For decades, scientists have chased the elusive dream of creating artificial blood--blood that would be universally compatible and readily available--and today a handful of U.S. companies is tantalizingly close to the finish line.
Experts predict that the first generation of so-called fake blood could hit the market within two years, easing the blood shortage, saving lives during medical emergencies and further reducing the potential dangers from infectious diseases carried by donor blood.
"The field is really at a very advanced stage, the last stages of development," said Abdu I. Alayash, who heads the research program on blood substitutes for the Food and Drug Administration. "There is a real excitement."
Artificial blood, however, is no panacea and is never expected to replace the real thing. It only performs the job of red blood cells, and doesn't do many things that natural blood does. It also does not last long in the body--which makes it valuable as a stopgap during emergencies, but not as a long-term solution.
And it has potential safety problems. There is some early evidence that some products can cause high blood pressure, or lead to stroke or cardiac arrest.
Still, experts say it could prove lifesaving in emergency situations in the field, preventing life-threatening shock, a sudden, precipitous drop in blood flow that deprives the body of oxygen; on the battlefield; in those who refuse transfused blood, such as Jehovah's Witnesses; and in patients with such blood incompatibilities as sickle cell anemia.
Unlike donated blood, artificial blood has a longer shelf life, is unlikely to be tainted with infectious agents, can be stored at room temperature and doesn't need to be matched to a recipient's blood type.
Dr. Linda Chambers, senior medical officer for the American Red Cross, says artificial blood helps ease chronic blood shortages nationwide by freeing up large quantities of blood in long-term storage in thousands of small hospitals that don't do surgeries or handle many emergencies, but feel they need to have blood on hand, just in case.
"We have a lot of blood in refrigerators in small hospitals that doesn't get used," she said. "They could store the artificial blood instead, and the donated blood could get to where it's really needed. It could make a big difference."
Herbert Kay, for one, is sold on the concept. When he checked into the hospital last year for surgery to repair a potentially life-threatening aortic aneurysm, he was terrified of having a blood transfusion, and told his doctors he didn't want one.
The odds were that he wouldn't even need it. But Kay, now 71, a semiretired industrial research psychologist from West Caldwell, N.J., was taking no chances.
"I know the blood supply is relatively safe, but things do happen," he said. "There are always slip-ups. And I didn't want to become the victim of a slip-up."
So when Kay unexpectedly began bleeding excessively during surgery, instead of donated blood, he was given--with his permission--an experimental artificial blood. The milky white liquid began flowing through his veins, performing the same job as red blood cells in carrying life-sustaining oxygen to his tissues and organs.
"I would definitely go that route again," he said recently. "I think it saved my life."
In this country, more than a half-dozen blood substitute products are in development. Alliance Pharmaceutical Corp. of San Diego has developed a blood substitute called Oxygent. Biopure Corp., a Cambridge, Mass., company whose product is made from the hemoglobin of beef cattle, was recently licensed in South Africa. Sonus Pharmaceuticals of Seattle is developing its own product.
Some substitutes are being studied in humans, and are well along; others are in the preclinical phase. The first application for FDA approval is expected sometime this summer.
None of these, however, is being studied in trauma cases--such as automobile accidents or gunshot wounds--where many researchers believe they will prove most valuable. Trauma patients, whose cases are fraught with medical perils, are difficult to study for that reason--and it is virtually impossible to obtain "informed consent" from them.
Still, experts predict that once the first products are licensed--even if approved initially for limited uses--they eventually will become a mainstay during medical emergencies, including trauma, heart attack and stroke.
"I envision every ambulance is going to be carrying this," said Dr. Aryeh Shander, executive medical director of the New Jersey Institute for the Advancement of Bloodless Medicine. "If we are convinced it will help in trauma mortality, then clearly it will be a first-line treatment." Dr. Richard K. Spence, a researcher who studied artificial blood during the 1980s, recalls a heart attack victim some years ago--a former boxer in his 50s--who was given a blood substitute as part of a study at Cooper Hospital in Camden, N.J.
The idea was to try to prevent heart muscle damage that occurs when the organ is deprived of oxygen.
"He was having chest pain; he was in trouble. We got him into bed and put all the lines in," said Spence, who now is director of surgical education at Baptist Health Systems in Birmingham, Ala. "I remember it well because it was the weekend of the Super Bowl--within an hour, his pain was gone, his EKG [electrocardiogram] was normal. He sat up, pulled out his [intravenous tubes] and went out into the waiting room to watch the game."
Beyond U.S. borders, the impact of artificial blood could be even more dramatic.
Experts say it could transform the health picture of developing nations, where the leading cause of bleeding death is childbirth, followed by malaria-induced anemia in children.
"Blood transfusion in the developing world is the great unwritten tragedy," said Dr. Harvey Klein, chief of the department of transfusion medicine at the National Institutes of Health clinical center. "There is very little blood available in most developing countries, and what there is generally is highly infectious and frequently untested."
This is likely the reason why South Africa recently became the first country to approve a blood substitute, and why it may take longer in the United States, where the blood supply is considered very safe.
Not everyone thinks artificial blood will be a medical hit here. The products likely will be expensive at first, and complicated to use, according to Keith Berman, the Los Angeles-based editor of a blood products newsletter.
He maintains "there is no meaningful U.S. market for these agents in elective surgery," although he predicts they may be useful as "a transient oxygen-supplying 'bridge' in massively bleeding patients where there are problems getting access to enough red blood cells, or in rare cases where patients reject all types of donor blood."
He and others also have concerns about product safety. The substitutes only have been studied in a small number of people, and some red flags already have been raised.
"The major question . . . in the United States is their relative safety compared to blood transfusions," said Dr. William D. Hoffman, director of the cardiac surgical intensive care unit at Massachusetts General Hospital, who has studied blood substitutes.
Because the blood supply here is so safe, any potential risks from fake blood must be taken very seriously before any products are licensed, according to experts.
Some of the experimental products raise blood pressure, and others might be related to cardiac problems and stroke.
In a heart bypass study of one experimental product, for example, researchers were baffled by a higher than expected number of strokes experienced by those who received it, compared with the control group.
Scientists suspended the study to try to figure out the connection--if there is one.
And other products--those that start with a hemoglobin base, such as from cows--can bind to nitric oxide, a smooth-muscle relaxant produced naturally by the body.
Nitric oxide acts like an antioxidant by gobbling up free radicals, which are substances linked to certain diseases. Researchers theorize that this could explain the high blood pressure problems experienced by some patients.
"These products are delivering oxygen by a totally different mechanism as red cells in the blood," Klein said. "But we don't know yet what this means physiologically."
And the one attempt to study fake blood in trauma proved troublesome, and was stopped. In the mid-1990s, Baxter Healthcare's blood substitute product appeared to be a leading candidate for FDA approval. But the company abruptly stopped the trial after an unexpectedly high number of recipients--24 of 52--died.
Because shock trauma involves multiple factors, no one was sure exactly what prompted the deaths.
"Trauma trials are very difficult trials to do," Klein said. "I give Baxter credit for trying, but it's a very difficult area to study. I think most people feel that it's foolish to study trauma at this point."
Most experimental artificial blood products fall into two types. One group starts with a hemoglobin base, from animals or even humans, then is modified to become more efficient than real red cells at carrying oxygen.
The second is created from a class of synthetic compounds known as perfluorocarbons, which soak up oxygen, but don't bind to it--meaning that tissues can grab the oxygen easily as the substance flows through the body.
Technically, these are not true blood substitutes, but supplements. They don't do everything blood does, such as fight infections; their primary job is to carry oxygen to body tissues, which is what the body's hemoglobin (red blood cells) does--and the reason for most blood transfusions.
And they do it faster and more efficiently than real blood, because the oxygen-carrying molecules are tinier than red blood cells--a grain of sand compared to a basketball--and can get to hard-to-reach places.
But the benefits don't last as long--a day, compared with red cells, which circulate in the body for months.
With all the caveats and possible risks, most experts remain confident that the problems will be solved, and that artificial blood will have a place in medicine.
"Once scientists know the art, they can always fine-tune the products," the FDA's Alayash said. "People are already thinking ahead about the second and third generation" of blood substitutes.
If they didn't believe the obstacles could be overcome, he added, "they wouldn't have invested such time and effort over all these years."