At 5:30 A.M. on February 19, 2010, 20-year-old Bennie F. Abram started his first day of football practice as a junior at the University of Mississippi. Several hours later he collapsed and died. Last month Abram’s family settled their wrongful-death lawsuit with Ole Miss, receiving $275,000 from the National Collegiate Athletic Association (NCAA) and $50,000 from the university.

Later in 2010, 20-year-old Jospin Milandu and 15-year-old Oliver Louis also died unexpectedly while working out with their teams. Autopsies of all three revealed one striking commonality: long, sickle-shaped blood cells that indicated they had at least one mutation for sickle-cell anemia, a genetic condition that primarily affects some people of African descent but is also, if more rarely, seen in Caucasians, Hispanics and Mediterranean populations. Testing for sickle-cell mutations has become more common in an effort to reduce the number of premature deaths, but the risks and rewards of these programs remain unclear.

Sickle-cell anemia and a related condition called sickle-cell trait follow classic patterns of genetic inheritance. People who receive two copies of the mutated gene from their parents have sickle-cell anemia, a condition in which their red blood cells are always sickle-shaped. Those who inherit just one copy of the gene are said to have sickle-cell trait. Their blood cells look normal and they experience no side effects—most of the time. But there are a handful of situations that puts those with sickle-cell trait in danger—circumstances that deprive their body of oxygen, such as climbing a mountain, free diving (diving in the deep ocean without supplemental oxygen) or, as a handful of football players have learned, intensive exercise.

In these low-oxygen conditions something changes and those with sickle cell trait become more prone to sudden death. Researchers do not know exactly what causes mortality under these conditions, although they have some ideas. For some reason, the low-oxygen conditions seem to cause skeletal muscle to break down. This might result in the release of substances such as potassium, which can lead to heart failure, and the protein myoglobin, which can cause kidney failure. Football makes sickle-cell trait particularly risky for a number of reasons: practice tends to start during some of the hottest months of the year and players often practice in pads, which can add to the heat stress.

Three years ago in an attempt to avoid more deaths like Abram’s, the NCAA adopted a policy that requires mandatory testing of all Division I athletes for the sickle-cell trait. But the move was controversial. Simply testing everyone for the trait won’t necessarily save players, and most athletes with sickle-cell trait will never need saving. If done correctly, however, testing for sickle cell could help coaches and future players avoid Abram’s fate.

Understanding how to protect against the occasional side effects of sickle cell trait is complicated by the fact that it can be hard to know for sure whether the mutation is the source of a particular problem in the first place. An autopsy of anyone with sickle-cell trait will reveal sickle-shaped cells whether or not the genetic defect was the true cause of their death. After all, low-oxygen conditions are common during death, resulting in sickling of red blood cells in anyone with the mutation.

Another complicating factor stems from the fact that not all athletes with sickle-cell trait face the same degree of risk—for both biological reasons as well as their choice of sport. Between 2004 and 2008 there were 273 athlete deaths in the NCAA, five of which occurred among players with sickle-cell trait. When researchers broke down the numbers by sport, they found that football could be especially dangerous for players with the trait. The data showed that an NCAA Division I football player with sickle-cell trait was 37 times more likely to die from exertion during practice than a player without it. In fact, all sickle-cell trait deaths recorded in the past 20 years in the NCAA have been in men, and all but one played football, says Kim Harmon, a professor of sports medicine at the University of Washington.

Harmon, the lead researcher on the study that looked at sickle-cell trait deaths in NCAA athletes, says that the ethos of football probably also has something to do with its greater risk. “There's a macho culture, you can't quit. You're just not allowed to quit,” she says. “We don't see sickle cell death in people who can self-regulate. We only see them when people are being pushed by coaches.”

This was part of the reasoning behind the NCAA policy to test athletes—the idea being that if coaches knew which of their players had sickle-cell trait, they could watch them for signs of an episode, and listen to them when they asked for a break. “I like to know who my sickle-cell trait guys are,” says Harmon, who is also a sports physiologist for the University of Washington football team. For her, the policy helps trainers respond correctly and quickly if a player is having trouble, and it helps her coaches know whom they can push and whom they should give more space.

But some argue that rather than singling out sickle-cell trait players, universal changes should be made to reduce the risk of heat stroke and exhaustion for all players. University of Pennsylvania bioethicist Arthur Caplan puts it this way: “Not everyone has the same risk for concussions,” he says. If brain scans could predict who was more prone to concussions, should they be tested and told to avoid hard tackles? “Or should you insist on better helmets for everyone?”

Whereas universal precautions would be great, Harmon says, they’re not realistic. “They’re probably right, they should [add more precautions],” she says, “but that's just not what happens.”

Others worry that coaches might bench sickle-cell trait players more or pull them out of practices, putting them at a disadvantage. This fear isn’t totally unreasonable. When Devaughn Darling died from a sickle-cell trait episode during practice at The Florida State University, his identical twin Devard was barred from playing by the team’s medical staff. And players themselves are worried about their NFL draft prospects. Carroll Flansburg is a double-masters student at the University of South Florida studying how the different types of sickle-cell mutations might change the health outcomes of players, and has only been able to recruit 15 players.* “It seems that a lot of people are concerned that it will affect their NFL prospects,” she says. And although the NCAA policy aims to have all players tested for the trait, Flansburg says that many teams will collectively waive the testing.

Harmon, for her part, points to times when discrimination has not been an issue. Two of her sickle-cell trait players are starters. Devaughn Darling’s twin Devard went on to play for the NFL without incident. And although no one knows the exact number of players in the NFL with sickle-cell trait, estimates put the number at around 90 out of over 1,600 players, including the New York Jets wide receiver Santonio Holmes, Cincinnati Bengals lineman Geno Atkins and six-time Pro Bowl receiver Terrell Owens. None of them have ever had trouble. Ryan Clarke, a safety for the Pittsburgh Steelers, nearly died during a sickle-cell trait episode in Denver in 2007, however. He still plays but sits out when his team goes back to the mile-high city, and hasn’t had an incident since.

Like many genetic tests the question of sickle-cell trait boils down to whether knowing a person’s health status will actually help save them. Do doctors and coaches know enough about the risks of sickle-cell trait to make testing an effective prevention approach? Do scientists know enough about the pathology of sickle cell to be able to recommend a prevention strategy? Yale University epidemiologist Yaw Amoateng-Adjepong thinks so. “We may not know the exact sequence of events, we may not be able to predict things with fineness—but frankly, in medicine, we've never had absolute certainty for most of the things that we do, but we go ahead and act,” he says. So far, three years into the NCAA testing program no one has died from a sickle-cell trait episode.

In July, after Abram’s family settled with the University of Mississippi the NCAA agreed to add more detailed information about sickle-cell trait in their 2012–2013 NCAA Sports Medicine Handbook. With more information available, coaches should be better prepared to keep their sickle-cell trait players safe—and with more research, scientists hope to better understand exactly what creates the risk these players face. Because whereas coaches certainly want to win, Harmon says, “they do not want to kill these kids.”

*Correction (8/22/13): This sentence was edited after posting. The original incorrectly stated that Carroll Flansburg attends the University of Florida.