NIH unveils final guidelines for stem cell research: Is your facility ready?
Researchers gain access, but have reservations
Following almost a year of sometimes contentious debate among politicians, scientists, bioethicists, and social activists, the National Institutes of Health (NIH) in Bethesda, MD, cleared the way for researchers to seek federal funds to study pluripotent stem cells (PSCs) derived from human embryos.
These types of stem cells have the potential to develop into any form of tissue in the human body. Scientists believe they may eventually be able to direct these cells to form replacement tissue and organs for people stricken with illness or injury, such as Parkinson’s disease, heart disease, multiple sclerosis, burns, and spinal cord injuries. (See "Feds consider supporting human embryo research," Medical Ethics Advisor, July 1999, p. 77.)
Obtaining those cells, however, involves the destruction of an early human embryo, a fact that has raised ethical questions in the scientific community and sparked strong opposition from anti-abortion groups and some religious organizations. Last month, a Senate subcommittee heard testimony from both sides of the debate.
In early 1999, legal counsel for the U.S. Department of Health and Human Services (HHS) issued an opinion that funding for research using PSCs did not violate the federal ban on use of federal funds in research that involved the destruction of human embryos, as long as the federal funds were not used to derive the cells from embryos, but only to study the cells themselves.
NIH director Harold Varmus formed a special working group to develop guidelines for what types of research should be eligible for federal funding and what oversight protections should be in place.
A draft guideline was developed in April 1999 (see "Guidelines for use of embryos, fetal tissue," MEA, July 1999, p. 79), but the finalized version wasn’t issued until Aug. 25, 2000, in order to allow the NIH to get comments from a variety of sources. The guidelines are effective now, but researchers must first complete an extensive approval process before work can start. Federal funding for that type of research, however, will not be approved until fiscal year 2002.
Move to speed research progress
Allowing researchers access to public funding should accelerate the pace of research by allowing more academic institutions to take part and facilitating the sharing of information between researchers, say many experts. Currently, laboratories receiving federal funds cannot conduct this type of research.
"We are very enthusiastic about the funding, and applaud the NIH for taking this bold step," says Carl Gulbrandsen, managing director of the Wisconsin Alumni Research Foundation (WARF), an intellectual property organization formed to license certain intellectual property rights and clinical applications of research conducted at the University of Wisconsin-Madison.
A team of University of Wisconsin researchers led by James Thomson, MD, was the first to derive PSCs from human embryos. WARF formed a nonprofit subsidiary in 1999, WiCell Research Institute, to supply stem cells to researchers.
One of WiCell’s goals, prior to the availability of NIH funding for stem cell research, was to make their cells available to academic researchers at a lower cost. Use of NIH funding may allow some institutions to pursue stem cell research that previously could not, Gulbrandsen says.
In developing the guidelines, the NIH struck the proper balance between encouraging needed research while instituting protections against potential abuses, such as buying and selling human embryos for profit, creating embryos solely for the purpose of scientific research, and the merging of human cells with animals, he believes.
"This is a very new area," says Gulbrandsen, noting that PSCs were first derived just two years ago. "And, I think we need to proceed carefully."
The final NIH guidelines are essentially similar to the draft guidelines formed in April of 1999. Federal funding cannot be used for the actual derivation of stem cells from embryos, but solely for research on cells derived through a privately funded process.
Must be in excess of need
Federal funds can only be used to study cells that were derived from embryos created for the purposes of fertility treatments and were in excess of clinical need, not embryos created for research purposes. And, the guidelines stipulate that there must be a clear distinction between the decision to undergo the fertility treatment, and the decision to donate embryos for research.
The guidelines also specifically prohibit inducements for the sale of embryos or stem cells. Researchers interested in using federal funding can only provide payment that reimburses the deriver the reasonable cost of transportation, processing, preservation, storage, and quality control of the PSCs.
In addition, the researchers using the cells must provide documentation that the deriver conducted an appropriate informed consent process with the embryo donor(s).
Finally, the guidelines specify several areas of research that are ineligible for funding. (See summary, inserted in this issue.)
Some feel guidelines are too political’
Although many researchers express enthusiasm about the simple availability of federal funding for this purpose, some health policy experts have reservations about the final guidelines and how they were developed.
"While these guidelines are progress, I think that the issue [of stem cell research] has been viewed primarily through the prism of abortion politics," says Gregory Stock, PhD, MBA, a professor of neuropsychiatry and biobehavior, and the director of the Program on Medicine, Technology, and Society at the University of California-Los Angeles. "I think the intrusion into the field of laboratory research by people outside of science to be disturbing."
While it is appropriate to have government regulation of research involving human subjects, and on applications of research that affect people, such a strenuous level of oversight is not necessary for determining how researchers behave while working with groups of cells, says Stock.
In particular, he points to the requirements covering the informed consent of the embryo donors. The guidelines require not only that the donors be informed that the embryos are donated for research purposes, but also that they be informed what kind of research will be conducted, that the cells or cell lines derived may be kept for several years, and that the embryo will not survive the derivation process.
"The traditional place of informed consent is at the level where you have clinical applications of research, where you are going to an [institutional review board] to look at actions that will affect human subjects," he says. "Not at the level where you are researching cells in the lab."
In some ways, the debate over appropriate stem cell research has focused almost exclusively on protecting the embryo as a "potential" human being, without balancing consideration of the likely benefits to hundreds of thousands of actual human beings, he adds.
Down to political hairsplitting
In most proposed protocols, researchers want to use stem cells from embryos that were left over from fertility procedures, embryos that most likely would be disposed of anyway.
"In some instances, it seems that we have gotten down to philosophical hairsplitting about some of these issues without looking at the other costs in terms of the delays in lifesaving treatments to critically ill people," he says.
The real result of the guidelines is that biomedical researchers will have to invest a great deal of time and effort in complying with the extensive documentation requirements for this research, which, Stock feels, will unnecessarily slow progress.
"You will have researchers concerned about filling out a lot of paperwork, and not crossing certain lines, and it does not free them to be flexible or creative in the laboratory, which is what you want to see in biomedical research," he says.
But, University of Wisconsin’s Gulbrandsen says he feels concern over the types of laboratory research conducted involving embryonic stem cells is appropriate.
In fact, WiCell’s program was put through a second level of institutional review, by a university panel dedicated to reviewing genetic research, and the program already had implemented an informed consent process for embryo donors that mirrors the one described in the guidelines.
In addition, WiCell requires those receiving cells to sign a licensing agreement that restricts the types of research that are performed on the cells — specifically, use of the cells for experimental cloning or intermingling with intact embryos is prohibited.
"As we learn more and more about these types of cells at the earliest stages of human life, all sorts of new issues will be raised," he says. "It is very important research that will be conducted, but we should proceed with caution."
Hurdles still ahead for researchers
Although the guidelines were effective on Aug. 25, they require researchers to go through not only an institutional review process, but also a review by the yet-to-be named NIH working group, the Human Pluripotent Stem Cell Review Group (HPSCRG).
It remains to be seen how many researchers make it through the initial process, says Stock. Grants are not expected to be available until early 2001, and some opponents of embryonic stem cell research have declared an intention to file suit against HHS, claiming that the research funding violates the federal ban on human embryo research (see related story, below).
Gulbrandsen says applications for stem cells from WiCell have not jumped dramatically since the NIH announcement, and he thinks that will not change until the HPSCRG is named.
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