Why not derive stem cells from adults?
There are several approaches now in human clinical trials that utilize mature stem cells (such as blood-forming cells, neuron-forming cells and cartilage-forming cells). However, because adult cells are already specialized, their potential to regenerate damaged tissue is very limited: skin cells will only become skin and cartilage cells will only become cartilage. Adults do not have stem cells in many vital organs, so when those tissues are damaged, scar tissue develops. Only embryonic stem cells, which have the capacity to become any kind of human tissue, have the potential to repair vital organs.
Another limitation of adult stem cells is their inability to proliferate in culture. Unlike embryonic stem cells, which have a capacity to reproduce indefinitely in the laboratory, adult stem cells are difficult to grow in the lab and their potential to reproduce diminishes with age. Therefore, obtaining clinically significant amounts of adult stem cells may prove to be difficult.
Studies of adult stem cells are important and will provide valuable insights into the use of stem cell in transplantation procedures. However, only through exploration of all types of stem cell research will scientists find the most efficient and effective ways to treat diseases.
What are the benefits of studying embryonic stem cells?
Pluripotent stem cells represent hope for millions of Americans. They have the potential to treat or cure a myriad of diseases, including Parkinson's, Alzheimer's, diabetes, heart disease, stroke, spinal cord injuries and burns.
This extraordinary research is still in its infancy and practical application will only be possible with additional study. Scientists need to understand what leads cells to specialization in order to direct cells to become particular types of tissue. For example, islet cells control insulin production in the pancreas, which is disrupted in people with diabetes. If an individual with diabetes is to be cured, the stem cells used for treatment must develop into new insulin-producing islet cells, not heart tissue or other cells. Research is required to determine how to control the differentiation of stem cells so they will be therapeutically effective. Research is also necessary to study the potential of immune rejection of the cells, and how to overcome that problem.
In a set of meticulous experiments, scientists have demonstrated the ability of human embryonic stem cells to develop into nascent brain cells and, seeded into the intact brains of baby mice, further develop into healthy, functioning neural cells.
In a paper published in the journal Nature Biotechnology (December, 2001), a team of scientists from UW-Madison, along with colleagues from the University of Bonn Medical Center, show that the blank-slate stem cells taken from early human embryos can, in a laboratory dish, be guided down the developmental pathway to becoming precursor brain cells.
Transplanted into the brains of baby mice, the precursor cells subsequently showed their ability to further differentiate into neurons and astrocytes, the cell species that populate the different regions of the brain and spinal cord.
The work represents a critical step toward a high-stakes payoff for human embryonic stem cell technology - an inexhaustible supply of transplantable neural cells and tissue to repair everything from spinal cord injuries to the ravages of Parkinson's disease. The new work was conducted largely at the WiCell Institute in Madison, and is being continued at the Waisman Center.
"This is a very important step. The cells work" as they should, says Su-Chun Zhang, a UW-Madison professor of anatomy and neurology and the lead author of the Nature Biotechnology paper. Co-authors include James A. Thomson and Ian D. Duncan, also of UW-Madison, and Marius Wernig and Oliver Brustle of the University of Bonn Medical Center.
The newly published work is critically important for two reasons: One, it establishes the fact that human embryonic stem cells can be guided down the developmental pathway to becoming brain cells and, two, it shows that they can be transplanted into animals and further develop into the more specific types of cells necessary for normal brain function.
"The neuron that we're seeing after transplant is almost identical to what the neuron should be in the healthy brain," says Zhang. "These are the cells that will be used, ultimately, to treat Parkinson's and other central nervous system disorders."
The human stem cells were transplanted into the brains of newborn mice to co-opt the developmental cues that occur as the animal grows and the brain develops.
"These transplanted cells had no experience in the brain, and we wanted to see if they would mirror the development of the mouse brain," Zhang says. "And they do."
Zhang stressed that the work, in essence, is a demonstration of a system for directing the cells to become the specific types of cells needed for repairing the damaged or ailing brain. Key steps yet to be performed before the technology can be attempted in humans is to assess function and actually treat a condition such as Parkinson's in an animal model such as primates.
"We are nowhere near clinical application," Zhang says. "It will still be some years before we can even try this in people."
However, the new work is strong evidence that human stem cell therapies are likely to live up to their billing as revolutionary treatments for a host of heretofore intractable cell-based diseases.
Moreover, the work performed by Zhang and his colleagues exhibited an important ancillary result: the complete absence of teratomas or tumors in the mice that received the cell transplants. Of concern in any potential stem cell therapy is that tumors may arise from contamination of precursor cells by undifferentiated cells.
"We put a lot of cells, in one instance half-a-million, in a mouse," says Zhang. "The more cells you put in, the more likely you are to have a tumor. The absence of tumors shows our methods for purifying the precursor cells are pretty good."
Support for the study was provided by the Myelin Project of Washington, D.C., and the Consolidated Anti-Aging Foundation of Naples, Fla.
Q: What, exactly, did President Bush announce last night?
A: He said federal money may be used to study only those embryonic stem cells that have previously been harvested from embryos left over at fertility clinics. He prohibited government subsidies of research involving the creation or destruction of additional embryos.
Q: Can government-paid research make use of future embryos that will be produced at fertility clinics, even if those embryos are destined for eventual destruction?
A: No, not under the president's decision.
Q: The president said there are 60 existing stem cell colonies, or "lines," that can "regenerate themselves indefinitely." Is this a sufficient supply for medical researchers?
A: Many scientists fear it's not. First, they question whether there are 60 lines. Scientific journals have reported fewer than 10, with perhaps another 10 described at scientific meetings. A recent National Institutes of Health report estimated that only 30 stem cell lines existed. Researchers want as wide a variety as possible because stem cell lines have subtle genetic differences that can affect how they behave.
Q: Whatever the actual number is, are these existing stem cell lines safe and reliable?
A: Not necessarily. Stem cell lines have a rather precarious existence, and they could "crash" at any time, making them useless for medical breakthroughs.
Q: Given these concerns among scientists, why are some conservative religious groups unhappy with the president's restrictions?
A: They wanted him to ban federal funding of research on all human embryos, which have the potential of developing into a person.
Q: Can Congress override the president's decision?
A: Yes.
Q: Can privately funded research continue on human embryos that fall outside the group sanctioned by President Bush?
A: Yes. But scientists say private funds can supply only a fraction of the money needed in this burgeoning field of research.
Q: Scientists say stem cells hold promise for major diseases including Alzheimer's, Parkinson's and diabetes. Have their curing powers been proven?
A: No. Human stem cells have been implanted in animals and in a few cases seem even to have had some positive effects, but they have not been proven safe yet for delivery into humans.
Q: Given the president's restrictions, how can regulators be sure federal funds aren't used on stem cells created after his policy is enacted?
A: That's unclear. Bush did not specify how scientists will know if certain cell lines are "pre-approved" or not. It can be difficult to "fingerprint" cell lines to ensure their provenance. With cells being mailed from lab to lab, lineages could get mixed up.
Q: Where do stem cells come from, and why are they so important?
A: They are retrieved from the core of five-day-old human embryos, typically left over from invitro fertilization processes used by couples trying to have a baby. Stem cells can morph into virtually every kind of tissue, providing a potentially bottomless source of replacement parts.
Q: Can't stem cells also be found in adult tissues?
A: Yes. But scientists believe embryonic stem cells are more versatile and therefore hold greater promise in curing diseases and injuries such as spinal cord damage.
Human cloning may soon become an accepted means of producing human embryonic stem cells for use in medical therapies. The Donaldson Report, released in August by a government advisory commission headed by Britain’s Chief Medical Officer Liam Donaldson, sanctions the use of just such a practice. If passed by Parliament, Britain would likely become the first country in the world to explicitly permit the cloning of human embryos. The Report endorses the process of transferring someone’s DNA (the chemical basis of our genes) into a human egg stripped of its own DNA, resulting in a cloned human embryo. The commission approves only of what is being called "therapeutic cloning" - cloning in which the therapeutic benefits are bestowed upon patients in need of treatments developed from the cloned embryo’s stem cells. Although this may bring therapeutic benefits to the patient, it is critical to recognize that no therapy whatsoever is bestowed upon the cloned embryo as - much to the contrary - obtaining the stem cells necessarily results in his or her death. In fact, the Donaldson Report ensures that no cloned embryo survives by requiring the destruction of all such embryos after 14 days as a means of preventing the development of cloned fetuses and babies - a process which has been termed "reproductive cloning." To prohibit human cloning is a good thing - but not if such prohibition demands the mandatory destruction of a human being who has already been cloned for the express benefit of someone else. Those who support the Donaldson Report, as well as many who favor human embryonic stem cell research in the U.S., have succumbed to the utilitarian drive to maximize the ends without considering the means.
Named the Breakthrough of the Year for 1999 by the prestigious journal Science, human embryonic stem cell research may indeed have the potential to benefit many people who suffer from serious debilitating conditions. Because embryonic stem cells can develop into many different types of tissues, researchers hope these cells can be coaxed into replacing tissues whose function has been lost or compromised as a result of injury or disease. For example, someone with diabetes might be given replacement pancreatic cells that produce normal amounts of insulin. Similar treatments might be developed for Parkinson’s and Alzheimer’s diseases.
The British interest in cloning arises largely in response to a chief obstacle encountered by scientists doing research on embryonic stem cells - namely, how to transplant cells or tissue derived from an embryo into a patient without that patient rejecting the implanted material. Obtaining cells from an embryo which has been cloned by inserting a patient’s own DNA into an egg cell devoid of genetic material circumvents the risk of tissue rejection which would likely be posed if stem cells were derived from non-cloned embryos who do not share the patient’s genetic material. For example, a patient suffering from severe burns could have embryos cloned using genetic material derived from his or her own cells. If the stem cells obtained from these cloned embryos could be coaxed into becoming skin cells, they would be genetically identical to the patient and would pose no risk of rejection.
The Donaldson Report, as well as human embryonic stem cell research which does not involve cloning, displays a particularly problematic approach to human life that has broad implications. By definition, research on embryonic stem cells involves the destruction of some human beings for the so-called benefit of others. Therapeutic cloning goes one step further and entails the deliberate creation-as well as the sacrifice-of human embryos for the alleged good of others. It treats human life as a commodity to be manufactured when needed and destroyed when desired to achieve some "greater" purpose. The utilitarian ethic, which justifies treating some humans as means to the end of benefitting others, is employed by those who promote both of these intrinsically objectionable practices. At their core, these acts are violations of human dignity.
The Council of Europe affirmed as much when the preamble to its 1998 Convention on Human Rights and Biomedicine: Additional Protocol on the Prohibition of Cloning Human Beings declared "that the instrumentalisation of human beings through the deliberate creation of genetically identical human beings is contrary to human dignity and thus constitutes a misuse of biology and medicine." Article 1.1 of this protocol states that "Any intervention seeking to create a human being genetically identical to another human being, whether living or dead, is prohibited." This serves to reinforce Article 18.2 of the original 1997 Convention, which stated: "The creation of human embryos for research purposes is prohibited." Little wonder an ethics spokesman for the political right in Germany declared that "the UK has now left the European community in terms of moral values."
While the recently released NIH guidelines for federally funding destructive human embryonic stem cell research stop short of sanctioning human cloning as a means of producing embryonic stem cells, government sanctioning of embryo destruction is itself not commendable - regardless of whether cloning is employed. Currently, a congressional ban prohibits federal funding for "research in which a human embryo or embryos are destroyed, discarded, or knowingly subjected to risk of injury or death." The only way to obtain human embryonic stem cells is to destroy human embryos. The NIH guidelines make the astonishing claim that so long as private funds are used to kill the embryos, public funds can be used to support research on the cells derived from such embryos. They allege that such research is itself untainted by the fact that it necessitates the destruction of innocent human beings. However, federal funding of embryonic stem cell research provides the very motivation for obtaining these stem cells and thereby destroying human embryos. Funding this research knowingly subjects human embryos to certain death. The fact that the NIH does not fund the destructive aspects of the research in no way absolves them of grave wrongdoing. To suggest otherwise is to disingenuously circumvent the existing law.
The area of stem cell research has been marked by many unprecedented advances. Ironically, the day before the Donaldson Report was released, the Journal of Neuroscience Research published a study demonstrating that stem cells taken from adult bone marrow had been transformed into nerve cells. This was previously believed to be impossible. Other long-held beliefs, such as the idea that the brain was incapable of regeneration, are being overturned because of research on stem cells derived from non-embryonic sources. With each passing month, research with these stem cells is revealing the huge potential of this area. The hopes of alleviating many devastating illnesses may be achieved via methods which are not dependent upon embryonic stem cells and which therefore do not require the destruction of embryos. As Christians, we should wholly affirm the desire to develop new treatments for diseases and should vigorously support research into adult stem cells and other non-embryonic sources.
The stem cell/cloning controversy raises, once again, the fundamental issue of personhood and the ensuing considerations of how human persons should be treated. Unfortunately, Christians cannot turn to the Bible for a specific verse to tell us if the embryo has the same rights as other humans. However, when Scripture mentions the unborn, the context is almost always one of God’s protection for them and His vision for their lives (Psalm 139:13-17; Isaiah 44:1-2; Jeremiah 1:3). Human dignity arises from our being created in the image of God. If we ask "Who is an image of God?," we may receive no easy answer. But Jesus was asked, "Who is my neighbor?" His reply with the parable of the Good Samaritan redirects the question (Luke 10:29-37) and emphasizes our responsibility to care for all human beings in whatever ways we can. Are we acting as good neighbors to these embryos? Do we reflect the image of God when we endorse the destruction of other human beings? Hardly.
It is indeed difficult to accept the disability or premature death of any human being because such tragedy marks the loss of potential. Who might this person have become? What might he or she have accomplished? Yet precisely the same potential is lost when a human embryo, cloned or not, is torn apart to supply stem cells for the benefit of another. Who would these embryonic beings have become, if only they had been protected and nurtured? Instead of sanctioning their sacrifice, those who brought these embryos into being should act as caretakers, nurturing and protecting these tiny human lives. In that way, they act as faithful images of God, reflecting His character to the world. Endorsing the destruction of human embryos fails miserably to reach this end, as it makes it ever easier for society to abdicate its responsibilities to the weak and vulnerable at all stages of development. Policies which promote human cloning and research on stem cells derived from human embryos reflect ominously on the state of a society and the values which characterize it.
Donal O'Mathuna - Mount Carmel College of Nursing
