You Are on the Embryonic Stem Cell Research Page November 25, 2001

Anyone who has listened to mainstream news in the recent past (linear timeframe, of course :) has surely heard something of the debate over whether or not research should proceed with the use of stem cells derived from human embryos. There is much controversy and misunderstanding surrounding this topic. Scientists, religious leaders and politicians are all fencing over the merit and moral issues surrounding the use of embronic stem cells. On July 12, 2001, a company by the name of Advanced Cell Technology (Worcester, Massachusetts) annonced plans to clone human embryos using somatic cell nuclear transfer to generate stem cells to treat diseases such as diabetes. They plan to use the patient's own cells to make a clone (using a donor egg) to produce the embyonic stem cells. Once harvested, the stem cells would be programed to generate whatever type of tissue was needed. That tissue would, in turn, be transplanted into the patient to mitigate the disease at hand. The beauty of this plan is that the diseased individual would be using his or her own tissue to generate the cells, thus eliminating difficulties with transplant rejection etc. We are years away from realizing this goal, and much research needs to be done if it is to be a reality. On Sunday November 25, 2001, the first step toward realization of this goal became reality as Cibelli et al of Advanced Cell Technology, published a paper entitled "Somatic Cell Nuclear Transfer in Humans: Pronuclear and Early Embryonic Development" in the Journal of Regenerative Medicine. In this paper, these researches announced successful somatic cell nuclear transfer which resulted in the production of early human embryos from which stem cells could be derived.

Of course, religious leaders who maintain that life begins at the moment of conception, view this as a macabre scenario, where babies are being created and sacrificed. Alternatively, many believe that this therapy involves the use of benign tissue which has only the potential to develop into a human, not a human, to save lives and improve the quality of life. Go to "What is a stem cell?"; and "How are embryonic stem cells harvested?" further down on this page for more details.

Currently, the US congress has three bills pending which address this research. One bill entitled "Stem Cell Research Act of 2001" (HR2059 in the House of Representatives and S 723 in the Senate) proposes to use federal funds to support research using stem cells derived from donated IVF embryos which would otherwise be discarded. The Act stipulates that these embryos must be obtained with the informed consent of the progenitors, and that cells derived from such embryos may not be used in the production of a human embryo or in the reproductive cloning of a human being. there are stiff fines, including time in prison and monetary fees for violation of the rules. The act also stipulates that NIH (National Institutes of Health) would establish guidelines for the research, and would collaborate with the Secretary of Health and Human Services in preparing annual reports.

Another bill, entitled "Responsible Stem Cell Research Act of 2001" (HR2096) proposes that a donor bank be established whereby stem cells from spontaneous abortions, umbilical cord blood, placentas etc. could be deposited. These cells would then become available for researchers willing to follow federal guidelines.

On August 1, 2001, the US house of Representatives voted 265 to 162 to ban all human cloning; and 249 to 178 to ban even limited human cloning for research purposes to treat disease (Advanced Cell Technology proposal above). The Senate has yet to vote. On the same day, Japan approved guidelines for stem cell research which would allow the use of embryos leftover from fertility procedures in research, but bans cloning of human embryos. And finally, on August 1, 2001, Isreaeli researchers announced that they had been successful in turning human embryonic stem cells into functioning heart cells. This is an important step in the treatment of cardiovascular disease. On September 4, 2001, Scientists at the University of Wisconsin announced that they have successfully re-programmed or converted human embryonic stem cells to blood cells.

In Great Britain it has been legal since January of 2001 to clone human embryos for purposes of conducting stem cell research. A recent poll reported by ABC news, conducted from July26-30, 2001, reports that 63% of the American public backs embryonic stem cell research. On August 10, 2001, US President George Bush announced that he would endorse federal funding for stem cell research, but that it would be restricted to use on cell lines which had already been created. In other words, he would not allow the use of federal funds to do research with embryos leftover from fertility clinics, nor would he allow the creation of new embryos for research purposes. However, final decisions about these issues will not be made until congress re-convenes in September. Members of congress have announced they will push for guidelines which allow a broader range of research. As of September 5, congress is questioning whether the 64 stem cell lines President Bush said were available worldwide are actually available. Senator Arlen Spector of Pennsylvania suggested that his research into the matter concludes that only 20-25 lines are actually ready and would be available for researchers, and that 200 lines would be necessary. Health and Human Services Secretary Tommy Thompson acknowledged the limited number of lines, but maintained that they would be sufficient. Who do we believe? Can we ever trust what these guys are telling us?

So why does it matter if the US Congress decides to provide federal funding for this research? The main reasons are that, 1) so long as the research is conducted in a private arena, the research will be biased toward making a profit: and 2) private research will be conducted in secret, without the usual public and academic peer-review. A privately conducted, profit-motivated line of inquiry will be biased, and not necessarily in the best and highest interest of all. If the US wishes to play a role in the responsible development of these technologies, it should not drive away research and scientists to other countries, by banning it altogether, or to private industry, where the research will be cloaked in secrecy and become the patented trade secret of a corporation. It seems that the potential for mis-direction of a technology are greatest in proportion to the number of secrets involved.

What is a stem cell?

A stem cell is a special type of cell found in animals, including humans. It is essentially a "blank" cell which has the capacity to grow and develop into different types of cells. We have stem cells to assist in the regeneration and repair of damaged or diseased tissues. Stem cells in post-natal humans are referred to as adult stem cells (AS). In scientific jargon, AS are undifferentiated cells found in differentiated tissues. These cells are rare, and have been found in the bone marrow, skin, brain, fat, muscle, cornea and retina of the eye, and lining of the small intestine. These cells are responsible for regeneration of bone, blood cells, cartilage, fat, muscle, skin and intestinal lining. These types of cells were only just isolated in the 1990's. There is much debate over whether these cells can be reprogramed to form any type of cell which can then be produced in culture. It is known that AS are different from embryonic stem cells (see below), and cannot be replicated indefinitely in culture.

There is another type of "blank" or stem cell found in the early stages of development of an embryo. These cells are even more fundamental ("less differentiated" in scientific language) than the adult stem cells, in that they retain the ability to develop into almost every type of cell. There are also other fundamental differences between these cells and adult stem cells (see the July, 2001 NIH report listed below under "resources") which make them important to scientists. These cells are the subject of great interest to scientists because 1) we can learn about the timing and control of human development: something important in understanding diseases such as cancer; and 2) the possibility that one could program the cells to develop into any type of tissue one might need to aid in the treatment of a wide range of debility and disease. Take, for example, somebody who has a severed spinal cord. Theory has it that embryonic stem cells could be used to grow new spinal cells, which could then be transplanted and stimulated to grow at the location where the cord was severed.

But there is a great need for research on human embryonic stem cells to learn the timing and procedures necessary for programming these cells and development of tissues from these cells in culture. It is known that there are important differences in the timing and development of human and other animal embryos, and thus, agencies such as the National Bioethics Advisory Commission and the NIH have recognized that while some information can be gleaned from other animal cells, research with actual human cells will be necessary for successful therapeutic use of embryonic stem cells in humans.

How are embryonic stem cells harvested?

We have to visit human development and some basic scientific terms to understand where embryonic stem cells come from.

In a normal human female, eggs are released each month into one of two fallopian tubes, which lead to the uterus. If sperm are present, the egg is normally fertilized in the fallopian tube. A fertilized egg is called a "zygote". The zygote begins the process of cell division while still in the fallopian tube. At thirty-six hours, there are two cells; at 60 hours there are 4 cells; at 3 to 4 days, there are 16 cells . At this point, the zygote is called a morula, and leaves the fallopian tube and enters the uterus. At the morula stage, all 16 cells are identical, and have the capability of developing into a complete human. If the cell mass were to split at this or any previous stage, identical twins, triplets, quadruplets etc. would form, depending on the number of splits. The morula continues to divide, and the first specialization of cells occurs at around day 6 post-ferilization. At this point, the cells form a hollow ball (about 100 cells total: the size of a period at the end of a sentence), and the outer cells (about 70 or 80 cells) become programmed to form the placenta and tissues which nourish the placenta. Once this happens, these specialized outer cells no longer have the capability of differentiating into (becoming) any type of cell. About 20 or 30 of the cells inside this hollow ball are called "the inner cell mass". These cells retain the ability to differentiate into any type of tissue, but are currently not believed capable of generating a complete human (see 2001 NIH report in "resources" below). This hollow ball with an inner cell mass is called a blastocyst. It is from the inner cell mass of the blastocyst that the stem cells are harvested. When the blastocyst implants into the uterine wall (day 7 or 8 post-fertilization), it becomes an "embryo". In another week, the embryo is about 2000 cells and 0.5 mm in diameter. By week three, most organ and tissue precursors are in place and the embryo is 2.3 mm long. By around the third month post fertilization, the embryo has most of its organs developed, and is called a "fetus". The rest of the pregnancy involves growth of the existing differentiated organs and tissues, culminating at birth at approximately 267 days post-fertilization (The source of this information is the National Bioethics Advisory Commission report entitled "Ethical Issues in Stem Cell Research". Slight differences in the timing and cell numbers are found in other sources. For example, the 2001 NIH report says the blastocyst forms on day 5, and is approximately 200 cells in composition).

So, the embryonic stem cells which are the subject of this research are the cells harvested from the inner cell mass of a 5-7-day-old clump of fewer than 200 cells (total) which have not yet implanted into the uterus. It is a known fact that 3 out of 4 of such blastocysts never implant in a normal healthy human female, and are excreted in the monthly flow. However, the 1 in 4 that does implant, has the potential to develop into a healthy baby. Is a blastocyst a person, or a potential person? Is harvesting stem cells from a blastocyst to treat disease a wise use of technology or a morally reprehensible act? Should legislation be passed to regulate or ban such research? You decide. Here are some resources to help you learn more about embryonic stem cell research:

Resources