Thomas Williams' earliest childhood memory is of being in the hospital. At 33, he has been in and out of hospitals so often for his sickle cell anemia that he has given up trying to plan his life. It only sharpens the disappointment every time a sickle cell "crisis" distrupts his dreams of a vacation or a steady job.

The son of a woman who died of sickle cell anemia when he was 4 years old, and the father of a 6-year-old who has the disease as well, Williams lives a life punctuated by pain. He once tried to commit suicide by wrecking his car.

Since then, he has decided to struggle on, wanly hoping that new discoveries about the hereditary anemia will help him and about 50,000 other black Americans who have it.

"I get depressed now, but before I blow up I think a little better than I did," he said. "My mother died young. Maybe I'm living my life for her. I want to live and help my son. If he does have the sickle cell like they say, he needs me . . . because I understand it more than anybody else can."

Sickle cell anemia afflicts one in about every 400 black babies born in Washington, according to a Howard University study. For many victims, it is a devastating illness, producing periodic pain, increased susceptibility to infections and often early death from stroke, kidney failure or other complications.

The gene bearing potential for the disease is carried by 1 in 12 black Americans. Though carriers have no symptoms, if two of them marry, each of their children has a 1 in 4 chance of being born with the disease.

Doctors have learned in fascinating detail how a slip-up in the body's manufacture of hemoglobin -- the protein that carries oxygen in the blood -- produces rigid and misshapen blood cells that pile up in tiny vessels like cars on a freeway at rush hour. Yet they have much to learn about how the deformed cells and clogged vessels lead to bone pain and stomach cramps, promote infections and, in many patients, destroy tissue in vital organs.

Nor do they understand why sickle cell anemia kills some victims in childhood while allowing others to lead relatively healthy lives into their 70s. Some researchers speculate that the disease's course may depend on other genetically coded proteins in blood cells, on the size and makeup of a patient's blood vessels, or on his immune defense system.

Treatment of sickle cell anemia has lagged behind discoveries about its molecular basis. But now, study of its victims' abnormal hemoglobin is beginning to pay off in ingenious schemes for outwitting the defective protein molecule. However, such treatments are still experimental -- and meanwhile, Thomas Williams and other victims of the disease live from one "sickle crisis" to the next, making do with the stopgap therapy that is available.

Compared to some sickle cell anemia victims, Thomas Williams considers that he has been lucky. Encouraged by the aunt and uncle who reared him, he played basketball and other sports even though he believes he sometimes paid for it with pain a day or two later. He escaped the serious infections and strokes that some children with the illness suffer. By his mid-20s, he had a government job and needed hospitalization for pain only every four to six months. He felt he had gotten off easy.

When he married at age 25, his wife knew he had sickle cell anemia. But things got more complicated when the couple learned that Monica Williams was a carrier of the sickle cell gene.

"The doctor said, 'You shoudn't have any kids,'" Williams recalled. But the couple decided not to follow that advice. Williams wanted to try to live a normal life.

"I just look at it [that] you just here to be here. Ain't nothin' you can do. If I didn't pray as much as I did, I wouldn't be here."

But living a normal life turned out to be harder than he expected. After four or five years of marriage, Williams' pain crisis became more frequent, and he now averages two hospitalizations every three months. His sick leave ran out, his bills accumulated, and his coworkers' ignorance of his illness began to make his days at the General Services Administration uncomfortable.

"Down where I work, they don't understand," he said. "I could be feeling all right now and 10 or 15 minutes later I could be feeling bad. People don't seem to believe that. They think it's a normal pain that every person would have. Once you get sick, there's nothin' in the drugstore that you can buy to stop the pain."

His supervisor knew he had the disease, but Williams kept it a secret from his coworkers. When he was hurting, he avoided them. "The minute I get sick, I just want to be by myself," he said. "I see somebody well off, and I always wonder, 'Why me?'"

When his son was born with sickle cell anemia, Williams' worries and expenses multiplied. The episodes of pain multiplied too, and he believes anger and depression were the reason. He started drinking to dull the agony.

"I'd drink two or three fifths a day because I was in that much pain and I didn't have no faith in the doctors," he recalled. "I'd come home and have no kind of affection toward my wife. . . . I didn't take no time with my son. I just turned against everybody."

The first time he came to Howard University Hospital as a patient, in April 1979, Williams threw chairs, tore out his intravenous lines, attacked doctors and told his wife and foster parents not to visit him.

He remembers hallucinating believing that a group of doctors were standing around the bed laughing. "I just went almost completely off," he said. "I think it had something to do with the alcohol and medications."

Since then, Williams has cut down his drinking and his condition has improved, but he is still angry. Because he has run out of sick leave and cannot afford loss of income from hospitalizations, he has reluctantly decided to quit work and apply for disability. Money worries are fraying his marriage. Most of all, he gets angry at people who don't understand about sickle cell anemia: doctors who look askance when he asks for pills to ease the bone pain, teachers who doubt his son's veracity when the child gets sick at school.

"They tell you one thing and you know what's going on in your body," he said.

The many complications of sickle cell anemia all result from a single slip-up in the gene that provides the chemical blueprint for hemoglobin, the protein in red blood cells that carries oxygen from lungs to tissues. A mistake in the gene sequence translates into a mistake in the protein's manufacture, producing an abnormal form of hemoglobin -- called hemoglobin S -- which, under certain conditions, "gells" inside blood cells so that they become more rigid and often assume a curved shape resembling a sickle.

Hemoglobin S gells while the cells are passing through small blood vessels where they deliver oxygen to surrounding tissues. Once gelling occurs, the rigid cells may become trapped in vessels, blocking them and preventing oxygen delivery, or they may make it through the bottleneck and return to the lungs, where renewed contact with oxygen restores hemoglobin S to its normal chemical state.

But repeated sickling and unsickling apparently damages the blood cells, so that instead of living 120 days, a red cell's normal lifespan, they die after only 10 to 20 days. Blood vessel blockages, and premature death of red cells, account for the major symptoms of the disease: organ damage from oxygen deprivation and anemia from deficient numbers of blood cells.

People who carry one copy of the defective gene are said to have sickle cell trait. They are spared the disease because they also possess a normal gene, which supplies enough healthy hemoglobin to prevent gelling and its consequences. But some children of two persons with sickle cell trait inherit two copies of the defective gene, one from each parent. Because their cells contain almost exclusively hemoglobin S, they develop the illness.

The severity of sickle cell anemia varies greatly from patient to patient, according to Dr. Oswaldo Castro, associate director of Howard University's Center for Sickle Cell Disease. In some people, the disease is mild. But in many, tissue injury from blood vessel blockages produces recurrent pain in bones or intestines; damage to the lungs or liver; strokes during childhood, causing seizures or paralysis; skin ulcers; destruction of the spleen, which combines with blood abnormalities to lower resistance to infections, or progressive kidney failure, which may kill as many as one-fifth of sickle cell anemia victims.

Castro said West African tribes knew of the existence of the painful illness and described its inheritance pattern some 300 years ago. But the mutation responsible, and the reason it arose and persisted over generations, were mysteries until recently.

Scientists now believe sickle cell anemia originated centuries ago through mutations in the genes of two individuals in separate areas of Africa. tThe decendants of these original carriers passed the mutated gene to succeeding generations, spreading it through migration and intermarriage as far east as India and as far west as the Americas.

Despite the gene's potential to cause severe illness in children born to two carriers, the gene never died out of the population because, in tropical areas, it confers an evolutionary advantage: those who have sickle cell trait are partly resistant to infection with a dangerous type of malaria.

Doctors can do a simple blood test to check for sickle cell trait. Screening programs to identify carriers were widely promoted in the early 1970s, but have received less emphasis in recent years, partly because blacks with sickle cell trait sometimes experienced discrimination when they sought jobs or medical insurance. One NIH official said this occurred because, until a few years ago, medical textbooks falsely stated that sickle cell trait was a mild form of the disease. In reality, the trait is not an illness.

"People are not telling the employer that they have the trait or the disease," said Samuel Ray McElroy, a psychologist at Howard University College of Medicine who has sickle cell anemia. McElroy said he was discharged from the Navy because he had the disease, even though his case was so mild that he had completed training for active duty and had flown and skin-dived with no ill effects.

"It's almost a hidden secret," he said. "Nobody wants to admit it because there are so many repercussions."

Screening programs now concentrate on testing babies at birth, so that those with sickle cell anemia can be treated intensively in case of infection, according to Dr. Clarice Reid, chief of the NIH sickle cell disease branch. She said black women should also be checked for the trait early in pregenancy to identify couples with the trait.

"If you screen everybody [during childhood], a 12-year-old might not remember when he gets married at age 21 that he has sickle cell trait," she said.

If two carriers marry, the woman can be tested during pregnancy to find out whether she is carrying a baby with the disease. But the simplest test, which involves sampling cells from fluid surrounding the fetus, can make the diagnosis only 60 to 80 percent of the time, and is not widely available because cells must be sent to one of a handful of medical centers for gene-mapping. If sickle cell anemia is diagnosed early in pregnancy, a woman may choose to have an abortion.

Once a child is born with sickle cell anemia, doctors cannot cure the patient, nor can they prevent organ damage or periodic pain crises. They can do little more than vaccinate against infections and administer oxygen, fluids and pain medicines when crises occur.

But researchers at the National Institutes of Health, Howard University, and other centers are developing experimental treatments that could change that. They include:

Lowering the concentration of hemoglobin S inside the cell. In an experiment that prevented pain crises in three patients, Drs. Robert M. Rosa and H. Franklin Bunn of Harvard Medical School diluted hemoglobin in patients' cells by eliminating salt from their diet, having them drink extra fluid and giving a drug to induce fluid retention. Rosa said the treatment shows promise, but may be difficult to follow outside the hospital because it requires strict abstention from salt.

Tightening hemoglobin's hold on oxygen. Since gelling occurs only when the hemoglobin S molecule releases oxygen to tissues, researchers are seeking drugs that increase hemoglobin's oxygen retention just enough to prevent gelling. One such drug, sodium cyanate, has too many side effects to be used for treatment so far, but related drugs may prove safer.

Computer-designed drugs to block gelling. At NIH, researchers have programmed computers to design molecules that will fit into the contact points where one hemoglobin S molecule binds to another during gelling. "The binding is so weak, and there are so many [hemoglobin] molecules. . . . it's very hard to get something to fit in with high enough affinity," said Dr. Alan N. Schechter, chief of macromolecular biology in the division conducting the research. But he believes computers have the best chance of coming up with an ideal blocker with few side effects.

Treating a patient's blood outside his body. Castro is able to freeze the blood of sickle cell anemia victims, then thaw it for later use. He believes it may be possible to use drugs to treat defective blood outside the body one unit at a time and then transfuse it back into its owner. If this approach works on chimpanzees, it could allow the use of drugs like sodium cyanate, whose side effects have interfered with their success in patients. An alternative way to remove blood for treatment, which involves hooking patients up to a machine like the pump used for kidney dialysis, is being tested elsewhere.

Genetic engineering. Schechter foresees efforts to "switch off" defective hemoglobin genes and "switch on" alternative genes coding for fetal hemoglobin, a protein manufactured by babies in the womb and during the first year of life. Theoretically such a switch could cure the disease, but he said it is still many years in the future.

Schechter and Castro believe scientists' increasing understanding of the links between a single genetic misstep and its disastrous consequences will someday pay off in an answer to sickle cell animia. But Thomas Williams doubts that it will come soon enough.

"They say they'll find a cure for it somehow," he said. "I won't be around, I know this."