Pharmaceutical Release into the Environment During a Pandemic
Earlier this month, PaCCS Communications Officer Kate McNeil sat down with Dr Andrew Singer, Senior Scientist at the UK Centre for Ecology and Hydrology, to discuss his work on Pharmaceutical Release into the Environment during Pandemics and Regional Epidemics. This work was funded by NERC and was designated as falling under the Global Uncertainties umbrella.
The following conversation has been edited and condensed for clarity and concision.
Kate McNeil: Thanks for taking the time to chat today. To get started, would you mind telling me a bit about your background and the circumstances that led to your work studying the release of pharmaceuticals into the environment during pandemics?
Dr Andrew Singer: My background is in environmental pollution. I’m interested in understanding how environmental microbes interact with pollution and how human pathogens interact in the environment. I have researched topics ranging from bioremediation to the environmental drivers of antibiotic resistance. At the time I started work on Pharmaceutical Release into the Environment during Pandemics and Regional Epidemics, in the early 2000s, there was an H5N1 influenza outbreak ongoing in Southeast Asia. It was incredibly virulent, and there was a lot of concern about whether it would turn into a pandemic. Ideas about possible treatments and medications started to get thrown about, and in the following years many countries expressed an interest in stockpiling Tamiflu.
The threat of the H5N1 pandemic and the apparent medical response, e.g., Tamiflu stockpiling, got me to thinking about the wider implications of such a response. It became clear to me that Tamiflu was going to be a novel environmental pollutant – used in a way that we’ve never used any other drug before, and likely to end up in our waterways in concentrations that potentially far exceeded most other pharmaceutical pollutants. Normally, if we introduce a new medication, it builds its way into a population over time, but Tamiflu didn’t have that luxury – we were going to need massive amounts of it in the first and second waves of influenza response. So, I began to model the environmental concentrations of Tamiflu given our assumptions of usage and persistence in wastewater and the environment. The resulting publication of these models predated the 2009 influenza pandemic. The insights provided by this research facilitated my inclusion on the Strategic Pandemic Influenza Advisory Group – a similar group is now producing models to inform the government on the COVID-19 emergency response.
As we all now know, there didn’t end up being an H5N1 pandemic. The 2009 influenza pandemic was caused by H1N1, a virus no one was watching. Thankfully H1N1 infection was much less severe than H5N1. Those responding to coronavirus now are benefiting from the models and knowledge which was generated for earlier responses to pandemic influenza.
What did you learn over the course of this project?
We learned that there would be some downstream risks from knowing that there was going to be all this Tamiflu in wastewater treatment plans and sewage-impated rivers. One of those is that the virus and Tamiflu will both be entering the environment every time a flu patient flushed the toilet. When these enter the environment, two things can happen—the virus can infect wildfowl, which happen to love the warm nutrient-rich effluent from sewage and Tamiflu can drive the resistance of Tamiflu-resistant influenza in the exposed wildfowl in the sewage-impacted rivers. The risk of increasing the prevalence of Tamiflu-resistance in wildfowl leads to a future risk to humans from zoonotic disease transmission—reinfection of humans with drug-resistant avian influenza. In this way, the cycle of a pandemic continues, but gets worse with each iteration.
It became apparent that Tamiflu also reduced the ability of some bacteria to form biofilms. As sewage treatment facilities use bacterial biofims to process waste, we realized that sewage works might cease to operate appropriately because of the high concentration of Tamiflu. That in turn has downstream implications for both human health and infrastructure. As soon as you have failing sewage works, you have untreated sewage going into your rivers.
So, my project explored those downstream risks and the possibility of mitigation. We got together the researchers working in this area in an international meeting and came up with a consensus document indicating what we knew about the impact of Tamiflu on the environment, and what we still needed more information on. We needed to know how readily Tamiflu persists in the environment, and we learned that it could become a chronic pollutant because if people are continually taking the medication, even as the medication is degrading, more is being released into the water system. It’s replacing at a rate that is faster than its decay rate. We also didn’t know the extent to which the theoretical risk of generating Tamiflu resistance in wildfowl was possible. These studies proceeded in the years following the pandemic, confirming that Tamiflu is environmentally persistant and capable of driving Tamiflu-resistance in wildfowl at concentrations in the river that are achievable during a pandemic.
Much of your work at this time focused on Tamiflu and influenza. Are there things we can learn from your work which are relevant to other types of pharmaceuticals or other causes of pandemics?
While our initial work focused exclusively on Tamiflu, in the context of pandemics you also need to consider the wider medical interventions during a pandemic. Just as has been happening during coronavirus today, primary viral infections can be accompanied by secondary infections including bacterial pneumonia. The increase in antibiotic usage in the context of pandemics is something we need to be cognisant of in terms of antibiotic resistance, and in terms of functioning sewage treatment facilities and the ever-present risk of driving antimicrobial resistance in humans, sewage and the environment.
During the inter-pandemic period, society uses a lot of antibiotics. We predicted that the bacteria within sewage treatment plants are just about coping with the current load of antibiotics—just below their tipping point – the point at which the operation of the sewage treatment plant will be compromised. The additional surge of antibiotics used during pandemics was predicted to place us at risk of losing the proper function of a significant fraction of UK sewage works.
Based on the lessons you learned during this project and through your work on the H1N1 response, what do you think policymakers need to be thinking about now?
We have the tendency to learn environmental lessons very slowly. When you have a medical crisis, everyone listens to doctors and the last thing you want to do is limit what the medical options are based on the advice of an environmental scientist. I think that there’s better awareness among the research community now that there will be implications to pharmaceutical and medical responses than there was when the influenza pandemic happened 12 years ago. We need to keep being aware that the chemicals we use have consequences, and we need to maintain institutional memory of the fact that there could be an environmental impact to the medical decisions we make and the pharmaceuticals we use and stockpile.
Dame Sally Davies oversaw much of the early work building up to the pandemic influenza response in 2009, and I think she’s perhaps uniquely aware of the extent of the environmental component of medical responses because of her work on antimicrobial resistance. I also think that policymakers and advisory groups need to keep in mind that there’s value in having disciplinary diversity in the rooms where evidence is being reviewed and decisions are being made. Participating in the Scientific Pandemic Influenza Advisory Group during the H1N1 pandemic helped me to be better informed about the knowledge gaps that can help to inform policy. These rare insights into policy for environmental scientists, such as myself, can benefit the discipline as a whole—creating a policy-relevant nucleating point that has a lasting effect on the trajectory of the discipline.
How does your work in environmental science fit into the notion of ‘One Health’?
When I first started work in this field, the focus was on human health, with a small amount of attention also paid to animal health. The Water, Sanitation and Health (WASH) research community were probably the first One Health champions. Environmental scientists and environmental microbiologists, like myself, have only relatively recently been brought into the wider One Health umbrella. As such, there is a lot of work to be done by us to demonstrate relevance, but at the same time, those squarely within the human health part of the One Health umbrella need to open their minds to the possibility that the world is interconnected in important ways with the environment, not humans, at the centre. The more research we do, the more we realize that the environment matters, and we ignore it at our peril.