Medical researchers in San Francisco have made artificial red blood cells and then used them, in salt water, to replace half the blood in rats. The animals, which ordinarily would have died from such a blood loss, survived with only minimal side effects, showing that the artificial cells were able to pick up oxygen in the lungs and deliver it to the rest of the body.
The feat, believed to be the first of its kind, shows that it may be possible to develop a new kind of blood substitute that doctors could use in emergencies to treat human victims of massive blood loss.
The newly created artificial blood cells, however, can only be of temporary value because they perform only one of the many functions of red blood cells. In addition to carrying oxygen, red cells must process carbon dioxide, a bodily waste product, and regulate the acidity of blood.
In addition to red cells, blood also contains a liquid called plasma and several other types of cells that are part of the infection-fighting immune system.
Because the artificial cells lack these other abilities, they could never substitute entirely for real blood. Still, the researchers found, the ersatz cells were able to sustain rats when substituted for 95 percent of the animals' blood. Two of five rats tested this way survived for a surprising 18 hours.
One advantage of the artificial blood cells is that they can be stored for at least six months, about six times longer than natural blood, and could theoreti- cally be given without regard to the recipient's blood type.
The scientists who made the artificial cells stress that their development is only an experimental prototype and that it will be several years before they are proven to be safe and effective for use in human beings.
"I have no doubt that eventually we will see the construction of viable artificial red blood cells from scratch that will prove useful as a temporary substitute for red cells," said C. Anthony Hunt, a pharmaceutical chemist at the University of California, San Francisco.
Hunt and three colleagues, Ronald R. Burnette, Roderick D. MacGregor and Anne E. Strubbe, report their feat in next week's issue of the journal Science, released yesterday.
Research on blood substitutes began more than 50 years ago, but in recent years most attention has focused on a synthetic oil called perfluorocarbon. Cheap and relatively nontoxic, this substance is able to carry oxygen, but the Food and Drug Administration has refused to allow its use in humans because it does not carry enough oxygen and because it has other adverse effects.
As a result, scientific attention turned to a search for new ways of using the body's own oxygen-carrying molecule, hemoglobin. Hemoglobin is available in large quantities of donated blood that has been kept too long in blood banks to be safe. While such blood must now be thrown away, the hemoglobin inside the red blood cells is still good.
"What we've done is found a way to take that perfectly good hemoglobin and repackage it inside an artificial cell," Hunt said.
Hemoglobin by itself has not proved effective because, once outside the protective environment of a cell, it loses its ability to give up oxygen, which it must do if body cells are to receive the oxygen. Isolated hemoglobin also quickly breaks down.
While some researchers are working on ways of chemically treating hemoglobin to help it retain its useful abilities, others, such as Hunt, are taking the alternative route of creating artificial red cells.
The artificial cells consist of microcapsules whose walls are made of special fat molecules that spontaneously align themselves into sheets or bubbles, much like the membranes surrounding most animal cells. They are manufactured in a process like that developed years ago to encapsulate "scratch and sniff" scents or the chemicals impregnated in carbonless "carbon paper."
Instead of these chemicals, the fatty membrane surrounding the artificial blood cell contains hemoglobin. Oxygen molecules easily diffuse in and out of the membrane.
Hunt said laboratory studies show that once transfused into an animal, the artificial cells are gradually broken down with a half-life of about six hours. In other words, about half the cells break down in six hours, half the remaining cells deteriorate in the next six hours, and so on.
Hunt said that such limited survival of the cells would be useful in emergency treatment of humans, tiding them over long enough, for example, to be transported from the scene of an accident to a hospital. But he said his goal is to improve the cells to extend their half-life to somewhere between 24 and 72 hours. In this event, the body's normal process of manufacturing true red cells could keep pace with the loss of artificial cells.
In addition to emergency medical treatment, Hunt said that artificial red cells could be used in surgery for patients with rare blood types or where donor blood is to be avoided.
Also, artificial cells may be useful in treating injuries where swelling constricts blood vessels too much to allow true red cells to pass. The artificial cells, being much smaller, might still circulate if injected into vessels near the swelling.
Yet another possibility, Hunt said, is veterinary medicine, where there are no blood banks.