20 Dec 2019

The perfect predator? Inside the Tbilisi clinic pioneering a radical superbug treatment

The laboratory, with its faded white walls and the smell of yeast in the air, seems an unlikely battleground for one of the most urgent fights facing modern medicine.

But the Eliava Institute – housed in a Stalin-era building overlooking the Mtkvari river in Tbilisi, Georgia – has come to global attention as antibiotic resistance increases and once treatable diseases are left without a ready cure.

The centre has been producing an alternative to antibiotics since the early Soviet period – tiny viruses called bacteriophages, or simply “phages,” that invade bacteria and multiply until they burst out and destroy their host.

Phages are the most abundant organisms on the planet and are used to treat bacterial diseases in humans on the principle that “my enemy’s enemy is my friend”.

The therapy has been common in Georgia for almost a century but now hundreds of foreign patients are coming to Tbilisi every year for treatment.  The majority are from mainland Europe but the centre also sees patients from the UK, US and Asia.

Is it just another false hope, an unregulated money making exercise? Or might phages really have a role to play in modern medicine, especially as antibiotics start to fail?

Taking to the lab and its patients, it does feel a bit Heath Robinson, a bit too good to be true.

“Most people who are coming here, they are taking antibiotics for many, many years and they have not been treated completely,” says Dr Nina Chanishvili, the head of research and development at Eliava. Common complaints from visitors include skin infections, chronic prostatitis, chronic cystitis, bronchiectasis and complications arising from cystic fibrosis.

Patients either drink the phages cultivated in the lab or have them applied topically as a liquid or cream.

Roy Schnauss, an estate agent from Florida who heard about Eliava online, had taken multiple rounds of antibiotic treatments over several years for flu-like symptoms and fatigue linked to a bacterial infection.

In Tbilisi he underwent blood, urine and other tests to pinpoint the bacteria behind the symptoms and allow doctors to find a phage that could attack the strain.

“Since I’ve been here I’ve noticed a difference in my activity level,” the 45-year-old says, after more than a week of taking phage orally, twice a day. “When I got here I was just tired and sleeping and staying in the hotel. But as I continue I’m going out and enjoying the city.”

Mr Schnauss will stay in private accommodation and return to the treatment centre on the institute’s grounds every day for another week before returning to the US. He will later come back to Georgia for further tests and treatment with a second phage.

Despite the slightly over enthusiastic marketing, phages do have a serious role to play in medicine – perhaps even a revolutionary one.

Dr Ghada Zoubiane, an independent consultant on antimicrobial resistance, said that in the past 20 years or so Western scientists have renewed their interest in phages as infections that are resistant to the antibiotics we are so dependent on are becoming a greater threat.

“As a scientist I’m always hopeful that science is progressing and developing. And we should be open to all types of therapies, including phages, as long as they are safe, effective and available when needed,” she said.

“But phage therapy isn’t ready to be used at population level because they are a bit hit and miss. In order to have a phage working properly they have to be targeted at a specific bacteria in a specific patient,” she said.

“It can take two or three months to find the right phage and patients have to take the treatment in hospital.”

Martha Clokie, professor of microbiology at Leicester University, has been conducting research on phages for a number of years. They have a lot of potential “but there’s a dearth of fundamental research”.

She says phages could be a solution to the rising threat of AMR but adds: “They’re not an instant solution because there’s a lot of work to be done.”

Prof Clokie has explored the use of phages in the treatment of urinary tract infections but the research is still at an early stage.

She adds that phages are unlikely to replace antibiotics. “We don’t have to think of either phages or antibiotics. In most cases they are synergistic with antibiotics.”

Phage therapy was pioneered in the 1910s by the French-Canadian scientist Felix d’Herelle and came to Georgia via his research partner, George Eliava.

The treatment was used in the West but soon fell out of favour with the development of antibiotics, which can treat a vast range of infections whereas phages must be specifically adapted.

The shift was also partly political. In 1937, Eliava was killed in Stalin’s purges and in the decades that followed, the centre he founded was cut off from Western institutes by the Iron Curtain.

After the collapse of the Soviet Union in the 1990s, its funding disappeared and staff went unpaid for two years. “I don’t know how we survived it,” says Dr Chanishvili, who like other scientists took vials of the viruses home to store in fridges rather than leave them in laboratories without electricity.

The institute was saved by private grants, and then funding injections from the Georgian government and the European Union. In 2011, Eliava began cantering for foreign patients at a new treatment centre. So far some 2,000 people from abroad and 10,000 Georgians have undergone phage therapy there.

A course of therapy at Eliava costs 3,900 euros, though in some cases doctors can send phages abroad for 1,900 euros. If researchers cannot find the phage to attack a certain bacteria in their archive of almost 2,000 phages and phage mixtures, they can cultivate a new one, for an additional 1,400 euros.

The treatment centre claims a success rate of between 75 to 80 per cent, though there have as yet been no major clinical trials that prove the efficacy of phage. The therapy has not been approved for use in Europe or the US.

Dr Chanishvili tells of a Western researcher who, after a meeting with Soviet counterparts towards the end of World War II, described phage therapy as an “impressionistic science”.

“Now we are going from phage impressionism to phage realism,” says Dr Chanishvili, pointing to ongoing clinical trials and collaborations with research institutes in Belgium, Switzerland and the US, as well as separate work under way elsewhere.

At Eliava, researchers in horn-rimmed spectacles who have been at the institute for decades work alongside graduate students balancing petri dishes over open Bunsen burners. Jars of bacterial media – food for the phages’ hosts – are the source of the yeasty odour.

The centre is researching whether phages can be used to help people with asthma, as well as attack gut bacteria that have been linked to autism by some studies.

“[The widespread use of phages] requires repeated experiments, a more sanitised environment, results that are more statistically reliable. I think finally we will have the scientific and experimental approval that phages are efficient,” Dr Chanishvili adds.

Interest in the treatment has exploded not only because of the threat of antibiotic resistance that the World Health Organization has called one of the “biggest threats to global health, food security, and development today,” but also because a number of high profile cases outside Georgia where phages have proved successful.

Among them is the case of Thomas Patterson, a scientist from the US, who was struck down by a near lethal multidrug-resistant bacterial infection in his pancreas, spending months in a coma before finally being treated with phages. His story this year became the subject of a book called The Perfect Predator.

“I think it’s going to be more mainstream,” says Peter Mullany, professor of molecular microbiology at University College London. “The problems of antibiotic resistance will push it along a bit.”

But he says the relatively low-tech approach of the Eliava Institute until now means that many of the most interesting developments in phages are happening in labs in Western Europe.

“They seem to be good at what they do, and they have good techniques, but they haven’t got the sophisticated molecular biology techniques that they have in the West.”

Dr Chanishvili, meanwhile, cautions that phages should not be seen as a silver bullet for the antibiotic crisis, not least because of the time it takes to find the correct phage for treatment.

“When you have a severe case and you have to act immediately – when there’s not a minute to save you – you have to use antibiotics. Bacteriophages will never replace antibiotic therapy, I am absolutely sure of that.”

Source: https://www.telegraph.co.uk/global-health/science-and-disease/perfect-predator-inside-tbilisi-clinic-pioneering-radical-superbug/