Researchers recently sounded the alarm in a new report: antibiotic resistance has been growing by five to fifteen percent in recent years. Already, 35,000 people die each year, and at the current rate of growth, 10 million people could die each year by 2050 because antibiotics no longer work.
When Velema was a student twenty years ago, he already learned about antibiotic resistance, and the problem has only grown since then. It is not that scientists have been sitting idle; in recent decades, they have been working with varying degrees of success on various solutions, including the so-called antisense technique.
To explain how this technique works, Velema first explains a little about how we humans are put together. ‘Every living creature has a genetic code, DNA. In addition, every human being has RNA. This molecule is very similar to DNA, with the difference that RNA “overwrites” the genetic information from the DNA and then “translates” it. RNA also ensures the production of proteins. These proteins, in turn, are crucial for the structure of cells and tissues and for creating reactions and connections between cells.’
But if RNA feeds proteins to the cells that make you sick, you can safely say that it is like sand in the engine. And that is where the antisense technique comes in handy. ‘Where traditional medicines penetrate a cell to (temporarily) shut down proteins, antisense allows you to take a step back and very specifically switch off pieces of RNA to prevent the production of disease-causing proteins that attack cells.’
Trojan horse
Problem solved, you might say, but nothing could be further from the truth. ‘The antisense molecules are very large, which means they cannot pass through the cell membrane of the bacterium,’ says Velema, who, together with colleagues, has found a way to outsmart bacteria. ‘Bacteria also need nutrients. That's why we are developing molecules to which we attach a metabolite. This is a substance that the bacteria need. Like a Trojan horse, not only does the necessary nutrient enter the cell, but also the molecule that disables the bacteria.’
Bacteria come in all shapes and sizes, so not every molecule with a metabolite successfully reaches its destination. ‘Recently, we have achieved successful results with E. coli bacteria, which cause urinary tract infections, among other things. Now that this is working, we have started developing molecules that can penetrate a group of bacteria summarised under the acronym ESKAPE.’
An unwinnable race
Velema admits that he and his colleagues are actually participating in an unwinnable race. ‘Disease-causing bacteria will always be around, because they have an enormous evolutionary advantage. Roughly every twenty minutes, bacteria multiply, creating new bacteria that are all genetically slightly different from each other. By chance, there only needs to be one bacterium among them that is resistant to antibiotics, and that bacterium will then be resistant.’ Scientists who develop antibiotics, sometimes spending years doing so, are therefore primarily focused on staying as close as possible to disease-causing bacteria and developing as many different types of antibiotics as possible. This reduces the chance that they will be resistant to everything.
Although new, more virulent bacteria will always continue to emerge, Velema believes that the current resistance problem can be tackled within a relatively short period of time. ‘Antibiotics must, of course, be developed and financed, and we are currently seeing promising research too often getting stuck in the discovery phase. If enough parties take this problem seriously, we can solve it within a few years. I am convinced of that.’
Would you like to contribute to research into new antibiotics? Then donate to the Radboud Fund. This will support scientists such as Willem Velema and enable them to continue their research.