Production of active pharmaceutical ingredients – compounds sold in bulk to be used in making pills and capsules – has been booming for years in India and China. Now, thanks to even more intense pressure in the global North to hold down prescription drug prices, the better part of the world’s production of both bulk and finished drugs is shifting to Asia.
That is ominous news for people and ecosystems in the vicinity of the industrial facilities where the increased production will occur. And if, as predicted, some of those unlucky communities become incubators for antibiotic-resistant bacteria, their problems will become everyone’s problem.
Take a water sample just about anywhere in the world these days, and if you have it tested, it will probably contain drugs of some sort. It has long been recognised that pharmaceutical compounds, usually in low concentrations, find their way into streams, lakes, and groundwater by way of hospital wastes, household sewage, and livestock facilities. But only in recent years, confronted by an relentless stream of often shocking research results, have we become fully aware of the threat from drug-manufacturing plants.
“The researchers noted that the antibiotic ciprofloxacin was flowing from the plant’s outlet pipe at the rate of 45 kilogrammes per day – about 45,000 typical daily doses.“
The valley of Patancheru in south-central India lies downstream from scores of pharmaceutical factories. Its waters have suffered heavy pollution by all sorts of industrial effluents for decades, with dire consequences for village residents and farmers. But neither Patancheru nor the scientific world was prepared for a report that came out of the valley in 2007.
That year, a team of researchers led by Joakim Larsson of the University of Gothenburg in Sweden published their chemical analysis of effluents from a water treatment plant that was receiving wastes from Patancheru’s industrial estates. They tested water flowing out of the plant (into a small local stream, after being treated) for 11 drugs – antibiotics, as well as remedies for high blood pressure, ulcers, and allergies. The result, they wrote, was that “to the best of our knowledge, the concentrations of these 11 drugs were all above the previously highest values reported in any sewage effluent”.
The researchers noted that the antibiotic ciprofloxacin was flowing from the plant’s outlet pipe at the rate of 45 kilogrammes per day – about 45,000 typical daily doses. As we will see, that was almost certainly having far-reaching ecological consequences. But people living downstream might have seen more immediate effects. Fluoroquinolones, the class of antibiotics to which Cipro and some of the other drugs being made in Patancheru belong, are known in some cases to have frightening physical and mental side effects, even after a single dose.
In 2009, the team returned to find drugs at high concentrations in village wells downstream from the plant. And in one nearby lake, concentrations of ciprofloxacin and ceterizine (an antihistamine) exceeded the concentrations of those drugs that would be found in the bloodstream of a patient who is being treated with them!
By 2010, all effluents from the Patancheru water plant were being diverted through a pipeline to a larger treatment plant 18 kilometres away. That has reduced the valley’s pollution problems simply by sending the effluents, still drug-laced but more dilute, into a different river.
A dosed planet
Patancheru is just one example of what turns out to be a worldwide threat:
In China’s Hebei Province, a water treatment plant serving drug-manufacturing facilities was found to be discharging 275kg of the antibiotic oxytetracycline per day into the Xiao River. The concentration of antibiotic in the waste water was 20 times what it would be in the bloodstream of a person being treated with the drug.
- Waste water flowing into rivers from four drug production facilities in Taiwan was shown to contain high levels of a wide range of drugs: human and veterinary antibiotics, estrogen, painkillers, and a cholesterol drug.
- A Korean study comparing concentrations of a wide range of pharmaceuticals in the inflow and outflow of water-treatment plants found drugs more often and at higher levels when wastes came from manufacturing and animal-raising than when they came from hospitals.
- Industrial pharmaceutical pollution isn’t something that happens only in Asia. Between 2005 and 2009, US Geological Survey scientists sampled effluents from two water treatment plants in New York State. The plants take in waste water from facilities that formulate and package finished prescription drugs for sale, and the researchers analysed the samples for a barbiturate, an amphetamine, two muscle relaxants, a tranquiliser, and two opium derivatives. Total drug concentrations were 10 to 1,000 times as high as they were in water treatment plants not located near drug factories, and were similar to the eye-popping pollution levels found in the Patancheru studies.
The threat of resistant bacteria
In many water treatment plants, bacteria-laden human wastes mingle with high concentrations of antibiotic compounds. The effluents that emerge not only are a potential threat to local aquatic ecosystems. They can also breed bacteria that are resistant to treatment by multiple drugs – potentially triggering global health emergencies.
“Drug resistance may be the scariest consequence of industrial drug pollution, but it’s far from the only one. Downstream from factories, entire aquatic ecosystems are at risk.“
In Hebei, for example, effluents from antibiotic manufacturing facilities being discharged into nearby river waters contained diverse populations of bacteria with “unexpectedly high levels of multiple antibiotic resistance”, according to researchers.
Larsson and colleagues found that river sediments downstream from the Patancheru treatment plants were loaded with large populations of antibiotic-resistant bacteria. They also discovered that local bacterial populations were building up a rich arsenal of genetic elements that allowed them to shuffle resistance genes and exchange them between species. Those specialised genes increase the likelihood that new, even more dangerous combinations of antibiotic-resistance genes will be transferred from friendly bacterial species into ones that cause human disease.
Drug resistance may be the scariest consequence of industrial drug pollution, but it’s far from the only one. Downstream from factories, entire aquatic ecosystems are at risk. Last year, a group of researchers reported on populations of a fish species known as the gudgeon that they had sampled from three locations along the Dore River in central France. Among fish taken upstream from a pharmaceutical manufacturing site, they found a fairly normal sex ratio, with similar numbers of male and female fish. But at two sites downstream from the factory, only 5 to 15 per cent of fish were female; an average of 60 per cent were “intersex”, with gonads having both male and female characteristics.
Is there a cure?
There is broad concern in the global North over the effectiveness and safety of drugs imported from Asia; however, the impact on people and the environment in the places where drugs are produced is rarely considered. The US Food and Drug Administration is carrying out more inspections of foreign drug plants than it once did, but the focus of those inspections remains on the quality of the product being exported, not on the effluents going out the back door.
Technical fixes are available. Treatment of effluents with ozone, ultraviolet light, or activated carbon can break down drug compounds. But manufacturers who depend on selling their products as cheaply as possible will oppose any additional processing that would increase their costs. And the municipal sewage-treatment plants that receive drug-factory wastes shouldn’t be expected to take on such costly processing – to provide, in effect, a subsidy to a single industry.
Joakim Larsson, whose group’s landmark research has put the global spotlight on drug manufacturers, says much could be done on the demand side to curb the problem. Recently in Sweden, for example, county councils have begun requesting that companies supplying them with prescription drugs provide environmental emissions data from the faraway factories that produced the drugs. And the Swedish government has proposed that official “good manufacturing practices”, which are required of all facilities that produce drugs for sale in Europe, be amended to mandate pollution control, wherever the production takes place.
Larsson has also been a vocal advocate of a more transparent production chain, under which sources of all active ingredients in all drugs are published and available to all, so that medical personnel and patients can keep away from “dirty” drugs.
Such measures at the production and consumption ends of the pharmaceutical industry, along with concerted efforts to curb the overprescribing of drugs – a pervasive problem in affluent societies – are needed if we are to avoid doing grave harm on one side of the world while doing good on the other.
Stan Cox is a senior scientist at The Land Institute in Salina, Kansas, USA and author of Sick Planet: Corporate Food and Medicine.