A Primer on Human Embryonic Stem Cells

Metanexus VIEWS 2001.08.16. 2473 words

Below is "A Primer on Human Embryonic Stem Cells" written by Scott Gilbert, a Professor of Biology at Swarthmore College. The Q&A format isexceptionally clear and deals with scientific, historical, and ethicalissues. 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 heteaches 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=lWriting 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

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

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

The Science =20What are embryonic stem cells?

When the fertilized human egg divides, it forms two groups of cells. By theten-cell stage, there are outside cells and inside cells. The outside cell=sbecome the fetal part of the placenta. These cells will attach to theuterus. 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, andeach half will develop into a whole embryo. This is how identical twins areformed. These inner cells have this ability to form any type of the 220cell types of the body, and this capacity is called totipotency. Now if onewere 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 calledembryonic 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=nbe found in fetuses. However, this means getting the immature sperm and egg=sfrom 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 ourbody that are "committed stem cells" (sometimes called "progenitor cells").For instance, our bone marrow is full of blood progenitor cells, because weneed to make billions of new blood cells every day. Some of these blood ste=mcells can make every type of red and white blood cell. There is thepossibility these committed stem cells can be "tricked" into becomingtotipotent cells. However, scientists have not yet been able to make theseprogenitor cells into totipotent cells. So right now, the best source ofstem cells are the hundreds of thousands of 32-64-cell embryos frozen awayin fertility clinics.

What do you mean frozen embryos?

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

Why are embryonic stem cells so special?

These cells are special for two reasons. First, they are totipotent. Theycan become any cell type in the body. Second, if scientists give them themolecules they might encounter inside the embryo, they can respond to theseproteins by becoming a certain type of cell. For instance, mouse embryonicstem cells can respond to a chemical called retinoic acid by becoming neura=lprogenitor cells, a progenitor cell that produces neurons. When mice thathave severed spinal cords are given these neural progenitor cells, theprogenitor cells form neurons, these neurons follow the old pathways, andthe mice begin walking again. Recent papers have shown that mouse embryonicstem cells can make the neurons deficient in Parkinson's disease, andseveral laboratories are attempting to grow the pancreatic cells deficientin certain types of diabetes. The ability to form blood progenitor cellsfrom embryonic stem cells would mean that blood cells would be available fo=rpeople 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 researcherswho produced Dolly and other clones) are against the "reproductive" cloningof humans. First, most of the attempts to produce cloned animals resulted i=naborted fetuses and stillborn animals, something that would not be tolerate=dwith humans. Second, even those animals that have been cloned (such asDolly) are not healthy animals. Many have growth problems and heartabnormalities. But "therapeutic" human cloning can be very important inallowing embryonic stem cells to function in humans. So far, experiments onembryonic stem cells have been done in mice, because mouse strains areinbred. They are genetically identical (with the exception of the genes tha=tmake them male or female). Each mouse of a particular strain is like anidentical twin to the others of its strain. So an embryonic stem cell linefrom a particular strain of mouse will not elicit an immune response whentransplanted into an adult mouse of the same strain. Humans, however, arenot inbred. If I were to put a stem cell from a human embryo into you, yourimmune system would recognize it as foreign and would reject it, just as itwould reject a skin graft. However, if one of your own nuclei were placedinto an enucleated egg (as in cloning) and that egg were to divide into a64-cell stage embryo, the inner cells could be isolated and made intoembryonic stem cells. These cells would be "yours" and would not berejected. For more information on human embryonic stem cells, one can go totwo 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'sstem 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 differentideas as to what constitutes human dignity. There is an abstract notion ofhuman dignity which maintains that there is something special about beinghuman which sets us apart from other animals. This something special couldbe rationality, soul, or even the possibility of redemption. One need not b=ereligious to have this intuition that there is something special about bein=ghuman. Laws against slavery and cannibalism recognize the inherent worth ofthe human being. However, this notion of human dignity can be used to thwar=timprovements in the human condition. Conservatives religious groups (theCatholic 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 ofserum from a cow into a human was an affront to human dignity. TheologianCotton Mather's home was firebombed by Bostonians who felt his support ofvaccination blasphemous. Another definition of human dignity is moreconcrete. Physicians often note that disease not only affects the body butit can rob the dignity from a person. Thus, supporters of human stem cellresearch argue that such study has the potential to restore dignity to thesuffering. Such research might enable the Alzheimer patient to be able todress himself and recall experiences, the Parkinson's patient to control he=rmovements, 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'=
sbrain to ameliorate the consequences of disease. Supporters of stem cellresearch feel that it is more important to restore dignity to adult humansthan to accord an abstract concept of human dignity to an embryo that hasnot 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 thissecond vision of human dignity is that one can enter upon a slippery slopewherein any technological procedure that can be done should be done. Themoral debate about stem cells is not about good versus evil (or scienceagainst religion). It is about two competing notions of what is good forhuman dignity. Some religious groups, such as the Catholic Church, favor th=efirst model of human dignity. Other religious groups, such as thePresbyterians 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 humanlife begins. One position is that human life begins when the human egg andsperm nuclei fuse at fertilization. This is the "genetic view." A secondposition is that human life begins when the embryo becomes an individual.This is the time, 14 days after fertilization, when each embryo can produceonly one individual, rather than twins or triplets. In religious terms, thi=swould 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 biologicalresearch, and it has been adopted by the entire biomedical researchcommunity there. It has the force of law in the Human Fertilisation andEmbryology Authority that licenses and governs Britain's embryo and stemcell research. A third position is that human life begins when thehuman-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 scientistshave argued that the acquisition of this EEG pattern be considered the timewhen the fetus becomes human. The fourth position is that human life beginswhen it can be metabolically independent from the mother, the traditional"birthday." So there are several scientifically defensible positions as towhen 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 theUnited States? Other countries are proceeding with stem cell research. It i=spossible, though, that without federal funding, this country's humanembryonic stem cell research could only be done by corporations. The Bushadministration claims that there are 60 "lines" of stem cells alreadyavailable. Many scientists dispute this, saying that there are less than adozen lines of stem cells that meet the administration's criteria, and mostof these are the property of private companies or foreign countries. Wereally don't know what's available right now. Many of these lines arethought to be at the limits of their totipotency, Bioethicist Arthur Caplanhas called president Bush's policy against using new lines "a ban," and hepoints out that the restrictions on federal funds for scientists to make ne=wstem cell lines could mean that the only scientists in America who could dohuman embryonic stem cell research would be those funded by corporations.Thus, "embryonic stem cell research will become a business withoutregulation 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 atomicenergy, embryonic stem cell research is incredibly powerful and can be usedfor all sorts of ends, good and bad. One can start manipulating stem cellsby adding genes to them. The same techniques that can cure disease couldaugment a person's ability. Do we want this? Probably not; but if the marke=teconomy is the only regulator of embryonic stem cell use, then we can expec=tto see muscle-forming stem cells injected into our wealthier high schoolathletes. If there are no federal regulations, will the wealthy be allowedto extend their lives continuously? There is nothing now to prevent thatfrom happening. With atomic energy, the United States established the Atomi=cEnergy Commission (and later, the Nuclear Regulatory Commission) to overseeand regulate nuclear energy programs in our country. We have nothingcomparable for human embryonic stem cells. In Britain, the HumanFertilisation and Embryology Authority has the power to license fertilityclinics and ensure that scientists experimenting on embryonic stem cellsmeet 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=yto be an unregulated business enterprise. But Bush's policies mayeffectively take away human stem cell research away from the American publi=cand put it into the hands of foreign governments and corporations. That,too, is an ethical issue.

By Scott GilbertSwarthmore College

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