When Herbert Kay faced major surgery in January to repair an aortic aneurysm, he told his doctor that he did not want to receive a blood transfusion unless his life was in danger.

The risk of contracting HIV, hepatitis C or even "mad cow disease" from donated blood was a concern to the 70-year-old research psychologist. "I wanted them to use a transfusion only as a last resort," he says.

Kay got his wish: His operation was done using a milky white substance that scientists hope will prove to be a major breakthrough in the effort to find a viable blood substitute. If it does, "bloodless surgery," preferred by increasing numbers of patients and doctors, could become commonplace.

Kay, of West Caldwell, N.J., was part of a clinical trial that is testing the substance, called Oxygent. The concoction, which looks somewhat like baby formula, has been used in hundreds of patients around the world during clinical trials and appears to be headed for federal approval and widespread use.

"I'm convinced that within the next year or so, we will have a licensed product," says Harvey Klein, chief of the department of transfusion medicine at the National Institutes of Health. NIH funds some research in the field, but most is done by private companies.

Doctors and scientists call Oxygent an oxygen carrier, not a blood substitute. They cannot yet come close to matching the miraculous jobs that blood cells perform in our bodies. But Oxygent, made by Alliance Pharmaceutical Corp. of San Diego, appears to do a key, lifesaving job well: It delivers oxygen in ways that are often better than the body's own red cells.

Beyond use in surgery, doctors see the substance as being a lifesaver for heart attack and stroke victims and severe trauma patients who can die in the minutes that it takes to identify the patient's blood type, acquire donated blood that matches and deliver a transfusion.

Federal officials caution that it is too early to know whether further clinical testing will find unexpected downsides, but there is growing optimism that Oxygent and other oxygen carriers might finally provide a safe alternative for donated blood and ease the strain on the nation's already overtaxed blood banks.

The U.S. blood supply is chronically low; American blood banks are expected to come up about 250,000 units short this year. Officials are forecasting a national shortage in July, when regular donors go on vacation and college students scatter.

Because the nation has a robust and competitive blood collection system, shortages are usually filled before lives are threatened. But coming up short means that elective surgeries and other non-critical needs are not met. The supply is so fragile that severe weather such as snowstorms or hurricanes often lead to surgeries being canceled. Donated blood is only good for about 42 days, and less than 5% of eligible donors give blood.

While blood is a scarce resource, it also comes with a risk. New viral screening processes are being tested, but scientists have not been able to call donated blood 100% safe. Hepatitis C is transmitted about once in every 100,000 transfusions, and HIV, the AIDS virus, about once in every 676,000. There are 11 million transfusions a year.

Long, difficult road

Attempts over the past 25 years to create a safe blood substitute have seen high hopes turn to tragic disappointment.

Some experts predicted in the mid-1990s that Baxter Healthcare's HemAssist, a hemoglobin-based substitute, would be approved within a few years. But the company halted its clinical trial suddenly when trauma patients died at an unexpected rate. Of the 52 trauma patients who got HemAssist, 24 died.

When doctors and scientists looked more closely at what had happened, they were surprised to see that the blood substitute had caused the blood pressure to rise dramatically. "It reflected that we didn't understand what these things were doing at the cellular level," Klein says.

Baxter has moved to a new generation of hemoglobin-based substitutes. The company is genetically engineering hemoglobin cells but has not begun human testing. Baxter cautiously predicts its new version could be on the market by 2007.

Unlike other competitions within the drug industry, where successes and failures largely remain trade secrets, the rest of the industry has learned from Baxter's failure. The Food and Drug Administration held public meetings so all scientists could learn from one another. Baxter gets high praise from federal officials for sharing its lessons. "We're much farther ahead than we were when Baxter stopped their trials," Klein says.

The Alliance trial of Oxygent is typical of the way trials have been redesigned since HemAssist failed in emergency rooms. Test subjects now are picked from stable surgery patients instead of those who are fighting for their lives, thus reducing the chances that unexpected medical complications will skew the tests.

The product is administered in the operating room under the supervision of top anesthetists instead of in the chaotic emergency room. That allows the doctor at the head of the operating table to watch the patient closely for trouble.

Instead of determining the value of the substitute largely by patient survival, today's studies allow doctors to monitor all the patient's vital signs and blood functions closely before, during and for many days after surgery. That allows doctors to track more subtle changes in the body after the substitute is given.

Doctors involved in the study say the early results are remarkable, with great benefit to the patients and no signs of serious side effects. But others say that the big hurdle -- testing in trauma patients -- remains. Baxter's HemAssist passed similar, well-controlled surgical trials only to fail the real test of trauma cases.

Alliance says that the problems that led to the HemAssist failure were seen on a smaller scale in the surgical trials and that there have been no serious side effects of Oxygent. But some blood experts caution that today's enthusiasm for blood substitutes is not unlike the previous waves of excitement.

"I would be surprised if something got through the FDA in two years," says Linda Chambers, a senior medical officer at the Red Cross. "It's been a long road with a lot of bumps. The FDA will be very careful approving any of these."

Competing with nature

Human blood is a perfect stew of platelets and red and white cells in plasma. It performs countless life-sustaining tasks, not all of which are fully understood.

Blood transfusions are used for many medical purposes today. But it's when a patient is in shock, when medics need to deliver oxygen throughout the body within seconds to save a life, that blood transfusions can take too long. Blood must be preserved carefully, so it's not always handy. Blood must be matched to each recipient, and those tests take time.

This urgent need for an oxygen delivery device has driven scientists down two general paths: modifying the blood's own hemoglobin and developing synthetic substitutes. Hemoglobin-based substitutes such as HemAssist and others require donated blood from either people or cows; Alliance's Oxygent is made primarily of inexpensive, easy-to-produce fluorocarbons.

They dissolve gases, moving oxygen from the lungs to vital organs and remote regions of the body and cleansing the body of carbon dioxide. In surgery, the fluorocarbon delivers to the body about twice as much oxygen twice as fast as the same amount of the blood's own hemoglobin. And because these particles are tiny compared to the body's red blood cells, they can swirl freely through the body's 60,000 miles of capillaries and breeze through blocked arteries in heart attack or stroke victims.

If Oxygent is approved for use in surgery, experts say, doctors will begin using it "off label" for other purposes, such as getting oxygen into a damaged brain.

"There is potential for this to be used in stroke patients where you want to deliver oxygen to an area where the blood vessel is severely compromised," says Ronald Pellegrini, a surgeon who has given Oxygent to some patients at the University of Pittsburgh Medical Center. "It can get through very small spots."

Pellegrini and other doctors who are using the oxygen carrier say the benefits are obvious. But some downsides are noticeable, too. Patients sometimes get flu-like symptoms as their bodies try to filter the substance from the blood. And the number of platelet cells in the blood, key for forming blood clots, drops several days after Oxygent has been given.

Alliance says neither is a significant side effect, but federal officials say much more analysis is needed before the product can be judged for safety.

Alliance hopes to have tested Oxygent on more than 1,000 patients by the end of the year. More trials, including emergency cases, will likely follow. Even so, side effects that only occur once in every 10,000 cases might remain hidden. Eventually, the FDA must decide if the risk of what is still unknown outweighs the benefit of a substitute for blood. Officials say more tests on more patients will be needed to make such a decision.

"This is unlike any other biologic product out there," says Abdu Alayash with the FDA. "We're going against nature, so we are constantly surprised by some of the things that we discover as we go along. This is really new science."

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How to qualify as a donor

A blood transfusion is needed in the USA every two seconds. Donors can give blood every 56 days if they are:

* 17 or older.

* 110 pounds or more.

* In good health.

To find the nearest blood center or blood drive, call 800-448- 3543 or 888-256-6388. Or on the Internet: www.redcross.org or www.americasblood.org.