Stem cell research and cloning: the state of the science.

Although stem cell research has the potential to cure human diseases, the field is young and is filled with ethical questions. On the one hand, stem cell research has extraordinarily high potential, but on the other hand, it involves manipulating human beings. In general, adult stem cell research is viewed as ethically appropriate to pursue. However, ethical controversy dominates embryonic stem cell research and therapeutic cloning. It generally is accepted that human reproductive cloning is unethical and should be banned. The great debate in embryonic stem cell research concerns the moral status of the human embryo. Some view the human embryo as the smallest, least developed member of the human species that ought to be nurtured and developed, not put to death in research. They claim that even the benefit of developing new therapies does not justify deliberately creating and/or killing human embryos. On the other side of this issue are those who give the human embryo a lower moral status than humans offer birth. Those with this perspective range from some who view the embryo as no more than a ball of cells to others who see the human embryo as entitled to profound respect. They claim that cloning human embryos and destroying them to remove their stem cells fulls within the bounds of respecting them. This article discusses the ethical debate surrounding embryonic and adult stem cell research as well as the issues surrounding human and therapeutic cloning.

Key Words: adult stem cells, cloning, embryonic stem cells, epigenetic reprogramming, human cloning, stem cells, therapeutic cloning

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Immediately after Wilco Conradi was born, he had blood drawn and sent away for testing. (1) The results confirmed that he has the genetic disease that has plagued his family for generations. Because of this genetic defect, Wilco does not produce an enzyme essential for making some of his immune cells. This leaves him highly vulnerable to any sort of infection. The most famous person with this condition was nicknamed the "bubble boy" because of the plastic enclosure in which he lived germ-flee for 12 years.

The only option for boys with this disease has been a bone marrow transplant and monthly infusions with antibodies from donated blood. But Wilco was offered an experimental treatment, one that highlights the potential of stem cell research. Doctors removed some of Wilco's bone marrow from which they then extracted stem cells. The stem cells were mixed with a virus carrying the gene for his missing enzyme. The hope was that the virus could get the normal gene into the stem cells and restore Wilco's immune system.

Wilco received one injection of his gene therapy-treated stem cells. Close monitoring soon revealed an apparently normal immune system. Soon he was able to go outside and play with other children. In April 2002 he caught chicken pox, an infection that is normally lethal for people with his disease. Wilco recovered completely because of his revitalized immune system. His disease is, for all intents and purposes, cured.

Wilco is not alone in being treated this way. (2,3) His is but one dramatic example of the type of treatment that research on stem cells may one day make more widely available. Although actual therapies are few thus far, the potential seems limitless. Some people see stem cells leading to treatment for almost every disease, from cardiovascular problems to cancer, spinal cord injuries to birth defects. (4) Millions of Americans have these diseases, and for many of them--like Parkinson's disease, diabetes, Alzheimer's disease, and spinal cord injury--there are few or no treatments currently available. (5)

Medicine seems to be poised on the verge of a revolution that will transform it into molecular medicine and usher in the age of biotechnology. The future seems to be one where stem cells could allow the replacement of almost any tissue, organ, or gene that has become defective, thus eliminating the disease itself. The face of medicine could be radically changed if stem cell research leads to even some of what it is said to be capable of producing.

What could be in the way of realizing the huge potential of stem cell research? As with any area of new research, the difference between potentiality and reality can be substantial. It is sometimes difficult to remember that the promise of stem cell research is only a few years old. Much remains to be discovered about stem cells before they will become clinically effective therapies. Although there are scientific questions, there are also questions of a different nature. No discussion of stem cell research can avoid the issue of cloning. And that raises profound ethical, societal, and religious questions that sometimes overshadow the science of cloning and stem cell research. Although the ethical issues will be described, this article will focus on reviewing the state of the science involved in stem cell research and cloning.

Stem cells

The recent medical controversy over stem cell research began with a 1998 publication. (6) Dr. James A. Thomson of the University of Wisconsin reported that he and his colleagues had isolated stem cells from human embryos. These embryos had been made using in vitro fertilization (IVF) technology, but were donated to research rather than being implanted. Embryonic stem cells had been isolated before this from other species, but these were the first isolated from human embryos. A closely related development at the same time was the isolation of embryonic germ cells from 5- to 9-week old human fetuses obtained from elective abortions. (7) Embryonic germ cells have many, but not all, of the same properties as embryonic stem cells. To understand the differences, however, some embryo terminology will be reviewed.

Embryonic stem cells

An egg that has been fertilized is called a zygote. (5) After about a day, the cells in the zygote begin to divide. Embryonic stem cells usually are removed from an embryo in its blastocyst stage, which is reached about 5 or 6 days after fertilization. The blastocyst is made up of an outer layer of cells (the trophoblast) and an inner cluster of cells called the inner cell mass. The embryonic stem cells are located in the inner cell mass. These stem cells can be removed from the embryo and grown indefinitely in laboratories as cell culture lines. Removing the stem cells results in the death of the embryo. (See Figure 1.)

[FIGURE 1 OMITTED]

If the embryo continues to grow and develop, its cells start to specialize and differentiate. One of the first major specializations is between germ and somatic cells. Embryonic germ cells are those that will develop into sperm and eggs in the older organism. Early in the embryo's development, they are separated from the other cells that eventually give rise to all the other tissues in the organism. These cells divide into 3 layers that produce the 3 major classes of tissue: the mesoderm, endoderm, and ectoderm. Within each layer, further specialization occurs. (See Table 1 for examples.)

Embryonic stem cells were defined by Thomson as cells with 3 essential characteristics. (6) First, they are derived from the preimplantation stage of the embryo.

Second, they will grow and replicate without differentiating for extended periods of time. In other words, they remain unspecialized undergoing what is called long-term self-renewal. Sometimes this also is referred to as producing immortal cell lines. Embryonic germ cells do not appear to be able to replicate for as long as embryonic stem cells. (8) Third, any one embryonic stem cell can develop into cells of various tissue types. This property is what makes stem cells practically attractive. If methods can be developed to determine which tissue a stem cell will form, those tissues could be transplanted into patients to replace damaged or diseased tissues.

An important area of controversy with stem cells surrounds the terms totipotent, pluripotent, and multipotent. There is considerable debate, even within the scientific community, regarding the definitions and distinctions between these terms. (9) Totipotency has been used to refer to a cell that can develop into a complete organism, or to a stem cell that can develop into any of the more than 200 types of tissues in the human body. Pluripotency initially was used to distinguish between stem cells that could develop into many, but not all, tissue types and those that were totipotent. Given the difficulty of resolving these disagreements, the term multipotent will be used to describe the stem cell's ability to develop into many, but not necessarily all, tissue types.

Human embryonic stem cells have been maintained in labs for up to 2 years. (5) In contrast to other embryonic cells, the stem cells have remained stable and have not developed abnormalities. However, very little is known about human embryonic stems cells compared to mouse ones, primarily …