Phage of reason

Bacteriophages, perhaps the world’s best hope of combating antibiotic-resistant bacteria, will be the main topic of discussion by international experts gathering in Poland next month at the Institute of Immunology and Experimental Therapy in Wrocław, marking the 100th anniversary of the discovery of bacteriophages and the 10th anniversary of establishment of its Phage Therapy Unit, the only such centre in the EU. The one-day conference, Clinical Phage Therapy 2015, will be taking place at the centre on 26 September.

First identified by bacteriologist Frederick Twort in 1915 and Felix d’Herelle in 1917, bacteriophages (devourers of bacteria) are bactericidal micro-organisms. Unlike traditional antibiotics, which wipe out beneficial bacteria along with bacterial pathogens when introduced into the human body, phages attack specific bacteria and can therefore be targeted without detriment to natural gut flora and evolve with the bacteria, so preventing the development of resistance.

Although phage therapy was initially developed in the inter-war years and successfully used to treat Soviet soldiers in World War II, by the 1950s in the rest of the world phages had been replaced by antibiotics, which were easier to apply quickly without having to identify a particular pathogen. So, a naturally occurring treatment was replaced by the ‘wonder-drugs’ that were antibiotics. However, as we are now aware, with over-use ‘wonder-drugs’ do not remain effective forever and the nightmare of a post-antibiotic world of ‘superbugs’ is a real possibility without alternatives. Therefore the importance of bringing together current expertise on antimicrobial research and development cannot be over-emphasised.

Professor Andrzej Górski, MD, PhD, scientific director of the event, says such rapid growth of antimicrobial resistance constitutes an opportunity for phage, which should not be missed, to move them to the human clinic: “I think we have reached the point of no return; there will be no other eclipse.”

Górski says the purpose of the international conference, on 26 September, is to summarise the results achieved by the phage therapy outpatient clinic emphasising that it has been active for 10 years now, but is still the only such centre operating in Europe, and the only one observing all current administrative, legal and ethical rules in effect in EU countries. As a consequence, the value approach has been confirmed and should, he suggests, be promoted elsewhere: “The major accomplishment has been to offer a chance to help or alleviate symptoms of disease in a significant proportion of patients who had been treated sometimes for many years without clear effect.”

Knowledge and understanding of phage is very limited, even among the medical/scientific community, he lamented. “The conference should therefore update and promote knowledge about phage and phage therapy, as well as about current development in administrative, legislative and ethical rules of experimental therapy including ‘compassionate use’ (Europe), ‘expanded access’ and ‘right to try’ (a very hot issue in USA today).”

Dr Elizabeth Kutter, Evergreen State College, Olympia and co-author of, Bacteriophages: Biology and Applications, says, “The conference in Poland will be a wonderful and important celebration of their many years of large and innovative contributions to the field of phage therapy, and particularly the work they have done over the past 10 years in their important Phage Therapy centre, pushing the work as far as they could within existing EU limits and providing key data to hopefully expand those soon, as well as of phage therapy work in general.”

Another expert, Dr David R. Harper of Evolution Biotechnologies, says phages have the potential to replace, combine with, or at least supplement antibiotics in some specific indications compatible with their narrow spectrum of activity: “Delivery will take time, but they are on the way and show considerable promise. Because of their size and composition they are far more suited to topical (or at least accessible) uses such as skin or lung than for true systemic use, although that could be possible in time.”

Kutter broadly agrees: “Phage therapy will never replace traditional antibiotics for a whole variety of reasons,” she explains. “There will never be just one answer for the problem of antibiotic resistance - but it can already wonderfully complement them for a variety of applications, particularly topical ones including ones where topical or peritoneal application lets some phage get into the bloodstream, be carried throughout the body, get into sites of infection even across such things as the blood-brain barrier, and kill bacteria there.”

Górski adds that medical wisdom and experience teaches that combined treatments are usually more efficacious and frequently safer than single ones.

Beyond bacteria

The promise extends even further than as an answer to the antibiotic crisis, in which the world has found itself recently. Research is extending to include anti-viral applications and even as a treatment for, or preventative against, certain cancers.

“I hope that the event will provide an impetus for novel ideas regarding phage research, such as the potential use of phages in viral infections, as well as our novel hypothesis on phages targeting infected tissues and organs,” says Górski. “We have shown that T4 coliphage inhibits adsorption and replication of adenoviruses. We do not have data regarding the EBV (Epstein-Bar Virus, which remains latent in B cells and has been linked to several diseases beyond those it causes initially); but, this is an exciting possibility.”

Górski also reveals that data from mouse studies at the centre suggest that phages may help combat induced cancer. However, uncertainty remains because of the difficulty in translating these mouse studies to human testing and application. “I think there is more space for prevention, that is eradication of carrier status,” he states.

Dąbrowska’s current focus is on engineered bacteriophages that display anticancer peptides or proteins. “I think that phage display offers a great tool for selection and testing new anticancer agents. Interestingly, anticancer and antibacterial activity of bacteriophages can be used in parallel,” she explains.

Harper comments, “Phage display has a real role in cancer therapy, but mediating the immune system is a very complex business and this is a long way from anything practical for phages.”

Dąbrowska feels that the conference will stimulate progress in those aspects of phage research, which are practice-oriented, the very important ones: “I believe that it will increase public awareness and of course it will facilitate networking within the phage community.”

In all, the upcoming conference promises to take medical knowledge and treatment forward and may just save the human race.

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