Human Embryonic Stem Cell Debate

It’s been more than three years since President George W. Bush announced the U.S. policy for research using human embryonic stem cells (hESCs), which limits the use of federal funds to work on hESC lines derived before Aug. 9, 2001. Since that time, scientists—using a mix of federal, state, and private funds—have set up research programs that are providing insight into the basic scientific understanding of these cells and bringing researchers closer to realizing the cells’ potential to treat and cure a variety of diseases. Currently, however, researchers doing this work in the U.S. lack a set of guidelines to govern their studies.

To address this deficiency, the National Academies has set up a committee tasked with deriving guidelines for the derivation, use, and handling of hESCs. The committee held a workshop on Oct. 12 and 13 to collect information on related scientific, ethical, and policy issues, as well as to gather input on what should be included in such a set of guidelines. The project is a collaboration between the Board on Life Sciences at the National Research Council and the Board on Health Sciences Policy at the Institute of Medicine and is funded by the National Academies, Ellison Medical Foundation, and Greenwall Foundation.

“From the many basic science questions that can be addressed today to the therapeutic uses of stem cells on a more distant horizon, we must move forward with this research in a responsible way, and this workshop is an important part of that effort,” said Bruce Alberts, president of the National Academy of Sciences.

Alberts also noted that the committee’s purview does not include whether hESC research should continue or whether human reproductive cloning should be banned. Both issues have already been studied by the National Academies, with reports issued in favor of continued hESC research and for banning reproductive cloning.

Public interest in stem cell research was sparked in 1997 when Dolly, the cloned sheep, was introduced to the world, several presenters noted. A year later, the derivation of the first hESC line was reported by James Thomson, a biologist at the University of Wisconsin.

According to Anne McLaren, principal research associate at the Wellcome Trust/Cancer Research U.K. Gurdon Institute at the University of Cambridge, the order of these events was unfortunate. If stem cells had been introduced before Dolly, then people would have been able to see the benefits of this work before they were influenced by the negative aspects of cloning, she explained. Now, many people assume cloning is a necessary part of stem cell research, she added.

It is this association that led some of the presenters to recommend that separate guidelines be developed for hESC research and for cloning. The area of cloning, they noted, has two distinct aspects: reproductive cloning—which all presenters and the National Academies already agree is unviable and should be banned—and therapeutic cloning, also known as somatic cell nuclear transfer (SCNT)—which some argued should be allowed with proper oversight.

RESEARCH
Pushing The Frontiers Of Stem Cells

As a National Academies committee works toward developing a set of guidelines to govern human embryonic stem cell research in the U.S., research in the field moves forward. Leading the way are two research groups from Harvard University--one of which is led by Harvard Stem Cell Institute Codirector Douglas A. Melton and has reportedly applied for permission to derive cell lines from cloned embryos from the university's ethics board.

The two groups--both of whom are part of the Harvard Stem Cell Institute--are working toward using somatic cell nuclear transfer (SCNT) to create embryos that carry the genetic material of patients with diseases such as type 1 diabetes and Parkinson's. Cell lines derived from these embryos could be used to study and develop cures for these diseases. If permission is granted and the research is successful, it will be the first time that an embryo has been cloned for biomedical research in the U.S.

Also helping to move the field forward is a state initiative in California. Proposition 71, as it is known, is a 10-year, $3 billion bond measure that would be used solely to fund medical research that will likely include studies involving SCNT. California Gov. Arnold Schwarzenegger (R) has endorsed this measure, but it is up to Californians to cast their votes on Nov. 2.

IN SCNT, cloned embryos are created by removing an egg’s genetic material and replacing it with the nuclear material from a somatic cell (such as a skin cell) of a person or animal. Once the material is inserted, the process of deriving hESC lines is the same as with any embryo—the inner cell mass is harvested from the blastocyst to produce the cell lines. The advantage of SCNT is that it allows researchers to generate models of specific human diseases for study. Also, in the long term, SCNT-derived cell lines will allow researchers to generate cells that are a genetic match to the donor and would remove the rejection risk in therapeutic applications.

One individual who doesn’t think SCNT should be allowed is Leon R. Kass, Hertog Fellow at the American Enterprise Institute and chairman of the President’s Council on Bioethics. Speaking on his own behalf, he provided several ethical concerns for the committee to consider in formulating guidelines related to SCNT.

One of Kass’s concerns involves being forthright in calling “an embryo an embryo and a cloned embryo a cloned embryo.” According to Kass, “if one wants to be trusted by those who hold different views, one must not hide the existence of the moral question by calling SCNT-produced embryos ‘cells.’ ” To this end, he proposed the phrase “cloning for biomedical research” as a better representation of the research currently known as SCNT.

Among Kass’s other concerns is the issue of deliberately creating embryos solely for research purposes. Unlike in the case of deriving hESC lines from “spare” embryos that were produced using in vitro fertilization procedures—where the embryo was created with the intent of being implanted and becoming a child but is no longer needed—using SCNT to produce stem cells creates an embryo as an instrument or natural resource for the sake of research with the eventual benefit of others.

Also, he warned, once SCNT is allowed, it will be impossible to limit its use solely for research to stem cell derivation. In the end, Kass proposed that the committee consider calling for a “voluntary, self-imposed three-year moratorium on all human cloning for biomedical research,” including SCNT research involving human embryos. This moratorium would give scientists time to explore alternative ways of accomplishing the same research goals and give society time to set up moral boundaries and oversight systems.

The issues and concerns raised by Kass and their influence on research policies are not unique to the U.S. In fact, the policies surrounding hESC research vary around the world. To help the committee understand the range of policies at play, a breakdown of the world’s hESC policies was presented by LeRoy Walters, professor at the Kennedy Institute of Ethics at Georgetown University.

The first and most conservative policy prohibits human embryo research and doesn’t explicitly permit research with existing hESC lines, Walters explained. In Europe, countries such as Italy, Ireland, and Norway follow this policy. In some other European countries, such as France and Germany, a slightly more liberal policy is in place that allows research with existing hESC lines but prohibits research on new lines derived through the destruction of embryos.

Leaning toward more liberal policies, Spain, Russia, Iran, Canada, and Australia all permit the derivation of new hESC lines but only through the use of unused embryos from infertility clinics, according to Walters. Taking this policy one step further to include SCNT to produce new hESC lines is a growing number of countries including Belgium, India, Israel, South Korea, and the U.K.

According to Walters, the U.S. as a whole, with its policy of providing federal funds only for research with hESC lines derived before Aug. 9, 2001, would fall into the same category as France and Germany. But if one looks at the individual states, there is actually a patchwork of policies in place. Nine states, including Florida, Pennsylvania, and Wisconsin, have adopted the most conservative policy option, while two states—California and New Jersey—have adopted the most liberal policy, he pointed out. However, the majority of states—35 of them—have a legal void when it comes to hESC research.

THIS EVALUATION of hESC policies is only a snapshot of where various countries—and states—stand on the issue, Walters pointed out. He noted that the collection of countries subscribing to each policy is in a state of flux, with no fewer than 12 countries liberalizing their policies since 2002. The United Nations also may soon weigh in on this issue and seek a potential ban of both reproductive and therapeutic cloning or SCNT, he said, adding that if this happens several countries that already allow SCNT have said that they would not follow the UN policy. (The UN held its debate on Oct. 21 and 22, but did not vote on the issue at that time.)

Walters cautioned the committee to take note of the changing state of the science as evidenced by the rate of change in policies in setting up guidelines. For this reason, he advised the committee to ensure that any guidelines or oversight system that they recommend has a mechanism for regular reevaluation to keep pace.

The academies’ committee is scheduled to meet two more times, later this month and in January, to gather information on embryonic stem cell issues. It is expected to publish its guidelines early next spring.