 About 100 years ago, a curious blood disease was discovered that was characterized by the presence of peculiarly shaped red blood cells, which had a crescent or sickle shape, instead of the normal disc-shaped cells. This disease was coined sickle cell disease, or SCD. As the disease progresses, SCD patients experience increasingly debilitating pain and damage to the brain, liver, heart, lung, and other organs. Today, SCD affects 100,000 people in the U.S. alone. Over 40 years ago, it was discovered that SCD was an inherited disease passed on from parent to child if both parents carried a copy of the sickling gene, a mutated version of the beta-globin gene. Beta-globin is one of the four core units of hemoglobin, which is essential to carry oxygen to tissues throughout the body. Normal disc-shaped red blood cells are flexible and can easily move through large and small blood vessels to deliver oxygen to tissues. In sickle cell disease, mutations in beta-globin turn hemoglobin into stiff rods, changing the normal disc-shaped red blood cells into a sickle form. These inflexible sickle-shaped red blood cells can stick to vessel walls, causing a blockage that slows or stops blood flow, preventing oxygen from reaching all tissues and causing pain and organ damage. In 1973, the life expectancy for sickle cell disease was 14 years. Since then, much progress has been made. SCD patients in the U.S. can expect to live 40 to 60 years, although with recurring chronic pain. Sickle cell disease can be cured by blood stem cell transplantation, where a patient's diseased bone marrow, where the red blood cells are produced, is eliminated and blood-forming cells, including stem cells from the bone marrow of a healthy donor, are introduced. Over time, they will produce healthy disc-shaped red blood cells to replace the sickle ones, curing SCD. However, access to bone marrow from someone who is a perfect immune system match is extremely rare. Only 10 to 15% of sickle cell patients find that perfect bone marrow to cure their disease. But for the 85 to 90% of those who don't, stem cell therapy offers the best immediate hope. To overcome this, a group of scientists led by Don Cohn at the Bird Stem Cell Research Center at UCLA are using a combination of stem cell research and gene therapy to make patients their own red blood cell donors, using the patient's own stem cells. Using funding from California's Proposition 71, the UCLA team is enriching blood stem cells from the bone marrow of SCD patients and introducing a modified version of the beta-globin gene. The engineered stem cells make red blood cells with the modified beta-globin, which blocks sickling of red blood cells, which makes the red blood cells disc-shaped in a laboratory petri dish. The engineered stem cells are then returned to the patient, where they should start producing new disc-shaped red blood cells, containing the modified beta-globin gene, eventually replacing all of the sickled red blood cells. The scientists have tested this technique in a mouse model sickle cell, where the modified stem cells created disc-shaped red blood cells and cured SCD. A human clinical trial is currently underway at UCLA to test this approach in SCD patients. Although early attempts to use gene therapy to cure disease were not successful, new techniques to introduce genes into stem cells have made this process much safer and effective. In fact, with the support of donors, the NIH and California's Proposition 71 funds, a fatal disease called SCD, or the bubble baby disease, has been cured by a similar approach to replace a missing gene in stem cells. This approach was proven to be safe by Dr. Don Cohn and his team in a clinical trial at UCLA last year. All 23 babies who were born without working immune systems were cured of this life-threatening disease after receiving their own modified stem cells. The implications of this work are significant. With an efficient way to engineer stem cells, we can replace abnormal cells in many diseases, including neurodegenerative, metabolic, or autoimmune diseases. But only with support for biomedical research can we make this possible. As scientists and patient advocates build on the progress that Proposition 71 funding has enabled, we must keep the momentum going, understanding that there is still much work to be done. We must remember that human trials will celebrate successes, but barriers will surface along with complications and challenges, so patients and understanding of the scientific discovery process are essential.