Pigs Altered to Make Human Hemoglobin
In a discovery that experts say marks an important step toward finding a substitute for blood, biologists attending an Anaheim conference announced Sunday that they have used genetic engineering techniques to create pigs that produce human hemoglobin.
In their announcement at the World Congress on Cell and Tissue Culture, officials of DNX Corp. of Princeton, N. J., said they have developed three so-called “transgenic pigs” that produce hemoglobin, the component of red blood cells that carries oxygen through the body.
“This is exactly the same sequence of human hemoglobin present in you and I,” said Dr. John Logan, director of research at DNX.
“Think of this just as a new manufacturing system. It is a human product, and the manufacturing site happens to be a pig.”
The company also says it has found a method for purifying the hemoglobin that will make it free of both animal and human infections--such as AIDS and hepatitis--and thus safe for all types of blood transfusions.
But doctors say that hemoglobin on its own can act only as a temporary substitute for blood. And company officials acknowledge that before the pig-produced hemoglobin can be approved for commercial use, it must pass a host of testing hurdles--a process that could take at least five years.
If the hemoglobin is eventually marketed as a blood substitute, experts say it could be stored at room temperature and transported in a way that blood cannot, and would thus help save lives on battlefields and in disaster zones. In addition, the hemoglobin would eliminate the need for matching blood types and could be stockpiled for use in the event of blood shortages.
The breakthrough is also significant because it marks one of the few times that scientists have successfully reproduced human proteins by using genetic engineering techniques with large animals. Dr. S. Gerald Sandler, chief medical officer for blood services at the American Red Cross, said that aspect of the DNX team’s work may ultimately have far greater applications than the creation of the pig-produced hemoglobin.
For example, he said, animals could produce proteins that could later be injected into humans who need them, in a manner somewhat akin to the way a diabetic injects insulin.
“There’s a textbook full of diseases that are inherited and they manifest themselves by the absence of a human protein,” Sandler said. “The principle of this is much more important than the very specific product, which is hemoglobin.”
According to Sandler, even if the hemoglobin were approved for transfusions it would not reduce the need for blood donations.
Hemoglobin that is not contained in red blood cells is filtered out of blood in just a few hours and does the recipient little good. Most researchers agree that a blood substitute must persist in circulation for at least 48 hours to be useful.
To get around this problem, many researchers have devised techniques for linking hemoglobin molecules together so they remain in the blood stream for several days. Earlier this year, Biopure Corp. of Boston began human tests of such a polymerized hemoglobin made from cow hemoglobin, which is very similar to human hemoglobin.
The key to making the pig-produced hemoglobin available for mass use will be the company’s ability to purify it, according to Dr. Paul McCurdy, an expert in hematology at the National Heart, Lung and Blood Institute in Bethesda, Md. He noted that other researchers have run into serious safety problems when trying to use hemoglobin extracted from animals in human blood transfusions.
“If they indeed have found a way of purifying it, then more power to them,” McCurdy said. “It is useful research and, I think, a desirable thing to do, but (finding a way to purify hemoglobin) has been a pot of gold at the end of the rainbow for at least 10 or 15 years.”
Biopure was forced to abandon its U. S. trials of the cow hemoglobin about two months after they started, although the company has not announced a reason for the stoppage. Trials of the product continue in other countries.
According to Logan, DNX began its research project in 1986.
The company selected pigs because they give birth in litters--thus giving the researchers the chance to breed the pigs on a large scale--and because they do not contract human diseases like AIDS and hepatitis.
Logan said the researchers injected fertilized, one-cell eggs from “donor pigs” with the gene for human hemoglobin DNA, and then transferred the cells to other pigs.
Logan would not reveal when the first hemoglobin-producing pig was born, but said an average of five such pigs are produced in every 1,000 born as part of the experiment. Once the pigs carry the human hemoglobin, they can be mated; DNX says the mating process has already begun.
Times science writer Thomas H. Maugh II contributed to this story.
