Below is "A Primer on Human Embryonic Stem Cells" written by Scott Gilbert, a Professor of Biology at Swarthmore College. The Q&A format is exceptionally clear and deals with scientific, historical, and ethical issues. As always, you are encouraged to forward this to your friends, colleagues, and students, something which in this case they would certainly be appreciative of, as the essay is excellent in distilling a complicated technical and moral debate into a short space. Gilbert ends with his own editorial on the recent Bush decision regarding Federal Funding of Stem Cell Research. You are invited to add your own feedback and questions via the comments interface at the bottom of this essay on our webpage <http://www.metanexus.net>.

Scott F. Gilbert is Professor of Biology at Swarthmore College where he teaches developmental genetics, embryology, and the history and critiques of biology. He received his B.A. in both biology and religion from Wesleyan University, and he earned his PhD in biology from the pediatric genetics laboratory of Dr. Barbara Migeon at the Johns Hopkins University. His M.A. in the history of science, also from The Johns Hopkins University, was done under the supervision of Dr. Donna Haraway. He pursued postdoctoral research at the University of Wisconsin in the laboratories of Dr. Masayasu Nomura and Dr. Robert Auerbach. Dr. Gilbert is currently on the Board of the Directors of the International Society for Differentiation and is a fellow of the AAAS. He also serves on the education committee of the Society for Developmental Biology. He has written the textbook Developmental Biology (presently in its sixth edition), as well as editing A Conceptual History of Embryology and (along with his wife, Anne M. Raunio) Embryology: Constructing the Organism. He has received several awards, including the Medal of Fran=E7ois I from the Coll=E8ge de France, the Dwight J. Ingle Memoria= l Writing Award, the Choice Outstanding Academic Book Award, an honorary doctorate from the University of Helsinki, and a John Simon Guggenheim Foundation Grant. His present research is in evolutionary developmental biology, focusing on that most interesting of topics--how the turtle forms its shell. Dr. Gilbert continues to write both in developmental biology and in the history and philosophy of biology.

-- Billy Grassie

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From: Scott Gilbert < sgilber1@swarthmore.edu> Subject: HUMAN EMBRYONIC STEM CELLS: A PRIMER

I teach embryology to undergraduate poets, musicians, and language majors, so my friends and family assume that I can tell them what's going o= n about stem cells. So here is my list of Frequently Asked Questions, along with my answers.

The Science =20 What are embryonic stem cells?

When the fertilized human egg divides, it forms two groups of cells. By the ten-cell stage, there are outside cells and inside cells. The outside cell= s become the fetal part of the placenta. These cells will attach to the uterus. The inner cells are those cells that are going to become the embryo= , itself. Each of these inner cells can become any type of cell in the body. In fact, before day 14, this group of inner cells can split in half, and each half will develop into a whole embryo. This is how identical twins are formed. These inner cells have this ability to form any type of the 220 cell types of the body, and this capacity is called totipotency. Now if one were to take the inner cells of a 5-day human embryo (less than 50 cells) and put them into a flask and give them the right vitamins, hormones, nutrients, and structural supports, they will keep on growing and dividing. Moreover, they will retain their totipotency. These cells are called embryonic stem cells.

Are there other ways of getting embryonic stem cells?

The cells that form the sperm and the egg are also totipotent, and these ca= n be found in fetuses. However, this means getting the immature sperm and egg= s from aborted fetuses or from fetuses that have died from some other cause. This is very difficult to do. There are also a group of stem cells in our body that are "committed stem cells" (sometimes called "progenitor cells"). For instance, our bone marrow is full of blood progenitor cells, because we need to make billions of new blood cells every day. Some of these blood ste= m cells can make every type of red and white blood cell. There is the possibility these committed stem cells can be "tricked" into becoming totipotent cells. However, scientists have not yet been able to make these progenitor cells into totipotent cells. So right now, the best source of stem cells are the hundreds of thousands of 32-64-cell embryos frozen away in fertility clinics.

What do you mean frozen embryos?

When a woman is going to provide eggs for in vitro fertilization, she takes hormones that make her ovulate as many as 20 eggs, instead of the one egg that she would normally ovulate that month. These eggs are then fertilized in a small plate. The embryos that appear to be the healthiest are implante= d into the woman's uterus in the hopes that one of them will survive. Since only a fraction of the embryos placed into the uterus will actually develop (even under natural conditions), usually three or four embryos are placed into the womb. The rest of the fertilized embryos--usually around a dozen--are either discarded or frozen away. It is estimated that hundreds o= f thousands of such embryos are frozen.

Why are embryonic stem cells so special?

These cells are special for two reasons. First, they are totipotent. They can become any cell type in the body. Second, if scientists give them the molecules they might encounter inside the embryo, they can respond to these proteins by becoming a certain type of cell. For instance, mouse embryonic stem cells can respond to a chemical called retinoic acid by becoming neura= l progenitor cells, a progenitor cell that produces neurons. When mice that have severed spinal cords are given these neural progenitor cells, the progenitor cells form neurons, these neurons follow the old pathways, and the mice begin walking again. Recent papers have shown that mouse embryonic stem cells can make the neurons deficient in Parkinson's disease, and several laboratories are attempting to grow the pancreatic cells deficient in certain types of diabetes. The ability to form blood progenitor cells from embryonic stem cells would mean that blood cells would be available fo= r people with leukemias. These are special cells.

Do embryonic stem cells have anything to do with cloning?

Yes, but in an interesting way. Most scientists (including the researchers who produced Dolly and other clones) are against the "reproductive" cloning of humans. First, most of the attempts to produce cloned animals resulted i= n aborted fetuses and stillborn animals, something that would not be tolerate= d with humans. Second, even those animals that have been cloned (such as Dolly) are not healthy animals. Many have growth problems and heart abnormalities. But "therapeutic" human cloning can be very important in allowing embryonic stem cells to function in humans. So far, experiments on embryonic stem cells have been done in mice, because mouse strains are inbred. They are genetically identical (with the exception of the genes tha= t make them male or female). Each mouse of a particular strain is like an identical twin to the others of its strain. So an embryonic stem cell line from a particular strain of mouse will not elicit an immune response when transplanted into an adult mouse of the same strain. Humans, however, are not inbred. If I were to put a stem cell from a human embryo into you, your immune system would recognize it as foreign and would reject it, just as it would reject a skin graft. However, if one of your own nuclei were placed into an enucleated egg (as in cloning) and that egg were to divide into a 64-cell stage embryo, the inner cells could be isolated and made into embryonic stem cells. These cells would be "yours" and would not be rejected. For more information on human embryonic stem cells, one can go to two sites of the National Institutes of Health (http://www.nih.gov/news/stemcell/scireport.htm orhttp://www.nih.gov/news/stemcell/primer.htm) or the British government's stem cell report, (http://www.doh.gov.uk/cegc/stemcellreport.htm).

The Ethical and Legal Issues

Are scientists concerned about human dignity?

Yes. It must be remembered, though, that people have always had different ideas as to what constitutes human dignity. There is an abstract notion of human dignity which maintains that there is something special about being human which sets us apart from other animals. This something special could be rationality, soul, or even the possibility of redemption. One need not b= e religious to have this intuition that there is something special about bein= g human. Laws against slavery and cannibalism recognize the inherent worth of the human being. However, this notion of human dignity can be used to thwar= t improvements in the human condition. Conservatives religious groups (the Catholic Church among them) vehemently opposed vaccination against smallpox= , even a hundred years after its first use. Small pox antiserum came from cow= s (hence the term "vaccination"), and these groups felt that the injection of serum from a cow into a human was an affront to human dignity. Theologian Cotton Mather's home was firebombed by Bostonians who felt his support of vaccination blasphemous. Another definition of human dignity is more concrete. Physicians often note that disease not only affects the body but it can rob the dignity from a person. Thus, supporters of human stem cell research argue that such study has the potential to restore dignity to the suffering. Such research might enable the Alzheimer patient to be able to dress himself and recall experiences, the Parkinson's patient to control he= r movements, and the paraplegic to walk and to control his bowels. Moreover, in this definition, part of our human dignity is found in the using of one'=
s brain to ameliorate the consequences of disease. Supporters of stem cell research feel that it is more important to restore dignity to adult humans than to accord an abstract concept of human dignity to an embryo that has not yet become an individual (it can still form twins) and has no head, heart, arms, or even a distinguishable front or back. The danger of this second vision of human dignity is that one can enter upon a slippery slope wherein any technological procedure that can be done should be done. The moral debate about stem cells is not about good versus evil (or science against religion). It is about two competing notions of what is good for human dignity. Some religious groups, such as the Catholic Church, favor th= e first model of human dignity. Other religious groups, such as the Presbyterians and Orthodox Jews, have come out in favor the second model.

Are scientists agreed that human life begins at fertilization?

No. There are several scientifically defensible positions as to when human life begins. One position is that human life begins when the human egg and sperm nuclei fuse at fertilization. This is the "genetic view." A second position is that human life begins when the embryo becomes an individual. This is the time, 14 days after fertilization, when each embryo can produce only one individual, rather than twins or triplets. In religious terms, thi= s would mean that ensoulment (whatever that may be) must occur after day 14, since twins are separate individuals. In the United Kingdom, this 14-day "embryologic view" of human individuality is the basis for human biological research, and it has been adopted by the entire biomedical research community there. It has the force of law in the Human Fertilisation and Embryology Authority that licenses and governs Britain's embryo and stem cell research. A third position is that human life begins when the human-specific electroencephalogram (EEG) is acquired at around 25 weeks. Since our society has defined human death as the loss of the EEG pattern (and not, say, when the heart stopping or the cells dye), some scientists have argued that the acquisition of this EEG pattern be considered the time when the fetus becomes human. The fourth position is that human life begins when it can be metabolically independent from the mother, the traditional "birthday." So there are several scientifically defensible positions as to when a new human life begins.

Will Bush's policy allow human stem cell research?

The question really is: Will Bush's policy stop stem cell research in the United States? Other countries are proceeding with stem cell research. It i= s possible, though, that without federal funding, this country's human embryonic stem cell research could only be done by corporations. The Bush administration claims that there are 60 "lines" of stem cells already available. Many scientists dispute this, saying that there are less than a dozen lines of stem cells that meet the administration's criteria, and most of these are the property of private companies or foreign countries. We really don't know what's available right now. Many of these lines are thought to be at the limits of their totipotency, Bioethicist Arthur Caplan has called president Bush's policy against using new lines "a ban," and he points out that the restrictions on federal funds for scientists to make ne= w stem cell lines could mean that the only scientists in America who could do human embryonic stem cell research would be those funded by corporations. Thus, "embryonic stem cell research will become a business without regulation or accountability of any sort."

What are the problems of corporations controlling stem cell research?

It's a matter of responsibility and public accountability. Like atomic energy, embryonic stem cell research is incredibly powerful and can be used for all sorts of ends, good and bad. One can start manipulating stem cells by adding genes to them. The same techniques that can cure disease could augment a person's ability. Do we want this? Probably not; but if the marke= t economy is the only regulator of embryonic stem cell use, then we can expec= t to see muscle-forming stem cells injected into our wealthier high school athletes. If there are no federal regulations, will the wealthy be allowed to extend their lives continuously? There is nothing now to prevent that from happening. With atomic energy, the United States established the Atomi= c Energy Commission (and later, the Nuclear Regulatory Commission) to oversee and regulate nuclear energy programs in our country. We have nothing comparable for human embryonic stem cells. In Britain, the Human Fertilisation and Embryology Authority has the power to license fertility clinics and ensure that scientists experimenting on embryonic stem cells meet their strict guidelines. In America, it is strictly entrepreneurship, and embryonic stem cell entrepreneurship has already begun,

I suspect that neither the American public wants embryonic stem cell therap= y to be an unregulated business enterprise. But Bush's policies may effectively take away human stem cell research away from the American publi= c and put it into the hands of foreign governments and corporations. That, too, is an ethical issue.

By Scott Gilbert Swarthmore College

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Published   2001.08.16