Jennifer Lake's Blog

August 6, 2009

Bacteriophage III

Filed under: DNA - RNA,Medicine — jenniferlake @ 12:30 am
Tags: , , , , ,

The role of phage research can hardly be overstated as the basis of recombination and genetic engineering; today’s “biotechnology”. The discoverers of phage, Frederick Twort and Felix d’Herelle, had vastly different experiences in their respective careers but both were relegated to obscurity near the end of their lives. They in themselves pose a mystery in the story of bacteriophage. D’Herelle, who as a self-taught scientist with a dominant personality, enjoyed “spectacular success” in the 1920s and 30s until he ran afoul of his colleagues at the Pasteur Institute, a concerted undermining that began in 1921. A biography written by William Summers (link below) notes that the only period of scientific stability for d’Herelle came during a five-year stint at Yale, a period from 1928 to 1933. Similar conflicts that he endured with the staff of Pasteur came to mark d’Herelle’s departure from Yale.

Speculation is that d’Herelle’s heresy against vaccines and the false process of creating “laboratory” diseases violated the vested interests of the burgeoning western medical establishment. This is given as his reason to accept the welcoming offer of Joseph Stalin that created a number of insitutes devoted to the study of bacteriophage and doubtlessly set the Soviets up with advanced bioweapons. It’s inconceivable to absurdity to believe the west did not also construct it’s biowar programs on phage research. Phage, and it’s multiple functions, are a weaponeer’s germ-theory dream come true. Phages have the distinctive capacity of target-specific destruction and the more abstract potential to alter the genomic basis of life on earth. This is no abstraction, however. It’s tangible and it’s happening.

The renaissance of bacteriophage experimentation is well underway, in fact it never did go away but became a supressed technology too good to lose. As the multi-field influence of physics and chemistry entered the laboratories to study phage, in the words of Salvador Luria, this “opened the way to the Holy Grail of biophysics”. Luria’s interest is noted to have been especially “in how radiation affects bacteriophages by causing mutations”. Prior to coming to the United States as a ‘displaced scholar’ and setting up shop, Luria had spent a year with Enrico Fermi’s physics team in Rome. Physicist Max Delbruck, friend and colleague to the fathers of the Bomb, was encouraged to pursue radiation biology and along with Luria became a leader of the field. Summer bacteriophage sessions at the Cold Spring Harbor lab under the auspices of the Carnegie Foundation became part of the backbone of American genetic science. Mutant recombinant influenza viruses exist because of this experimentation. It is well demonstrated in the journals. The year after flu specialist George K. Hirst claims that phage-influenza research was “dropped” in 1956, the next great pandemic of a new strain, Asian flu, swept around the globe.

 1915, discoverer of phage, Frederick Twort and more,

Link to an abbreviated version of William Summers’ biography on Felix d’Herelle

Read between the lines here, on d’Herelle and the nature of his heresy…

…”d’Herelle and his disciples affirmed that vaccines and serotherapies did not work, at least not in accordance with the theories of conventional medicine. Sera, for example, would have been active exclusively against bacterial toxins and not the bacterium responsible for disease (3). In diseases with relapse, antibodies would be at their peak during the relapse and possibly at the time of death, demonstrating that the bacteria were not rendered impotent (42). For instance, vaccines and serotherapy against cholera were considered by d’Herelle to be ineffective and dangerous. This was confirmed, according to d’Herelle, by the deaths in the regions where they were used. In general, every therapy and preventive measure derived from traditional immunology was a real “public danger” (42).”

So many questions are begged by the experiences of Twort and d’Herelle in addition to who they were and what they believed. The author of the (nih) Stanier Institute paper would have us believe that the success or failure of research pursuits are intrinsically entwined with the cult-of-personality status achieved by individual scientists. The intrepid d’Herelle, who found himself in relative isolation, was just the right sort to advance the potential of bacteriophage to the growing ‘establishment’. In time, I hope to understand his role much better. In the present, his general theories are deemed to be correct.


Commercial bacteriophage

“D’Herelle’s commercial laboratory in Paris produced at least five phage preparations against various bacterial infections. The preparations were called Bacté-coli-phage, Bacté-rhino-phage, Bacté-intesti-phage, Bacté-pyo-phage, and Bacté-staphy-phage, and they were marketed by what later became the large French company L’Oréal (68). Therapeutic phages were also produced in the United States. In the 1940s, the Eli Lilly Company (Indianapolis, Ind.) produced seven phage products for human use, including preparations targeted against staphylococci, streptococci, Escherichia coli, and other bacterial pathogens. These preparations consisted of phage-lysed, bacteriologically sterile broth cultures of the targeted bacteria (e.g., Colo-lysate, Ento-lysate, Neiso-lysate, and Staphylo-lysate) or the same preparations in a water-soluble jelly base (e.g., Colo-jel, Ento-jel, and Staphylo-jel). They were used to treat various infections, including abscesses, suppurating wounds, vaginitis, acute and chronic infections of the upper respiratory tract, and mastoid infections. However, the efficacy of phage preparations was controversial (20, 26), and with the advent of antibiotics, commercial production of therapeutic phages ceased in most of the Western world. Nevertheless, phages continued to be used therapeutically---together with or instead of antibiotics---in Eastern Europe and in the former Soviet Union. Several institutions in these countries were actively involved in therapeutic phage research and production, with activities centered at the Eliava Institute of Bacteriophage, Microbiology, and Virology (EIBMV) of the Georgian Academy of Sciences, Tbilisi, Georgia, and the Hirszfeld Institute of Immunology and Experimental Therapy (HIIET) of the Polish Academy of Sciences, Wroclaw, Poland.”

Dismissed in the United States

 “Starting with the first known use of phages in humans (the Enfants-Malades trials) and in all subsequent trials, d’Herelle administered phages to all sick patients. This failure to include placebo groups may be explained by the possibility that d’Herelle might have been reluctant to deprive anyone of therapy he believed could save his or her life. It could also have been due to the personal scientific style of d’Herelle, as he also failed to include placebo groups during his studies with chickens, when ethical considerations were not an issue (72). Similar failures were very common during the early history of phage therapy, and therefore the results frequently were controversial. To address this controversy, the Council on Pharmacy and Chemistry of the American Medical Association requested that a full review of the available literature on phage therapy be prepared for the Council’s consideration. Consequently, Monroe Eaton and Stanhope Bayne-Jones reviewed more than 100 papers on bacteriophage therapy and in 1934 they published a detailed review of phage therapy (20). This report is one of the most detailed reviews of phage therapy ever published, and its conclusions were clearly not in favor of phage therapy. Among other conclusions, the authors stated that “d’Herelle’s theory that the material is a living virus parasite of bacteria has not been proved. On the contrary, the facts appear to indicate that the material is inanimate, possibly an enzyme.” The authors further stated that “since it has not been shown conclusively that bacteriophage is a living organism, it is unwarranted to attribute its effect on cultures of bacteria or its possible therapeutic action to a vital property of the substance.” At the present time it is clear that the above conclusions of the report were incorrect. However, the report delivered a severe blow to the interest of Western scientists in evaluating the utility of phages for therapeutic purposes and it undoubtedly had a strong negative impact on the enthusiasm of funding agencies to support therapeutic phage research. In addition, 7 years after the Eaton-Bayne-Jones report, a second unfavorable report was published by Albert Krueger and Jane Scribner (26) as a sequel to the Eaton-Bayne-Jones report. The authors justified the need to write the second review because “much more information about both phage itself and its clinical utility has accumulated.” However, the authors’ conclusions about the nature of phages also was incorrect since they stated “It is a protein of high molecular weight and appears to be formed from a precursor originating within the bacterium.” The authors further concluded that “it is equally evident that phage solutions possess no measurable degree of superiority over well known and accepted preparations.” Although the authors suggested that further evaluation of the therapeutic potential of phages might be warranted under thoroughly controlled conditions, their assessment (together with that of Eaton and Bayne-Jones) effectively stopped all major studies of phage therapy in the United States.”

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