“Without effective antibiotics, we’ll lose the advances made by modern medicine.”
Interview: Urs Hafner
Christoph Dehio from the University of Basel’s Biozentrum heads the National Center of Competence in Research (NCCR) AntiResist. The microbiologist argues for a paradigm shift in antibiotic research, the aim being to make the development of new drugs that overcome antibiotic resistance easier through a better understanding of the physiology of bacteria in humans.
UNI NOVA: Professor Dehio, when my head cold had still not cleared after three weeks, my family physician told me I would have to take an antibiotic. I thought now I’m going to put my body through shock therapy, but I’ll be fit again afterward. Is that right?
CHRISTOPH DEHIO: Colds are primarily caused by viruses. Antibiotics don’t help in these cases. You must have had a secondary infection with bacteria and the doctor prescribed the antibiotic to fight that. You probably got better quickly, but we don’t know if it was really necessary to use an antibiotic in this circumstance.
UNI NOVA: When is it really necessary?
DEHIO: For example, if you’re taken to hospital with sepsis. Your life is in danger and every minute counts. An antibiotic can save your life, provided that it’s actually effective. The steady increase in the appearance of resistant germs is making antibiotics more and more ineffective.
UNI NOVA: We live in one of the cleanest countries in the world with excellent high-tech medicine. Reading the description of the NCCR AntiResist that you head, creates the impression that we’re acutely threatened by all kinds of resistant germs that are spreading. Are you being a bit over dramatic?
DEHIO: Unfortunately not. However, compared with many other countries, Switzerland is still a small paradise. This doesn’t mean we don’t have any problems, but we have them still under control. However, antibiotic resistance does not stop at borders in our globalized world. Antibiotic-resistant germs are coming to us from Southern Europe and the Far East. Sooner or later, medical interventions that are largely safe today will become a risk. That includes routine operations of every kind, chemotherapies against cancer, organ transplants, even the treatment of bacterial pneumonia following an influenza infection. Older people will be especially impacted. Without effective antibiotics, the tiniest infected wound may become a deadly risk again.
UNI NOVA: How did we let it get to the stage where our healthcare system has such a gap in provision?
DEHIO: In 1928, Alexander Fleming discovered the antibiotic penicillin. After the end of the Second World War, this medication was considered a panacea for decades. Further antibiotics were discovered in quick succession, for example, streptomycin, with which tuberculosis could be combated effectively for the first time. That was the golden era of antibiotics research. Medicine cabinets were stuffed full of effective antibiotics. We had the feeling we had the problem of bacterial infection under control, but then resistance kicked in.
UNI NOVA: A drug suddenly stopped working?
DEHIO: Exactly. So we took another one out of the cabinet, but in time multidrug resistance arose. All of a sudden, certain germs were resistant to all available antibiotics. No therapy will work at all in this case.
UNI NOVA: How did resistance come about?
DEHIO: Through the widespread use of antibiotics, human beings have accelerated a natural evolutionary process to the point that it has become a major problem for medicine. Bacteria in the soil produce antibiotics to prevent other bacteria from growing. So that they themselves can grow, these antibiotic producers also express resistances. Those were always there, just not in the germs that are dangerous for us humans. However, bacteria exchange their genetic information. That is how resistant genes ended up in germs that cause disease in humans. So treatment with antibiotics actually breeds resistant pathogens. The more widely the active substance is used, the bigger the problem caused by the spread of these resistant pathogens.
UNI NOVA: If you now develop new antibiotics as part of your research, won’t you aggravate the problem and accelerate this vicious circle?
DEHIO: No, on the contrary. We urgently need new antibiotics based on new principles that can kill the existing multidrug-resistant germs. But that’s only ever a short-lived victory because resistance to any new active substance will arise sooner or later. We need new active substances from time to time to get one step ahead of the resistant germs in the race against bacterial evolution.
UNI NOVA: Why has the pharmaceutical industry not produced any new antibiotics recently?
DEHIO: First of all, the market has stopped working. There is no money in antibiotics any more. The main reason is that the known antibiotics are ridiculously cheap because the patent rights have expired. Compared with other medical therapies, treatment with antibiotics, which saves human lives rather than just prolonging them, is almost free. Secondly, the industry has made serious attempts to develop new antibiotics in recent decades but has not succeeded. This may in large part be due to the artificial laboratory conditions they work in. The cultivated bacteria do not resemble the physiological condition of the germs in our bodies. In the laboratory, bacteria grow at maximum speed, but in the body only slowly or not at all. Initially, work was successful under these conditions, but the method has reached its limits. Innovation has ground to a halt and we only ever find out what we already knew.
UNI NOVA: So research used to be very successful even though it worked under non-natural conditions?
DEHIO: Exactly. Most known antibiotics were discovered using these artificial conditions.
UNI NOVA: How do you intend to work?
DEHIO: In the lab, we try to simulate as realistically as possible the conditions that exist in infected tissues of our body. We still know astonishingly little about this. To close this gap in our knowledge, we first need material from patients, that is tissue samples from infected people.
UNI NOVA: Where do you get the samples from?
DEHIO: We use patient material resulting from routine examinations in the hospital, for example urine, bronchial secretions or infected tissue that is removed in orthopedic operations. With these samples, we determine the physiology of the bacteria in the human body. We then simulate the infection process on a miniature scale, for example, by using human mini-tissue on a biochip. In this way, we can search for new active substances.
UNI NOVA: Is this process also used elsewhere?
DEHIO: Only to some extent. Our unique characteristic is the ideal research environment in Basel. Here at the Biozentrum, we have excellent fundamental researchers who interact closely with infectious disease specialists at the University Hospital. We also collaborate with bioengineers at the Department of Biosystems Science and Engineering (D-BSSE) of the ETH Zurich in Basel, who work with mini-tissues. And, importantly, we have pharmaceutical companies here, such as Roche, as well as SMEs already active in antibiotics development.
UNI NOVA: And the intention is that the pharmaceutical industry will bring the new drugs to market.
DEHIO: Yes, and with our research we’ll create a new basis for the drug discovery and development process. The interface with industry is very important. We involved companies early in the development of our research concept.
UNI NOVA: The market is not working, you said. So what has to change?
DEHIO: One way is for health systems to spend more money on antibiotic treatments. This is already the case in the UK, and other countries, such as the US, are considering it. As soon as there is money to be made again, more companies and investors will get back into antibiotics development. Or you create new incentive systems: The company that develops a new antibiotic earns a market entry reward if it is successfully introduced to the market. This instrument takes account of the fact that a new antibiotic is first supplied only to a cabinet of reserved medications so that initial sales are low.
UNI NOVA: Why?
DEHIO: Because a new antibiotic that is deployed too widely will immediately give rise to resistance and would soon become ineffective. It has to be reserved for seriously sick patients who urgently need effective medication.
UNI NOVA: You’re a biologist. Do you wish you were also an economist?
DEHIO: No, the market mechanisms and regulatory measures are the preserve of business and politics. Our NCCR is concerned with scientific innovations at the early stage of antibiotics discovery and development.
UNI NOVA: What if the NCCR and the new antibiotics it is helping to develop did not exist? What would happen?
DEHIO: With the NCCR, we want to bring about a paradigm shift in antibiotics research, but luckily there are more research activities in this field, in both the academic and the industrial sector, that could contribute to innovation. If collectively we do not succeed in developing new antibiotics, humanity will increasingly suffer from the impacts of resistance. A study commissioned by the British government forecast that by 2050 more people would die from antibiotic resistance than from cancer in this scenario. You can imagine what that would mean for society and what costs would be incurred. The risk of dying from a routine medical intervention or a simple infection would suddenly be as great as in the 19th century. We have to prevent that.
National Center of Competence in Research "AntiResist"
The National Center of Competence in Research (NCCR) AntiResist is searching for new strategies to combat antibiotic-resistant germs. It undertakes interdisciplinary research into how the biochemical and biophysical processes of bacterial pathogens progress in infected patients. These processes are then simulated in tissue models intended to enable the development of new active substances and working principles. The main location of the NCCR is the Biozentrum of the University of Basel, with the involvement of the Department of Biomedicine of the university, University Hospital Basel, the Department of Biosystems Science and Engineering (D-BSSE) of the ETH Zurich in Basel and other academic institutions in Zurich and Lausanne. The Swiss National Science Foundation is supporting the NCCR in its initial funding phase with 17 million Swiss francs.
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