The box of prescription drugs had been forgotten in a back closet of a retail pharmacy for so long that some of the pills predated the 1969 moon landing. Most were 30 to 40 years past their expiration dates — possibly toxic, probably worthless.

But to Lee Cantrell, who helps run the California Poison Control System, the cache was an opportunity to answer an enduring question about the actual shelf life of drugs: Could these drugs from the bell-bottom era still be potent?

Cantrell called Roy Gerona, a University of California, San Francisco researcher who specializes in analyzing chemicals. Gerona grew up in the Philippines and had seen people recover from sickness by taking expired drugs with no apparent ill effects.

"This was very cool," Gerona says. "Who gets the chance of analyzing drugs that have been in storage for more than 30 years?"

The age of the drugs might have been bizarre, but the question the researchers wanted to answer wasn't. Pharmacies across the country in major medical centers and in neighborhood strip malls routinely toss out tons of scarce and potentially valuable prescription drugs when they hit their expiration dates.

Gerona, a pharmacist; and Cantrell, a toxicologist, knew that the term "expiration date" was a misnomer. The dates on drug labels are simply the point up to which the Food and Drug Administration and pharmaceutical companies guarantee their effectiveness, typically at two or three years. But the dates don't necessarily mean they're ineffective immediately after they "expire" — just that there's no incentive for drugmakers to study whether they could still be usable.

ProPublica has been researching why the U.S. health care system is the most expensive in the world. One answer, broadly, is waste — some of it buried in practices that the medical establishment and the rest of us take for granted. We've documented how hospitals often discard pricey new supplies, how nursing homes trash valuable medications after patients die or move out, and how drug companies create expensive combinations of cheap drugs. Experts estimate such squandering eats up about $765 billion a year — as much as a quarter of all the country's health care spending.

What if the system is destroying drugs that are technically "expired" but could still be safely used?

In his lab, Gerona ran tests on the decades-old drugs, including some now defunct brands such as the diet pills Obocell (once pitched to doctors with a portly figurine called "Mr. Obocell") and Bamadex. Overall, the bottles contained 14 different compounds, including antihistamines, pain relievers and stimulants. All the drugs tested were in their original sealed containers.

The findings surprised both researchers: A dozen of the 14 compounds were still as potent as they were when they were manufactured, some at almost 100 percent of their labeled concentrations.

"Lo and behold," Cantrell says, "The active ingredients are pretty darn stable."

Cantrell and Gerona knew their findings had big implications. Perhaps no area of health care has provoked as much anger in recent years as prescription drugs. The news media are rife with stories of medications priced out of reach or of shortages of crucial drugs, sometimes because producing them is no longer profitable.

Tossing such drugs when they expire is doubly hard. One pharmacist at Newton-Wellesley Hospital outside Boston said the 240-bed facility is able to return some expired drugs for credit but had to destroy about $200,000 worth last year. A commentary in the journal Mayo Clinic Proceedings cited similar losses at the nearby Tufts Medical Center. Play that out at hospitals across the country and the tab is significant: about $800 million per year. And that doesn't include the costs of expired drugs at long-term-care and retail pharmacies and in consumer medicine cabinets.

Pharmacist Candy Tin checks dates and lot numbers with pharmacy technician Nikki Wong to pull expired medications at Newton-Wellesley Hospital.
Erik Jacobs for ProPublica

After Cantrell and Gerona published their findings in Archives of Internal Medicine in 2012, some readers accused them of being irresponsible and advising patients that it was OK to take expired drugs. Cantrell says they weren't recommending the use of expired medication, just reviewing the arbitrary way the dates are set.

"Refining our prescription drug dating process could save billions," he says.

But after a brief burst of attention, the response to their study faded. That raises an even bigger question: If some drugs remain effective well beyond the date on their labels, why hasn't there been a push to extend their expiration dates?

It turns out that the FDA, the agency that helps set the dates, has long known the shelf life of some drugs can be extended, sometimes by years.

In fact, the federal government has saved a fortune by doing this.

At a goverment stockpile, drugs don't expire as fast

For decades, the federal government has stockpiled massive stashes of medication, antidotes and vaccines in secure locations throughout the country. The drugs are worth tens of billions of dollars and would provide a first line of defense in case of a large-scale emergency.

Maintaining these stockpiles is expensive. The drugs have to be kept secure and at the proper humidity and temperature so they don't degrade. Luckily, the country has rarely needed to tap into many of the drugs, but this means they often reach their expiration dates. Though the government requires pharmacies to throw away expired drugs, it doesn't always follow these instructions itself. Instead, for more than 30 years, it has pulled some medicines and tested their quality.

The idea that drugs expire on specified dates goes back at least a half-century, when the FDA began requiring manufacturers to add this information to the label. The time limits allow the agency to ensure medications work safely and effectively for patients. To determine a new drug's shelf life, its maker zaps it with intense heat and soaks it with moisture to see how it degrades under stress. It also checks how it breaks down over time. The drug company then proposes an expiration date to the FDA, which reviews the data to ensure they support the date and then approves it. Despite the difference in drugs' makeup, most "expire" after two or three years.

Once a drug is launched, the makers run tests to ensure it continues to be effective up to its labeled expiration date. Since they are not required to check beyond it, most don't, largely because regulations make it expensive and time-consuming for manufacturers to extend expiration dates, says Yan Wu, an analytical chemist who is part of a focus group at the American Association of Pharmaceutical Scientists that looks at the long-term stability of drugs. Most companies, she said, would rather sell new drugs and develop additional products.

Pharmacists and researchers say there is no economic "win" for drug companies to investigate further. They ring up more sales when medications are tossed as "expired" by hospitals, retail pharmacies and consumers despite retaining their safety and effectiveness.

Pharmacy technician Nikki Wong sorts medications in drug boxes at Newton-Wellesley Hospital.
Erik Jacobs for ProPublica

Industry officials say patient safety is their highest priority. Olivia Shopshear, director of science and regulatory advocacy for the drug industry trade group Pharmaceutical Research and Manufacturers of America, says expiration dates are chosen "based on the period of time when any given lot will maintain its identity, potency and purity, which translates into safety for the patient."

That being said, it's an open secret among medical professionals that many drugs maintain their ability to combat ailments well after their labels say they don't. One pharmacist says he sometimes takes home expired over-the-counter medicine from his pharmacy so he and his family can use it.

The federal agencies that stockpile drugs — including the military, the Centers for Disease Control and Prevention and the U.S. Department of Veterans Affairs — have long realized the savings in revisiting expiration dates.

In 1986, the Air Force, hoping to save on replacement costs, asked the FDA if certain drugs' expiration dates could be extended. In response, the FDA and Defense Department created the Shelf Life Extension Program.

Each year, drugs from the stockpiles are selected based on their value and pending expiration, and analyzed in batches to determine whether their end dates could be safely extended. For several decades, the program has found that the actual shelf life of many drugs is well beyond the original expiration dates.

A 2006 study of 122 drugs tested by the program showed that two-thirds of the expired medications were stable every time a lot was tested. Each of them had their expiration dates extended, on average, by more than four years, according to research published in the Journal of Pharmaceutical Sciences.

Some that failed to hold their potency include the common asthma inhalant albuterol, the topical rash spray diphenhydramine, and a local anesthetic made from lidocaine and epinephrine, the study said. But neither Cantrell nor Dr. Cathleen Clancy, associate medical director of National Capital Poison Center, a nonprofit organization affiliated with the George Washington University Medical Center, had heard of anyone being harmed by any expired drugs. Cantrell says there has been no recorded instance of such harm in medical literature.

Marc Young, a pharmacist who helped run the extension program from 2006 to 2009, says it has had a "ridiculous" return on investment. Each year the federal government saved $600 million to $800 million because it did not have to replace expired medication, he says.

An official with the Department of Defense, which maintains about $13.6 billion worth of drugs in its stockpile, says that in 2016 it cost $3.1 million to run the extension program — which saved the department from replacing $2.1 billion in expired drugs. To put the magnitude of that return on investment into everyday terms: It's like spending a dollar to save $677.

"We didn't have any idea that some of the products would be so damn stable — so robustly stable beyond the shelf life," says Ajaz Hussain, one of the scientists who formerly helped oversee the extension program.

Hussain is now president of the National Institute for Pharmaceutical Technology and Education, an organization of 17 universities working to reduce the cost of pharmaceutical development. He says the high price of drugs and shortages make it time to re-examine drug expiration dates in the commercial market.

"It's a shame to throw away good drugs," Hussain says.