The Long Quest for Artificial Blood

All this excitement came to an abrupt end when, during the winter of 1667, Denis began transfusing the blood of a calf into a thirty-four-year-old manservant named Antoine Mauroy, who was subject to “phrensies” during which he would beat his wife, take off all his clothes, and run around Paris setting homes on fire. Denis hoped that blood from the gentle calf might serve as a kind of tranquillizer, calming the troubled Mauroy. After the first couple of infusions, Mauroy sweated, vomited, complained of lower-back pain, and pissed charcoal-black fluid—all, we now know, symptoms of a severe transfusion reaction in which the recipient’s antibodies attempt to destroy the newly introduced foreign substance. Nonetheless, he soon not only recovered but seemed to be a changed man, speaking lucidly, whistling merrily, and treating his wife with unprecedented tenderness. Unfortunately, a couple of months later, just as the third transfusion was about to get under way, he died. Suspicion fell on his wife, who had, it was alleged, put arsenic in Mauroy’s soup, but the damage had been done: before long, the French authorities had officially banned blood transfusion in humans, with the British government and the Pope following suit shortly thereafter.

It took more than a century for medicine to return to the technique, this time as a means to replace blood lost during childbirth. Gradually, blood transfusions came to be seen as a potentially lifesaving—sometimes near-miraculous—treatment in otherwise dire cases of traumatic injury and hemorrhage. It “raised hopes where formerly there had not been any,” as Geoffrey Keynes, the surgeon brother of the economist John Maynard, put it in his memoir, recalling how, during the First World War, he would “steal into the moribund ward,” conduct a transfusion on one of the patients, and pull “many men back from the jaws of death.”

Yet death was still a frequent result of transfusion, and it was only in the early decades of the twentieth century that some of the procedure’s most significant problems were ironed out. The Nobel Prize-winning discovery of blood types, in 1900, ultimately improved the odds of survival; no longer was the avoidance of dangerous transfusion reactions a matter of luck. Still, blood’s habit of coagulating, so useful in the body, proved a challenge outside of it: within a few minutes of beginning a transfusion, clots would gum up the needles and tubes, seriously limiting the quantity of blood that could be moved from person to person. In the nineteen-tens, a doctor at Mount Sinai Hospital, in New York, discovered that adding a tiny amount of sodium citrate to donor blood would keep it flowing without poisoning the recipient, an advance so transformative that, according to one of his colleagues, it “was almost as if the sun had been made to stand still.” Then, there was the storage issue.

“People forget that blood is alive,” Allan Doctor told me. “They think it’s like urine or something. It is a bodily fluid—but it’s living cells.” Keeping those cells alive outside the body requires very particular conditions, and, through the nineteen-twenties, blood transfusion required the presence of a live donor. In London, Geoffrey Keynes relied on a directory of on-call volunteers; in a time when many people didn’t have a telephone, policemen and priests were often enlisted to track down donors at any hour of the day. It wasn’t until the Spanish Civil War in 1936 that a Canadian surgeon figured out how to keep blood intact for up to a week, refrigerated in glass milk bottles, and the modern era of blood transfusion finally began.

In Filton, a suburb on Bristol’s northern edge, Britain’s National Health Service operates a blood factory that can receive and process up to three thousand units a day. Inside the vast, white manufacturing hall, bags and bags of blood dangle overhead, suspended from a steel rail like macabre baubles. “They’ll usually come in warm,” Naomi Jones, the center’s then deputy head, who was clad in a hairnet and blue coveralls, told me. The fresh blood separates slightly as it hangs: the dark-red cells, heavy owing to their iron content, sink to the bottom, and the plasma, which makes up more than half of blood’s volume, sits on top. Each bag looked different in ways that, Jones told me, can reflect its donor’s health—some had more or fewer red cells, while the plasma ranged in shade from lemonade to Coca-Cola. “If you’re on the pill or anything like that, the hormones will make it green,” she said. “And people who have lots of fats in their blood, it’s like a banana milkshake.”

During the blood’s sojourn on the rack, white blood cells are filtered out. Then, in dedicated pods staffed by one or two people, the bags are broken down into the rest of their component parts, which are weighed, labelled, and put on conveyor belts that transport them into storage. Red blood cells are stacked in plastic crates in a refrigerator, separated by blood type; plasma is blast-frozen; and platelets, which must be kept in gentle motion, are extracted from the thin beige layers in between, pooled together, and placed on metal shelves inside an incubator that jiggles from side to side.

Modern on-demand blood, it turns out, is a logistical miracle: rubber tubing and milk bottles have been replaced by an engineered process that gathers the liquid, tests it, and then stores each of its elements for maximum shelf life, before getting it to the patients who need it. But not to all of them. Despite the high throughput of the N.H.S.B.T. blood factory, and despite the fact that a unit of blood is transfused every two seconds in the United States, there just isn’t enough.

Part of the problem is that a lot of people need it. An astonishing number of civilians die of injury each year—upward of a hundred and fifty thousand in the U.S., and more than five million globally. “Every! Year!” John Holcomb, the trauma surgeon, said. “It’s the leading cause of life years lost.” Accidental injury is the primary cause of death for anyone forty-four or younger, and blood loss is the most common cause of potentially preventable trauma deaths. Holcomb and his colleagues estimate that in the U.S. alone there are likely thirty thousand preventable deaths each year, owing to hemorrhage. In one paper, they combed through the 2014 mortality data for the county encompassing Houston, Texas: even in a major metropolitan area with a well-resourced trauma-care network, more than one in three people who died from bleeding could have possibly been saved.

“If you go into hemorrhagic shock, you need blood products,” Holcomb said. “And the data are clear that, the earlier you get blood products, the better your survival.” Every minute matters; ideally, injured individuals would receive blood on the street or in an ambulance, before they even reach a hospital. Many of them don’t, for reasons that are demographic, biological, and economic. “No. 1, there’s not enough blood,” Holcomb said. “You probably need another sixty to a hundred thousand units of blood available nationwide.” In the U.K., N.H.S.B.T. aims to have five to seven days’ supply on hand; in the U.S., the goal is similar. The reality is that, at times, blood isn’t available. Ghevaert told me that, on a recent trip to the U.S., he’d been informed that, on that particular day, there were no platelets left at 11 A.M. in the New Orleans area. Platelets are what allow blood to clot—they’re lifesaving for patients who are hemorrhaging after surgery, traumatic injury, or childbirth.

This shortage is caused by the fact that too few people give blood. Of the thirty-eight per cent of Americans who are eligible to donate, less than three per cent regularly do. (Some trauma experts suggest that reintroducing payment for blood donations, which are currently voluntary, would boost supply, though the U.S. has a sordid history of such arrangements leading to the exploitation of the poor.) “In addition to that bad stuff, our population is aging,” Philip Spinella, an expert in transfusion medicine at the University of Pittsburgh and a co-founder of KaloCyte, the company developing ErythroMer, explained. “In the next ten years, there’ll be twenty million more people above the age of sixty-five.” Across the developed world, societies are increasingly elderly, which squeezes the blood supply from two directions. “Baby boomers and the Greatest Generation—they were the blood donors,” Mark Gladwin, the dean of the University of Maryland School of Medicine, told me. “Our young generation is not donating blood.” Meanwhile, the people over sixty-five “get cancer and have heart surgery—they need platelets and red cells,” Spinella went on. “Where’s it going to come from? Right now, our donor base can’t support today’s needs. What about 2030?”

Blood’s innate fragility exacerbates this crisis. It has a remarkably short shelf life: five days for platelets, and forty-two for red blood cells. If you add a cryoprotectant, red blood cells can be successfully frozen—but then they have to be defrosted, and the antifreeze has to be washed out with extreme care, so as not to damage the cells. This can delay the process by hours, during which time most hemorrhaging patients will be long gone. What’s more, even meticulously stored blood is gradually dying. “When you put fish in the refrigerator and leave it for five days, it’s less good,” Holcomb said. “Blood is the same.” Doctor showed me research that measured how much oxygen cold-stored red blood cells were capable of moving. “It’s down to forty per cent of normal before it’s even outdated,” he said.

The rapid turnover rate of fresh blood, combined with the equipment required to slow its decline, means that its use tends to be restricted to large trauma centers in major urban areas—which means that people who get injured far from such resources, whether they are an hour outside Houston or almost anywhere in the developing world, have a much higher chance of dying from trauma. There are ways around this: in Rwanda, blood is often delivered by drone; in the United States, it could be carried in an ice chest on every ambulance or medevac helicopter. The fact that it is not is almost purely economic.

“The problem here is that there’s practically no reimbursement for prehospital blood by insurance and agencies,” Holcomb said. “There’s nothing that has a bigger impact on survival than prehospital blood. Nothing. And yet the major impediment is not logistics—we’ve worked through that. It’s not how to store the blood. It’s reimbursement. And, in our system, if you don’t get reimbursed you don’t do it.” Spinella, who told me about a trial in Pittsburgh demonstrating that prehospital plasma greatly improves survival rates, is also outraged. “We had to stop it after the trial was over because our E.M.S. system can’t afford to put blood on the ambulances,” he said. “So we proved it, and now we can’t do it, because it’s unaffordable. It’s criminal.”