Guidelines for research involving human embryonic stem cells

The National Academies today recommended guidelines for research involving human embryonic stem cells, and urged all institutions conducting such research to establish oversight committees to ensure that the new guidelines will be followed.

The guidelines are intended to enhance the integrity of privately funded human embryonic stem cell research by encouraging responsible practices, said the committee that wrote the report, a joint project between the National Academies' National Research Council and Institute of Medicine.

"Heightened oversight is essential to assure the public that stem cell research is being carried out in an ethical manner," said committee co-chair Jonathan D. Moreno, Emily Davie and Joseph S. Kornfeld Professor of Biomedical Ethics and director of the Center for Biomedical Ethics at the University of Virginia, Charlottesville. "The oversight we call for will in many instances set a higher standard than required by existing laws or regulations. And while we were hesitant to recommend another bureaucratic oversight entity, the burden in this case is justified, given the novel and controversial nature of embryonic stem cell research."

"A standard set of requirements for deriving, storing, distributing, and using embryonic stem cell lines -- one to which the entire U.S. scientific community adheres -- is the best way for this research to move forward," added committee co-chair Richard O. Hynes, Daniel K. Ludwig Professor of Cancer Research and a Howard Hughes Medical Institute investigator at the Massachusetts Institute of Technology, Cambridge.

Embryonic Stem Cell Research Oversight, or ESCRO, committees should be established, but not as replacements for other research compliance bodies such as institutional review boards, the guidelines say. In addition to experts in biology and stem cell research, ESCRO committees should include legal and ethical experts as well as representatives of the public.

Stem cells usually are harvested after three to five days from a blastocyst -- an early stage of development before implantation in the uterus. The ESCRO committees should review proposals for research that takes stem cells from excess blastocysts at IN VITRO fertilization clinics or from blastocysts created expressly for stem cell research. They also should review any proposed use of blastocysts created by nuclear transfer, often referred to as therapeutic cloning. Nuclear transfer must not be used for reproductive cloning, the guidelines committee said, reiterating a recommendation from a previous National Academies report.

Proposals to generate additional human embryonic stem cell lines by any means should be reviewed and approved by an ESCRO committee, the guidelines say. They add that human embryos used for research should not be grown in culture for longer than 14 days, or until the point when the body axis and central nervous system -- called the primitive streak -- begin to form.

Although an ESCRO committee should approve new stem cell research, federal regulations already require institutional review boards (IRBs) to review the procurement of all eggs, sperm, or blastocysts to be used in generating new stem cell lines, and they should continue to do so, according to the new guidelines. An IRB also should review the donation of somatic cells to be used in creating a blastocyst via nuclear transfer.

Donor consent must be obtained before a blastocyst is used to generate stem cells, and donors should be informed that they have the right to withdraw their consent at any point before a stem cell line is derived, the guidelines say. Practices for obtaining consent should be scrutinized for potential conflict of interests; for example, researchers proposing to derive stem cells should not influence decisions about creating embryos for fertility treatment. The guidelines also emphasize that no payments should be made to donors. Blastocysts left over at IN VITRO fertilization clinics may not be donated for research without consent, and researchers should not ask fertility doctors to create more embryos than necessary for reproductive treatments.

According to the guidelines, donors should be told that information about them, including their names, may be retained and could become known by those who derive or work with resulting stem cell lines, but that donors' identities will be encoded and not readily ascertainable. They should be asked whether they want to receive information obtained through studies of the cell lines. Consent forms should inform the donor that embryos will be destroyed in the process of deriving stem cells and that the resulting cell lines may be kept for many years. The forms also should state that cells might be manipulated genetically or transplanted into animals for preclinical testing. Donors also need to be told that although research involving their stem cells may have commercial potential, donors will not share in any financial benefit. Research on existing anonymous or coded embryonic stem cell lines does not require IRB review unless the cells are going to be transplanted into patients or the donor's identity is likely to become known by researchers. Researchers working on previously derived stem cell lines, however, should provide documentation on the origin of the cell lines -- including evidence that the procurement process was reviewed by an IRB -- to newly formed ESCRO committees, the guidelines committee said.

The ESCRO committee should maintain a registry of stem cell lines banked at an institution, the guidelines add. The registry should include a proof of informed consent, a medical history of the donors, and a characterization of any genetic markers on the cell lines. Repositories of stem cell lines also need a secure coding system to protect the identity of donors.

The Academies' guidelines also address how far scientists should go in mixing human and animal cells to create so-called chimeras, which researchers may need to do in order to test the therapeutic potential of human stem cells in animal models. The guidelines say no animal embryonic stem cells should be transplanted into a human blastocyst, and approval by an ESCRO committee should be secured before any human embryonic stem cells are put into an animal. Also, no animal into which human embryonic stem cells have been introduced should be allowed to breed. In addition, no human embryonic stem cells should be put into nonhuman primate blastocysts.

Human embryonic stem cells should be introduced into nonhuman mammals only under circumstances where no other experiment can provide the information needed, the guidelines say. Experiments in which there is a possibility that human cells could contribute in a "major organized way" to the brain of an animal require strong scientific justification, the committee added.

The committee urged the formation of a national independent body to periodically review whether the guidelines need to be updated in light of unforeseen advances in stem cell science and evolving public attitudes.

The National Academies developed the guidelines on behalf of the scientific community and without government involvement. Although compliance is voluntary, the committee called on private funders, professional societies, journals, research institutions, and others involved in embryonic stem cell studies, to require adherence to the guidelines.