Blood of the Future

New research is based on chemically synthesized products and hemoglobin solutions

Manipulation of transgenic plants in Meristem Therapeutics' laboratories.

For several decades, scientists have been searching for a blood substitute that would eliminate blood group compatibility problems and the serious risk of viral contamination. An artificial blood would also counter increasing blood supply difficulties. The objective was to create a product capable of supplementing the vital role of carrying oxygen from the lungs to the body tissues.

Over the last few years, research teams in France have focused primarily on two different paths: chemically synthesized products and hemoglobin solutions. Early research on chemically synthesized products has been oriented toward the study of oxygen carriers known as perfluorocarbons (PFC), made up of a carbon atom chain and fluoride. These composites are characterized by two properties -- a highly stable carbon-fluoride bond, and the ability to considerably increase the solubility of gases in their medium. PFCs are the best known solvents of oxygen and carbon dioxide, dissolving 50% of their volume in oxygen, whereas water dissolves only 2%.

Since fluorocarbons are chemically inert and insoluble in plasma, they must be made into an emulsion for injection into the bloodstream. Unlike hemoglobin, which actively captures and releases oxygen, oxygen passes directly from the lungs to the PFCs suspended in the plasma without going through the red blood cells. When equal quantities are compared, perfluorocarbons provide more oxygen than hemoglobin, if the patient is in an oxygen-enriched environment such as respiratory assistance.

The first generation of perfluorocarbons used as blood substitutes in mice during the 1960s had a major drawback -- poorly eliminated by the organism, they accumulated in the tissues of the body. During the 1980s the Green Cross Corporation, Osaka, Japan, developed a new type of fluorocarbon emulsion as a way to oxygenate the heart muscle during coronary angioplasties. However, this product was too unstable for use.

A product called Oxygent, developed in the 1990s by Alliance Pharmaceutical Corporation, San Diego, CA, seems to have overcome these obstacles. Alliance used a water-based emulsion of phospholipids and bromo-perfluoro-octane, a fluorocarbon that is quickly excreted by the lungs. This blood substitute can be produced in large quantities and stored for two years at 41°F, and for more than four months at 86°F, compared to 40 days at 39°F for natural blood. Oxygent can be used during surgical operations and clinical trials are currently underway for this substitute.

Hemoglobin from transgenic plants

The other approach in the development of artificial blood is that of biotechnology. Genetic engineering has given a new impetus to research focused on the biosynthesis of human recombinant hemoglobin, that could be injected into patients as a hemoglobin solution.

The use of genetically modified plants could provide a solution. In this case, there would be no need to build other reactor vessels, since the hemoglobin would be produced in situ, in the plant directly. Two French research teams have succeeded in growing tobacco plants capable of synthesizing human hemoglobin.

A feasibility study has shown that human hemoglobin can be reproduced from a plant, using means available in a molecular biology laboratory (identification of genes, construction of the expression cassette, cloning techniques and genetic transformation). However, the output of this model needs to be increased, as the hemoglobin obtained from the tobacco plant represents only a small percentage of all the proteins extracted.

Although the development of artificial blood is still hindered by technological limitations, progress made in the last few years has been considerable. Both the scientific and industrial communities have unanimously recognized that artificial blood has become a reality, and blood substitutes should be available in the next two to three years.--FR

For more information:

Circle 575 - French Technology Press Office

Blood Supply Basics

• 30 million units of blood are transfused every year throughout the world, with one transfusion taking place every second in the industrialized world. Approximately 60% of these transfusions occur during surgery.
• 15.8 million pints of additional blood are needed each year throughout the world.
• 4 million units of blood is the estimated yearly deficit worldwide for the next 30 years.
• $13.5 billion dollars represents the worldwide market value of blood for all developed countries. The artificial blood market is estimated at between two and four billion dollars per year.