Phages: Early Research

Phages: Early Research.

It was Felix d’Herelle, a Canadian working at the Pasteur
Institute in Paris, who gave these newly discovered
organisms the name bacteriophages—using the suffix phage
“not in its strict sense of to eat, but in that of developing at
the expense of.” He carefully characterized them as
viruses that multiply in bacteria, and he worked out the
details of infection of different bacterial hosts by various
phages under a variety of environmental conditions. The
90th Annual Meeting of the British Medical Association
in Glasgow featured a very interesting discussion among
d’Herelle, Twort, and several other eminent scientists of
the day on the nature and properties of bacteriophages.
The main question was whether the observed bacteriolytic
principle was an enzyme produced by bacterial
activity or a form of tiny virus. Gradually, it became clear
that the phage is indeed viral in nature, able to reproduce
and direct the synthesis of its own enzymes.

D’Herelle summarized the early phage work in a
300-page book, The Bacteriophage: Its Role in Immunity.
He wrote classic descriptions of plaque formation and
composition, infective centers, the lysis process, host
specificity of adsorption and multiplication, the dependence
of phage production on the precise state of the
host, isolation of phages from sources of infectious bacteria,
and the factors controlling stability of the free phage.
He quickly became fascinated with the apparent role
of phages in the natural control of microbial infections.
He noted, for example, the frequent specificities of the
phages isolated from recuperating patients for disease
organisms infecting them and the rather rapid variations
over time of the phage populations. Throughout his life,
he worked to develop the therapeutic potential of properly
selected phages against the most devastating health
problems of the day. However, he initially focused on
simply understanding phage biology. Thus, the first
known report of successful phage therapy came from
Bruynoghe and Maisin,13 who used phage to treat staphylococcal
skin infections.

After much travel, including the study of epidemics
in Latin America and a year at the Pasteur branch in
Saigon, d’Herelle left the Pasteur Institute in 1922.
He worked in Holland and then became employed as
a health officer by the League of Nations, based in
Alexandria, Egypt. Phage therapy and sanitation measures
were the primary tools in his arsenal to deal with
major outbreaks of infectious disease throughout the
Middle East and India. In 1928, he was invited to Stanford
to give the prestigious Lane lectures; his discussions were
published as the monograph The Bacteriophage and its
Clinical Applications.14 He gave many lectures for medical
schools and societies as he crossed the country. He
accepted a regular faculty position at Yale, where he was
supported by George Smith, translator of his first two
books into English. D’Herelle continued to spend summers
in Paris working with the phage company he had
established there and returned permanently to France in
1933, with excursions to Tbilisi, Georgia, to help establish
phage work there.

George Eliava, director of the Georgian Institute of
Microbiology, saw bacteriocidal action of the water of
the Koura River in Tbilisi (Tiflis) that he could not
explain until he became familiar with d’Herelle’s work
while spending 1920 to 1921 at the Pasteur Institute. He
became a very early collaborator of d’Herelle’s; several
of his phage papers are cited by d’Herelle.12 The two
developed the dream of founding an Institute of
Bacteriophage Research in Tbilisi—to be a world center
of phage therapy for infectious disease, including scientific
and industrial facilities, and supplied with its own
experimental clinics. The dream quickly became a reality
through the support of Sergo Orjonikidze, the People’s
Commissar of Heavy Industry, despite KGB opposition
to this “foreign project.” A large campus on the river
Mtkvari was allotted for the project in 1926. D’Herelle
sent supplies, equipment, and library materials. In 1934
and 1935, he visited Tbilisi for a total of 6 months and
wrote a book, The Bacteriophage and the Phenomenon of
Recovery,15 which was translated into Russian by Eliava.
D’Herelle intended to move to Georgia; in fact, a cottage
built for his use still stands on the institute’s grounds.
However, in 1937, Eliava was arrested as a “people’s
enemy” by Beria, then head of the KGB in Georgia and
soon to direct the Soviet KGB as Stalin’s much-feared
henchman. Eliava was soon executed, sharing the tragic
fate of many Georgian and Russian progressive intellectuals
of the time, and d’Herelle, disillusioned, never
returned to Georgia. However, their institute survived
and is still functioning at its original site on the Mtkvari
(which it now shares with the more modern Institute of
Molecular Biology & Biophysics and Institute of Animal
Physiology).

In 1938, the Bacteriophage Institute was merged with
the Institute of Microbiology & Epidemiology under
the direction of the People’s Commissary of Health of
Georgia. In 1951, it was formally transferred to the All-
Union Ministry of Health set of Institutes of Vaccine and
Sera, taking on the leadership role in providing bacteriophages
for therapy and bacterial typing throughout the
former Soviet Union. Under orders from the Ministry of
Health, hundreds of thousands of samples of pathogenic
bacteria were sent to the institute from throughout the
Soviet Union to isolate more effective phage strains and
to better characterize their usefulness. In 1988, an official
Scientific Industrial Union “Bacteriophage” was formed,
centered in Tbilisi with branches in Ufa, Habarovsk, and
Ghorki.

Article acknowledgment to Evergreen University's Elizabeth Kutter for an
excellent, informative article.

For the full text, visit href="http://academic.evergreen.edu/projects/phage/docs/textbookofnat
uralmedicinephage.pdf">Evergreen University