Abstract
About 5β10 years ago it became popular to say that we understood the genetic and molecular basis for sickle cell anemia better than for any other disease and yet had no effective treatment. It was correctly pointed out that very little money was being spent at that time on sickle cell research relative to diseases of equal frequency which occur primarily in whites. The implication was that this contemporary financial and scientific neglect of the disease was a major reason for the lack of an adequate therapeutic approach. In the succeeding years a significant incremental amount of money was spent on sickle cell research, yet we still have no widely accepted antisickling* agent to offer sickle cell anemia patients. Sickle cell anemia has proven to be a formidable foe. These days, I hear molecular biologists frequently saying that if we could simply better understand the molecular mechanisms of sickle hemoglobin polymerization, we could surely design a drug which would be effective in preventing that process and would then have a therapy to offer patients. If the implication is that we should make our strongest efforts in the direction of hemoglobin polymerization and antipolymerization studies, I tend to disagree. A recent new insight offers hope for a different approach to the disease, one involving the red cell membrane, which I will briefly review. But first I wish to briefly review recent efforts at therapy and deal with some thoughts on why the frontal assault on sickle hemoglobin itself has not worked and probably will not work, at least for the near future.
Following the hypothesis of Murayama (1, 2) that polymerization of deoxyhemoglobinβS molecules occurs because of hydrophobic bonding between molecules, Nalbandian et al. (3β5) began a search for agents which might interfere with this type of aggregation. They came up with urea and were able to show that urea inhibited and even reversed this area are in their infancy and need to be strongly pursued. Such a course, coupled with vigorous exploration of new insights into some of the complications of sickle cell anemia, may yet turn the tide in the not too distant future against this crippling disease.