by Kate Kruschwitz
As Director and Associate Director of Children's Hospital Boston's Stem Cell Research Program and world-renowned experts in blood diseases and cancer, Leonard Zon, MD, and George Daley, MD, PhD, are members of the stem cell research revolution's elite vanguard. And as pediatric hematologists, they are on the clinical frontline, treating small patients battling big diseases like leukemia, sickle-cell anemia and immune deficiency.
Combining these two areas of expertise, Zon and Daley are intent on translating pioneering therapies from the lab bench to the bedside—and quickly, because they are well acquainted with real sickbeds, real children, real families. Their singular mission—to be the first to use embryonic stem cells to successfully cure childhood disease—could transform medicine as we know it.
This mission also has been embraced by the Stem Cell Task Force, a group of business leaders, venture capitalists, entrepreneurs and philanthropists inspired by Children's to pool their skills and strengths to help the hospital advance the field of stem cell research.
Zon is enthusiastic about the task force's involvement. "We're aiming to translate science into cures, but knew the stem cell field needed non-traditional strategies," he says. "We faced so many decisions about how to allocate our limited human and financial resources, and needed business experts whose high caliber matched the strength of our scientific team to help us make those decisions."
Michael Stansky, managing director and partner of Tudor Investments, brings 21 years of health care investment experience to the task force. "It's exciting to have something to offer world-class scientists like Len Zon and George Daley," he says. "They're willing to listen to us, take our recommendations and suggestions and come back with answers."
The task force members' organizational and financial expertise helped Zon and Daley develop a strategy akin to a start-
up company's business plan. And their knowledge of the pharmaceutical and bio-tech industries, product development, and intellectual property issues helped frame the plan to achieve the fastest and best clinical results.
Among other recommendations, the task force counseled the program to focus on what Zon and Daley know best—blood diseases. Children's has been a world leader in blood research since the 1940s, when physician scientists developed the first successful treatment for Rh disease and achieved the first remission of
leukemia. Zon and Daley are extending that leadership into the stem cell era. Children's investigators were the first to transform embryonic stem cells into blood stem cells, and the first to use genetically corrected, lab-grown blood stem cells to restore normal functioning in an animal model of human blood disease, thereby establishing that cell therapy can work.
"Our understanding of blood stem cells makes treatments for severe anemias, immune deficiency disorders and leukemia the first priority," says Zon.
Daley envisions a day when stem cells might be customized to match a patient's tissue type—a process he was the first to achieve successfully in mice. To cure a disease like sickle-cell anemia, for example, researchers would harvest the nucleus from one of the patient's own cells. They'd then implant that nucleus into an egg cell from which the original nucleus had been removed, a procedure called somatic nuclear transfer. The egg cell would be prompted to divide, becoming a clump of embryonic stem cells containing the patient's own DNA. Researchers would repair the faulty copy of the sickle-cell gene, coax the embryonic cells into forming blood stem cells and transplant normal blood stem cells back into the patient, reconstituting the sick child's bone marrow with healthy cells. This treatment should last a lifetime because the new bone marrow would generate perfectly shaped red blood cells instead of sickle cells.
Following the task force's advice, Children's researchers will add to their blood stem cell knowledge and capitalize and expand their expertise in nuclear transfer. They plan to extend this knowledge to other research areas like diabetes, Duchenne muscular dystrophy, spinal cord injury and Alzheimer's disease. Like other task force members, Devette Russo is
inspired by these possibilities, and cleared-eyed about their costs. "Having even a peripheral role in helping bring cell-based treatments to the clinic is enormously gratifying," she says. "Dr. Zon, Dr. Daley and the stem cell team have the strategic plan and the human talent to achieve the big breakthrough—generating cures for these heart breaking diseases. But speed is of the essence, and they need more horsepower. Their only limitation is funding."
Stansky agrees. "Government funding is diminishing, and its stem cell restrictions limit researchers' ability to follow the most promising paths," he says. "We need private donors and creative business collaborations to step into the gap. The return on investment is huge, in monetary terms, as well as in human lives, if we can find cures for Parkinson's, Alzheimer's, diabetes and blood diseases."