophages can alter the phenotype of the host bacterium. If the prophage expresses a
toxin gene, then the bacterium will be lysogenically converted for toxin production. For
example, the virulence of Vibrio cholerae is largely dependent on infection by the bacterio-
phage CTXØ, in that the cholera toxin is encoded within the genome of this temperate and
nonlytic filamentous phage, and only strains of vibrio infected by CTXØ are capable of
causing epidemic disease.12
Most phages have double-stranded DNAs encapsulated into an icosahedral shell
of protein attached to a tail. At the end of the tail there are proteins that attach to cells. A
simple explanation is as follows: the virus particle with its protein and DNA first lands on
the outside of the specific bacterial cell and injects its DNA into the cell. The DNA of the
bacterial virus then takes over the cell and is converted into a virus factory. The bacterial
cell dies, and hundreds of virus particles are released. The process, of course, is much
more complex, consisting of a cascade of events involving several structural and regula-
tory genes.
Medical Uses
Not long after his discovery, d’Herelle used phages to treat dysentery. The studies were
conducted in Paris in 1919. The phage preparation was ingested by d’Herelle, the treat-
ing physician, and several hospital interns to confirm its safety before administering it to
patients.13 The successful results of these studies, however, were not immediately pub-
lished and, therefore, the first reported application of phages to treat infectious diseases
of humans came from Bruynoghe and Maisin in France in 1921. They used phages to treat
staphylococcal skin disease.14
Several promising studies followed and, encouraged by these early results, d’Herelle
used various phage preparations to treat thousands of patients having cholera and/
or bubonic plague in India. D’Herelle also owned a commercial laboratory in Paris that
produced several phage preparations against various bacterial infections. In the early
1930s, at least four major manufacturers in the US manufactured and sold phage products,
including Parke Davis, E. R. Squibb and Sons, Swan-Myers of Abbott Laboratories and Eli
Lilly and Company. All four suppliers focused primarily on staphylococci phages, which
were administered to treat furuncles, carbuncles and boils.15 As late as the 1940s, Eli Lilly
was producing seven phage products for human use, including preparations targeted
against staphylococci, streptococci, E. coli and other bacterial pathogens. These prepa-
rations consisted of phagelysed, bacteriologically sterile broth cultures of the targeted
bacteria, or the same preparations in a watersoluble jelly base. The products were used
to treat various infections, including abscesses, suppurating wounds, vaginitis, acute and
chronic infections of the upper respiratory tract and mastoid infections.16
In addition to these uses, phages have also been used to treat anthrax, enteritis caused
by Campylobacter species, Clostridium difficile gastrointestinal infections, gas gangrene,
Bacteriophages: Beyond Antibiotics
billion years ago, but only in recent years has science begun to understand the genetic
mechanisms behind that evolution and the role they play in the evolution of their bacterial
hosts. It also has become clear that not only are tailed phages remarkably abundant in the
environment, but that they probably constitute a numerical majority of organisms on the
planet.8 Estimates of the total population are on the order of 1031 total viral particles, an
astronomical number, in that 1031 tailed phages laid end to end, would extend into space
to a distance of 200 million light years. Estimates of the longevity of phages in the environ-
ment suggests that the entire population turns over every few days.9
Phages can assume many different lifestyles—lytic or temperate. “Lytic” phages infect
a bacterium and immediately begin replicating, disintegrating the cell a short time later.10
“Temperate” phages can arm a bacterium with an additional poisonous gene and turn it
into a lethal weapon.11 They also integrate their DNA into the bacterial chromosome, lead-
ing to a state of lysogeny. (A phage in the lysogenic state is called a “prophage.”) Certain
prophages can alter the phenotype of the host bacterium. If the prophage expresses a
toxin gene, then the bacterium will be lysogenically converted for toxin production. For
example, the virulence of Vibrio cholerae is largely dependent on infection by the bacterio-
phage CTXØ, in that the cholera toxin is encoded within the genome of this temperate and
nonlytic filamentous phage, and only strains of vibrio infected by CTXØ are capable of
causing epidemic disease.12
Most phages have double-stranded DNAs encapsulated into an icosahedral shell
of protein attached to a tail. At the end of the tail there are proteins that attach to cells. A
simple explanation is as follows: the virus particle with its protein and DNA first lands on
the outside of the specific bacterial cell and injects its DNA into the cell. The DNA of the
bacterial virus then takes over the cell and is converted into a virus factory. The bacterial
cell dies, and hundreds of virus particles are released. The process, of course, is much
more complex, consisting of a cascade of events involving several structural and regula-
tory genes.
Medical Uses
Not long after his discovery, d’Herelle used phages to treat dysentery. The studies were
conducted in Paris in 1919. The phage preparation was ingested by d’Herelle, the treat-
ing physician, and several hospital interns to confirm its safety before administering it to
patients.13 The successful results of these studies, however, were not immediately pub-
lished and, therefore, the first reported application of phages to treat infectious diseases
of humans came from Bruynoghe and Maisin in France in 1921. They used phages to treat
staphylococcal skin disease.14
Several promising studies followed and, encouraged by these early results, d’Herelle
used various phage preparations to treat thousands of patients having cholera and/
or bubonic plague in India. D’Herelle also owned a commercial laboratory in Paris that
produced several phage preparations against various bacterial infections. In the early
1930s, at least four major manufacturers in the US manufactured and sold phage products,
including Parke Davis, E. R. Squibb and Sons, Swan-Myers of Abbott Laboratories and Eli
Lilly and Company. All four suppliers focused primarily on staphylococci phages, which
were administered to treat furuncles, carbuncles and boils.15 As late as the 1940s, Eli Lilly
was producing seven phage products for human use, including preparations targeted
against staphylococci, streptococci, E. coli and other bacterial pathogens. These prepa-
rations consisted of phagelysed, bacteriologically sterile broth cultures of the targeted
bacteria, or the same preparations in a watersoluble jelly base. The products were used
to treat various infections, including abscesses, suppurating wounds, vaginitis, acute and
chronic infections of the upper respiratory tract and mastoid infections.16
In addition to these uses, phages have also been used to treat anthrax, enteritis caused
by Campylobacter species, Clostridium difficile gastrointestinal infections, gas gangrene,
Bacteriophages: Beyond Antibiotics