Report: Stem Cell Research – Science and Policy

Stem Cell Research: Science and Policy

Peter A. Kessler

9th Grade, the Lovett School, Atlanta, GA

Abstract

Stem cell research represents one of the most polarized biomedical controversies of our time. There are many types of stem cells, but the one with the most potential is the embryonic stem (ES) cell. Such cells are derived from human embryos, and are undifferentiated, unlike other specialized cells in the human body. ES are pluripotent, as they can transform into almost any human cell type. This makes them potentially capable to help in effectively combatting a variety of degenerative diseases and conditions such as spinal cord injury, stroke or heart attacks. However, the removal of embryonic stem cells destroys the early embryo. Proponents of stem cell research claim that the blastocyst is not human yet, and the embryos used for stem cell harvest are typically leftover from in vitro fertilization procedures with minimal chance that a human could ever develop from them. Adversaries of stem cell research argue that embryos are human and destroying one is equal to murdering a child. There are other, less controversial alternatives to embryonic stem cells, such as adult, fetal, cord blood, and induced pluripotent stem cells, but they have other biological restrictions that make them less promising for use in regenerative medicine at this time. Considering the great potential of embryonic stem cell research, it is argued here that their research be allowed to be legal, federally funded, and its development a national priority. Ethical rules need, however, to be in place so that scientific research always respects the life and freedom of individuals, and there is no abuse of this research potential to serve other goals.

Introduction: The issue and its context

Stem cell research is one of the most controversial issues in modern medicine. There are many types of stem cells, but most of the controversy surrounds embryonic stem cells, as they are derived from human embryos. The source of embryos is from those fertilized in vitro, and then donated for research with donor consent. Embryonic stem cells are totally undifferentiated and have the ability to divide and create multiple specialized cell types. When the stem cells divide, the new cell may remain a stem cell to divide again or may differentiate to become any of the 200 types of specialized cells in the human body. They can thus develop into brain, muscle, blood, skin, and other tissues and can, in theory, help with many health conditions involving organ dysfunction or failure, as well as cancer, injury, and may even address degenerative and  otherwise incurable diseases such as Parkinson’s and Alzheimer’s disease. 

The controversy over embryonic stem cell research is caused by the fact that the procurement of these stem cells involves the destruction of the embryo produced during in vitro fertilization. Adversaries support that it is unethical to destroy an embryo and is, in religious terms, a sin. Proponents, on the other hand, believe that embryos have not yet been guaranteed their human rights because they are only blastocysts, and the benefits of such research outweigh the concerns. The question at the heart of this issue is, where and when does life begin? Does it begin at conception, during a certain stage while maturing in a mother’s womb during gestation, or when a child is born?

Governments today are only starting to focus on stem cell legislation. In the United States currently embryonic stem cell research is allowed but there has been a lot of public controversy and legal setbacks. Two bills were proposed: The first one was the Stem Cell Research Advancement Act, which passed in both the House of Representatives and the Senate but was vetoed by President George W. Bush. The second was proposed by Representative Diana DeGette, but it has not yet been passed. This newer bill calls for prioritizing federally assisted advancement of embryonic stem cell research (1). Additionally, there have been two executive orders focusing on embryonic stem cells, one released by President George W. Bush prohibiting embryonic stem cell research and related federal funding, the other by President Barack Obama reversing the previous order but still with restrictions in place (2). This showcases the ambivalence of public perception, policy and legislation about stem cell research.

The Science: Types of Stem Cells and their potential applications

Every human being is composed of over 37 trillion cells, the smallest units of an organism. Cells are essential for the proper functioning of all organisms, as they produce energy and execute particular tasks in the body. Most cells are specialized in their function,  such as blood cells, muscle cells, brain cells, and skin cells, just to name a few of the approximately 200 different types of cells in the human body (3).

Cells duplicate during a process termed mitosis, during which they split into two identical copies of the same type as the parent cell. When highly specialized cells are damaged or destroyed, other cells types cannot replace or regenerate them. For example, Parkinson’s disease is a neurodegenerative condition in which particular brain cells slowly degenerate, causing dysfunction in the cerebellum and thus in movement. Parkinson’s disease cannot be cured, as the cells that degenerate cannot be regenerated by other cells in the brain (4). Other diseases such as Alzheimer’s disease, many types of arthritis, diabetes, as well as spinal cord injury, cancer, and over two hundred other conditions cannot be cured because of the loss of highly specialized cells without regenerating ability (3).

However, there are some cells that are undifferentiated. These cells, named stem cells, have a unique ability: they act like cell factories. When the stem cells divide, the new cell may remain a stem cell to divide again or become any other type of differentiated cell in the human body. Consequently, these cells could theoretically replace any damaged cells in the body, acting as an internal repair system (5). There were some indications of “special” such cells in the late 1800s and early 1900s, but the first published study that identified stem cells was in 1961, when Canadian scientists James Till and Ernest McCulloch were experimenting with lethal doses of radiation and their effects on mice at the Ontario Cancer Institute. They realized that mice injected with the (still undiscovered) stem cells had a higher chance of surviving radiation. They published their findings in the journal “Radiation Research” and thus “accidentally” proved the existence of stem cells (6).

There are several different types of stem cells; the two major ones, adult (or somatic) stem cells and embryonic stem cells, are the best known and mostly studied so far. Other types of stem cells such as fetal stem cells, cord blood stem cells, and the newly discovered induced pluripotent stem cells are other types of stem cells. The most discussed are the embryonic stem cells, for their great potential, but also for their great controversy (7). 

In 1998 James Thomson and Jeffrey Jones derived the first human embryonic stem cells (NIH). Embryonic stem cells (ES cells) are derived from pre-implantation embryos and have the potential to become almost any cell in the human body (and are called pluripotent, in contrast to the many but not all cell types the adult stem cells can become -thus called multipotent). ES cells cannot become all specialized cells because the only totipotent cells, or stem cells that can become any cell, disappear as the embryo’s first cell divisions occur.  The embryonic stem cells used today are left over from in vitro fertilization, willingly donated by the donors. These leftover blastocysts have the cells from their inner cell mass region removed and placed in a culture plate, while the removal of the cells ultimately destroys the embryo. Growth factors and nutrients are added to the culture plate until the cells start dividing, forming embryonic stem cells (8). Through years of research, scientists have established experimental protocols for the directed differentiation of ES into some specific cell types (3).  ES cells could thus be used in regenerating lost tissue or grow organs for transplantation. However, they may also have risks, as they could replicate uncontrollably in the body, which could lead to cancer. Much more research is needed in order to minimize the risks and maximize the benefits of embryonic cells. Even though government and privately funded research using stem cells for the development of treatment modalities has started, there is currently no medical treatment using embryonic stem cells in practice in the United States. 

Adult stem cells are multipotent; they can divide into many different types of cells, but not as many as pluripotent stem cells like the ES cells. Many tissues such as bone marrow, skin, intestine, blood vessels, muscle, heart and even brain, have their own stem cells. It is not yet clear if all organs and tissues contain stem cells, but many more have been recently discovered, which has generated great enthusiasm for their potential to be used for transplantation-based therapies (9). An additional advantage of adult stem cells is the fact that they are less likely to initiate rejection after transplantation, as they are the patient’s own (3).  Little, if any, controversy surrounds adult stem cell research; however, determining the methods by which they can reliably repopulate or reform the tissue after transplant is still under investigation (3) Adult stem cells are expected to be able to cure conditions such as arthritis and non-healing bone fractures and they are currently used in bone marrow transplantation to cure some types of hematopoietic cell cancer.

The term “adult stem cells” is often loosely used to also name fetal and cord blood  stem cells, though they are not the same. Fetal stem cells are also taken from a maturing organism, but at a stage of at least 10 weeks from conception, when the embryo is no longer considered an embryo, but a fetus. The embryonic stem cells have disappeared from the fetus at this stage, rendering the fetal stem cells multipotent, and the stem cells become more like adult stem cells in terms of being tissue-specific and generating cell types reflecting the tissue where they are located (7).  Adult stem cells have provided many therapies for conditions such as leukemia, sickle cell anemia, Parkinson’s disease and heart disease (3).

Cord blood stem cells are taken from the umbilical cord during a baby’s birth, and specialize in blood-forming stem cells. Like the fetal and adult stem cells, cord blood stem cells are tissue-specific, and are currently used to treat diseases of the blood or to restore the blood after cancer treatment. Cord blood stem cells are also considered multipotent, and they are used in bone marrow transplantation (10).

The invention of another type of stem cell, the induced pluripotent stem cell (iPS) led to the 2012 Nobel Prize in Medicine for Sinya Yamanaka and John Gurdon (11).  These scientists managed to “reprogram” or revert an adult specialized cell to an embryonic stem cell-like state in the laboratory by injecting special proteins. ES and iPS cells have similar abilities, as the cells they divide into can become any cell of any tissue or any organ, but despite that they behave differently in the laboratory (10). Given their recent discovery, there has been much less research conducted with these cells than with embryonic stem cells to-date, and despite them having almost the same potential, the cells sometimes behave erratically and can act differently than the seemingly more stable embryonic stem cells (1). In animal studies, the virus used to introduce stem cell factors sometimes causes cancers (3), so alternative methods of reprogramming are being investigated. This research is clearly still in its embryonic stages! IPS cells could represent a very useful alternative to ES research, but the process must be refined before it can be considered a real replacement of embryonic stem cell research (1).

An alternative technique was developed by researchers at Harvard University, led by Kevin Eggan and Savitri Marajh, in which the nucleus of a somatic cell was transferred into an existing embryonic stem cell, thus creating a new stem cell line (3). This is referred to as somatic cell nuclear transfer (SCNT).

In 2009, the FDA approved the first human clinical trials using ES cells (3). In July 2013, Japanese scientists led by Shinya Yamanaka regrew an entire liver from embryonic stem cells. Inspired by this example, British scientists in April 2014 announced that they began creating custom-made tissues for patients by growing organs and tissues from embryonic stem cells with the aim to implant them (12).

Because of the stem cells” unique ability to replace or repair damaged cells in the body, therapies based on stem cell research could, theoretically, help treat over 100 million Americans who suffer from degenerative diseases, injuries, organ failure, or cancer, representing approximately one third of the US population. Furthermore, if this ratio is applied to the world population (7.2 billion), 2.4 billion people could benefit from this research worldwide (3). This potential application is all the more important, as the need for transplantable organs and tissues is far greater than the supply (3). Stem cells, directed in the laboratory to grow and differentiate into specific cell types, offer the potential for a renewable source of tissues to treat diseases such as spinal cord injury, diabetes, burns, arthritis, stroke, heart disease, and macular degeneration (3). In addition to using stem cells for reparative medicine applications, research on how to grow them in the laboratory may aid in gaining a better understanding on how cell proliferation is regulated during embryonic development or during abnormal cell division that leads to cancer (3).  

Human stem cells are also used currently to test the safety of new drugs. Many cells lines used for this purpose are generated from human pluripotent cell lines (3). Cancer cell lines, for example, are used to screen potential anti-neoplastic agents.

Legislative battles in the U.S.

In 1974, the National Research Act established the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, to protect human rights in scientific experiments. This commission was a staunch adversary and has strongly advocated against stem cell research.

In 1988, the Human Fetal Tissue Transplantation Research Panel voted to approve federal funding of embryo research.  However, the Dickey-Wicker Amendment of 1995 signed into law on January 21, 1996 by President Clinton, contained a statute stating that “(1) the creation of a human embryo or embryos for research purposes and (2) 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” is prohibited” (13).

The National Institutes of Health (NIH) attempted to change the Dickey-Wicker amendment, stating that research on unused embryos from in vitro fertilization should be allowed with informed consent of the donors. NIH also argued for the creation of embryos for research purposes, but the Clinton administration rejected this proposal.

After the Dickey Wicker Amendment was passed, scientist James Thomson left the United States and while out of the country managed to first isolate human embryonic stem cells and display their potential use in 1999. This major discovery also instigated the ethical debate of human embryonic stem cell research because the embryos were destroyed during isolation of the stem cells. The government was split as to whether stem cell experimentation and usage should be legal; adversaries claimed that the Dickey-Wicker Amendment of 1995 prohibits stem cell research because it directly prohibits research that harms or destroys embryos, while proponents claimed that the benefits of stem cell research outweighed the concerns and the Dickey-Wicker Amendment did not apply to human stem cells. In 1999, the President’s National Bioethics Advisory Commission recommended that human ES cells harvested from embryos discarded after in vitro fertilization treatments, but not from embryos created expressly for experimentation, be eligible for federal funding (3). The Clinton administration had decided that it would be permissible under the Dickey amendment to fund such research as long as it did not directly cause destruction of the embryo, and issued its proposed regulation in 2001. However, the incoming President George W. Bush decided to reconsider the issue (3).

President Bush publicly announced his misgivings about stem cell research and halted the federal funding of research using embryonic stem cell lines created after August 9, 2001 in a presidential executive order that stipulated that no federal funds could be used to create new human stem cell lines. There was a very limited number of lines before this executive order, and so it gravely restricted the research of ES cells. Congress and the Senate attempted to permit more federal funding, but Bush repeatedly vetoed

When President Obama succeeded President Bush, he signed Executive Order 13505 and lifted the limit Bush had placed on government funding for newer stem cell lines (10.)  Two days after Obama removed the restriction, the President then signed the Omnibus Appropriations Act of 2009, which still contained the Dickey-Wicker provision with bans federal funding of research in which a human embryo is destroyed or discarded, thus effectively preventing federal funding from being used to create new stem cell lines by many of the known methods. So, while scientists might not be free to create new lines with federal funding, President Obama’s policy allows the potential of such research involving the existing stem cell lines as well as any further lines created using private or state-level funding. The ability to apply for federal funding for stem cell lines created in the private sector is a major expansion of options over the limits imposed by President Bush, who had restricted funding to the 21 viable stem cell lines that had been created prior to his decision in 2001 (3).

Where are we today with stem cell research?

It is clear that embryonic stem cell research needs more governmental funding to progress to something that can benefit modern science. Only federal government can cover the costs of research of this scope and magnitude; in addition, federal funding allows the government to oversee the research and make sure it is ethical and congruous. However, the remnants of President Bush’s anti-embryonic stem cell policy today in the government are still impeding this research. Private funding is simply too small to lead to substantial advancements, and even if it were adequate, the public would still have no assurance that the research is conducted ethically. NIH has a yearly budget of 30 billion dollars, and 900 million dollars on embryonic stem cells each year, a figure private donors cannot match. Also, Bush’s executive order meant that many scientists working in this area left the United States to foreign countries that continued the research (14).

Given the great potential of stem cell research, and in order for such research to advance in the U.S., an exception must be made to the Dickey Wicker Amendment and the government should allow the development of stem cell research. There is however the need for government regulation. Since stem cells from a person’s body are not considered a drug, they do not need FDA approval. Numerous clinics have opened treatment centers using stem cells without consistent trials or proof. Stem cell “treatment providers” are taking advantage of people who are desperate for a cure, and trick them into buying unproven stem cell therapies in places such as Mexico or Russia treatment that is not effective. Thus regulations are needed, but not regulations that hinder the research advancement process.

The United States government has hesitated in allowing stem cell research because of ethical concerns and consequently has fallen behind other countries on this research. Those ethical concerns, however, may be the key to making sure that embryonic stem cells are used responsibly.

The ethical debate

As mentioned, the main source of the controversy over stem cell research is the destruction of the embryo during their harvesting. Critics also fear that embryos may be created simply for the purpose of harvesting those stem cells. This ethical debate has been based to a great extent on religious beliefs. The rights of an embryo is the main point that is debated. Ethicists, scientists, government officials, and religious leaders today are arguing on whether an embryo is considered a human being or if it has some human rights. Critics of ES research believe that such research violates the sanctity of human life (15). Dr. Richard Whittington from the University of Pennsylvania is strictly against embryonic stem cell research, believing that embryos are human (16). He also specifically asks what is defined as a person and when does that “person” become a person. In one extreme case, biologist Joseph Panno compares the destruction of the embryos to “the cruel experiments that prisoners were forced to endure at the hands of the Nazis during World War II.” The question is when life starts: at conception, when through fertilization a zygote is formed, at some point in gestation, or at birth? If it starts at zygote, then using embryos could be ethically and morally wrong because the embryos are destroyed after obtaining embryonic stem cells. If not, then it would be more permissible to use the stem cells. 

Embryonic stem cell research supporters argue that the embryos made during in vitro fertilization that are not implanted are leftovers and will never mature to babies. Indeed, most of them will remain in cold storage for a long time, long past their viable storage life, and will be eventually discarded. In the United States alone, there are estimated to be at least 400,000 such embryos (3).

The opposing view is supported by the so-called utilitarian arguments (3), which are listed below: The embryos used to acquire embryonic stem cells are only a few days old and have approximately 150 cells in a ball-shaped formation called a blastocyst. Cells are removed from the blastocyst by scientists from the inner cell mass area destroying the embryo. The blastocyst does not look “human”, has not developed into an embryo yet, nor can it survive and grow without being in a womb; thus it only has the potential for life. Further, the cells in the blastocyst have not differentiated into distinct organ tissues yet; therefore the inner cell mass may be no more “human” than a skin cell (3). Therefore, many ethicists believe that it is not the same as a human being nor does it have the same rights as humans. It could be compared to cell lines in the laboratory, which are alive but are not a human life. Moreover, over a third of all early embryos are naturally lost because they fail to get implanted in the womb. In other words, far more embryos are lost due to chance than are proposed to be used for embryonic stem cell research and treatments (3). James Thompson, the first scientist to create a human embryonic stem cell line, has stated  that “regardless of what you think of what those embryos are, it makes sense to me that it’s a better moral decision to use them to help people than to just throw them out” (10). Besides, no new embryos have to be destroyed to work with the existing cell lines, so it would be wasteful to not make use of these cell lines (3).

Conclusions

Embryonic stem cell research has great potential in advancing medicine and providing cure for many diseases that cannot be treated today, but should be monitored carefully to ensure that all such applications are practiced in a highly ethical way (17, 18). We argue that embryonic stem cell research needs to be legal, federally funded, and be made a national priority. The research can potentially help millions of people with varying ailments and help advance medical science to save even more lives. There are many ethical guidelines in place today to ensure that the science is practiced both legally and morally. In addition, steps have been taken to ensure that the embryos are treated humanely and with respect during research phases. All of the embryos to be destroyed by this research are leftover embryos donated by willing parents from in vitro fertilization with written informed consent. Those embryos have very little chance of ever maturing, and the donors’ informed contribution can help improve human lives. Great amounts of research must still be undertaken in all types of stem cells, most importantly the embryonic and induced pluripotent stem cells, so that knowledge can be applied for treatments as early as possible, as well as for alternative methods that do not require destruction of embryos. Continued debate and dialogue among scientists, ethicists, religious representatives, and the public is necessary in moving forward and in assuring that appropriate guidelines and safeguards are in place to harness the great potential of stem cell research and avoid any misuse.

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