Tears, Sweat, and Blood
The growing thirst for hemoglobin stand-ins
But substitutes would do more than just buttress the slimming stockpile. Indeed, the need for them "is enormous from several standpoints," says Harvey Klein, chief of transfusion medicine at the National Institutes of Health. The products are universally compatible because they lack A and B antigens, the proteins that distinguish blood as type A, B, AB, or O. Physicians therefore wouldn't have to waste time during emergencies trying to match blood types, says Steven Gould, president of Northfield Laboratories. "You can simply pull the product off the shelf and infuse it rapidly."
Many of the home-brewed substances promise to be less contaminated than human blood because they are grown in carefully controlled, sterilized conditions. They could potentially be tapped if another infectious disease like HIV unexpectedly invaded the blood supply. What's more, some of the new synthetics can be stored at room temperature, and their shelf lives are measured in years, not weeks, as is the case for regular blood. These qualities make them valuable for battlefield transfusions, rural ambulance care, and developing nations that don't have extensive access to refrigeration.
There are obstacles to overcome. Some of the substitutes, with their high-tech design and processing, could cost as much as $1,000 per unit--compared with $130 to $150 for banked blood. But even more problematic, biotech researchers are finding out that they don't really understand how synthetic bloods work once they are out of the test tube and inside a human being. "A lot of these companies tried to hit the home run without having the big knowledge base," says George Nemo, a virologist at the National Heart, Lung, and Blood Institute. In 1998, for example, one company had to halt its clinical trials because patients receiving its blood product were dying at more than twice the rate of those receiving a saline solution.
Scavenger. Now the company has gone back to the drawing board. It is unclear exactly what led to the deaths, but one idea is that naked hemoglobin--which isn't encapsulated by red blood cells--causes severe hypertension. Such free-floating hemoglobin has a tendency to scavenge nitric oxide, a chemical that normally helps relax blood vessels. Without the nitric oxide, blood vessels become constricted and pressure rises. Other scientists have also witnessed this hypertensive effect in animal and human studies with other blood substitutes, though they previously thought it wasn't so detrimental.
A major focus in the field, then, is trying to undo this untoward hypertensive effect. Some researchers are attempting to make a safer substitute by tinkering with human hemoglobin genes and inserting them into bacteria that will produce batches of the modified protein. The altered genes cause a subtle change in the structure of the protein, which in turn prevents the new molecule from "catching" the nitric oxide. "You can engineer out the bad side effects," says John Olson, a Rice University biochemist working on the project. "We want to redesign the molecule, reprogram it inside out."
At least four different products are now at the end stages of testing. If and when they will be approved is another question, since the Food and Drug Administration is prepared to move cautiously. "This is a product that doesn't exist in nature," says Abdu Alayash, head of the FDA's research program on blood substitutes. "It is a very unique situation." Perhaps so, but the early signs are raising hopes that patients like Edward Lee won't be sent home when their number finally gets called.
Blood squeeze
[Chart data are not available.]
[Chart labels] Units of blood; Collected from donors; Distributed to hospitals; (daily average); Jan. 2000; July; Jan. 2001; May
Source: American Red Cross
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