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Molecules adapted to the environment

Scientists who deal with the evolution of chemicals need to take responsibility for their activities in terms of hormone residues in rivers, cytostatic drugs in lakes, and painkillers in groundwater. Up until now, the majority of pharmaceutical companies have only used molecular design methods to improve the therapeutic effect of pharmaceutically active substances. However, a very small handful of people are convinced that the same techniques could also help to make drugs more environmentally friendly. The vast majority of people do not realise the huge economic advantages such techniques would bring about. For many years, Prof. Dr. Klaus Kümmerer from the University Medical Centre Freiburg has been investigating how the chemical structures of drugs and other chemicals can be modified in order to enable them to be degraded more quickly in rivers and soils. “There has to be a new way of thinking,” said Kümmerer going on to add “the appropriate methods are already in place.”

Seepage of toxic chemicals from an industrial plant © www.wikipedia.de / Andrew Dunn, 1992

Water is the medium in which our cells swim. It is also a staple food. By polluting water, we are sawing off the branch we are sitting on. Female hormones in birth control pills, pain relievers, anti-cancer drugs - all these compounds enter the cycle, either through our excretions or through the improper disposal of unused drugs by flushing them down toilets. This is also the case with other chemicals, compounds contained in washing agents or textile additives and drugs used for animal treatment. What kind of effect do these compounds have on the environment? Are organ damage to fish or the death of plankton the only problems? Or is the inexplicable increase in the incidence of cancer over the last few years evidence of the gradual effects compounds of this kind have on humans? "Comprehensive investigations are not yet available, so we do not know," said Prof. Dr. Klaus Kümmerer from the Institute of Environmental Medicine and Hospital Hygiene at the University Medical Centre Freiburg. "However, one thing is clear: The pollution of lakes and rivers is increasing and we are constantly exposed to the residues of drugs and other chemicals. So, shouldn't we do something before it is too late?"

Optimisation using virtual building blocks

The action needed is relatively simple. We start at the beginning of the causal chain, i.e. with drugs and chemicals. Modern pharmaceutical companies looking for suitable drugs for the treatment of cancer or epilepsy are increasingly tending to use a method known as rational design. Companies no longer produce hundreds of thousands of related molecules to put in cell cultures and use in animal experiments in order to discover the molecule with the best effect. This is now done in silico with computers. Scientists assemble molecules from certain lead structures, in the same way as pieces of Lego are assembled. The computers are fed data on the probable effect of certain chemical groups and come up with models that predict the potential effect of certain assembled molecules. Such models are excellent tools for predicting the therapeutic effect of a potential drug without needing to synthesise the sought-after substance. In addition, in silico modelling is relatively quick and cheap. Which chemical group needs to be added to a drug in order to increase its efficiency? As it is not necessary to do nearly as many experiments, savings can be made in material and labour time. “Pharmaceutical companies could also use the same method to make drugs more environmentally friendly,” said Kümmerer.

This would have no effect at all on the therapeutic affect of the drugs, contrary to what opponents of such an approach often claim. Any chemical substance, be it a drug or a pesticide, has a life cycle. It is produced, interacts with target structures and subsequently degrades. It is never present in an isolated form; it always interacts with its chemical environment. A drug only exerts its effect because it is targeted at the chemical environment in the human organism. Certain chemical groups that form part of its structure interact with chemical groups of enzymes or lipids in the human body. However, when the drug is excreted through urine and enters rivers or lakes, it is exposed to completely different conditions – temperatures, pH and chemical composition of rivers and lakes can be completely different from those in the human body. Eventually, the molecule is taken up by microorganisms that have a completely different interior environment. Other molecule domains might now interact with the enzymes of the bacteria, which leads to the degradation of the drug and eventually renders it harmless.

Sustainable pharmacy and chemistry are possible

“Applying molecular design to improve the degradability of drugs, does not necessarily change the effect of a drug or the desired properties of other chemicals,” said Kümmerer going on to add “the effect and degradability is usually governed by different domains of a molecule.” For example, Kümmerer and his team are working with the German Cancer Research Center (DKFZ) in Heidelberg on the optimisation of an anti-cancer drug, in a project funded by the German Federal Environment Agency (DBU). The DKFZ researchers used computers to manipulate the structure of the compound in order to make it more effective in inhibiting the growth of cancer cells. “While the computer came up with suggestions, we were closely following the process and we also thought about how other areas of the molecule could be manipulated,” said Kümmerer. “Then in our laboratory we tested how well the substance could be degraded by light or bacteria.” The researchers were thus able to increase the degradation rate threefold.

Chemical formula of ifosfamide. © Jürgen Martens

Kümmerer and his colleagues know of many positive examples of drugs that have a strong therapeutic effect at the same time as being excellently degradable in the environment. This is something that has happened accidentally during the drug development process. One such example is the anti-cancer drug glufosfamide, which was produced by modifying the anti-cancer substance ifosfamide. The new drug has much better pharmacological properties than the original substance and is also better tolerated by patients. Kümmerer therefore calls on scientists and other stakeholders to adopt a new way of thinking. Sustainable pharmacy and chemistry are possible. In addition, this does not cost any more; quite the contrary in fact. "A growing number of patients and doctors ask about the environmental compatibility of drugs," said Kümmerer. "As the ecological awareness of customers is increasing, the market for green drugs is also increasing." And it goes without saying that if drugs are environmentally friendly, it would no longer be necessary to fish them out of the groundwater. Methods used in sewage plants, for example oxidation involving light or chemicals, are relatively expensive, lead to the discharge of CO2 into the atmosphere and are not always efficient. These methods also often lead to conversion products that might turn out to be even more toxic than the original drugs or chemicals.

In one of his papers, Kümmerer has formulated a strategy to encourage a gradual process of rethinking. In the paper, he suggests that politicians encourage new ways of thinking, for example through awards and funding programmes. This new way of thinking needs to be part of university teaching to ensure that chemists of the future have a different view of the job they do: they will not just be the synthesisers of a drug or washing agent additives; they need to see themselves as designers who are doing something that is important for society as a whole and for the environment. Those who "play" evolution must also be aware of their responsibility. And in this particular case, such awareness would also prove to be lucrative.

Further information:

Prof. Dr. Klaus Kümmerer
Institute of Environmental Medicine and Hospital Hygiene
University Medical Centre Freiburg
Tel.: +49-(0)761/270-8235,-8236
Fax: +49-(0)761/270-8213
E-mail: klaus.kuemmerer(at)uniklinik-freiburg.de

Website address: https://www.biooekonomie-bw.de/en/articles/news/molecules-adapted-to-the-environment