Stem Cells: Science and Ethics
By Dr. Rizwana Rahim
Chicago, IL


From research labs to the media, the places of worship, the public squares, the government corridors to the White House, very few scientific issues have generated as much interest and controversy in recent years as have the stem cells. And, if it weren’t for Dolly, the sheep (first mammal ever cloned from an adult cell), whose birth was announced in 1997, most people would have continued to think of ‘cloning’ as just science fiction. With all this, also follow public concerns, confusion and controversies – some of which even managed to get into last year’s election debate.
The basic feature of a stem cell is its potential and ability (i) to become (or differentiate itself into) any specific type of tissue (liver, nerves, skin, etc), i.e., it is ‘pluri-potent’ or ‘toti-potent’, and (ii) to divide and proliferate almost continuously, i.e., its self-renewal to build a pool of unspecialized and undifferentiated cells, much like the original stem cell, with the same ability to grow into any other cell of any type of tissue (but without actually transforming themselves into any other specific cell-type, while kept in culture).
An early embryo is one of the sources of stems cells of highest quality. In humans, for instance, a 5-7 day old embryo (more than a week before its implantation in the uterus) is the best source. An egg, when fertilized (i.e., a zygote), begins to divide and, in 5-7 days becomes a hollow ball (0.14 mm in diameter) of about 100 cells (blastocyst) . The inner mass of the blastocyst contains just a few embryonic stem cells (ESCs). In a normal, growing embryo, these ESCs will continue to divide and get programmed (i.e., committed or destined) to become specialized/differentiated cells for different organs.
Although the extraction of ESCs kills the embryo, the ESCs themselves can grow and proliferate in Petri dish cultures and keep their initial identity and flexibility. Human embryonic stem cells (HESCs) in culture can also be induced, when grown in Petri dishes (in vitro), to differentiate into various specific tissue-type or organ cells. Most of this has been done with animal ESCs, and when the induced ESCs are implanted in animals with injury in that organ, they migrate to the damage site to regenerate/repair the damaged tissue. Its therapeutic use in humans is still years away, but as the animal data are being confirmed, though on a limited scale, the prospects of HESC use for therapeutic and regenerative purposes appear promising and bright. People with a number of now-incurable tissue injuries or various diseases (from nervous system-related multiple sclerosis, Alzheimer's, Parkinson's to Type I diabetes, cancer and those involving the immune-system) can then hope to find some cure. Notable in the public pressure is the advocacy of such celebrity patients as Christpher Reeves (the ‘Superman’ fought it bravely till his death) and Michael J. Fox, and the family of many others (including President Reagan’s).
In addition to early embryos, stem cells can be extracted from three different places : (i) fetuses (generally aborted), (ii) umbilical cords, and (iii) adult tissues. However, stem cells from none of these sources are in general as flexible as ESCs. Those from adult tissue, besides being free from the objections and controversy that others face, offer occasional hope but these stem cells do not remain stable in culture (i.e., replicate themselves indefinitely as the ESCs do), and turn soon into the specialized cells of that tissue, which limits their ability to be coaxed into any other tissue cells. A gene (Oct4) which keeps the ESCs stable in their original state during their culture has been isolated; addition of this gene to adult stem cell cultures could also keep them longer in the original state and prevent them from becoming a specialized cell, but it is still in early experimental stages to materialize as a viable option.
Most of the moral/ethical and religious controversies surround HESCs, because it involves human experimentation with, and on, human fetuses, and the embryo is destroyed when its stem cells are extracted. This also raises the specter of a possible ‘slippery slope’, reminders of the ‘Brave New World’ and ‘The Boys from Brazil’ scenarios. That is, HESCs used in factory-style production of human-organs and in the universally reprehensible human cloning and human-engineering for designer genes and traits.
Such fears were triggered in 1997 by the birth-announcement of cloned Dolly. Since then, a lot has happened. A number of other cloned animals have been created, recently a cat. A year ago, a team led by South Korean scientist, Woo Suk Hwang, created a cloned human embryo, and about a month ago, they, in collaboration with US scientists, extracted stem cells from cloned embryos of a macaque monkey. They also grew 11 batches of stem cells, derived from the skin cells of patients of genetic immune disorders, spinal cord injuries, and diabetes. Since these stem cells came the donors themselves, they were a genetic match: this important finding does allay the fears of immunologic rejection which is likely with established stem cell lines. The South Korean effort has received a lot of support ($26 million), including another $1 million just recently; the kind of support that no American researchers have received from the US Government because of the restrictions. The UK authorities have just given permission to Ian Wilmut (Dolly’s ‘creator’) for research on motor neuron diseases using HESCs.
As if the HESC science itself wasn’t complicated enough and the public opinion on it weren’t already too polarized, the government also stepped in a few years ago. President Bush, in a national TV address on 9 August 2001, announced that federal support for research will be restricted ONLY to the HESC lines established and available up to that day. No federal support for either the creation of new HESCs or research on them. These restrictions do not affect research efforts in the private sector. He also created “National Bioethics Advisory Commission” (NBAC) to oversee the implementation of his decision, and also said that HESC research raises "fundamental questions about the beginnings of life and the ends of science." Since the government funding supports most research conducted in US academic and research institutions, these restrictions have had an enormous impact on US research and scientists. Dozens of congressmen and respected scientists (many Nobelists, among them) have appealed Bush’s decision, but without any effect.
Now, access to the approved HESCs itself has become a major issue. On the day federal restriction went into effect, there were about 60 such viable HESC lines. Since then, because of various problems, only 22 of these lines are now available, which further strains the scope of federally funded research. The other major problem is the possible contamination in the existing HESC lines. Since all available HESC lines were cultured on a scaffolding of mouse ‘feeder’ cells, it is possible that human cells may have acquired some features of a mouse cell, including a mouse cell-surface sugar which differs from its human counterpart by one oxygen atom. A lot of basic research done with these HESCs seems not only compromised, but these HESCs may also be NOT suitable for clinical studies. If, for instance, these HESCs (or their derivatives) are implanted in humans, the mouse cell-surface sugar may be enough to make them appear as ‘foreign’, which may provoke a major immunologic response and eventual rejection of the implanted cells. The private sector is now busy trying to develop a non-biological scaffolding for establishing fresh, contaminant-free HESC lines. It has been reported that Reproductive Genetics Institute (Chicago) already has 105 HESC lines from normal embryos, and 20 HESC lines with mutations.
Since the Presidential restrictions of August, 2001, one ray of hope is a recent development : just a few weeks ago, the US House of Representatives passed the Stem Cell Research Enhancement Act, HR 810 (by 238 votes to 194); its chances in the Senate appear encouraging. This effort was initiated by Coalition for the Advancement of Medical Research (CAMR) of over 90 patient groups, universities and scientific societies. Though the Presidential threatens to veto it, a Senate sponsor of the Bill, Republican Arlen Specter, claims to have enough Senate support to overrule the Bush veto if it comes to that. The act would allow federally funded researchers the use of HESCs derived from spare or rejected IVF embryos, provided the couples who donate them are not paid; however, various non-governmental research groups in the US already have access to hundreds of cell lines from similar human embryos. NIH Director, Dr. Elias Zerhouni, and others agree that the current US Stem cell policy is not sufficient, and have testified in Congressional committees to that effect
In addition to the scientific and political problems, HESC research also faces major moral, ethical and religious questions, arising from concerns over the protection and destruction of life as an individual. Some are very basic questions, such as: At what stage does the life really begin? At fertilization, or at uterine implantation, or at birth? Is embryo an individual that needs protection under the law? Since extraction of HESCs leads to the destruction of embryo, is it considered tantamount to deliberate killing or murder of an individual? For in vitro fertilization (IVF), embryos are created and frozen for later use, and extra ones are sometimes discarded: Is using extra, to-be-discarded embryos for HESC extraction also equivalent to killing individual life? Is work with embryos a form of human experimentation? What guarantees are there that HESC research would not go down the ‘slippery slope’ to human organ factories and human (or reproductive) cloning?
Scientific interpretations of when the individual life actually begins may not offer much help to theologians and ethicists. For instance, biologically and genetically, one could say the life starts when the egg is fertilized. Embryologically, it is more complicated: Since twins can be formed as late as 12 days after conception, one could say that the individual life starts after this period, which ensures that an embryo produces one individual, not two. Physiologically, one can view individual life starting when the fetus is able to survive on its own, separately and independently (that is, at birth after cutting the umbilical cord) .
The NBAC sought and included Judeo-Christian and Islamic perspectives in its report (but unfortunately none from Hindu, Sikh and Buddhist religious scholars and groups). Jewish and Islamic (Sharia) perspectives seem, by and large, clearer than those of Christianity. The report notes many qualms over HESC research and the views on when the individual life really begins vary a lot, but no clear consensus even within one faith group. These opinions are summarized as follows:
Jewish : Abortion to save a mother’s life is allowed; opinions on using such fetuses for research “morally neutral.” A fetus is considered part of woman’s body (not a separate individual life) up to 40 days after fertilization. HESCs in culture are not considered human because they do not exist in the womb.
Christian: Considerable variation exists. The Catholics think life begins at fertilization and deliberate destruction of an embryo (for research or any other purpose) immoral, and abortion is tantamount to taking life. The Protestant view seems a little flexible. According to an ABC News poll (2000), among evangelical white Protestants, 50% supported stem cell research, with 40% opposing. The same poll showed 54% of Catholics favoring this research, but in a church poll in which embryo destruction was mentioned in the question a great majority of Catholics (70%) opposed the research. A research poll which mentioned possible cure of ‘deadly diseases’ but didn’t mention embryo destruction received 77% support.
Islamic (Sharia): Minor differences exist between Sunni and Shia views. Abortion for health reasons is allowed, and since ‘ensoulment’ is believed to occur 4 months after fertilization, only after this is the fetus considered sacred life. It is neutral on HESCs and research on them.
If you wondered why so much fuss about human embryonic stem cells, this account would give you just a glimpse of the bioethics and bio-politics involved.
Selected References:
1. http://stemcells.nih.gov/index.asp
[NIH Stem cell Info page]
2. National Academy of Sciences Committee on the Biological and Biomedical Applications of Stem Cell Research, Board on Life Sciences National Research Council, and Board on Neuroscience and Behavioral Health Institute of Medicine. "Stem Cells and the Future of Regenerative Medicine." Washington, D.C.: National Academy Press, 2001. http://www.nap.edu/books/0309076307/html/
3. Bush, President George W. "Remarks by the President on Stem Cell Research" made on August 9, 2001. http://www.whitehouse.gov/news/releases/2001/08/20010809-2.html

4. National Bioethics Advisory Commission. "Ethical Issues in Human Stem Cell Research, Volume III: Religious Perspectives." Rockville, Maryland: NBAC, 2000. http://bioethics.gov/pubs.html

(Dr Rizwana Rahim holds a PhD in Biological Sciences. She has been a senior researcher with Toxicology-Cancer, Chicago, and has taught courses in various biology areas from general, cell and molecular biology to human physiology & anatomy and ecology in different Chicago-area universities and colleges. Her articles in science, politics and other areas have been published in various English and Urdu newspapers of the Indo-Pak subcontinent, including Dawn, Nation, Pakistan Journal, Pakistan Link, India Worldwide, Deccan Chronicle, Siasat, Rahnuma-e-Deccan)

 


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