Robert M. Winslow of the University of California at San Diego replies:
"The concept of 'artificial blood' sounds simple, but it isn't. When William Harvey first described the circulation of blood in 1616, scientists starting thinking about whether blood could be removed and replaced by other liquids, such as wine and milk, for example. They thought that by doing so, diseases could be cured and even that personalities could be changed. Obviously, there were some interesting but disappointing experiments!
"Modern efforts to produce artificial blood were spurred on by the military in World Wars I and II and, more recently, by the discovery in the early 1980s that HIV could be transmitted by blood transfusion. Blood is now safe, thanks to improved collection and screening by blood banks. But it still has to be cross-matched and can be stored for only a few weeks before it has to be discarded. If a solution that could replace blood were immediately available, if it were completely safe, and if it could be stored for long periods, it would be extremely useful in emergencies, disaster and wars--not to mention in countries where blood is not collected and stored as it is in the U.S and western Europe.
"Blood does many things, of course, and artificial blood is designed to do only one of them: carry oxygen and carbon dioxide. No substitutes have yet been invented that can replace the other vital functions of blood: coagulation and immune defense. Therefore, the replacement solutions being developed today are more accurately described as oxygen carriers. There are basically two types of oxygen carriers, which differ in the way they transport oxygen. One is based on perfluorochemicals, the other on hemoglobin.
"Perfluorochemicals are inert materials that can dissolve approximately 50 times more oxygen than blood plasma, the liquid that surrounds the red cells. Perfluorochemicals are cheap to produce and are completely free of biological materials so there is no risk of infectious agents contaminating them. In order to work, however, they must be combined with other materials that enable them to mix in with the bloodstream. These companion materials are fatty compounds known as lipids. They take the form of an emulsion, a suspension of extremely small particles in a liquid that can be injected into a patient. One such lipid product was approved by the Food and Drug Administration, but it has not proved successful, because the amount that can be administered is not enough to achieve a significant benefit. Improved versions of perfluorocarbon emulsions are being developed but have not yet reached the market.
"Hemoglobin-based oxygen carriers (HBOCs) utilize the same oxygen-carrying protein molecule found in blood. Oxygen bonds chemically to the hemoglobin, whereas it dissolves only into the perfluorocarbon emulsions. HBOCs differ from red blood cells in that the hemoglobin is not contained within a membrane. The membrane of a red blood cell contains the antigen molecules that determine the 'type' of the blood (A, B, AB or O). Because HBOCs have no membranes, they do not need to be cross-matched by type and can be given to any patient without previous testing. In addition, these artificial oxygen carriers can be stored for long periods, greatly simplifying the work of the blood bank. Best of all, HBOCs can be used in situations and locations where real blood is not available, as at disaster sites, underdeveloped countries or battle zones.
"Two main problems arise when hemoglobin is removed from the red blood cells; these problems account for the large amount of scientific research that has been conducted so far in this area. First, the red cell membrane protects hemoglobin from degradation and protects tissues from the toxic effects of free hemoglobin. Second, when oxygen is being delivered by a cell-free carrier instead of red blood cells, complex biological mechanisms alter the flow through the smallest blood vessels (the arterioles and capillaries). Major advances have been made in overcoming both of these problems, and several HBOC products are now in advanced human trials. It is anticipated that in the next one to two years the first of these products will become available to physicians for use in patients.