CHAPEL HILL -- At 3 years old, Ricky LaGrande has undergone a life change.

He had a bone-marrow transplant last September, and now he no longer has sickle-cell anemia. His twin brother, Rayshawn, still has this genetic disease and may face a lifetime of intermittent, excruciating pain unless he, too, gets a transplant.

The marrow is waiting in a freezer at the University of North Carolina Hospitals. The twins' sister, Etascia, gave enough for them both on the day of Ricky's transplant. She is 4.

"I just told her that she's going to help her brothers," recalled the children's mother, Evelyn West of High Point. "It wasn't anything foreign for her."

West is not sure Rayshawn understands what his brother has been going through. He asks, "What's wrong with Ricky? Why's he got a tube in his nose?" Says West, "He's going to travel the same road."

The transplant has turned her family life upside-down. While she has stayed with Ricky in the hospital, the twins' father has kept Etascia and Rayshawn at home, an hour and fifteen minutes' drive from Chapel Hill.

West gave up her position in customer service at United Parcel Service so she wouldn't have to choose between her job and her children. Medicaid and disability benefits cover the twins' medical bills, but their father still has to earn a living. Each day when he goes to his maintenance job, his mother keeps the children.

West looks forward to their all being in one place again. But she also knows that her boys are fortunate to get the chance of a cure.

A mistake in a gene

Like many African Americans, West grew up with some knowledge of sickle-cell anemia. She has sickle-cell trait. From one of her parents, West got a copy of a hemoglobin gene with a mistake in it. From the other parent, she got a normal copy of that same gene. West's normal gene compensates for the bad one, so she does not have sickle-cell disease. But she has the ability to pass it on.

Whether genes have mistakes is important, because our genes contain instructions on assembling proteins -- chains of amino acids -- that do the work to keep our bodies functioning.

Four protein chains -- two alpha chains and two beta chains -- make up every molecule of hemoglobin. People with sickle-cell disease have two copies of a gene that codes for a mistake in the sixth amino acid of the 146-amino acid beta-hemoglobin chain. Each red-blood cell contains millions of hemoglobin molecules, which carry oxygen from our lungs to tissues all over our bodies. When red-blood cells are on the way back to the lungs for more oxygen, sickle hemoglobin molecules are particularly likely to stick to each other. At first, they do this randomly, but then they form long fibers with a uniform pattern.

This distorts the red-blood cells -- which normally resemble a hole-less bagel -- into banana or sickle shapes. Once elongated, the cells become rigid and lose the flexibility that normally enables them to zip through blood vessels and squeeze into capillaries. If these red-blood cells can get back to the lungs and become reoxygenated, the long fibers that ensure rigidity fall away from each other; sickled red-blood cells again resume their normal bagel-like shape. Eventually, though, a red-blood cell's membrane loses its flexibility, and the cells become irreversibly sickled. When they travel through the spleen, irreversibly sickled cells are recognized as abnormal and destroyed, which accounts for the anemia in sickle-cell anemia.

The anemia is by far the milder problem. When red-blood cells are sickled, they can cause blockages in the circulatory system. That means nonsickled cells can't carry oxygen to whatever tissue lies beyond the blockage. The tissue deprived of oxygen dies. And dying tissue causes pain.

Pain crises, as they are called, can be brought on by circumstances considered nonthreatening by most of us: exposure to cold, dehydration, high altitude, infection, rigorous exercise. Anything that makes the body expend oxygen affects the solubility of sickle hemoglobin.

An example: Sugar in tea

Think about dissolving sugar in tea. If the tea is hot, the sugar dissolves more easily. If the tea is cold, the sugar tends to stay crystallized and settle in the bottom of the glass. Likewise, trying to dissolve a little sugar in a big glass of tea is easier than trying to dissolve a lot of sugar in a small glass of tea. Of course, crystallized sickle hemoglobin in a solution of normal hemoglobin is far more serious than the iced-tea analogy indicates. The pain that results when sickle hemoglobin crystallizes and causes blockages in the circulatory system can send sickle-cell sufferers screaming to the emergency room.

Blockages cause sickle-cell patients even more serious problems than pain. People with sickle-cell disease get strokes from circulatory blockages in the brain or spinal cord. Blockages in ducts can cause their livers or spleens to enlarge and die. Sickle-cell patients get poorly healing ulcers on their ankles from nearby blockages. Their fingers and toes grow to different lengths because of blockages in their bones.

Watching her boys suffer

Because she has sickle-cell trait, Evelyn West's body makes only 25 percent to 45 percent sickle hemoglobin. She makes enough normal hemoglobin to escape the kind of pain she has had to watch her sons endure. By the time they were a year old, Ricky and Rayshawn were both suffering severe pain crises. Enrolling them in a chronic blood-transfusion program cut the frequency of the crises, because the infusions of normal hemoglobin diluted the sickle hemoglobin and helped prevent molecules from sticking together and leading to blockages. But the boys -- especially Ricky -- were still experiencing symptoms usually suffered by much older sickle-cell patients.

A bone-marrow transplant offered hope. The doctors wanted to use high-dose chemotherapy and radiation to kill Ricky's bone marrow, the factory for red-blood cells. Then the doctors wanted to infuse into Ricky undiseased bone marrow so that red-blood cells containing normal hemoglobin could grow.

To prevent Ricky's body from rejecting the transplant, his sister Etascia's bone marrow was used. However, Ricky still does not make normal hemoglobin. His sister has sickle-cell trait, and now, so does he. When they grow up and want to have children, they will realize that they, like their mother, could contribute to disease in the next generation.

Where the gene does good

An irony is that in parts of the world where malaria is a threat, having sickle-cell trait offers a protection. Malaria, caused by a parasite that is usually transmitted by mosquitoes, leads to fever, chills, sweating and even death. After an infected mosquito bites a person, that person's red-blood cells become little factories in which the parasite can flourish. But when the parasite gets into a red-blood cell containing sickle hemoglobin, that cell is even more likely to become banana-shaped. If it doesn't get stuck somewhere in the circulatory system, it travels to the spleen, where it is recognized as abnormal and destroyed. The malaria parasite is killed, as well, and has less opportunity to make the person ill. What's more, a sickled cell's loss of water or potassium or both may make it a poor home for the parasite.

People in the world's malaria belts who had neither sickle-cell disease nor deadly malaria were the ones who lived long enough to have children and keep sickle-cell trait in the population. In populations in equatorial Africa, the sickle-cell gene has a frequency ranging from 5 percent to 14 percent. The gene is also indigenous to Sicily, Greece, India, Saudi Arabia, Israel, Turkey and Iran.

The sickle-gene frequency among Caribbeans, Europeans and North and South Americans of African descent is about 4 percent.

Studies of beta-hemoglobin genes and clusters of mutations, or mistakes, from different populations suggest that the sickle mutation arose at least five different and independent times in history. Three arose in Africa: Senegal; Benin; and Bantu (which is also called CAR, for Central African Republic). A fourth type was found in populations in Cameroon, and a fifth was found in India and parts of Saudi Arabia.

Sickle cell in America

Most African Americans with sickle-cell disease have two bad copies of the beta-hemoglobin gene whose origins are some combination of the sickle-cell type from Senegal, Bantu and Benin -- a testament to the reach of slave traders early in American history. Today, sickle-cell disease is the most common genetic blood disorder in the United States, occurring in about 1 in 500 African-American newborns and 1 in 1,000 Hispanic newborns each year.

It was the first human disease to be defined at the molecular level. But almost 50 years after Linus Pauling and his colleagues identified sickle hemoglobin as different from normal hemoglobin, sickle-cell disease still has no cure other than bone-marrow transplantation. The best that most sufferers of sickle-cell disease get is treatment for their symptoms.

However, scientists who have studied sickle-cell disease have made progress in helping ensure that sufferers live longer and more comfortably. Until the late 1960s, it was widely believed that if sickle-cell disease didn't kill you as an infant, it would take your life by the time you reached 30. However, data now suggest that sickle-cell symptoms become milder as sufferers get older and that few seek medical attention after they reach age 30.

The conditions that have typically killed infants with sickle-cell disease include acute splenic sequestration, in which the spleen fills up with blood that can't escape; pneumococcal septicemia, in which bacteria that cause pneumonia get into the bloodstream; aplastic crises, in which tissue or an organ fails to develop normally; and acute chest syndrome, which can lead to congestive heart failure or respiratory failure.

Early diagnosis and treatment, as well as educating the parents of babies with sickle-cell disease, have reduced death from acute splenic sequestration by 90 percent. Getting children on a preventive regimen of penicillin helps keep pneumococcal infections at bay, but doctors and parents must watch out for other types of blood infections. Aplastic crises are believed to be a complication from human parvovirus infection and have been treated with blood transfusions. Less is understood about acute chest syndrome, but exchange transfusion is used to treat deteriorating pulmonary function. This therapy involves repetitive withdrawal of small amounts of blood and replacement with donor blood until a large proportion of the blood volume has been exchanged.

Sickle-cell sufferers are vulnerable to the aforementioned conditions but most often endure acute episodes of pain. Crises can last from a few hours to one or two weeks. And, beyond the medication prescribed for this pain, factors such as past pain experiences, social support networks, coping skills, mood and past treatment play a role.

Pervasive pain

Even when a sickle-cell sufferer gets medication, the pain can come back. Narcotic-abstinence syndrome can mimic pain crises. And some sickle-cell patients have almost constant pain of no clear source. While the severity of such pain has been compared to that from trauma or cancer, a number of studies suggest that health-care professionals have negative attitudes toward sickle-cell patients in comparison with patients who have cancer or who have suffered physical trauma.

Mostly, sickle-cell sufferers try to avoid crises. Basics such as good hygiene help prevent infections that can make the body use extra oxygen and create more red-blood cells that are vulnerable to sickling. Staying warm, resting after exercising, drinking enough water are all common-sense measures that sickle-cell sufferers are motivated to follow because of the pain that can result when they don't.

Twenty-six-year-old Donnell Ivy, of Carrboro, describes the pain this way: "Your head hurts like it's coming off. Your teeth hurt so bad, it's like they're going to come out of your gums. Your gut feels like a guillotine is cutting you in half."

He said this and more to a sickle-cell support group at a recent meeting in Raleigh. On a weeknight in a small room decorated with masks and shields reminiscent of African art, about two dozen African Americans gathered in a public-library branch to hear five young black men describe the problems they have faced because of sickle-cell anemia. Questions and answers were measured and respectful. Mothers nodded their heads in affirmation of their sons' words.

Ivy's story goes beyond the fact that a red-blood cell changes from looking like a bagel to a banana. His pain goes beyond the medical description of tissue that dies because it cannot get oxygen. He limps because of tissue death. He wonders if his disease prevents women from finding him attractive.

One man's story

He found out he had sickle-cell disease in a routine emergency-room visit after falling off a bunk bed when he was about 3 years old. After that came the pain crises. The temperature change from getting in and out of a swimming pool brought them on. So did the exercise from the sports he played. But other members of his family were athletic, and he didn't want to be different.

When he was about 11, he moved from Washington, D.C., to Goldsboro to live with his grandmother. She didn't believe in doctors and gave him home remedies. She also expected him to do chores. That, he now says, taught him to endure. "Little things don't get to me."

But what about the big things? Ivy's stepfather was in the Air Force, so Ivy wanted to fly F-15s. He took the armed-services test and says he was being recruited heavily by the four branches. He didn't reveal that he had sickle-cell disease, but his mother did. The armed services rejected him. Angry and upset, Ivy found himself facing the question: What do I do now?

He decided he wanted to be a doctor. "Sickle cell had destroyed my dreams, my hopes, and I wanted to get rid of it."

To that end, he graduated from North Carolina State University in 1997 with majors in zoology and microbiology. Then he finished 15th out of 75 participants in UNC-Chapel Hill's Medical Education Development program. He interned in the summer of '96 in the laboratory of Dr. Gene Orringer, a hematologist in the Comprehensive Sickle Cell Program at the UNC School of Medicine. Now Ivy works for Orringer as a part-time research assistant while taking a graduate course in cell biology.

Ivy met Orringer about two years ago. The young man remembers it well, because he was very, very sick. One November night in 1995, Ivy woke up in the dark and cold. A roommate had left the window open, and Ivy knew he was going to be sick. A full-blown crisis ensued. Ivy needed help. He remembers not wanting to summon a rescue squad: "That's a hundred bucks -- taxpayer money." But his friends with a car had been drinking, so he called the rescue squad anyway. Two days later, he was in the hospital getting oxygen and hooked up to a morphine drip.

He woke up, and they were prepping him for a blood transfusion. Then they put him on a respirator. Then the doctors at a medical center in Raleigh sent him by ambulance to UNC Hospitals in Chapel Hill. He was suffering acute chest syndrome.

Ivy spent 10 days in the intensive-care unit. "It was humiliating," he remembers. "You couldn't do anything for yourself. ...

"Dr. Orringer would come and visit me every day. That was the first time a doctor had done that for me." Orringer talked to Ivy and brought him literature. They discussed whether Ivy was a good candidate for a drug called hydroxyurea. Most important, says Ivy: "Dr. Orringer got me back to believing in myself."

The power of the mind

Attitude and its power were themes weaving constantly through the conversation at the sickle-cell support group meeting. "It's not the sickle cell that gets you down, it's the mindset. ... Long as you keep it positive, you'll be all right," said Shannon Saunders, 16, the first North Carolinian to receive a bone-marrow transplant for sickle cell. That was almost four years ago.

His life has changed considerably since. For one thing, he has grown 8 inches.

Physical stature was one of the first topics mentioned after the panel of young black men was introduced. Ernie, a 14-year-old who wanted only his first name used, told of being picked on at school because of his size.

Saunders said he hadn't liked having to abide by special rules his siblings hadn't had to follow. "The limitations were the hardest," agreed Clarence Henderson, 24, who studied psychology at Fayetteville State University and wants to go to graduate school in social work so he can help sickle-cell patients. When he was younger, he felt as if he had to work twice as hard as the other students because of the limits of his endurance and because of the number of days he missed due to pain crises.

Saunders continued: "I always wanted to be 'regular.' That's such a strong word. What does 'regular' really mean?"

He said, however, that he thought the stereotypes around sickle-cell disease would always be there and that they are compounded by the factor of race. He recalled a former teacher saying to him: "You're African American. I don't expect much, anyway."

Murmurs rippled across the room.

Black men and drugs

One stereotype that touches a particularly raw nerve in the black community is that of drug addiction. Lynnette Barber, whose 7-year-old son, Dominic, has sickle-cell disease, told of encountering a young nurse who thought Dominic was an addict because of the needle tracks on his arms and his demand for morphine during a pain crisis. Ernie voiced his fears about addiction and noted that while taking morphine, his hallucinations included crying doors and sumo wrestlers throwing beds across the room.

A 1996 article by the American Society of Hematology noted that drug abuse and addiction are not common among people with sickle-cell disease and that, in fact, addiction is more prevalent among health-care providers.

Making the best of it

As the conversation in the public library began winding down, Donnell Ivy noted that he spent his younger years in Washington, D.C., where many of the "normal" kids in his neighborhood have grown up to be crackheads. Did his disease keep him from being that kind of normal? he asked. Sickle-cell disease, he said, may have enabled him to get where he is today: the first person in his family not only to graduate from a university, but also to apply for medical school.

He believes that as an African-American doctor, he could make a difference in helping educate patients and society at large about sickle cell. Barber, the support-group moderator, said that their meeting was part of the effort to educate the African-American community. Added Sharon Reid, the mother of Shannon Saunders, "We can't do it by ourselves."

The need for education and, thus, better treatment for sickle-cell sufferers sent the conversation swirling around emergency-room memories. Every young man on the panel had a horror story. Saunders recalled being in the midst of a crisis but, nonetheless, bumped back for treatment because a trauma patient -- someone with a visible cause of pain -- had arrived. One woman noted that a part of educating others was courteously acknowledging other patients while still being aggressive about getting fast treatment for a child in crisis. Saunders' mother chimed in: What emergency room personnel didn't seem to understand was that when a parent -- someone who already knew how to handle a crisis -- came to the emergency room, that parent had already done everything possible for his child and needed professional help. And then they had to wait.

What if every emergency room had a sickle-cell team? someone mused.

Why current treatment suffers

According to one report, the fact that different health professionals approach pain management differently can undermine a patient's trust in doctors and nurses. Those at the support-group meeting expressed frustration over feelings that health-care providers didn't believe them when they said they were in pain. What's difficult for doctors is that the diagnosis of a crisis is based almost solely on subjective information -- the patient's word -- because physical findings are lacking and changes in lab findings are subtle or unreliable. And health professionals must try to manage a patient's pain while still enabling him or her to function well. Oversedation can depress respiratory function enough to lead to acute chest syndrome. Sedation and constipation from narcotics can lead a sickle-cell patient to drink less water, thus setting him up for another crisis.

Black patients, white doctors

Laura Porter, a Ph.D. in clinical psychology who comes to UNC's sickle-cell clinic to recruit participants in a pain-coping study, wonders what effect a health-care provider's race has on sickle-cell patients. According to the above-mentioned report, this, too, can undermine a patient's trust.

Joe Wiley, a pediatric oncologist-hematologist at UNC Hospitals, is white. Most of his patients are black. This isn't a big issue for him: "This is the patient -- period," he emphasized in a recent conversation. But he told the following story to acknowledge the undercurrent of tension.

Several weeks ago, Wiley was talking to one of his patients: a 6-year-old black boy with cancer. Wiley made reference to being the child's friend, and the boy responded that black people can't have white friends. Wiley was stunned. The child's mother was embarrassed. And the next time they met, she prompted her son to say he was wrong -- that one of his buddies had given him this idea but that it wasn't accurate.

What frustrates Wiley, he says, is that he goes out of his way to cater to patients with no means and that he champions those who are not sophisticated or educated. He tries to discover what he and his patients have in common. He avoids unnecessary medical jargon because of his concern it might intimidate families. Yet he also worries that he might come across as patronizing.

Evelyn West, whose child Ricky got a bone-marrow transplant, said her relationships with Joe Wiley and her doctor in Winston-Salem, Christine Johnson, were so good that she didn't consider race a factor. West said she was confident Wiley wouldn't steer her into anything that was bad for her children. And because he was knowledgeable and down-to-earth, she said, "He made it easier for me."

Making it easier for everyone

Making things easier for people with sickle-cell disease is one of Gene Orringer's goals. In the early 1980s, he saw only fragmented care for sickle-cell sufferers: "no single person or group of people who were focused on their care." People with sickle-cell disease got treatment during medical emergencies. But once the emergency was over, the patient went home and returned only during the next emergency.

In 1981, he helped establish the UNC Comprehensive Sickle Cell Program, which today serves from 400 to 450 patients. The patients either use UNC Hospitals for their primary medical care, or get primary care in their home communities and are seen at UNC Hospitals on a consultative basis. The program tries to accomplish a wide range of goals: to provide patients the best treatment possible from a familiar medical advocate; to coordinate that treatment with community, state and national care-givers and agencies; to educate sickle-cell patients and their families to try to prevent crises and medical emergencies; to provide social-work services and counseling; and to give patients quick access to the findings of sickle-cell research.

One example of recent research that has benefited many in the sickle-cell program: a study involving the drug hydroxyurea. The study, which is now in the follow-up stage, examined 299 sickle-cell sufferers from January 1992 until February 1995.

The 152 patients who received hydroxyurea suffered an average of 2.5 painful crises a year, compared with the 4.5 crises suffered by patients given placebo. What's more, the average time period between the first and second painful crisis was 3 months for those on hydroxyurea, as compared with 1.5 months for those in the control group. Fewer sickle-cell patients who took hydroxyurea had acute chest syndrome: 25, as compared with 51 in the control group.

We can get an idea of how hydroxyurea works by returning to the iced-tea analogy. When you have too much sugar in a glass of iced tea, crystals fail to dissolve. In blood that contains sickle hemoglobin, crystals result in circulatory-system blockages and tissue death. Hydroxyurea prompts one's body to make fetal hemoglobin, much like adding tea to the glass so there is more liquid in which the crystals can dissolve.

How hydroxyurea works

Remember that every molecule of adult hemoglobin is made up of four protein chains: two alpha and two beta. A fetus makes some beta-hemoglobin, but until the child is born and is three to six months old, most of its hemoglobin molecules consist of two alpha chains and two gamma chains. Gamma chains don't get stuck together the way sickle beta-hemoglobin chains do. And increasing the number of gamma chains tends to keep sickle beta-hemoglobin chains farther apart, making it harder for them to stick together.

Several drugs that increase the body's levels of fetal hemoglobin have been studied in animals, but hydroxyurea seems to be the safest and most effective for humans.

In the above-mentioned study, no deaths and no severe or unexpected detrimental outcomes were attributed to the treatment. Nevertheless, there are limitations and risks associated with its use. Hydroxyurea suppresses bone-marrow function, which means one's body is less able to manufacture, among other things: platelets, which help in clotting; white-blood cells, which help fight infection; and red-blood cells, which carry oxygen to tissue. The goal is to keep the patient as healthy as possible while still increasing levels of fetal hemoglobin. What makes that a challenge is that the dose that's best for one sickle-cell patient might be radically different from the dose that's best for another. One reason appears to be the origin of a sufferer's sickle-cell disease; people with the type that arose in Bantu are least likely to respond to hydroxyurea therapy, recent research suggests. However, the relevance for African Americans is unclear, given that most with the disease have a genetic mixture of sickle-cell types.

Hydroxyurea, which has not been approved by the Food and Drug Administration for use against sickle-cell disease, can cause birth defects, and its long-term use can result in leukemia or cancer. It has been shown to prevent painful crises but doesn't appear to help a patient in the midst of a crisis. Answers about the safety of its long-term use are years away.

Until then, hydroxyurea or more powerful drugs to fight sickle-cell anemia may also be tested in mice that have been genetically altered to produce only human hemoglobin in adult red-blood cells. Because the mice also exhibit the symptoms of sickle-cell disease that humans do, they could prove invaluable in the quest to conquer the disease without killing the humans who have it.

Other therapies

Risks and limitations are endemic among the currently used sickle-cell therapies. Bone-marrow transplants, such as those Shannon Saunders and Ricky LaGrande underwent, involve a long list. The first limitation involves the availability of bone marrow for transplant. The patient's body might reject the transplant -- either quickly or slowly -- by recognizing it as foreign. Or, more commonly, the immune cells from the donor might reject the patient's tissue in what is known as graft-versus-host disease. Even the chemotherapy that prepares a patient to receive a transplant may make that person sterile.

Chronic transfusions, such as those Ricky LaGrande and his twin, Rayshawn, have undergone, include risks, as well. Red-blood cells and hemoglobin are loaded with iron. Iron overload may require the transfusion recipient to undergo chelation, which actually prevents the metal poisoning that can cause heart or liver failure. Infections are a risk for transfusion recipients, and access to veins is a limitation. Among the most dangerous risk, however, is something called alloimmunization.

Native versus foreign

Alloimmunization occurs when a patient's body "immunizes" itself against substances from another person's body. This makes receiving a blood transfusion, for example, very hard on the patient's body: While he may need the transfusion to improve his condition, his body sees the new blood as foreign and not only fails to make use of it, but also expends energy trying to destroy it. This immune response can make the patient even sicker than he was before the transfusion was attempted.

We're familiar with the reasons a patient must receive a transfusion of his own blood type. A patient with blood type B has B antigens on the surface of his red-blood cells. That person's body will not produce antibodies against B antigens. But if he receives a transfusion of blood type A, the patient will produce antibodies against the A antigens, and the transfused blood cells will be destroyed.

One problem among sickle-cell sufferers is that even when a patient receives a transfusion of blood that is his type or is compatible with his type, his body might still try to reject it as foreign. This happens because there are many antigens other than A and B on the surface of red-blood cells, and matching those up means more if you are a sickle-cell patient. It can mean the difference in living and dying.

Recent studies indicate that almost no sickle-cell patients who get transfused with antigen-matched units of blood develop alloimmunization, while unmatched blood results in a 35 percent incidence. That's higher than for other groups of patients who undergo multiple transfusions. The problem seems to be racially discordant red-blood cells. Antigens that are less familiar than A or B but that exist on the surface of Caucasian blood are recognized as foreign by African-American transfusion recipients. One irony is that the rejection of black blood by white recipients is rare. Today, more hematologists are recommending that when sickle-cell patients need a transfusion, a match should exist regarding the six most common blood-group antigens that cause alloantibodies: K, C, E, S, Fy and Jk.

Wiley, a hematologist, says that while UNC Hospitals do not use race-specific blood, Eastern North Carolina University does. One difficulty in matching blood antigens for every transfusion is -- as with bone-marrow transplants -- availability of African-American donations.

A solution could be the use of umbilical-cord blood for transfusions. You don't need as much volume, and the red-blood cells from the umbilical cord have not yet traveled through the thymus and been "educated" -- become differentiated enough to have antigens on their surface. Without the antigens, perhaps alloantibodies might not present the problem they do with transfusions now.

What the future could hold

Because sickle-cell anemia is a genetic disease, it's logical to expect that, someday, scientists can fix the gene. Oliver Smithies, a professor of pathology and laboratory medicine at UNC, sees gene therapy for sickle-cell patients as a difficult challenge whose achievement may still be 10 to 20 years away.

Correction of the genetic defect itself requires that a gene that can produce normal beta-hemoglobin be introduced into stem cells in bone marrow. Stem cells are rare, don't divide easily and are not easy targets for gene therapy, Smithies said. What's more, the amount of normal beta-hemoglobin needed to correct sickle-cell disease is substantial, even though from our understanding of sickle-cell trait, we know that one's body does not have to produce 100 percent normal hemoglobin to alleviate the symptoms of sickle-cell disease.

Another focus of gene therapy is similar to that of hydroxyurea: inducing a patient's body to make less adult hemoglobin and more fetal hemoglobin, which replaces adult beta-hemoglobin with gamma-hemoglobin.

Until these goals are within reach, health-care professionals will focus on prevention of crises and damage control. Scientists will continue exploring drugs to improve oxygen delivery to cells, strengthen the membranes of red-blood cells to prevent their sickling, inhibit the adhesion of sickled cells to the inside walls of blood vessels, and decrease the risks inherent in bone-marrow transplants.

And those who have the disease will have to do the best they can.