Tens of thousands of people bleed to death each year in the United States before they can get to a hospital. That's because ambulances, medical helicopters and military medics can't routinely carry blood, which would go bad too fast without adequate refrigeration.
So scientists have been on a quest to develop artificial blood that could be stored in powdered form and reconstituted by medics on the spot to save lives.
At the University of Maryland School of Medicine in Baltimore, where some of this research is being conducted, a white rabbit lies on the floor of a cage. It's in a "special intensive care unit that we've created for our rabbit resuscitation," says Dr. Allan Doctor, a scientist at the school.
Doctor's team just drained blood from the animal to simulate what happens to a person who's hemorrhaging from an injury, such as from a car crash or battlefield wound.
"This rabbit is still in shock. You can see he's lying very still. It's as if he was at the scene of an accident," says Doctor. "If we didn't do anything, it would die."
But Doctor and his team are going to save this rabbit today. They're going to fill his veins with something they hope will finally enable them to achieve a goal that has stymied researchers for decades: developing safe and effective artificial blood.
"Good bunny," says Danielle Waters, a technician on Doctor's team, as she gently lifts the rabbit and starts infusing him with three big syringes of artificial blood.
Doctor's team makes synthetic blood from hemoglobin, the protein that nourishes the body with oxygen. The researchers extract hemoglobin from expired blood and enclose the protein in a bubble of fat, essentially creating artificial red blood cells.
The protective bubble is the innovation that Doctor thinks will solve the safety problems caused by other attempts at making synthetic blood. These other efforts also used hemoglobin, but exposed hemoglobin can be toxic to organs, he says.
"We have to veil the hemoglobin inside a cell. It's an artificial cell that makes it safe and effective," Doctor says.
The scientists then freeze-dry the artificial red blood cells into a powder that can stay good until an emergency.
"It's designed so that at the moment it's needed, a medic can mix it with water and within a minute you have blood," Doctor says.
"It is shelf-stable for years, and it can be easily transported. And so the point is so you can give a transfusion at the scene of an accident," Doctor says.
Stopping preventable deaths
In addition to use in emergency medicine, military medics could also use artificial blood to save wounded soldiers. The Defense Department is spending more than $58 million to help fund a consortium that's developing Doctor's synthetic blood, along with other components that enable clotting and maintain blood pressure.
"The No. 1 cause of preventable death on the battlefield is hemorrhage still today," says Col. Jeremy Pamplin, the project manager at the Defense Advanced Research Projects Agency. "That's a real problem for the military and for the civilian world."
Doctor is optimistic his team may be on the brink of solving that problem with his artificial red blood cells, dubbed ErythroMer. Doctor co-founded KaloCyte to develop the blood and serves on the board and as the firm's chief scientific officer.
"We've been able to successfully recapitulate all the functions of blood that are important for a resuscitation in a system that can be stored for years at ambient temperature and be used at the scene of an accident," he says.
Promising results in animal tests
Back in the lab, Waters is done infusing all three vials of synthetic blood into the rabbit after about 10 minutes.
"My goodness, bunny, you did it," she says as she places him back in his cage. "There we go."
Almost immediately, a monitor tracking the rabbit's vital signs show his heart rate, blood pressure and other important metrics have recovered from near death to nearly normal. He's starting to resume normal behavior, such as moving around on his own and drinking water.
"The really good sign is that he's very pink," Doctor says. "His eyes are pink. His ears are pink. That's a good sign he has a lot of oxygen in his blood and it's being effectively distributed. He's breathing comfortably and calm. It's amazing how quickly it can work."
Doctor's team has tested their artificial blood on hundreds of rabbits and so far it looks safe and effective.
"It would change the way that we could take care of people who are bleeding outside of hospitals," Doctor says. "It'd be transformative."
Like other rabbits used in these experiments, this animal will later be euthanized so the researchers can perform a necropsy to make sure the artificial blood didn't cause any tissue or organ damage.
Human trials still to come
While the results so far seem like cause for optimism, Doctor says he still needs to prove to the Food and Drug Administration that his artificial blood would be safe and effective for people.
But he hopes to start testing it in humans within two years. A Japanese team is already testing a similar synthetic blood in people.
"I'm very hopeful," Doctor says.
Other experts remain cautious. Many promising attempts to create artificial blood eventually proved unsafe.
"I think it's a reasonable approach," says Tim Estep, a scientist at Chart Biotech Consulting who consults with companies developing artificial blood.
"But because this field has been so challenging, the proof will be in the clinical trials," he adds. "While I'm overall optimistic, placing a bet on any one technology right now is overall difficult."
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