Artificial Blood From Cow Hemoglobin Passes Tests
A new form of artificial blood made from cow hemoglobin has been successfully tested in humans for the first time, a Boston-based company said Friday. The finding is a major step forward in the quest for blood substitutes that would both increase the blood supply and greatly reduce the risk of viral infections resulting from transfusions.
The tests on the artificial blood were conducted on 10 volunteers in Guatemala because the Food and Drug Administration has not yet given approval for testing in the United States, officials of Biopure Corp. said at a New York City press conference sponsored by the Guatemalan mission to the United Nations.
U.S. researchers were pleased, but remained cautious about the finding because it has not been replicated elsewhere.
“If it really works out and the data are there to support their conclusion, this would be a significant advance,” said hematologist George Nemo of the National Heart, Lung and Blood Institute in Bethesda, Md. “It’s very encouraging.”
“It certainly would be very exciting if it’s correct,” said hematologist Helen Ranney of the San Diego Veterans Administration Hospital, “but we would have to be fairly cautious about wider applications without further studies.”
The development of a blood substitute has been a major thrust of the biomedical community in the last decade because of many different problems with the blood supply. Currently, the world has a shortage of about 100 million units of blood per year, according to Carl Rausch, president of Biopure.
Another problem is the transmission of infectious diseases. Acquired immune deficiency syndrome is not considered a major problem, but about 250,000 of the 4 million Americans who receive a blood transfusion each year contract hepatitis.
“Every time you take blood, it’s like putting a quarter in a slot machine,” said hematologist Charles Huggins of Massachusetts General Hospital. “If you are unlucky and come up with three lemons, you can get hepatitis or something else.”
Whole blood is also very expensive to collect, store and administer. It is perishable, and cannot be stored for more than three weeks, even in refrigerators. It therefore cannot be used routinely for treatment of accident victims and battlefield casualties. The military, especially, would like to have a blood substitute that would remain stable for months or years.
Finally, if blood types are not matched carefully before a transfusion, the recipient can suffer a fatal reaction. Researchers would like to find a substitute that could be used universally.
Although scientists have had some success with inert compounds called fluorocarbons, much of the recent research has centered on an iron-containing protein called hemoglobin. Each red blood cell in the human body contains about 5 billion hemoglobin molecules. These molecules bind to oxygen in the lungs, then release it elsewhere in the body where it is needed.
Many researchers have experimented with extracting hemoglobin from human red cells and injecting it directly into the blood stream. But hemoglobin is so small that the kidneys clear it out of the bloodstream in a few hours. Most physicians agree that an effective blood substitute must persist in the bloodstream for 48 to 60 hours.
One solution to this problem is to chemically link individual hemoglobin molecules together into a much larger molecule, or polymer, that persists in the blood.
Several different groups have experimented with human hemoglobin and shown that the polymer is a safe and effective substitute for blood in a variety of animals, including rodents, dogs and primates.
But not much human hemoglobin is available. It would be obtained from outdated blood, and possibly no more than 3% of the 14 million units collected in the United States is discarded each year.
Many researchers have thus turned to cow hemoglobin--a prospect that is not as outrageous as it might seem. Hemoglobin is not easily rejected, and cow hemoglobin is similar to its human counterpart.
The use of bovine hemoglobin to replace human hemoglobin, researchers say, is little different than the use of insulin from pigs to treat human diabetics, a process that is widespread.
Bovine hemoglobin is also plentiful. An estimated 70 million cows are slaughtered in this country every year, and each has 5 to 7 gallons of blood, most of which goes to waste.
Biopure and other companies have polymerized cow hemoglobin and shown that it is as effective in animals as polymerized human hemoglobin, but the companies have not yet been able to carry out human trials in this country.
The delay was caused by discouraging results obtained with polymerized human hemoglobin in human experiments conducted by Northfield Laboratories Inc., of Northfield, Ill. Northfield found no side effects when they infused the human product into healthy individuals. But when five anemic individuals were infused with the product, they complained of chest pains, dizziness, and general discomfort.
At a March 14 meeting of researchers, the FDA recommended that no further human studies be conducted until the problems were investigated.
Biopure officials believe the adverse reaction was caused by impurities in the Northfield preparation that are not present in theirs, which is produced by a slightly different process. They encouraged their Guatemalan licensee, Hemo-Innovations, to conduct the studies at the Herrera Llerandi Hospital, which is affiliated with Francisco Marroquin University in Guatemala City.
Dr. Rudolf Garcia-Gallont first injected about a pint of the material into himself on Feb. 13. When that was successful, he injected a similar amount into nine volunteers from the United States, Guatemala, the Netherlands and Switzerland. They found that there were no negative responses and no side effects or discomfort to the volunteers.
“I started it with myself and I felt good enough to inform everybody that we have done it in Guatemala,” Garcia-Gallont said Friday.
The results were announced in a press conference rather than a formal paper because “we want to share the information with the international community because of the urgent need for a blood substitute,” said Guatemala’s U.N. Ambassador, Francisco Villagran de Leon.
The company has sent the information about the tests to the FDA, and the president of Guatemala, Vincio Cerezo, has invited the Pan American Health Organization to participate in the continuing experiments.
