It is not only antibiotics but also certain viruses - known as bacteriophages - that can kill off pathogenic bacteria. However, Switzerland lacks the legal framework for the use of these viruses in therapy. What would need to change so that more patients can benefit from this form of treatment? Researcher Alexander Harms explains.
Bacteriophages - or phages for short - are viruses that can infect and kill off bacteria. They are naturally present in their billions in our environment, as well as with bacteria in our intestines and on our skin. Physicians have been using phages to combat pathogenic bacteria for over 100 years. This form of treatment was - and continues to be - particularly widespread in Georgia. Following the discovery of antibiotics, phage therapy largely vanished in the Western world. Around ten years ago, it was rediscovered as an alternative - partly because many pathogens have now developed resistance to antibiotics and the medicines are no longer effective.
ETH News: Alexander Harms, we find ourselves in an antibiotic resistance crisis. Are phages the miracle cure that will free us from this predicament?
Alexander Harms: It's certainly true that there's a lot of hype around phages right now - and it's no wonder given the increasing levels of antibiotic resistance. We need new ways to treat bacterial infections. As natural adversaries of bacteria, phages have great potential in this regard. Having developed in parallel to bacteria over millions of years, they know their tricks and are able to fight them. The advantage of phages is that they multiply faster than bacteria. If bacteria develop resistance to phages, the phages can quickly adapt to - and overcome - this resistance. Still, I wouldn't describe bacteriophages as a miracle cure.
Why not?
Phages are less suited to acute infections such as blood poisoning and more suited to chronic infections. This is for time reasons - although phages act very specifically against certain bacterial strains, finding the right phages for treatment can be a complex process. Physicians sometimes have to enquire at various universities and hospitals around the world to see whether they have a suitable candidate in their phage collection. Tests are also needed on every occasion. This takes at least two or three days - and generally longer.
Is the situation less urgent in the case of chronic infections?
Yes, these are infections that have existed for a longer period of time and can no longer be treated - or cannot be treated completely - using antibiotics, e.g. due to antibiotic resistance. Here, I see phages as a sensible complement to antibiotics. Typical applications of phages include infections of the lungs or urinary tract, infections occurring after bone fractures, or those related to chronic wounds.
About
Alexander Harms is Professor of Molecular Phage Biology at ETH Zurich. His group researches the basic principles of phage therapy, asking questions like how do phages behave in the body and how can they be used effectively?
How often is phage therapy used today?
Over the last ten years, there have been documented applications in a few hundred patients worldwide. In Switzerland, there have so far been less than ten treatments at different university hospitals. Despite a lack of clinical trials meeting modern standards, we can say from past experience that about three quarters of treatments are successful. Although the bacterial pathogens aren't always killed off entirely, the patient's condition improves significantly. Sometimes, phage therapy genuinely saves lives when there is no longer any other hope.
Why is phage therapy not used more often?
On the one hand, because it's a complex process as I mentioned earlier. But there's probably an even more important reason, namely that most countries lack a clear legal framework for the use of phages in medicine. Phages are a living medicine - viruses that multiply in the human body. That's a big difference between them and an antibiotic in tablet form. Accordingly, common pharmaceutical regulations aren't readily applicable to phages. Because phage therapy is a complex process and lacks a legal framework, the big pharmaceutical companies have not been interested in commercial applications to date.
Bacteriophages
Bacteriophages (red) are viruses that exclusively infect bacteria (purple). They attach themselves to bacteria, inject their genetic material into the bacteria and multiply inside them.
What is the legal situation in Switzerland?
In Switzerland, as in many other European countries, phages are not authorised as medicines. Patients therefore have almost no access to this form of therapy. Phages can only be used within the framework of experimental treatment attempts, which requires that other forms of treatment have already been exhausted. Moreover, phage therapy is only possible if there is a threat of serious consequences - such as death or amputation - without treatment.
Are there any countries that have a suitable legal framework?
In Belgium, doctors can have phage preparations made up directly at pharmacies in a process known as magistral preparation - including in the laboratories of hospital pharmacies. For this, the phage in question must be listed in the directory of medicines, which is already the case for some phages in Belgium. This makes it easier to gain access to phage therapy. In the European Union, individual countries can now adopt this Belgian model. I assume that phage therapy will therefore be used more often. It's already the case that some patients from Switzerland travel abroad for treatment.
What ought to change in Switzerland in your view?
First of all, we now need a public debate on how seriously ill people should gain access to phage therapy. In a project supported by the Swiss National Science Foundation, we're working to create a external page platform for dialogue between experts and the general public. As part of this, we also want to highlight the various options for statutory regulation. The Belgian model is one such option. Another is the approach used in Australia, where individual treatments are allowed as part of a large, joint clinical trial. In Switzerland, there needs to be a clear political will to achieve a suitable legal framework for the special characteristics of phage therapy and our country. At the same time, the question of financing must be resolved.
How much does phage therapy cost?
It's hard to put a figure on it, particularly as hospitals and patients have so far had to bear the costs themselves. One thing is clear: at present, phage therapy is still more expensive than treatment with antibiotics, as the process is more complex and less standardised. At the same time, successful phage therapy can help to avoid the considerable cost of many years of unsuccessful standard treatments. Moreover, the cost of phage therapy is sure to come down once we have more experience and there has been more research into phages.
What role will phage therapy play in the future?
I'm sure that greater use will be made of phage therapy in the future. There will be increasing pressure from patients who don't want to travel abroad for this type of treatment. I don't think there'll be a huge number of treatments in Switzerland, but the option should exist. Not every hospital needs offer phage therapy. It makes sense to set up centres specialising in specific applications at university hospitals and for these centres to implement treatment in collaboration with researchers from microbiology and other disciplines. Advances in science will make treatment even more effective. In the future, artificial intelligence could help to identify the appropriate phage type more quickly. Moreover, research is under way into the genetic modification of phages so that they produce additional toxins against bacteria, for example, or so that they can switch off resistance genes in the bacterium. In this way, phage therapy could become even more effective - and help even more patients.
