108th Congress

Stem Cell Research

Elias A. Zerhouni, M.D.
Director, National Institutes of Health
May 22, 2003

Mr. Chairman, Senator Harkin, and Members of the Subcommittee, I am pleased to appear before you today to testify about the progress of human embryonic stem cell research. In FY2002, NIH spent approximately $11 million for human embryonic stem cell research to increase the availability of stem cell lines for federal research, train scientists how to use these technically-challenging cells, and conduct basic, pre-clinical research that represents the first steps toward understanding how stem cells might be used to treat injuries and diseases.

More than 60 investigators at 48 institutions have received NIH awards, including 14 investigator-initiated grants and 44 administrative supplements. The administrative supplements allow investigators to rapidly incorporate research on human embryonic stem cells into their ongoing work. As you know, there are 78 lines fully eligible for Federal funding, in various stages of development. NIH support has helped increase to 11 the number of human embryonic stem cell lines that are widely available for all researchers. More lines will become available in the future, as we help the scientific community capitalize on this opportunity. I can report to you today that NIH's implementation of the policy set by the President on August 9, 2001 has enabled the field of stem cell research to advance. We continue to acquire new knowledge about human embryonic stem cells (hESCs). Some of the significant discoveries include the following research findings.

• NIH-supported researchers at the University of Wisconsin recently succeeded in replacing a specific stretch of DNA in human embryonic stem cells. This technique, called homologous recombination, opens the door to scientists who want to study the function of specific genes within these cells and also provides a way to modify hESC-derived tissues in a very precise matter for use in treating patients.
• Scientists at NIH have been able to demonstrate that differentiated mouse embryonic stem cells can be directed to become specialized cells in order to repair damage when transplanted into the brain or spinal cord. This finding could lead to the development of replacement therapy for cells that are destroyed through injury or disease, such as stroke, Parkinson's disease or Alzheimer's disease.
• In vitro studies have produced more specialized cells from human embryonic cells that might be used for blood cell transplantation therapies for patients with blood malignancies such as leukemia or myeloma.
• Scientists are currently working to identify those genes that are involved in the differentiation of hESCs, as well as those genes that permit embryonic stem cells to self-renew. This knowledge, along with research involving gene transfer techniques, potentially will allow scientists to coax hESCs into becoming insulin-producing beta cells to treat insulin-dependent diabetes
• Until recently, all hESCs were grown on mouse feeder layers. Now scientists are establishing conditions that allow hESCs to grow in the presence of human feeder cell layers. NIH-supported scientists in the United States, using stem cells eligible for federal research, have tested the ability of human feeder cells derived from fetal or adult tissues to support the growth of human embryonic stem cell lines. Both fetal and adult human feeder cells were able to support and maintain the cells in an undifferentiated state. Also, we have seen published research on the existence of one cell line, developed in Singapore, that was created and developed using human feeder layers. However, the Food and Drug Administration has informed NIH that, given the complexity of this area of research, it is difficult to predict whether newly derived human embryonic stem cells grown exclusively on human feeder cells would result in clinical trials sooner than the existing eligible cell lines either grown exclusively on mouse feeder cells or adapted to human feeder cells.

At the same time, we continue to learn more about other types of stem cells, including adult and those derived from umbilical cord blood.

• An NIH-supported researcher at the University of Minnesota isolated multipotent adult progenitor cells from human bone marrow. These cells demonstrate the potential to differentiate beyond bone marrow stem cells into other cell types, including liver, neurons and blood vessels.
• In a laboratory of the National Institute of Dental and Craniofacial Research, NIH intramural scientists have recently characterized a population of stem cells found in the dental pulp of deciduous, or "baby"teeth. These stem cells have the potential to become cells expressing molecular markers characteristic of dentin, bone, fat and nerve cells and may provide an accessible source of stem cells to repair damaged teeth, regenerate bone, and treat nerve injury or disease.
• Scientists established a number of years ago that umbilical cord stem cells can repopulate the bone marrow of a small child. Umbilical stem cells can be used today to treat certain childhood disorders such as Fanconi's anemia. With the current technology, however, these cord blood stem cells can only be harvested in small numbers, which limits their clinical utility. We are seeking methods to expand these cells in the laboratory to generate very large numbers of the cells needed for many other clinical applications.

Human embryonic stem cell research is still in its nascent stages, and there are many basic research studies that will be required before we can begin to plan clinical trials. NIH is supporting preliminary research to understand how to direct differentiation along specific pathways, to establish techniques for isolating specific cell types, to control cell proliferation, and to control interactions between the host immune system and transplanted cells that might mediate graft rejection.

Research using hESCs offers the potential to inform us about the earliest molecular and cellular processes that regulate normal development, and provides a tool to discover how a cell is able to be both pluripotent and indefinitely self-renewing. In addition, research using hESCs will help the scientific community to understand the molecular signals that specify differentiation into specific cell types, some of which may ultimately be useful for cell-based treatment of disorders, such as Type 1 diabetes or Parkinson's disease, that involve loss of a specific cell type.

As we continue our work with the research community to fund new research and facilitate the availability of additional stem cell lines, the NIH Stem Cell Task Force is continuously and vigorously evaluating the state of the science to lead the implementation of a vigorous research program envisioned by the President. Attaining basic knowledge about the characteristics and potential use of stem cells remains the immediate challenge before the research community today. Until we understand the basics, we cannot know with certainty the future research requirements for advancing into clinical trials using embryonic stem cells. The NIH will continue to monitor the state of the science and assimilate the body of research evidence in order to make informed, evidence-based recommendations on this important issue.

We are working hard to promote stem cell research, based on recommendations received from the research community by the NIH Stem Cell Task Force. The newest effort is the establishment of the NIH Characterization Unit, located on our campus in Bethesda, Maryland. This unit will provide reliable and standardized data derived from assays performed on human embryonic stem cell lines available for shipment to the research community. The unit will provide a direct side-by-side comparison to be made among the cell lines, and will facilitate comparison with adult stem cells. These data will be publicly available and will arm the scientific community with state-of-the-art information, so scientists can make an informed choice when ordering one or more of the available cell lines.

In response to additional recommendations from the research community, we continue our efforts to recruit new scientists to the field, to help mid-career investigators begin studies on embryonic stem cells, to monitor the state-of-the science through the NIH Stem Cell Task Force, to fund investigator-initiated grants, to disseminate information about the science and initiatives via the NIH Stem Cell Task Force website and to plan for a symposium that will bring together two hundred stem cell researchers from all over the country and several foreign universities.

Again, I want to assure the committee of NIH's commitment to pursuing embryonic stem cell research, as well as continuing our advances in the field of adult stem cell research. The President's policy has provided us the opportunity to be at the forefront of the latest groundbreaking discoveries in the culturing, characterization and differentiation of stem cells, and I am confident that NIH will keep its premier place in this field for years to come.