How can we make pharmaceutical drugs less toxic to the environment?

News and commentary about environmental issues.
Jan. 3 2011 10:12 AM

The Little Green Pill

How can we make pharmaceutical drugs less toxic to the environment?

Prescription pills.
How can we keep toxins from pills out of our soil and water?

The past few years have seen the advent of a new eco-scare: The unsettling afterlife of pharmaceuticals. Drug residues excreted by humans and livestock linger in our waterways, often for months, before decomposing. The effects of these residues are hard to isolate and poorly understood, but scientists have discovered hints of trouble. Some have found alarming numbers of intersex fish —that is, fish whose testes contain egg cells—in rivers laced with estrogens and estrogen-like compounds (from pharmaceuticals and other chemicals). Others have observed that anti-depressants like Prozac may disrupt frog maturation and hobble minnows.

As the Associated Press reported in a widely read 2008 investigation, even our drinking water contains traces of many drugs. The quantities are infinitesimal, and there is no evidence of harm to human health. But we don't know how chronic exposure to even the lowest concentrations of these compounds, in unpredictable mixtures, might affect us—precise testing of the long-term consequences is essentially impossible. Based on the precautionary principle, not to mention the intrinsic ickiness of drug-tainted water, vigilance is surely warranted. We have eco-friendly laundry detergent and nail polish remover, so why not develop greener drugs?

A handful of chemists are trying to do just that—drawing lessons from a few drugs that are green by chance while hunting for new strategies to shrink pharmaceuticals' environmental footprints. Enthusiasts such as Buzz Cue Jr. (a retired Pfizer scientist who now consults for the industry) and Klaus Kummerer (a German chemistry professor) publish papers and give talks at conferences, touting a new approach to pharmaceuticals that takes the post-toilet phase into account. While companies have done a good deal to reduce the environmental impact of drug manufacturing—cutting waste and using more innocuous solvents, for instance—they've done little to make the drugs themselves more eco-friendly.

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Developing "benign-by-design" drugs poses a series of vexing challenges. In general, the qualities that make drugs effective and stable—bioactivity and resistance to degradation—are the same ones that cause them to persist disturbingly after they've done their job. And presumably even hard-core eco-martyrs (the ones who keep the thermostat at 60 all winter and renounce air travel) would hesitate to sacrifice medical efficacy for the sake of aquatic wildlife. What's more, the molecular structures of pharmaceuticals are, in the words of Carnegie Mellon chemist Terry Collins, "exquisitely specific." Typically, you can't just tack on a feature like greenness to a drug without affecting its entire design, including important medical properties. 

Yet there are some drugs that just happen to work well but with minimal environmental impact. The pancreatic cancer treatment glufosfamide is impressively biodegradable, as is valproic acid, an epilepsy medication. "Biologics," which include insulin and vaccines, consist of natural (as opposed to synthesized) compounds, so they break down easily in the environment. One of the greener drugs turns out to be that little blue pill: The human body fully converts Viagra into significantly less potent metabolites. * (Well more than half of the antibiotic amoxicillin, by contrast, passes through the patient unchanged.) Such drugs offer tantalizing clues that scientists may be able to apply to future formulas.

While trying to learn from these accidentally green drugs, scientists are also seeking novel ways to keep minnows off Prozac. Cue and others dream of a "magic switch" that would allow a drug to remain stable until its release into the environment, at which point—presto!—it would become biodegradable. One way to do this is to make drugs "photodegradable" with light-sensitive molecular triggers, which would cause the drug to decompose in the waste treatment plant. Another possibility is to design an inherently less stable drug, and affix it to a temporary stabilizer that would break off only after arriving inside the body. This research, however, is in the conceptual stages, far from reaching your local Rite-Aid.

Efforts to reduce drug dosages—a complementary tactic—have made more headway. Take, for instance, a treatment in development for osteomyelitis, a type of bone infection. Rather than inundate your entire body with antibiotics, the medication uses a special molecule to ferry the antibiotics directly to the infection site. Similarly, several new cancer therapies can target malignant cells with greater precision than ever before. And researchers continue to enhance "bioavailability"—the proportion of the drug's active ingredients that actually reach the patient's relevant tissues. All of these approaches permit lower doses without compromising effectiveness. This means fewer side effects for the patient—and for the planet. (A caveat: In some of these cases, though doses are lower, the drug is more potent, which could cancel out the environmental gains.)

Today, companies have little incentive to make greener drugs unless doing so coincides with other profit-enhancing benefits, like reduced side effects. Designing drugs is painstaking and expensive, and adding another criterion makes it that much harder. In Europe, however, policies are starting to apply pressure: In 2006, the EU issued guidelines that pharmaceutical companies must follow to assess the environmental risk of new drugs. And since 2005, a government-sponsored Swedish database has included information about the biodegradability, bioaccumulation, and toxicity of drugs, so that doctors and patients can weigh eco-friendliness along with other factors. The United States has also taken notice of the problem. Approximately every five years, the Environmental Protection Agency compiles a list of "contaminant candidates" for possible regulation. The most recent list, completed in 2009, for the first time singled out pharmaceuticals—nearly a dozen of them. This doesn't necessarily mean the EPA will regulate the drugs, but it's a signal to pharma companies that the issue is on the government's radar.

Until greener drugs hit the pharmacy shelves, we can take modest steps on our own to mitigate damage by keeping the offending substances out of our medicine cabinets in the first place. Many drugs are godsends, of course, but there's plenty of evidence that Americans probably take more than we need. Patients expect to leave the doctor's office with a prescription, and doctors oblige, dangerously over-prescribing antibiotics. The practice of doling out Zoloft and other psychoactive drugs in lieu of talk therapy has already sparked a backlash. If we could scale back gratuitous and harmful drug use, we would all be better off—and so might the minnows.

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Correction, Jan. 19, 2011: An earlier version of this article stated that Viagra metabolites were relatively harmless. Definitive evidence about their potential for harm is not yet available. (Return to the corrected sentence.)

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