These aren’t spaceships – they’re phages landing on a bacteria to inject their DNA and then reproduce. | Photo: iStockphoto

“I’d contacted Exit because I couldn’t imagine continuing to live as I was”, says José-Maria Vidal in a film produced by the Swiss Academy of Sciences (SCNAT). He’d lain for months in a Genevan hospital, confined to his bed by a chronic lung infection. No antibiotics could help him.

Vidal’s story was taken up by the Swiss media back in 2023 because his fate took a surprising turn before he could embark on an assisted suicide. Thanks to the determination of his doctor, he was given access to phage therapy, which is not authorised in Switzerland. Viruses were introduced into his body to fight the bacteria in his lungs, and he felt noticeably better after just three days. Nine weeks later, he was back home.

Multi-resistant bacteria cause 3,500 deaths each day

Vidal’s illness was caused by what the World Health Organization (WHO) calls “one of the greatest threats to human health”, namely multidrug-resistant (MDR) bacteria that have become immune to the usual antibiotics.

For those affected, it means months in hospital, hooked up long-term to infusions with ever higher doses or mixtures of different antibiotics. This is a level of suffering that is well-nigh unimaginable to healthy people – and it generally doesn’t have Vidal’s happy end. In Switzerland, around one person every day dies from these infections. Worldwide, the death rate is almost 3,500 each day, and it’s rising.

Phages – or ‘bacteriophages’, as they are properly called – are regarded by many as a beacon of hope in the fight against MDR bacteria. Phages are viruses that exclusively infect bacteria. They introduce genetic material into these single-cell organisms, multiply inside them, and ultimately cause them to burst. They are harmless to humans because they only attack specific bugs. This means that they have no impact on beneficial microbes that exist in the body – in contrast to antibiotics, which also destroy the good flora inside us.

These microscopic ninjas can be found wherever bacteria live. Especially high concentrations of them exist in lakes, in the soil and in sewage treatment plants. Researchers can take phages directly from the environment, isolate them, test their efficacy in the lab, and prepare them for medical use. “Eureka!”, you might think. But this highly promising therapy is difficult to get in Switzerland.

Authorisation is complicated

Officially, phage therapy is deemed experimental in Switzerland. It may only be used in emergencies – in cases of life-threatening illnesses where there is no alternative, as with Vidal. The emphasis is on individual cases. “As soon as a doctor requests this therapy several times, things become difficult”, says Christian van Delden, an infectious diseases specialist at the Geneva University Hospitals (HUG). He’s the doctor who treated Vidal. “Repeated applications are no longer regarded as individual trials, but as research on human beings, which means the therapy has to be authorised by ethics and drug committees”.

If a therapy is to be afforded regular authorisation, the competent authority (Swissmedic) needs proof of efficacy in clinical trials, plus proof of production in accordance with international ‘Good Manufacturing Practices’ (GMP). Both these criteria have been obstacles until now. Studies have often failed because phages are very specific. This means that there are usually too few patients with the same bug for statistically reliable figures to emerge. And GMP drive up manufacturing costs. Thus far, the only laboratory in Switzerland that fulfils the necessary requirements is at the Lausanne University Hospital (CHUV).

“There are possible solutions, undoubtedly”, says Thomas Häusler, a science journalist who has been looking into phages for over 20 years. “So far, however, there’s been insufficient momentum in Switzerland for those solutions to be implemented”.

“In cases of rare diseases, for example, researchers are working on study designs that could deliver meaningful results, even with small numbers of patients. We could take inspiration from them”, says Häusler. A glance at worldwide databases shows that 50 clinical studies on phage therapy are currently listed, of which 24 are ongoing. But none of them is in Switzerland.

Steffi Lehmann is a pharmacologist at the Zurich University of Applied Sciences (ZHAW), and she points out the costs involved. “Clinical trials are expensive – if you haven’t got partners in industry, they’re just not possible”, she says. But businesses, for their part, find it difficult to calculate the economics of it all. Customised preparations mean high production costs and low profits. Some companies did start work on them, but have already had to give up.

Getting treatment means travelling to Georgia

Lehmann instead sees potential in standardised approaches: “For example, pharmacies could produce cocktails of several phages to fight common problem bugs. These would be somewhat less efficient, but they’d be quick, cheap, and broadly deployable”. This is the case in Georgia, for example, where phage therapy has a long tradition and is approved as a matter of course. Standard cocktails are regularly adapted to current problem bacteria. If no effective mix is found, then therapies are appropriately customised. Although the experts whom we contacted emphasise that the quality standards in Georgia don’t meet current European requirements, the easy access to phage therapy there attracts hundreds of patients from all over the world every year – including from Switzerland.

Phage banks exist

Researchers at ZHAW are also actively researching into phage cocktails. One hurdle at present is their shelf life. Lehmann and her colleagues are also working on strategies with individual molecules that have been isolated from phages and can target specific structures in bacterial cells and destroy them. This is an approach that could be suitable for industrial production.

In parallel with this, ETH Zurich has been investigating new approaches, genetically modifying phages to make them effective against a broader spectrum of bacteria. According to Enea Maffei, a postdoctoral researcher in the ETH’s Department of Health Sciences and Technology, they have already been preparing a clinical study on treating chronic urinary tract infections with modified phages.

Regulations should be relaxed

For customised therapies, researchers are relying on international phage banks. “They catalogue and preserve different phage strains there. If a patient falls ill with MDR bacteria, it’s possible to find out pretty quickly whether a suitable phage already exists”, says Thilo Köhler, a microbiologist at HUG. He was the person who found Vidal’s life-saving phage in a US collection.

Lars Fieseler works at ZHAW and he’s the President of the association phageSuisse. He’s calling for more cooperation, both nationally and internationally. He also emphasises that other countries are more pragmatic than Switzerland when it comes to giving access without regular authorisation: “Belgium and Portugal allow customised phages on medical prescription; they are produced in a central laboratory according to clear quality criteria. These criteria are less strict than GMP, but they nevertheless ensure that preparations are pure and safe”.

Lehmann also adds: “If standards are defined and adhered to, then something like that would also be conceivable in Switzerland”. GMP were developed to cope with conventional chemical drugs, and Lehmann feels that they are too restrictive when it comes to producing living organisms such as phages. The researchers are all convinced that the rules need to be adapted.

In Geneva, meanwhile, the focus is on setting up a joint phage centre for Western Switzerland. The goal is to use the collections in the two university hospitals (Geneva and Lausanne) to pool the production of phages in the GMP lab in Lausanne. Discussions are currently underway, but there’s no clarity as yet about the logistics and costs.

Pressure needed from society

Before Swissmedic will agree to simplify its guidelines, pressure is going to be needed from researchers, clinics, politicians – and from civil society. Häusler believes that this topic isn’t sufficiently visible to the Swiss public. This is why, together with other researchers, he’s organising a ‘Phage Therapy Forum’ that aims to bring together experts, representatives of the authorities and those who are actually affected, in hopes of developing real solutions and stimulating debate.

According to van Delden in Geneva, there’s also a lack of political support. “At present, there’s no national strategy for alternatives to antibiotics. The drug-resistance crisis is being overly monitored instead of actively combated”. For him, the question is this: “What priorities do we want to set as a society? Our healthcare system is already in crisis – shouldn’t we rather be pushing ahead with existing, effective therapies that can provide swift assistance to people who are suffering?”