At this stage of our knowledge, are claims that therapeutic cloning could be the cure for diseases such as diabetes and Parkinson's premature and misleading
At this stage of our knowledge, are claims that therapeutic cloning could be the cure for diseases such as diabetes and Parkinson's premature and misleading?
Viewpoint: Yes, therapeutic cloning is so fraught with controversy, and the technique is so far from perfect, that it may be decades before it is put into practical use.
Viewpoint: No, recent scientific advances in the area of therapeutic cloning indicate that cures for diseases such as diabetes and Parkinson's are possible in the not-too-distant future.
In July 2001, after a heated debate about human cloning, the U.S. House of Representatives voted to institute a total ban on all forms of human cloning. The House bill classified human cloning as a crime punishable by fines and imprisonment. The House rejected competing measures that would have banned cloning for reproductive purposes, but would have allowed therapeutic cloning. President George W. Bush immediately announced his support for the ban on human cloning and research involving human embryos. Opponents of all forms of experimentation on human embryos believe that therapeutic cloning eventually would lead to reproductive cloning. After the House vote, many scientists predicted that a ban on therapeutic cloning and stem cell research in the United States would lead pharmaceutical and biotechnology companies to move their laboratories to other countries.
The purpose of therapeutic cloning, also known as somatic cell nuclear transfer, is to generate embryonic stem cells that can be used in the treatment of human disease and the repair of damaged organs. Embryonic stem cells were first isolated from mouse embryos in the 1980s. Human embryonic stem cells were not isolated until 1998. Although therapeutic cloning is conceptually distinct from reproductive cloning, both techniques have generated major scientific, technical, political, and ethical disputes. Much of the controversy associated with therapeutic cloning is the result of confusion between reproductive cloning, in which the goal is to create a baby, and therapeutic cloning. Advocates of therapeutic cloning claim it is essential to the development of regenerative medicine, i.e., repairing the body by using immunologically compatible stem cells and signaling proteins. Biopharmaceutical companies believe therapeutic cloning and regenerative medicine could transform the practice of medicine within a decade. Even in the early phases of development, cloned human cells could be used in drug discovery and to screen out potentially dangerous drugs and toxic metabolic drug products.
In order to generate embryonic stem cells, a cell nucleus taken from the patient would be inserted into an enucleated donated human egg cell. Factors in the cytoplasm of the egg cell would reprogram the patient's cell nucleus so that it would behave as if it were the nucleus of a fertilized egg. However, because such cells are the result of nuclear transplantation rather than the product of the union of egg and sperm nuclei, some scientists suggest that they should be called activated cells rather than embryos. After about five days of development the egg cell would become a blastocyst, a hollow ball made up of some 250 cells. The inner cell mass of the blastocyst contains the embryonic stem cells. These so-called master cells can produce any of the approximately 260 specialized cell types found in the human body. That is, the original egg cell is totipotent (capable of forming a complete individual), but embryonic stem cells are pluripotent (able to form many specialized cells, but unable to form a new individual). Stem cells would be harvested, cultured, and transformed into specialized cells and tissues for use in the treatment of diseases such as diabetes, Parkinson's, and Alzheimer's, and in the repair of damaged organs such as the heart, pancreas, and spinal cord. Replacement cells and tissues generated by means of therapeutic cloning would match the patient's genotype. Therefore, the patient's immune system would not reject the new cells. In addition to producing possible medical breakthroughs, therapeutic cloning research could provide fundamental insights into human development. Indeed, therapeutic cloning might disclose mechanisms for reprogramming adult cells, thus eventually obviating the need for embryonic stem cells.
Stem cells also are found in differentiated tissues, but their ability to form different kinds of cells and tissues appears to be rather limited. Nevertheless, research carried out in 2000 suggested that adult-derived stem cells had previously unexpected possibilities. For example, neural stem cells differentiated into skeletal muscle cells and skeletal muscle stem cells differentiated into blood cells. The ethical and moral implications of these reports overshadowed their scientific and medical importance. Stem cell researchers warned that although adult stem cells might have interesting properties, they are far more limited in their ability to differentiate into various tissue types than embryonic stem cells. Opponents of embryonic research have argued that the potential uses of adult stem cells mean that banning therapeutic cloning would not inhibit the development of medicine. Researchers warn, however, that adult stem cells are very rare, difficult to isolate and purify, and may not exist for all tissues.
The House vote to ban all forms of human cloning demonstrated how controversial issues surrounding human cloning, stem cell research, and the abortion debate have become confounded and inextricably linked. Although many Americans believe that stem cell research and therapeutic cloning are morally justifiable because they offer the promise of curing disease and alleviating human suffering, others are unequivocally opposed to all forms of experimentation involving human embryos. In contrast, after assessing the risks and benefits of new approaches to research using human embryos, the United Kingdom concluded that the potential benefits stem cells derived from early embryos justified scientific research. In January 2001 the United Kingdom approved regulations that allowed the use of therapeutic cloning in order to promote embryonic stem cell research. A High Court ruling in November 2001 on a legal loophole in the January law pushed the government to then explicitly ban reproductive cloning in the United Kingdom.
In June 2001, under the sponsorship of the National Research Council, the National Academy of Sciences established a panel on the scientific and medical aspects of human cloning. The panel's final report, released in January 2002, recommended that human reproductive cloning be banned, but endorsed therapeutic cloning for generating stem cells "because of its considerable potential for developing new medical therapies to treat life-threatening disease and advancing our fundamental biomedical knowledge." However, a White House spokesman reiterated President Bush's opposition to all forms of human cloning.
—LOIS N. MAGNER
Viewpoint: Yes, therapeutic cloning is so fraught with controversy, and the technique is so far from perfect, that it may be decades before it is put into practical use.
Inside a forming embryo, no bigger than the period at the end of this sentence, lie hundreds of tiny stem cells. Initially these cells are undifferentiated, meaning that their fate is undecided. The power of a stem cell lies in its pluripotency: its potential to develop into every tissue, muscle, and organ in the human body. For decades, scientists have been attempting to discover these fledgling cells and then to harness their power. If scientists could direct stem cells to develop into specific tissues or organs in the lab, they could replace cells damaged by disease or injury. Imagine the potential of restoring motility to someone who has been wheelchair-bound by a spinal injury, returning memory to an Alzheimer's patient, or replacing skin that has been horribly burned.
Now imagine having a virtually limitless supply of stem cells, created in the laboratory by cloning an embryo out of a cell from a patient's own body and a donated egg. The resulting cells could then be coaxed into forming whatever tissue was needed, and there would be no risk of rejection because the cells and tissue would be made up of virtually the same genetic material as the patient.
What sounds like a miracle cure for everything from Alzheimer's to diabetes to Parkinson's disease is undoubtedly promising, but therapeutic cloning is so fraught with controversy, and the technique is so far from perfected, that it may be decades before it is put into practical use. Standing in the way of therapeutic cloning research is a trifold hurdle, one built of ethical, political, and scientific obstacles.
To harvest an embryo's stem cells, scientists must destroy it. Does that amount to "playing God" by, in effect, killing a potential human being? Will governments allow scientists to make such life-and-death decisions? Most countries already have said a vehement "no" to embryonic cloning. If governments withhold financial backing and restrict experimentation, will research organizations have the funding and the freedom to continue embryonic stem cell research? Even if they are permitted to pursue this line of research, can scientists harness the technology to put stem cell-based treatments into practical use in the foreseeable future?
Moral Debate
Where does life begin? This fundamental question is at the root of the debate over embryonic stem cell research. If you believe that life begins at conception, as many people do, then creating an embryo solely for the purpose of harvesting its stem cells, even if the embryo is only a few days old and no bigger than a speck, amounts to murder.
It is important to differentiate what we traditionally define as conception from cloning, however. A human being is created through the sexual conjoining of sperm from the father and egg from the mother. The resulting child inherits genetic material from both parents. In the case of cloning, scientists use a process called somatic cell nuclear transfer, in which the nucleus of the woman's egg is removed and replaced with the nucleus of a cell from another person. The resulting embryo carries the genetic material of the cell donor.
Regardless of the genetic distinctions between cloned and conceived embryos, the idea of tampering with human life in any way has been met with vehement debate in political and religious communities. At a U.S. House of Representatives subcommittee meeting in February 1998, religious groups and medical ethicists were furious even with the idea of cloning a human embryo. "This human being, who is a single-cell human embryo, or zygote, is not a 'potential' or 'possible' human being, but is an already existing human being—with the 'potential' or 'possibility' to simply grow and develop bigger and bigger," said Dianne N. Irving, a biochemist and professor of medical ethics at the Dominican House of Studies, a Roman Catholic seminary in Washington, D.C.
Take the issue of embryonic cloning one step further, and it comes under even greater fire. If scientists can create an embryo in the lab, wouldn't the next step be to implant that embryo into a surrogate mother's womb and allow it to develop into a baby? The idea of cloning human beings calls up frightening scenarios of designer babies, genetically engineered with the agility of Michael Jordan and the intellect of Stephen Hawking, or of parents trying to bring back a child who has died. An even more frightening, but far-flung, scenario is one in which scientists would genetically alter a forming embryo to create a brainless body that could be harvested for its organs.
In 1997, news that a group of Scottish researchers had successfully cloned the sheep Dolly from the cells of a six-year-old ewe incited fears around the world that human cloning would not be far behind. Those fears reemerged in early 2001, when Panayiotis Zavos, a former University of Kentucky professor, and Dr. Severino Antinori, an Italian fertility specialist, announced their intention to clone the first human being. But other scientists in the field were quick to point out the improbability that such attempts would be successful. Cloning Dolly took 277 attempts. Research with sheep, goats, mice, and other animals has shown that about 90% of cloned embryos die within the first trimester. Animals that make it to full term are often born abnormally large or with ill-functioning organs. Believing such research to be unethical and irresponsible, most scientists adhere to a self-imposed moratorium on cloning humans, and most governments have banned such experimentation.
Scientists could avoid the moral issue of creating and destroying embryos by making only the cells they need through cloning. A good idea, but one whose time has not yet come. Currently, there is no way to manipulate a cloned cell without creating an embryo.
Freedom to Clone—Will Governments Fund or Forbid?
The ethical debate alone may bring research into therapeutic cloning to a halt. But when bioethical concerns enter the public arena, the political fallout may sound the death knell for cloning research, as governments restrict the freedom and funds of research institutions.
In July 2001, Congress passed the Human Cloning Prohibition Act of 2001, which condemned all forms of human cloning, even therapeutic, as "displaying a profound disrespect for life," setting penalties at more than $1 million and 10 years of imprisonment. President George W. Bush said his administration was unequivocally "opposed to the cloning of human beings either for reproduction or research," and proved it by prohibiting the use of public funding for embryonic research, with the exception of 64 existing stem cell lines pulled from embryos that already had been destroyed. Other governments also have passed cloning research restrictions. In January 2001, the United Kingdom became the only country to legalize the creation of cloned human embryos for therapeutic research, but the practice is strictly regulated. Before gaining approval for their research, U.K. scientists must prove that no alternatives to embryonic research will achieve the same results.
A Technology in Its Infancy
Cloning has, in effect, been in use for centuries with plants, yet human embryonic stem cell research is still in its infancy. In 1981 researchers learned how to grow mouse embryonic stem cells in the laboratory, but it was not until 1998 that scientists at the University of Wisconsin-Madison were able to isolate cells from an early embryo and develop the first human stem cell lines. Since most of the research thus far has been limited to animals (usually mice), any existing knowledge of how stem cells replicate must still be translated into human terms. Human and mouse cells do not replicate the same way under laboratory conditions, and researchers do not know whether cells will behave the same way in the human body as they do in a mouse.
Scientists also are limited in their ability to direct a stem cell to differentiate into specific tissue or cell types, and to control that differentiation once the cells are transplanted into a patient. For example, in the case of diabetes, scientists must first create insulin-producing cells, then regulate how those cells produce insulin once they are in the body. Before gaining control over cell differentiation, scientists need to learn what triggers a cell to transform into, say, brain tissue over liver tissue. They also need to understand how that differentiation is controlled by environmental factors, and how best to replicate those factors in a laboratory. Before implanting the cells into a human patient, they also must prove that the cells can serve their intended function, by implanting them into an animal or other surrogate model.
The ability to steer differentiation becomes even more intricate when attempting to trigger cells to develop into human organs. Cloning a heart or a kidney from cultured cells could save some, if not all, of the estimated 4,000 people who die in the United States each year while awaiting an organ transplant. The complexity of these organs clearly necessitates years of further research before accurate replication can occur.
Once scientists are able to create the right type of stem cells and to direct them in completing a specified function, they still must address safety issues before putting the cells to use. Every step of the process gives rise to potential safety concerns—from the health of the egg donors to the way in which cells are manipulated in the lab.
Embryonic stem cells are created using a patient's own cell and a donor egg. That creates a problem in and of itself, as human eggs are not easy to come by and require willing female donors. Once donors are located, they must be carefully screened for hereditary diseases. Although the nucleus is removed from the donor egg, the egg still retains the mother's mitochondrial DNA (deoxyribonucleic acid). That genetic material can carry with it a hereditary defect—for example, if the mother had a predisposition to heart disease, she could theoretically pass that faulty gene to the patient receiving her egg.
Another source for concern is the way cloned cells and tissues will behave once they are implanted. Will they age too quickly if they are drawn from an older person's cells? Research already has proven that in clones created from an older person, the telomeres (DNA-containing ends of chromosomes) are shorter, reflecting the aging process. Also, will the cloned cells develop normally or will they be subject to malformations? If cells are implanted before becoming fully differentiated, they have the potential to give rise to teratomas (cancerous tumors), which could threaten the life they were designed to save. Scientists still do not know at which stage in the differentiation process the tumor risk declines.
Scientists also must improve the process by which they differentiate cells in culture. First, all procedures must be standardized, because cells differentiated by a variety of means might grow at varying rates or not all be equally effective. Second, researchers must gain more control over the differentiation process and find an alternate means to keep cells from differentiating before they are ready to steer them in the proper direction. Currently, scientists use mouse feeder cells to stop cells from differentiating. The feeder cells contain necessary materials to maintain the pluripotent capacity of undifferentiated cells. But mouse cells, as with any animal cells, can carry animal-borne viruses to a human stem cell recipient.
Promising Therapy Still Years Down the Road
When talking about therapeutic cloning, as with any new technology, it is important to maintain an historical perspective. Most scientific discoveries that seem to have occurred overnight actually were years in the making.
Even as scientists move forward in their understanding of and ability to master the technique of therapeutic cloning, the ethical and political debates will rage all the more fervently. Religious groups and many among the public and scientific communities stand firm in their belief that life begins at conception, and that to create life only to destroy it is morally wrong. Governments, mindful of the bioethical issues at stake, are unlikely to bend on previously enacted anticloning legislation.
Stem cells hold enormous potential. One day, they may be used to repair or replace cells and tissue lost from diseases like heart disease, Parkinson's, Alzheimer's, and cancer. It is more likely, at least in the near future, that stem cell research will be directed down less controversial avenues. One of the most promising alternate therapies involves adult stem cells, trained to act like embryonic stem cells without the need to create a new embryo. While not pluripotent like embryonic cells, stem cells culled from adult tissue or blood may be more malleable than scientists originally believed.
In October 2001 researchers at the H. Lee Moffitt Cancer Center and the University of South Florida identified a stem cell gene shared by both embryonic and adult stem cells, indicating a similarity between the two types of cells. In laboratory experiments, scientists have been able to coax adult mouse bone-marrow stem cells into becoming skeletal muscle and brain cells, and to grow blood and brain cells from liver cells. If scientists can reprogram human adult stem cells to act like embryonic stem cells, perfecting embryonic cloning and stem cell technology and overcoming the accompanying ethical and political hurdles may never be necessary.
—STEPHANIE WATSON
Viewpoint: No, recent scientific advances in the area of therapeutic cloning indicate that cures for diseases such as diabetes and Parkinson's are possible in the not-too-distant future.
Because of their potential to develop into many—if not all—cell types of the human body, embryonic stem cells have become the focus of much medical and research attention. The latest research has extended the study of embryonic stem cells to another level: therapeutic cloning, where a patient's own cells would be transformed into a living embryo whose stem cells could be used to create tissue to treat such diseases as diabetes and Parkinson's. Because the therapeutic cloning procedure would involve the cells of a given patient, stem cells derived from the embryo would be genetically identical to the patient's cells, and therefore would enable replacement or supplementation of the patient's diseased or damaged tissue without the risk of immune incompatibility and its lifelong treatment with immunosuppressive drugs and/or immunomodulatory protocols.
When researchers first considered the prospect of using human stem cells to cure disease in 1975, they were deterred by the ordeal of isolating the cells from the embryo. For a number of years thereafter, researchers' attempts to isolate embryonic cells from the model of choice—a mouse model—proved frustrating, as did attempts with other kinds of animals. Then, in the late 1990s and the early years of the new millennium, a number of developments involving stem cell research offered new information that set the stage for therapeutic cloning as a principal means for treating human disease.
Three research developments that have triggered a wave of excitement in this area are the derivation of stem cells from human embryos, the cloning of animals via somatic cell nuclear transfer, and evidence suggesting that stem cells from human embryos may have the potential to cure disease. In the minds of supporters, these three developments—when taken together—challenge the notion that claims of therapeutic cloning as a cure for diseases such as diabetes and Parkinson's are premature and misleading.
Development I: Derivation of Stem Cells from Human Embryos
Researchers had, for several years, been isolating embryonic stem cells from mice, hamsters, and other animals when in the late 1990s two teams of researchers announced that they had successfully produced human stem cells in their laboratories. In 1997 a research team led by John Gearhart, professor of gynecology and obstetrics at Johns Hopkins University, isolated stem cells from aborted fetal material and in a petri dish was able to differentiate the cells into several kinds of tissue. In late 1998 a research team led by James Thomson, a University of Wisconsin-Madison developmental biologist, was able to derive stem cells from surplus human embryos obtained from in vitro fertilization clinics and to produce a viable stem cell line—in other words to keep the cells in their undifferentiated state in culture. This achievement by Thomson and his team was singular, because in nature embryonic stem cells exist in their undifferentiated state for a very short time before developing into other cells.
Embryonic stem cells, taken from blastocysts (early stage embryos consisting of fewer than 100 cells), are useful entities because they are pluripotent; that is, they have within them the capacity to grow and specialize into any and all of the 260 cell types of the human body, such as cardiac and skeletal muscle, blood vessels, hematopoietic cells, insulin-secreting cells, and various neural cells. Stem cells, unlike somatic cells such as liver cells, brain cells, and skin cells that have taken on a specific function, are "blank" cells that have not gone through the differentiation process.
At this stage of their knowledge, many researchers believe that embryos undergoing early stage cell division (usually between the fifth and seventh day of development) are the best and only source of pluripotent stem cells. It is true that stem cells are also present in children and adults, but these stem cells (which are referred to as adult stem cells) are multipotent—that is, they are able to form only a limited number of other cell types in contrast to embryonic stem cells' potential to grow and specialize into more than 200 separate and distinct cell types. In their May 2001 report in the journal Cell, the pathologist Neil Theise of New York University and the stem cell biologist Diane Krause of Yale University and their colleagues confirmed the multipotency of adult stem cells when they claimed that an adult stem cell from the bone marrow of mice had the capacity to form only seven tissues—blood, lung, liver, stomach, esophagus, intestines, and skin. Besides their limitation to form only a limited number of other cell types, adult stem cells are not very plentiful, they are not found in the vital organs, they are difficult to grow in the laboratory, their potential to reproduce diminishes with age, and they have difficulty proliferating in culture (as do embryonic stem cells).
Development II: Cloning of Animals via Somatic Cell Nuclear Transfer
In 1997 scientists used somatic cell nuclear transfer to create Dolly, a Scottish lamb cloned from a cell taken from an adult sheep. Since this initial success, researchers have used the somatic cell nuclear transfer technique to produce a range of mammalian species, including goats created by geneticists at Tufts University in 1999 and rhesus monkeys created by researchers at Oregon Regional Primate Research Center in 2000. More specifically, Dolly was created by Ian Wilmut, an embryologist at the Roslin Institute in Edinburgh, Scotland, by taking a somatic cell from a ewe's mammary gland and fusing it with a denucleated oocyte (egg cell) to make a sheep embryo with the same genetic makeup (i.e., a clone) as that of the ewe. This ability to reprogram cells, researchers say, has brought the prospect of making human replacement cells for the treatment of degenerative diseases significantly closer to reality. In 1999 Wilmut stated, "Human stem cell therapy has the potential to provide treatments for several diseases for which no alternatives are available, such as Parkinson's disease and diabetes. Some research on human embryos is essential if these important therapies are to become available."
As Wilmut indicated, one purpose of therapeutic cloning and stem cell research is to serve as a principal means for treating human disease. There exists, however, a more underlying purpose: To serve as a learning tool that would enable researchers to understand and learn how a somatic cell (a cell that has only one purpose and does not have the ability to differentiate into other types of cells) can be programmed to forget its narrow destiny and to differentiate into other types of cells. Opinion leaders such as the Royal Society in London argue convincingly that, for now, therapeutic cloning is a necessary route to greater understanding of the stem cell differentiation process, and contend that therapeutic cloning eventually will put itself out of business as it unlocks the secrets of cell reprogramming and enables trained professionals to use healthy somatic cell bodies to create needed stem cell replacements. Researchers anticipate, for example, that a somatic cell, such as a cheek cell, could be reprogrammed to develop into a brain cell that would produce dopamine to alleviate or even cure Parkinson's disease.
Development III: Evidence Suggesting that Stem Cells from Human Embryos May Have the Potential to Cure Disease
The findings of three 2001 studies using mouse embryos provide evidence suggesting that stem cells from human embryos may have the potential to cure disease.
In the first study, Kiminobu Sugaya, assistant professor of physiology and biophysics in psychiatry at the University of Illinois, and his colleagues showed that old rats (24-month-old rats, which are equivalent in age to 80-year-old humans) performed better on a test of memory and learning after researchers injected neural stem brain cells from aborted human fetuses into the rats. The researchers explained the rats' improved performance in this way: The injected embryonic stem cells developed into neurons and other brain cells, providing added brain power and stimulating secretion of natural chemicals that nurtured the older brain cells.
In another study Ron McKay, a molecular biologist at the National Institutes of Health (NIH), and his colleagues converted noncloned mouse embryonic stem cells in laboratory dishes into complex, many-celled structures that looked and acted like the islets of Langerhans, the specialized parts of the pancreas responsible for regulating blood sugar levels. This work has been described by Doug Melton, the chairman of molecular and cell biology at Harvard University, as the most exciting study in the diabetes field in the last decade—partly because it supports the possibility that similar structures grown from human embryonic cells could be transplanted into diabetic children, who lack functioning islet cells.
In a third study Teruhiko Wakayama, a reproductive biologist at Advanced Cell Technology in Worcester, Massachusetts, and his colleagues showed that mouse embryos created in their laboratory contained true stem cells that could be converted into all of the major cell and tissue types. In a related mouse experiment, Wakayama and Peter Mombaerts from Rockefeller University worked with researchers from Rockefeller and the Sloan-Kettering Institute to create a blastocyst via somatic cell nuclear transfer from an easily accessible source of adult cells—the mouse's tail—and converted the extracted stem cells into a chunk of dopamine-secreting neurons (the type of brain cell that degenerates in Parkinson's disease). The work of Wakayama and his colleagues, say supporters, moves medical research a giant step closer to the ultimate, long-term goal for Parkinson's patients—to be able to grow compatible replacement neurons from their own cells.
Conclusion
Three recent research developments—the derivation of stem cells from human embryos, the cloning of animals via somatic cell nuclear transfer, and evidence from three 2001 studies (which suggests that stem cells from human embryos may have the potential to cure disease)—dispute the notion that claims of therapeutic cloning as a cure for diseases such as diabetes and Parkinson's are premature and misleading. With these developments in mind, researchers have expressed increased hopes for the prospect of one day growing spare cells for tissue engineering and spare parts for transplantation medicine over and above their immediate reservations. One reservation has to do with the perfection of the therapeutic cloning technique, which has largely been tested on mice. "More work has to be done before the therapeutic cloning technique can be successfully adapted to humans," explained McKay, the leader of the NIH study where mouse embryonic stem cells were converted into specialized pancreatic cells, "because the jump from animal to human studies is a tricky one." As mentioned earlier, Oregon researchers have done therapeutic cloning on rhesus monkeys, but that cloning did not focus on converting stem cells into pancreatic cells or any other specialized cells, as did McKay's research at the NIH.
Another reservation has to do with the ethical and legal controversy associated with therapeutic cloning. The controversy stems from the fact that the embryo must be destroyed in order to retrieve the stem cells. Opponents of therapeutic cloning consider the destruction of the embryo morally objectionable because they believe that human personhood begins at conception or, as in cloning and nuclear transfer, at the genetic beginning. Supporters of therapeutic cloning, on the other hand, believe that human personhood is not at stake if the embryos used are less than 14 days old—because at such an early stage of development, embryos are too immature to have developed any kind of individuality. In fact Michael West, the president and chief executive officer of Advanced Cell Technology, explained in late 2001 that before 14 days, embryos can split to become two or can fuse to become one. "There is no human entity there," said West.
A third reservation has to do with tissue engineering. While many of the cell types differentiated from therapeutic cloning will likely be useful in medicine as individual cells or small groups of cells, as in the treatment of diabetes and Parkinson's disease, a bigger remaining challenge will be to learn how to reconstitute in vitro simple tissues, such as skin and blood vessel substitutes, and more complex structures—vital organs, such as kidneys, livers, and ultimately hearts.
At this stage of their knowledge, researchers concede that some of these reservations may challenge their scientific ingenuity. But they vehemently assert, on the basis of the research developments discussed in this paper, that they do not consider claims that therapeutic cloning could be the cure for diseases such as diabetes and Parkinson's to be premature or misleading. Robert Lanza, the vice president of medical and scientific development at Advanced Cell Technology, recently called attention to a similar situation—when Dolly the lamb was cloned in 1997. Lanza pointed out that the cloning event brought to the scientific community a powerful new technology at a time when many thought that such a feat was impossible.
—ELAINE WACHOLTZ
Further Reading
Edwards, Robert G., and Patrick C. Steptoe. A Matter of Life: The Story of a Medical Breakthrough. London: Hutchinson, 1980.
"Embryonic Stem Cells. Research at the University of Wisconsin-Madison." <http://www.news.wisc.edu/packages/stemcells/>.
Hall, Stephen S. "Adult Stem Cells." Technology Review (November 2001): 42-9.
Ho, Mae-Wan, and Joe Cummins. "The Unnecessary Evil of 'Therapeutic' Human Cloning." Institute of Science in Society, London, 23 January 2001.
Kato, Y., et al. "Eight Calves Cloned from Somatic Cells of a Single Adult." Science 282 (11 December 1998): 2095-98.
Kind, A., and A. Colman. "Therapeutic Cloning: Needs and Prospects." Seminars in Cell and Developmental Biology 10 (1999): 279-86.
Lanza, Robert P., et al. "Human Therapeutic Cloning." Nature Medicine 5, no. 9 (September 1999): 975-77.
Naik, Gautam. "'Therapeutic Cloning' Holds Promise of Treating Disease." Wall Street Journal (27 April 2001), sec. B, p. 1.
Rantala, M. L., and Arthur J. Milgram, eds. For and Against. Vol. 3, Cloning. Chicago: Open Court, 1999.
Thomson, James A., et al. "Embryonic Stem Cell Lines Derived from Human Blastocysts." Science 282 (6 November 1998): 1145-47.
U.K. Department of Health. Chief Medical Officer's Expert Advisory Group on Therapeutic Cloning. Stem Cell Research: Medical Progress with Responsibility, 16 August 2000. London, 2000.
U.S. Department of Health and Human Services. National Institutes of Health. Stem Cells: Scientific Progress and Future Research Directions, June 2001. Bethesda, Md., 2001.
Wakayama, Teruhiko, et al. "Differentiation of Embryonic Stem Cell Lines Generated from Adult Somatic Cells by Nuclear Transfer." Science 292 (27 April 2001): 740-43.
——. "Full-Term Development of Mice from Enucleated Oocytes Injected with Cumulus Cell Nuclei." Nature 394 (23 July 1998): 369-74.
Wilmut, Ian. "Cloning for Medicine." Scientific American (December 1998).
——, et al. "Viable Offspring Derived from Fetal and Adult Mammalian Cells." Nature 385 (1997): 810-13.
——, Keith Campbell, and Colin Tudge. The Second Creation: Dolly and the Age of Biological Control. New York: Farrar, Straus, and Giroux, 2000.
KEY TERMS
DIFFERENTIATION:
The process by which an unspecialized cell becomes specialized to perform a particular function.
EMBRYONIC STEM CELLS:
Undifferentiated cells that are unlike any specific adult cell in that they have the ability to differentiate into any of the body's 260 different types of cells (e.g., bone, muscle, liver, and blood cells).
OOCYTE:
A cell from which an egg or ovum develops by meiosis; a female gametocyte.
PLURIPOTENT:
The term used to describe cells with the potential to develop into all of the cell types of an organism. In humans, pluripotent cells are able to develop into any and all of the body's 260 different types of cells.
SOMATIC CELL:
Any cell of a mammalian body other than egg or sperm cells.
SOMATIC CELL NUCLEAR TRANSFER:
The transfer of a cell nucleus from a somatic cell into an oocyte (or egg cell) from which the nucleus has been removed.
STEM CELL:
A cell taken from an embryo, fetus, or adult that can divide for indefinite periods in culture and create the specialized cells that make up various organs and tissues throughout the body.
TELOMERES:
Strands of DNA (deoxyribonucleic acid) that tie up the ends of chromosomes in a cell.
THERAPEUTIC CLONING:
The use of somatic cell nuclear transfer for the therapeutic purpose of providing cells, tissues, and organs for patients requiring replacement or supplementation of diseased or damaged tissue, rather than for reproduction purposes.
NUCLEAR CELL TRANSFER
Nuclear cell transfer, a much-used technique in the cloning of adult animals, requires two cells: a donor cell and an oocyte (egg cell). For the technique to be successful, the two cell cycles must somehow be synchronized. Some researchers accomplish synchronization by enucleating or removing the nucleus from the unfertilized egg cell and coaxing the donor cell into a dormant state—the state in which an egg cell is more likely to accept a donor nucleus as its own. Then, the dormant donor nucleus is inserted into the egg cell via cell fusion or transplantation.
Scientists have used different nuclear cell transfer techniques. The Roslin technique was used by Ian Wilmut, the creator of the sheep Dolly. Wilmut used sheep cells, which typically wait several hours before dividing. He accomplished dormancy in the donor cell by in vitro starvation. That is, he starved the cell outside the body of the donor before injecting it into an enucleated egg cell.
The Honolulu technique was used by Teruhiko Wakayama, who used three different kinds of mouse cells, two of which remained in the dormant state (not dividing) naturally, while the third was always either in the dormant state or nondormant (dividing) state. Wakayama injected the nucleus of a naturally dormant donor cell into an enucleated egg cell—without the added step of starving the donor cell. Wakayama's technique is considered the more efficient technique, because he was able to clone with a higher rate of success (three clones in 100 attempts) than Wilmut (one clone in 277 attempts).
—Elaine Wacholtz