In February 2005, the Commonwealth Commission of Pennsylvania Charged the Compass Consulting

Introduction

In February 2005, the Commonwealth Commission of Pennsylvania charged the Compass Consulting Group with exploring the possibility of Pennsylvania (PA) following the example of California (CA) and funding human embryonic stem (hES) cell research within the state. The Commission requested an examination of the scientific and medical prospects of stem cell research, the potential economic costs and benefits that the state may accrue, the ethical controversies surrounding government funding of this research, and an assessment of CA’s recently enacted Proposition 71 (Prop 71). These considerations have been researched and prepared in a timely manner for the Commonwealth Commission and this report serves to issue background regarding state funding and oversight of hES cell research.

An Overview of Stem Cells

Human embryonic stem cells, isolated from the blastocyst[1] by James Thomson and a research team at the University of Wisconsin in 1998, develop into different types of cells as an organism grows (Figure 1). hES cells offer scientific and therapeutic promise due to their undifferentiated nature, their ability to self-renew in culture, and their totipotency (NBAC). Removing hES cells from the blastocyst results in the destruction of the embryo, making these cells subject to significant ethical considerations (NBAC). However, other sources of stem cells exist and the ethical arguments differ depending on which type of stem cell is being discussed (Table 1).

Ethics

An embryo has biological significance because it has 23 pairs of chromosomes and the potential to grow into a human being. However, the moral significance of the embryo may be questioned (Peters). Ethicists who believe that an embryo has the moral status of a human at conception feel that hES cell research is unjust and can be conceived as a form of murder (Thomson). Stem cell proponents feel that blastocyst-stage embryos are not human beings due to their undifferentiated nature, or that while these embryos have biological significance, they do not have the moral significance of a human (Zoloth).

A second ethical argument against hES cell research centers on Immanuel Kant’s deontological view that people are rational beings who must be valued and treated with dignity. The Kantian view holds that people must never serve as a means to an end and that it is unethical to regard human beings simply as resources from which cells can be derived (Young). The worth of an individual is greater than the individual’s scientific contribution.

Furthermore, ethicists question the long-term effects of hES cell research. One implication is the fear that science may lead to a lack of genetic privacy (Juengst). In a scenario in which genetic testing were mandated, the government and potential employers could know everything about a person’s current and future health (Juengst). An individual who chooses to forgo stem cell research, whether for financial, ethical, or religious reasons, could potentially be at risk for diminished self worth. A second long-term societal ramification of hES cell research is the possible harm for women (Holland). This concern holds that hES cell research may lead to the commercialization of eggs for profit (Holland). The market could dictate the worth of eggs, and some may be valued more highly than others due to factors such as race, health, and education of the donor (Holland). This could lead to the further marginalization of women in our society.

If stem cell therapies live up their potential, existing patterns of separation in our society may result in unequal access to these treatments, at least until the technology has been profitable enough to make it widely available and covered by insurance. Additionally, some ethicists believe that funding, particularly government funding, of stem cell research may channel money into certain diseases while ignoring more relevant issues. For example, in PA, fiscal concerns have led to cuts in vital programs in health, education, and transit (Governor’s Office of the Budget).

Various religions have weighed in on the morality of stem cell research (Table 2). Religions with an active interest or opposition to stem cell research include: Protestant, Roman Catholicism and Judaism. Protestant leaders recognize the complexities of stem cell research while acknowledging the moral status of the human embryo (Meilaender). Similarly, the view of the Roman Catholic Church is echoed by Pope John Paul II:

"Experience is already showing how a tragic coarsening of consciences accompanies the assault on innocent human life in the womb, leading to accommodation and acquiescence in the face of other related evils such as… most recently, proposals for the creation for research purposes of human embryos, destined to be destroyed in the process." (How Catholic Ethics Guide Us)

On the contrary, leaders of the Jewish faith have been outspoken regarding their support of stem cell research because they believe the research shows great promise for curing disease and suffering throughout the world (Dorff).

Potential Medical Benefits

In dispute of these ethical arguments, some scientists suggest the long-term benefits of stem cell research. Researchers relate this to the utilitarian argument that what is morally good is determined by its overall net benefit (New Scientist). hES cell research has three main implications for biomedicine. First, the research may help in understanding human development. Knowledge of the molecular mechanisms by which cells form may allow scientists to determine why cell abnormalities, such as cancer, fertility disorders, and birth defects, occur (Okarma). A second application for hES cell research involves the use of specific cell types, derived from hES cells, for testing different chemical compounds in order to develop medicines to treat disease (Kemp). Third, and perhaps most significant, is that hES cells could be used in regenerative medicine. Regenerative medicine, or cell transplantation therapy, cultures stem cells into replacements for diseased or destroyed cells (Okarma). This may result in the treatment of diseases of organ failure such as diabetes and neurological disorders.

Cardiovascular disease is the leading cause of death in the U.S. (Heart Disease Weekly). After heart muscle is damaged, it is replaced with nonfunctional scar tissue (Okarma). hES cell research provides scientists with an opportunity to explore the possible methods of repairing or replacing damaged heart muscle (Okarma).

Parkinson’s disease affects over 1 million people in the United States (U.S.) (Okarma). It is a chronic and progressive neurological disease that results from a loss of dopamine-producing neurons (Okarma). Individuals suffering from the disease are subject to shaking in their limbs and may find it difficult to function in their daily environment (Begley). Currently, researchers are on experimenting on animals to develop possible medical therapies for diseases such as Parkinson’s. In an article from the Wall Street Journal, author Sharon Begley reported that “scientists took mouse embryonic stem cells, coaxed them to bloom into dopamine-making neurons, and transplanted them into the brains of rats suffering from a Parkinson’s-like disease, and the rats’ motor functions improved” (Begley).

Critics of hES cell research point to the possible exaggeration of benefits due to the undeveloped nature of the research. The main critique is that animal systems function differently than humans systems, so the efficacy of hES cell treatments on humans is unknown and the results of testing on mice cannot be extrapolated to humans with such enthusiasm (Therapeutics Company). Secondly, to date, no human has been treated or cured with hES cells and before the Food and Drug Administration approves clinical trials, many factors, including potential side effects of the treatment, must be accounted for (FDA Regulations). In addition, further technology needs to be developed before cell differentiation is fully understood and hES cell research can be maximized. Lastly, immune rejection in humans is a main concern because unless nuclear transfer was used for the therapy the patient could face immunogenic rejection (Okarma).

Historical and Current Legal Status of Embryonic Stem Cell Research

The issue of hES research became a presidential and congressional concern during President Bill Clinton’s first term in office. Since then, presidential policy and legislation have evolved (President Bush). In December 1994, through executive directive, President Clinton prohibited federal funding for the creation of human embryos for research and for any research that involved these embryos. In 1996, the U.S. Congress passed the Dickey Amendment stating that:

“…federally appropriated funds could not be used for the creation of a human embryo or embryos for research purposes or for research in which a human embryo or embryos are destroyed, discarded, or knowingly subjected to risk of injury or death greater than that allowed for research on fetuses in utero…” (Duffy 2002)

However, in 1998, Thomson’s isolation of hES cells and the ensuing enthusiasm regarding medical prospects forced the National Institutes of Health (NIH) to question these laws. The NIH requested a legal opinion from the Department of Health and Human Services (HHS) regarding the use of federal funds for research on hES cells (Duffy). The General Counsel of the NIH defined the human embryo, “…as an ‘organism’ that when implanted in the uterus is capable of becoming a human being” (Duffy). Using this definition, the NIH recommended that federal funding of hES cell research be permitted. President Clinton then established guidelines and an oversight committee. In September 1999, the National Bioethics Advisory Commission (NBAC) presented a review of hES cell research to President Clinton. However, funding was never granted during the Clinton administration (Duffy).

In January 2001, President George W. Bush announced that he would review stem cell research and in an executive address on August 9, 2001, he stated that no federal funding would be provided for hES cell research on newly destroyed embryos or for the creation or cloning of human embryos for research. The President limited federal funding to 64 existing stem cell lines. These lines were derived from excess embryos created solely for reproductive purposes with the informed consent of the donors and without any financial incentives to the donors. President Bush also declared the creation of the Presidents Council on Bioethics to monitor stem cell research, recommend appropriate guidelines and regulations, and explore the human and moral ramifications of hES cell research (Duffy).

In the executive address, President Bush reminded Americans that the U.S. government would spend $250 million on research on umbilical cord, placenta, adult and animal stem cells, all of which have proven to be beneficial and lack some of the moral dilemmas of hES cell research (President Bush, 2001) (Table 3). As a result of President Bush’s policy, the NIH created a Human Embryonic Stem Cell Registry that catalogs the stem cell lines eligible for use in federally funded research (CRS, 2004) (Table 4).

On July 14, 2004, HHS Secretary Tommy G. Thompson announced the establishment of the Centers for Excellence in Translational Stem Cell Research and the formation of a National Embryonic Stem Cell Bank. The center investigates how stem cells can be used to treat numerous diseases while the bank allows all lines available for federal funding to be located in one place (CRS, 2004). The NIH Stem Cell Task Force, which helps enable and accelerate research, is at the head of these initiatives. The task force also provides research training courses that cover a range of topics, including culturing, manipulating, and differentiating hES cells (National Human Neural Stem Cell Resource, 2004).

Researchers have raised five important questions regarding President Bush’s approved stem cell lines:

“whether the cell lines are indeed robust stem cell colonies; whether the procedures used to create the cells are consistent with high ethical standards; whether the different cell lines have sufficient genetic diversity; whether cells produced from the cell lines would be safe for implantation in humans; and whether the owners of the cell lines will make them available to researchers in a timely fashion and at a reasonable cost” (AAAS 2004).

Furthermore, current research has revealed that all the stem cell lines approved by President Bush are contaminated with N-glycolylneuraminic acid (Neu5Gc). Neu5Gc is a non-human cell surface sialic acid which compromises the potential therapeutic use of the stem cells in human subjects (EurekAlert 2005). While some researchers are attempting to find a test medium that corrects this problem and removes the Neu5Gc from the lines, most acknowledge the issue as a major setback for federally funded hES cell research (EurekAlert 2005).

Patent Laws

The1790 Patent Act stated that: “Any person at any time may cite to the Office in writing prior art consisting of patents or printed publications which that person believes to have a bearing on the patentability of any claim of a particular patent”(Bitlaw). Later, in 1870, a second statute passed saying that patents must contain claims. The claim is a description from the applicant of what is to be preempted. Another patent act passed in 1952 and established the precedent of infringement and non-obviousness. The section on infringement established rules

for suing patent violators while the section on non-obviousness stated that:

“one must look at everything that existed at the time that the invention was made and then ask whether it would be obvious to combine these devices or teachings in the manner combined in the invention sought to be patented in order to achieve the results achieved with the invention” (Pizarro).

Modern technology has raised the question of patenting life. This question has been addressed through case law precedent. The Diamond v. Chakrabarty, 1980 case involved patenting a bacterium that would break down crude oil and reduce the environmental dangers of oil spills. The plaintiff claimed the production of the bacterium, the use of the bacterium to whatever the spill may be and the bacterium itself. The plaintiff was denied the last two claims because the bacterium was a product of nature and living things are not patentable. However, the Supreme Court overturned this ruling and stated that patent laws were created for the widest possible area of patent because the U.S. should encourage intellectual inventions (US Code).

In light of new law and policy concerning hES cell research and patent law multiple federal lawsuits have occurred. In the case of Geron v. Wisconsin Alumni Research Foundation, 2001 the research guidelines at the time did “…not reach the specifics of licensing agreements between grant applicants and patent holders” (Duffy 2002). However, the issue of patents was addressed by the U.S. Congress in the 2004 Consolidation Appropriations Act. The act prevents the Patent and Trademark Office from issuing patents on claims directed to or encompassing human life (CRS 2004).