STATEMENT OF
HAROLD VARMUS, M.D.
DIRECTOR, NATIONAL INSTITUTES OF HEALTH
DEPARTMENT OF HEALTH AND HUMAN SERVICES
BEFORE THE
SENATE APPROPRIATIONS SUBCOMMITTEE ON LABOR, HEALTH AND HUMAN SERVICES, EDUCATION AND RELATED AGENCIES
DECEMBER 2, 1998
- Transplant of healthy heart muscle cells could provide new hope for heart attack victims. The hope is to develop heart muscle cells from human pluripotent stem cells and transplant them into the failing heart muscle in order to augment the function of the heart. Preliminary work in mice and other animals has demonstrated that healthy heart muscle cells transplanted into the heart successfully repopulate the heart tissue and integrate with the host cells. These experiments show that this type of transplantation is feasible.
- In the many individuals who suffer from Type I diabetes, the production of insulin by the pancreas by specialized cells called islet cells is disrupted. There is evidence that transplantation of either the entire pancreas or isolated islet cells could mitigate the need for insulin injections. Islet cell lines derived from human pluripotent stem cells could be used for this critical research and, ultimately, for transplantation.
While I have taken this opportunity to outline the promise of this research, there is much to be done before we can realize these innovations. First, we must do the basic research to understand the cellular events that lead to cell specialization in the human, so that we can direct these pluripotent stem cells to become the type(s) of tissue needed for transplantation in great numbers. And before we can use these cells for transplantation, we must overcome the well-known problem of immune rejection. Because human pluripotent stem cells derived from embryos or fetal tissue would likely be genetically different from the recipient, future research would need to focus on modifying human pluripotent stem cells to minimize tissue incompatibility. Technological challenges remain before these discoveries can be incorporated into clinical practice. These challenges, though significant, are not insurmountable.
How Are Pluripotent Stem Cells Produced?
There are several ways to produce human pluripotent stem cells. These methods have been developed over the past 17 years by researchers working with animals. The work you will hear about today builds on this important basic animal research.
As I mentioned earlier, one method of creating these pluripotent stem cells was described by Dr. Thomson and his coworkers. The techniques they used were initially developed using mice. Dr. Thomson first made stem cells from non-human primates. In the most recent work, they used inner cell mass cells from blastocyst stage human embryos that were created in the course of infertility treatment and donated by couples for research to derive stem cells. The researchers allowed cell division to continue in culture to the blastocyst stage and then removed the inner cell mass, which was cultured to derive pluripotent stem cells.
Pluripotent stem cells can also be derived from fetal tissue, as was first done using primordial germ cells from mouse fetal tissue. Dr. Gearhart and coworkers isolated human primordial germ cells, the cells that will go on to become eggs and sperm, from 5-9 week old fetal tissue obtained after pregnancy termination. When grown in culture, these stem cells appear to be pluripotent.
It may also be possible to make human pluripotent stem cells by using somatic cell nuclear transfer -- the technology that received so much attention with the announcement of the birth of the sheep, Dolly. Although there has been no scientific publication of this to date, presumably any cell from the human body (except the egg or sperm cell) could be fused with an enucleated egg cell and stimulated to return to highly immature, pluripotent and possibly totipotent state.
The Role of the Federal Government
Federal funds were not used in either of the experiments that you will hear about today. First, let me first address Dr. Thomson's work in which cells were derived from embryos created by in vitro fertilization but not used for infertility treatment. This work falls clearly within the Congressional ban on human embryo research. NIH could not, and did not, support Dr. Thomson's recent work developing this cell line.
The same restrictions do not apply to Dr. Gearhart's work, although it may be governed by other laws and regulations. Dr. Gearhart derived his pluripotent stem cells from fetal tissue from terminated pregnancies. The Public Health Service Act authorizes Federal funding of human fetal tissue research and provides safeguards for its conduct. The department may conduct or support research on the transplantation of human fetal tissue for therapeutic purposes if a number of statutory requirements are met. Thus, if Dr. Gearhart's research falls within these boundaries, NIH could have supported his recent work deriving pluripotent stem cells from fetal tissue, as long as he followed these Federal statutes and regulations. For the record, NIH did not, however, support any of this research.
Ethical Issues
I have just described the science and the medical promise of research on the pluripotent stem cell. But the realization of this promise is also dependent on a full and open examination of the social and ethical implications of this work. The fact that these stem cells were produced from embryos and fetal tissue raises a number of ethical concerns including, for example, the need to ensure that stem cell research not encourage the creation of embryos or the termination of pregnancies for research purposes. In strict accordance with the President's 1994 directive, no NIH funds will be used for the creation of human embryos for research purposes. We also will continue to abide by relevant statutes.
The ethical and social issues associated with stem cell research are complex and controversial and require thoughtful discourse in public fora to reach resolution. To this end, the President has asked the National Bioethics Advisory Commission to undertake a thorough review of the issues associated with human stem cell research, balancing all ethical and medical considerations.
Summary
The development of cell lines that may produce almost every tissue of the human body is an unprecedented scientific breakthrough. It is not too unrealistic to say that this research has the potential to revolutionize the practice of medicine and improve the quality and length of life.
Mr. Chairman, I am grateful to you for providing a forum to present information about this promising arena of science and medicine. I would be pleased to answer any questions you might have.