Liquid Assets

By Lori Oliwenstein|Wednesday, September 01, 1993
RELATED TAGS: HEALTH POLICY
Blood bank researchers are looking for ways to convert all their assets into a single currency--type O negative, which anyone can use.

Blood bank administrators live in fear of a shortage. Their fears are routinely justified. Blood donations fall off predictably during the summer and winter holidays, and sometimes for no discernible reason at all. The banks can’t simply stockpile blood, because it goes bad, and freezing it tends to damage the blood cells. Blood is generally not kept on the shelf more than 35 days. Even then, the red cells are not as perky as fresh cells, says Jack Goldstein, a biochemist with the Kimball Research Institute of the New York Blood Center. When we’re giving red cells in a trauma situation, what we’re giving are essentially oxygen carriers, and one would like to give the freshest carriers possible.

Short of importing blood (which the New York center already does; it buys 30 percent of its carefully screened supply from Europe) or synthesizing artificial blood (which no one is anywhere near doing), blood banks can’t do much to increase their supply besides encourage more donations. But they can try to manage the supply more efficiently. One of the greatest inefficiencies in blood banking results from the fact that there are four different blood types; a bank may be throwing out one type of blood even while it is faced with a shortage of another. Goldstein is trying to stop that waste by making a blood bank’s assets more liquid. He’s working on a way to convert all blood cell types into universal cells--O- type cells--that can be transfused into anyone.

The differences among the four blood types--A, B, AB, and O--are found at the surface of the red blood cell, which is studded with chains of sugar molecules. All four types have the same basic chain. The next to last sugar on the chain is called galactose; the last is called fucose. Where the blood types differ is in the identity of another sugar that branches off the galactose, alongside the fucose. On an A blood cell that second sugar is always an N-acetyl-galactosamine; on a B cell it’s another galactose, and on an AB cell, some chains have the one sugar and some have the other. But an O cell has no second sugar at all: its sugar chains all end with a lone fucose.

That’s why people with type O blood are universal donors. If a person receives blood cells carrying a sugar he doesn’t have, the foreign sugar acts as an antigen, stimulating his immune system to attack the transfused cells. Thus A-type blood can be given only to A- and AB-type people, B-type blood only to B- and AB-type people, and AB-type blood only to the ABs themselves (because only they have both antigens). But O-type blood can be given to anyone: because a type O cell only carries sugars that are found on every red blood cell, it is considered benign by all immune systems.

So, Goldstein reasoned, if you could get rid of the antigens-- strip the N-acetyl-galactosamine off the type A blood cell, and the second galactose off the type B--you could essentially convert other red blood cells into type O cells that you could transfuse into anyone. Then as long as a blood bank had any blood at all, it would have blood of the right type. And the way to get rid of the antigens, Goldstein realized, was with enzymes. The sugars were put on by enzymes, he explains, so different types of enzymes should be able to take them off. The problem is just to find the right ones.

Goldstein and his colleagues have already succeeded in converting type B cells into type O cells. The enzyme they used had been identified in previous, unrelated research; it came, oddly enough, from unroasted coffee beans. (Enzyme hunters leave no cell unturned.) But it did the necessary trick: when the researchers mixed it with B cells for two hours, it cut the terminal galactose off the cells’ sugar chains without also severing the penultimate galactose--the one that both the terminal galactose and the fucose were hanging from. Without the extra galactose, the type B cells became type O cells.

After testing the cells in a test tube to make sure they could still carry oxygen, then in gibbons to see if they were safe to use, the researchers began transfusing them into human volunteers of various blood types. The new O cells survived nicely--living for up to 120 days, like normal red blood cells--and weren’t attacked and destroyed by the body. People whose own blood was type O and who received large doses of the transformed B cells did experience an unexplained, short-lived rise in the number of anti-B cell antibodies floating in the blood. But the antibodies didn’t attack the transformed cells, and Goldstein and his colleagues are still trying to work out whether that phenomenon is something they ought to be concerned about.

Meanwhile they’re also trying to convert type A red blood cells into type O--a project that is proceeding more slowly. Finding an enzyme that cuts the N-acetyl-galactosamine sugar from an A-type chain has proved to be difficult. After screening an enormous number of organisms, from microbes to mammals, Goldstein and his colleagues finally found an enzyme in chicken livers that seemed to do the job. But it turned out to work on only one of two subtypes of type A people. So the search continues for the right enzyme--or combination of enzymes--that will convert all type A cells into type O cells.

Finally, there’s the question of the Rh factor, another antigen-- but a protein this time instead of a sugar--that is found on red blood cells. That’s another kettle of fish altogether, says Goldstein. The vast majority of people have this antigen, and are thus dubbed Rh-positive. Those who don’t are called Rh-negative, and if they receive a transfusion of Rh-positive red blood cells, their immune systems will recognize the foreign protein and attack and destroy the cell, even if they’re getting the right blood type in other respects. On the other hand, an Rh-positive person receiving Rh-negative blood won’t have such a reaction, since there’s no antigen to react to.

Since most people are Rh-positive, the Rh factor is not as big a problem for blood banks as different blood types are. But Goldstein and his colleagues are still trying to find a way to convert Rh-positive into Rh- negative--to strip the Rh antigens off the red blood cell at the same time they are removing the A or B antigens to convert it into a type O cell. Several labs are working on delineating the structure of this Rh protein, says Goldstein. Once we know what the structure is, we can attempt to remove it or alter it. Then we would have truly universal--O negative--red cells.
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