People cannot donate their blood if they are high risk for variant Creutzfeld-Jacobs Disease (vCJD), thought to be the human form of Mad Cow Disease.

Why are so many Americans considered high risk, and will we ever be able to give blood? After looking into those questions, I realized just how tricky they are.

From 1986–98, the UK saw an epidemic of bovine spongiform encephalopathy (BSE), a neurodegenerative disease in cattle likely caused by unsafe feeding practices. By ’96 the disease appeared to have crossed to humans, as scientists identified the first case of vCJD and strongly linked it to BSE.

The human form was fatal and incurable: as of May 2015, it had killed at least 228 people, including 177 in the UK and 27 in France. Scientists suspect that vCJD may also be transmissible through human donations of blood, organs, and tissue, based on animal studies and several cases where humans were diagnosed with the disease after a transfusion.

While human cases have declined sharply since 2000, the disease can theoretically incubate for decades, and experts have warned that a second wave could break out. Until recently, it was impossible to test for.

Who is at risk of vCJD? Theoretically, anyone who has consumed cattle products or received a blood or organ donation has at least some risk (likely very low), as (1) we have no perfect way of containing cattle products from infected areas and (2) any cow could spontaneously get BSE, though it’s rare, and (3) we have no perfect way of preventing blood, organ, and tissue transmission. But people who lived near the center of the epidemic may face much higher risk.

The Food and Drug Administration has spent the past 20 years trying to figure out the right mix of people to keep out of the blood pool. According to a 2015 report, its vCJD recommendations keep away an estimated 254,000 annual donors. Given that less than 10% of eligible donors give blood each year, we can safely assume that the number of Americans blocked because of vCJD risk therefore is in the millions.

But history shows that this group is pretty haphazard.

In 1999, the FDA recommended deferring anyone who had spent six months in the UK from 1980 to 1996 (when the UK implemented extensive controls to contain BSE).

In 2001, it expanded deferrals to include anyone who

—spent five years in any European country but the UK between 1980 and the present

—spent three months in the UK from 1980 through the end of 1996

—spent six months in Europe on a US military base from 1980 through the end of 1996

—received a blood transfusion in the UK from 1980 to present

Around that time, the FDA warned that the new policy would have turned away 5% of potential donors, or around 508,000 people, for a 90% reduction of vCJD blood transmission risk relative to how things were before the 1999 recommendations.

But experts continued to recommend changes one way or another.

In 2006, an FDA committee decided in a close vote not to recommend deferring French transfusion patients. In 2006, however, the FDA added them to the list anyway.

In 2011, after several vCJD cases were identified among people from Saudi Arabia, an FDA committee voted to defer people who had spent 5 years there since 1980. The FDA, however, chose to wait for a broader reevaluation of policy.

In 2015, an FDA committee considered clearing people who had spent time in European countries other than the UK, France, and Ireland. The proposal didn’t go through, with some members complaining about the risk model used or inconsistencies in how countries were treated.

Meanwhile, researchers found that a US man had died in 2014 of vCJD that he likely picked up while living in Kuwait, Russia, or Lebanon — countries not even on the FDA’s deferral list.

Some countries, of course, can’t afford to be as stringent as the US. Notably, the UK blocks blood transfusions only from locals who have themselves received donations or been diagnosed with vCJD, while also sourcing internationally for some blood products.

Ultimately, we’re waiting on science to end to the vCJD crisis, and there has been some meaningful progress there. Blood transfusions increasingly use leukoreduction, or the removal of white blood cells, which appears to limit risk of vCJD transmission and could be a step toward blocking it. Scientists have developed a vCJD test and are studying how it could be implemented. Scientists are also researching cures for prion diseases like vCJD.

We’re also waiting on studies in the UK and elsewhere to see just how widespread vCJD is and whether it might just fade away.