The Bizarre Quest for Artificial Blood

Picture yourself in a hospital about to undergo surgery. Your doctor enters the operating room . . . with a live goat. In 1878, Joseph Howe, a physician in New York City, did just that. His patient was suffering from tuberculosis, and Howe wanted to find out if he could cure her by injecting the goat’s milk directly into her veins. Fortunately the patient survived, but not all who received this treatment were so lucky. Back in Howe’s day, some doctors thought milk could work as a replacement for human blood.

The quest for a blood substitute started in the 1600s. Over the centuries, doctors injected patients with substances such as cow’s milk, sheep’s blood, and even urine. Such treatments were not only ineffective but also quite dangerous.

Today, people with certain blood disorders or those who have lost a great deal of blood because of an injury commonly receive blood transfusions. Medical staff transfer blood provided by human donors into a patient’s body. Donated blood is often in short supply though, and only certain types can be given safely to specific individuals.

That’s why scientists are still searching for a viable alternative to human blood. And they want to make sure any potential substitute actually has properties similar to real human blood so it helps people who are ill, instead of making them sicker. If scientists succeed, many lives could be saved. But the hunt for artificial blood has turned out to be trickier than anyone imagined.

Picture yourself in a hospital about to have surgery. Your doctor enters the operating room . . . with a live goat. In 1878, a doctor in New York City did just that. The patient was suffering from tuberculosis. Dr. Joseph Howe injected the goat’s milk directly into her veins. He wanted to find out if the treatment would help her. Luckily, the patient survived, but not all who received this treatment did. Back in Howe’s day, some doctors thought milk could replace human blood.

The search for a blood substitute started in the 1600s. Doctors injected patients with different substances over the years. They tried cow’s milk, sheep’s blood, and even urine. These treatments didn’t work, and they were also quite dangerous.

Sometimes people lose a great deal of blood because of an injury, and others have certain blood disorders. Today, these patients commonly receive blood transfusions. Human donors provide blood, and medical staff inject it into a patient’s body. But donated blood is often in short supply. And only certain types can be given safely to certain people.

That’s why scientists are still searching for a safe substitute for human blood. And they want to make sure it has features similar to real human blood. That way, it will help sick people, instead of making them worse. If scientists succeed, many lives could be saved. But the hunt for artificial blood has proved trickier than anyone imagined.

Blood is a remarkable substance. “The number of functions that blood has in our bodies is extremely large,” says Pedro Cabrales. He’s a bioengineer who is developing blood substitutes at the University of California, San Diego. Blood moves through a person’s veins, delivering nutrients to all the cells that make up the body. Blood also carries away waste, helps regulate body temperature, and transports chemical messengers called hormones between organs. And it contains white blood cells that fight off disease-causing germs (see What’s Blood Made Of?).

One of blood’s most important functions is transporting oxygen. Red blood cells contain hemoglobin. This molecule binds to oxygen breathed in by the lungs, enabling red blood cells to carry it to tissues throughout the body. This process is essential to life. Cells need oxygen to produce energy—that’s why a person who loses a lot of blood might not survive without a transfusion.

Blood is an amazing substance. “The number of functions that blood has in our bodies is extremely large,” says Pedro Cabrales. He’s a bioengineer who is developing blood substitutes at the University of California, San Diego. Blood moves through a person’s veins, and it delivers nutrients to all the cells in the body. Blood also carries away waste and helps control body temperature. It transports chemical messengers called hormones between organs. And it contains white blood cells. They fight off germs that cause disease (see What’s Blood Made Of?).

Blood also transports oxygen. That’s one of its most important jobs. Red blood cells contain hemoglobin. This molecule binds to oxygen breathed in by the lungs. Then red blood cells carry oxygen to tissues all over the body. This process is necessary for life. Cells need oxygen to produce energy. A person who loses a lot of blood might not survive. That’s why doctors may order a transfusion.

But a transfusion isn’t always ideal or even possible. Donated blood requires refrigeration and has a short shelf life, so it’s not always available. All blood isn’t alike, either. Every person has one of eight different blood types, determined by molecules on the surface of red blood cells. Patients must receive a compatible blood type from a donor, or they could have a severe reaction and die.

Sometimes patients refuse a blood transfusion because it conflicts with their religious beliefs. Others don’t want transfusions because they fear contracting a disease from an infected donor. That risk is small in the U.S., where donated blood is screened for common pathogens that can make people sick. But it’s a real concern in areas like sub-Saharan Africa, where consistent screening practices aren’t in place and infections such as HIV and hepatitis sicken large numbers of people.

Artificial blood could solve these problems. “Blood substitutes that can be transported, stored easily for a longer period, and transfused without matching for blood type have potential as replacements for standard blood transfusions,” says Abdu Alayash. He’s a biomedical research chemist at the U.S. Food and Drug Administration in Maryland.

But a transfusion isn’t always ideal or even possible. Donated blood must be refrigerated, and it has a short shelf life. So it’s not always on hand. All blood isn’t alike, either. Every person has one of eight different blood types. The type depends on molecules on the surface of red blood cells. Patients must receive the right blood type from a donor. If not, they could have a serious reaction and die.

Sometimes patients don’t want a blood transfusion. Some refuse it because it goes against their religious beliefs. Others fear they’ll get a disease from an infected donor. That risk is small in the U.S. Here, donated blood is tested for common pathogens that cause disease. But it’s a real worry in places like sub-Saharan Africa. There, testing practices aren’t always dependable. And large numbers of people are infected with illnesses like HIV and hepatitis.

Artificial blood could solve these problems. “Blood substitutes that can be transported, stored easily for a longer period, and transfused without matching for blood type have potential as replacements for standard blood transfusions,” says Abdu Alayash. He’s a biomedical research chemist at the U.S. Food and Drug Administration in Maryland.

Artificial blood wouldn’t have to perform all the functions of real blood to save lives. In most cases, it just needs to transport oxygen until the body produces enough red blood cells to do the job.

One strategy scientists are trying is taking hemoglobin from human or animal red blood cells and using it to create substances called hemoglobin-based oxygen carriers (HBOCs). But “hemoglobin outside a red blood cell is unstable and breaks down into smaller, toxic compounds,” says Alayash. These compounds increase a patient’s blood pressure and his or her risk of heart attack or stroke.

Artificial blood could save lives without doing all of the jobs of real blood. In most cases, it just needs to transport oxygen. That would give the body time to produce enough red blood cells to do the job.

Scientists are trying different approaches. One is taking hemoglobin from human or animal red blood cells. Then they use it to create substances called hemoglobin-based oxygen carriers (HBOCs). But “hemoglobin outside a red blood cell is unstable and breaks down into smaller, toxic compounds,” says Alayash. These compounds increase a patient’s blood pressure and the risk of heart attack or stroke.

Some researchers are looking for ways to prevent this toxic effect, while others are trying a different tactic: mimicking how other animal species’ blood transports oxygen. For example, bioengineer Cabrales and his team are making synthetic oxygen-carrying molecules inspired by earthworm blood. “These molecules have a unique structure that makes them less toxic than human hemoglobin,” he says.

Other researchers are trying to create synthetic blood substitutes out of chemicals called perfluorocarbons (PFCs). After PFCs are pumped into a patient’s veins, they dissolve oxygen from the lungs and carry it throughout the body. But in order for PFCs to work, the patient must be breathing in 100 percent oxygen. The air we normally breathe is just 21 percent oxygen. Higher oxygen concentrations can cause dangerous heart and lung problems.

Some researchers are looking for ways to prevent this toxic effect. Others are following a different plan. They’re copying how other animal species’ blood transports oxygen. For example, bioengineer Cabrales and his team are making artificial molecules that carry oxygen. Their idea came from earthworm blood. “These molecules have a unique structure that makes them less toxic than human hemoglobin,” he says.

Other researchers are trying to create artificial blood out of perfluorocarbons (PFCs). These chemicals are pumped into a patient’s veins. They dissolve oxygen from the lungs and carry it all over the body. But PFCs work only if the patient is breathing in 100 percent oxygen. The air we normally breathe is just 21 percent oxygen. Higher oxygen levels can cause dangerous heart and lung problems.

Despite these challenges, scientists have made some promising advances toward a true blood substitute. In South Africa, where the threat of contracting a serious infection from a blood transfusion is high, a hemoglobin-based oxygen carrier has been approved to treat patients. The U.S. permits this experimental treatment only in rare cases, since blood transfusions here are relatively safe.

When a blood transfusion isn’t possible, doctors do have options besides artificial blood. They can use devices to seal off severed blood vessels to minimize blood loss. They can inject the element iron (Fe)—the main component of hemoglobin—or hormones to boost red blood cell production. Certain fluids can increase blood volume, helping the patient’s remaining red blood cells continue to circulate and deliver oxygen.

But artificial blood remains highly sought after, and researchers are determined to succeed in their quest. “A safe alternative to blood will help a lot of people,” says Cabrales.

Even with these challenges, scientists have made headway toward a true blood substitute. In South Africa, a hemoglobin-based oxygen carrier has been approved to treat patients. There, the danger of getting a serious infection from a blood transfusion is high. Only in rare cases does the U.S. allow this experimental treatment. That’s because blood transfusions are safer here.

When a blood transfusion isn’t possible, doctors do have choices besides artificial blood. They can use devices to seal off cut blood vessels. That lessens blood loss. The element iron (Fe) is the main component of hemoglobin. Doctors can inject iron or hormones to raise red blood cell production. Certain fluids can increase blood volume. That helps the patient’s remaining red blood cells continue to flow and deliver oxygen.

But artificial blood is still highly desired, and researchers are determined to succeed in their search.  “A safe alternative to blood will help a lot of people,” says Cabrales.