Fixing Thalassemia - Magic or Reality

The Ham-Wasserman Lecture will be delivered today from 12:30 to 1:30 p.m. by Dr. Doug Higgs of the John Radcliffe Hospital at the Weatherall Institute of Molecular Medicine in Oxford. The title of this year’s lecture is “Gene Regulation in Hematopoiesis: New Lessons from Thalassemia.”

Hematologists have taken pride for five decades in the fact that we dissected the synthesis of hemoglobin, and, in so doing, we understood the general principles controlling gene expression long before any other specialty. By discovering and understanding how genes are switched on and off in hematopoietic cells, and by deciphering the regulation of alpha and beta globin genes, we were able to explain the manifestations of the different forms of thalassemia.

Dr. Higgs will elucidate for us how thalassemia pathogenetic understanding continues to evolve. Rather than all mutations revolving in or around globin loci, newer mutations, both inherited and acquired, are being identified in trans-acting areas. Just as in the past, these new investigations have implications for genetic disease far beyond hematology. All indications are that Dr. Higgs will deliver a lucid, enlightening journey from the past through the present and glimpsing into the future.

And it appears that the future might be arriving sooner than we think. Abstract #373 to be presented in the Thalassemia and Globin Gene Regulation I session at 11:00 a.m. on Monday by Dr. Ryan will discuss the efforts by him and his colleagues to actually correct beta-thalassemia by homologous recombination in embryonic stem cells. Thalassemic mice have been previously generated by targeting gene deletion in adult murine beta-globin genes. In the present study, Ryan and colleagues derived embryonic stem cells from the beta-globin knockouts and produced genetically identical mutant mice by injecting the embryonic stem cells into tetraploid embryos. A targeting construct was then electroporated into the beta-thalassemic ES cells. Their results “demonstrate that a severe hemoglobinopathy can be cured after targeted gene replacement of a mutant gene(s) with a wild-type allele by homologous recombination in ES cells.” Thus, once again, we in the hematology field are blazing the trail in scientific investigation and proving that the future may be here before we know it. Therefore, no it’s not magic, it’s real and it’s terrific science.