The U. S. Food and Drug Administration gave approval Monday to a Massachusetts company to begin the first clinical trials of a new blood substitute that contains hemoglobin from cows.
The production of blood substitutes has been a “Holy Grail” for chemists because of both the worldwide shortage of about 100 million units of blood per year and the military’s need for blood replacements that can be stored near the battlefield without refrigeration. An artificial blood also would eliminate the risk of contracting AIDS, hepatitis and other viral diseases from a transfusion.
If successful, the new tests would represent a major step in this direction.
The product, made by Biopure Corp. of Boston, has been tested in only a handful of individuals in Guatemala and in animals. The initial U. S. tests will be conducted on 30 healthy volunteers in Kalamazoo, Mich., by the Upjohn Co., which has purchased rights to the artificial blood.
“The trials in Guatemala looked quite good,” said hematologist Helen Ranney of the San Diego Veterans Administration Medical Center.
Researchers would like to find a substitute that could be used universally. Although AIDS is no longer considered a significant risk in blood transfusions, as many as 250,000 of the 4 million Americans who receive transfusions each year contract hepatitis. Furthermore, if blood types are not matched carefully before a transfusion, the recipient can suffer a fatal reaction.
It is hoped that the new blood substitute, called Hemopure, will meet all of these requirements.
The artificial blood is made of an iron-containing protein called hemoglobin. Each red blood cell in the human body contains about 5 billion hemoglobin molecules, which bind to oxygen in the lungs, then release it elsewhere in the body.
It is possible to extract hemoglobin from red blood cells and inject it into the bloodstream. But the hemoglobin molecules don’t survive long enough to do the recipient much good. They are so small that the kidneys clear them out of the blood within a few hours, whereas a successful blood substitute would have to last for at least 48 hours, long enough for the body to start regenerating new red blood cells.
One solution is to chemically link individual hemoglobin molecules into a much larger molecule, or polymer, that lasts in the blood for a few days. Several groups have done this 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 there is not enough human hemoglobin available to make this a practical approach. Biopure thus turned to bovine hemoglobin, which is much more widely available. An estimated 70 million cows are slaughtered in this country every year, and each has five to seven gallons of blood, most of which is wasted.
Bovine hemoglobin is very similar to human hemoglobin. Using it as a blood substitute in humans, researchers say, is similar to using insulin from pigs to treat human diabetics, a widespread practice.
Biopure has developed a process for removing all of the contaminants from the hemoglobin so that they do not trigger an immune reaction in the recipient. The purified hemoglobin is polymerized so that the kidneys do not filter it out of blood.
Jim Van Sweden, an Upjohn spokesman, said human tests will begin within the next few weeks at Bronson Hospital in Kalamazoo. The volunteers will receive small quantities of Hemopure while physicians monitor them for potential adverse reactions. If no such reactions appear, the volunteers will receive escalating doses.
Van Sweden said the tests are expected to take no more than “a couple of months.” If they are successful, researchers will go to Phase 2 trials, which will test the product’s efficiency in carrying oxygen. Those trials will be conducted at a number of medical centers in the United States and Canada.
A German company, B. Braun Melsungen, will begin similar trials in Europe later this year, a Biopure spokesman said.