Emerging Pollutants 3: Biological CECs and Antibiotic Resistance

Chemicals dominate modern life. They're in the air we breathe, the food we eat, the products we use daily, and the rivers and soils that sustain us. Many are harmless or even helpful, but some present risks. For regulators, it's a daunting task to figure out which of the millions of compounds that swirl around us are potentially harmful. In this series of articles, 3E will help you navigate emergent pollutants to examine which substances are likely to attract regulatory attention in the future.

We've known for years that certain pharmaceutical products and their active molecules can linger in the environment and disrupt ecosystems. It was back in the 1980s that scientists started to notice that rising levels of estrogen in rivers were causing male fish to produce female proteins and even develop eggs in their testes.

But over the past couple of decades, there has been a growing recognition that there is a much broader and increasing number of biological and biochemical substances beyond just estrogen that are accumulating in the environment and could pose a risk to public or environmental health. These biological contaminants of emerging concern (CECs) often find their way into the environment as byproducts of agricultural practices, pharmaceutical manufacturing, or the actions of the wider healthcare sector.

Amy Pruden is an environmental scientist at Virginia Tech who leads a team of researchers that uses DNA sequencing and bioinformatics tools to track biological CECs in the environment. Pruden was one of the first scientists to discuss the concept of biological CECs in a 2006 research article. “That paper put out the idea that antibiotic resistance genes [ARGs] are emerging contaminants,” she told 3E. “I wanted people to know that biological contaminants can be emerging too.” Pruden says that biological CECs are becoming more prevalent, and regulators around the world are noticing and starting to act.

This is the third article in 3E's CEC series, and it looks specifically at biological CECs: It discusses the efforts of scientists to track biological CECs, the evidence behind their potential human health risks, and the efforts of regulators and public health bodies to stay on top the issue.

Fuelling Health Concerns

Biological CECs are distinct from other types of CECs, such as classical chemical molecules or microplastics, because they originate from substances such as medicines that are specifically designed to interact with human or animal biology. That means their potential to directly influence our well-being is of particular concern.

Studies have shown that biological CECs come from a variety of sources, including contraceptives, hormones used in animal husbandry, industrial byproducts, and other pharmaceutical products.

Drugs and pharmaceutical compounds are excreted by humans, and if they are not sufficiently degraded in sewage treatment centers, they will find their way into our waterways, soil, and drinking water. The route for agricultural antibiotics is shorter; the contents of crop sprays or animal waste are simply washed away by rainfall, and this runoff invariably ends up in rivers.

Most biological CEC research has focused on estrogen, building on the fish studies from the 1980s. But in a 2023 paper, scientists at Khalifa University argued that researchers and regulators need to pay more attention to other steroid hormones, notably progesterone and androgen. But expanding the focus to those three hormones would still only be scratching the surface of biological CECs, according to analyses carried out by Brazil, Canada, European Union (EU) countries, and the United States, which have identified more than 80 different pharmaceutical substances in water. These range from ARGs to proteins and even viral fragments.

Herein lies the challenge. For each biological CEC to get the attention it deserves, researchers must engage in a lot of grunt work - taking samples, analyzing them, creating standards so they can compare their results with other labs, and identifying sources.

Fortunately, it's a clarion call that the academic community seems to be responding to, says Pruden. “Scientists and engineers are really trying to help address the issue by identifying where these contaminants are coming from,” she says. “We're starting to see a lot of studies taking water samples from both upstream and downstream of wastewater treatment plants and other suspected sources.”

It’s also something that artificial intelligence (AI) can help with. As 3E has previously reported, AI is already being used to speed up sample taking and substance tracing efforts. New technology, coupled with willpower from the scientific community, means that regulators are starting to be supplied with the kind of data that helps them to act.

Biological CECs Case Study: Antibiotic Resistance Genes

Pruden says that human activity and industry are elevating ARGs in the environment, which logically increases the chances for bacteria to acquire resistance. That in turn increases the probability of people developing antibiotic-resistant infections.

Antibiotic use in agriculture has become the major driver, she says. The increase in use is one factor, but the way in which farmers use antibiotics also plays a significant part. Antibiotics aren't necessarily administered precisely to the individual plants or animals that need them. “Sometimes we spray them on whole orchards, so there's this mass output of antimicrobials and that's concerning,” says Pruden.

This was echoed by Ludovic Bernaudat, who leads the Knowledge and Risk Unit at the United Nations (UN) Environment Programme. He told 3E that the problem is especially acute in aquaculture. “In fish farming, the antibiotics are directly put into the water,” he says.

In addition to agriculture, pharmaceutical manufacturing and hospitals are also a source of ARGs. Essentially, anywhere that is making, storing, or using antibiotics in large quantities presents a risk.

Bernaudat says the leaching of ARGs into the environment is conspiring to worsen the global antimicrobial resistance (AMR) crisis. “Looking at biological CECs, AMR is of top importance,” he says. That's because people are already experiencing adverse medical outcomes because of antimicrobial resistance.

According to the Global Research on Antimicrobial Resistance Project at the University of Oxford, antimicrobial resistant infections have already killed more than 36 million people since 1990, and the death rate is set to climb further still. The United Nations has estimated that drug-resistant infections could kill as many as 10 million people worldwide each year if action is not taken (that's more than the number of people who currently die from cancer). So, the pressure is on. “More people will be affected by this issue very soon,” warns Bernaudat.

Action to reduce ARG contamination could take many forms. It could be the restriction and reduction of certain medications; it could be a change in the way those products are administered; or it could be a change in agricultural practice. Leon Barron, who leads the Emerging Chemical Contaminants Team at Imperial College London, told 3E that wastewater treatment processes and protocols may also need to be revisited.

“Most of the wastewater that is treated in the UK has a byproduct called sludge,” he says. “It's a solid material, and it's being used in agricultural land [as a fertilizer]. Now, if the wastewater treatment works and does what it should, and removes all these CECs from the water, then they're in the sludge. That means the CECs are just going round and round in the system.”

But ultimately, it will come down to a question of regulation, says Pruden, and the European Union is probably the furthest ahead on this score. The revised Urban Wastewater Treatment Directive (EU) 2024/3019 explicitly includes AMR monitoring in urban wastewater. The directive also tasks the European Commission with adopting a harmonized methodology in terms of methods, metrics, and frequency of sampling when it comes to AMR monitoring.

“If history is instructive, the EU tends to be more proactive and then the U.S. cautiously follows,” says Pruden.

Monitoring is only part of the picture, however, and it doesn't answer the question of who should be responsible for reducing and limiting ARG pollution. Should it be drugmakers? The agricultural industry? Sewage plants? Hospitals?

Pruden says that a “value chain approach,” in which the responsibility is divided between these various groups, would make the most sense because ARGs are such a complex issue. “It's going to have to be something that is adaptive to the unique aspects of antibiotic resistance,” she says.

For more information, read parts 1 and 2 of this series:

• Emerging Pollutants 1: Substances of First Step Toward Regulation
• Emerging Pollutants 2: Chemical CECs and the Regulation Gap