Q. Why have humans developed different blood types?

Concord

A. We don't know, says Dr. George Garratty, scientific adviser to the American Red Cross and a leading authority on blood types. He says we're just starting to realize that the antigen molecules that distinguish one blood type from another have a lot of other important jobs elsewhere in our bodies.

An antigen is a molecule that will set off the forces of the immune system to get rid of things that may be bad for us.

Here's how it works. All our cells have numerous molecules on the surface that, like little billboards, announce, `This cell is part of us. It's supposed to be here. Do not attack!'

Immune system cells traveling around in our blood are trained to recognize self molecules and pass right by. But if our immune system inspects a foreign cell in our blood and doesn't recognize a molecule on the surface, it treats that molecule as an antigen and attacks. That attack often involves creating a molecule called an antibody designed specifically to fit the unique shape of the foreign antigen. The antibody attaches to the antigen and, like a chemical loudspeaker, summons other components of the immune system to come destroy the invader.

In 1901 Karl Landsteiner of Austria noticed that some red blood cells had one kind of molecule on their outer surface, which he labeled simply A, and some had a different one that he labeled B.

Some didn't have either, and he called those O (as in zero, not the letter ``o''.) Those molecules turned out to be antigens. The discovery made transfusions possible and earned Landsteiner a Nobel prize. Since then, we've discovered nearly 300 different antigens on red blood cells, with names like Duffy, Lutheran, Dombrock, Kidd, Diego, P, Yt, and Kx.

They're mostly named for the people whose blood carried unique antibodies. Like Mr. Duffy, the English patient who got sick after a transfusion. He received the right ABO type. But there was another antigen on the transfused blood that his immune system didn't like. It made a special antibody cell nobody had ever seen before to fit onto and attack that antigen. That antigen was named Duffy.

Rh is another well-known red blood cell antigen. Rhesus monkeys experimentally transfused with human blood made the antibody this time, thus the Rh.

If you have this antigen (there are actually 40 antigens in the Rh family) you're Rh positive. If you don't, you're Rh negative. Rh and ABO antigens are the most important ones determining whether a transfusion will work.

But nature didn't put antigens on our red blood cells to make sure transfusions would work. Transfusions are not a natural occurrence. So what's going on?

It turns out that these molecules are involved in many other biological processes.

Remember Duffy? Well, many Africans and African-Americans don't have a Duffy antigen. As a result, they can survive a form of malaria that infects the cell only if it can attach to Duffy. No Duffy antigen, no P. vivax malaria.

Remember the P antigen? One species of E. coli bacteria needs that molecule to attach to tissue cells in the urinary tracts of children. Some children have that molecule. Some don't. Those without it don't get that kind of urinary infection.

The molecule that the bacterium H. pylori attaches to in the stomach lining to cause ulcers is an antigen when it's on red blood cells.

On some non-blood cells, antigens appear, or disappear, or change, as tumors go from benign to cancerous. Some antigen molecules appear to play a role in helping cancer spread through the body. Some help blood cell membranes maintain their shape. Some help cells process proteins.

Statistical associations, which don t automatically prove cause and effect, show that A's have more cancers than O's and that O's bleed more than A's. B's defecate the most. O's have the best teeth, but suffer more than other blood types from plague infections. A's have the worst hangovers.

There are wide racial, ethnic, and geographic differences in blood types around the world. There are twice as many O's among native Australians as among Japanese. Eskimos in Greenland are 25 times more likely to be B's than Navajos in North America. Citizens of India are four times more likely to be B's than residents of England.

All the findings suggest that molecules that distinguish blood types probably developed differently in different people as part of the random processes of mutation and evolution. As nature tests which ones are best, some will offer advantages, some disadvantages, in ways that immunohematologists like Garratty are only beginning to understand.