Science/Medicine : Blood Substitutes : Quest for a Wellspring of Life

November 30, 1987|SYDNEY JASON KEITH | S y dney Jason Keith is a Studio City-based free-lance writer. and

Stick a sterile pin into a fingertip and out comes a drop of your precious blood--precious because in just that tiny amount there are between 250,000 and 500,000 red blood cells from the "river of life" coursing throughout your body, carrying oxygen to and carbon dioxide from all your other body cells.

You won't miss that drop, really, because your bone marrow normally produces (and you lose) about 300 billion red cells every day--and that's only about 1% of the total number in your body.

If those numbers stagger you, consider that the red blood cell is the smallest in the human body. Its pinched, disc-like shape, size and flexibility enable it to travel through your arteries, veins and the tiniest of capillaries in between as it goes about its vital business.

In the absence of the oxygen it delivers to the body's cells, life would end in a few minutes. There is oxygen dissolved in the plasma (the liquid portion of the blood), but the red cells and their oxygen-holding protein, hemoglobin, carry about 99% of that life-sustaining gaseous element.

For more than 20 years now, researchers have been trying to find a safe and effective substitute for the red blood cell. But only recently has the research reached the stage of human clinical trials.

The advances come at a time when there is perhaps unprecedented concern about the purity of the nation's blood supply--spurred in large part by the AIDS crisis.

A blood substitute, then, would find widespread use.

Each year, about 4 million Americans receive blood transfusions, and 250,000 of them end up contracting hepatitis. A blood substitute also would greatly simplify transfusions by obviating the need to match the blood type of the recipient. In addition, a blood substitute would be a literal lifesaver in parts of the world where there are few blood banks, and in the treatment of trauma victims.

Many experts believe that the goal is within reach, but there are just as many who are convinced that it remains as elusive as ever.

The intensifying effort involves multibillion-dollar pharmaceutical companies, comparatively small and thinly financed independent laboratories, and scientific teams in both commercial and academic settings around the world.

Researchers are working on two approaches to the problem. One method uses chemical compounds known as perfluorocarbons, and the other involves the extraction and linking of hemoglobin molecules from natural red blood cells.

Perfluorocarbon chemicals--the Freon in today's refrigerators and aerosol propellents are examples--have been under study for more than 20 years. They can be formed into emulsions of particles suspended in ultramicroscopic dimension and capable of carrying oxygen to body cells while taking away their carbon dioxide waste, thereby imitating the role of hemoglobin, in part at least.

The promise of perfluorocarbons was demonstrated in experiments in 1966-67 during which the blood of a dozen laboratory mice was completely drawn off and then replaced for a few hours with oxygen-laden fluorocarbon liquids and water.

Dr. Leland Clark, who performed this and other pioneering experiments at the University of Cincinnati, reported that the lungs and other organs of his mice showed no damage after they subsequently lived out their normal life spans. His work demonstrated the potential of perfluorocarbons in the life-essential oxygen-carbon dioxide exchange.

However, perfluorocarbon particles carry less oxygen than hemoglobin, and recent clinical trials have indicated that their usefulness as a red-cell substitute, except in specialized treatments, is marginal. They can be prepared in higher oxygen concentrations, but at some risk to the lungs.

These perfluorochemical particles can be made at about 1/70th the size of red blood cells, according to the maker of Fluosol, Los Angeles-based Alpha Therapeutic Corp., a U.S. subsidiary of Green Cross Corp. of Osaka, Japan.

A thin, milky fluid that must be kept frozen until used, Fluosol has been tested extensively in humans and laboratory animals in Japan and this country over a period of years and has proved to be useful in certain coronary surgical procedures, cancer radiotherapy and chemotherapy. It was precisely because of their oxygen transport capabilities and incredibly ultramicroscopic size that perfluorochemical emulsions came to the attention of heart surgeons and cancer radiologists.

In balloon angioplasty, in which plaque-clogged arteries are opened by the inflation of a tiny balloon inside the blood vessel, blood flow to the part of the heart the artery serves is interrupted; pain and damage can result. But because of the tiny size of the perfluorocarbon particles, the use of Fluosol can assure the continuing flow of oxygen through the heart muscle and thus avert possible disaster, according to recent reports in medical journals.

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