Open Letter from the Foundation Director

Should the U.S. government support the creation of new lines of embryonic stem cells?

by Ann A Kiessling, PhD

The answer to that question is not simple. The rancorous US debate about embryonic stem cells bespeaks a healthy society with genuine concern about each and every member, the tiniest and the sickest. Everyone, on both sides of the debate, wants to do what’s right.

But what is “right?”

Should frozen embryos “left-over” in fertility clinics be “sacrificed” to create stem cells to treat heart failure, autoimmune diseases, diabetes, osteoporosis, cancer, Alzheimer’s disease, Parkinson’s disease, spinal cord injuries, and birth defects?

The answer is not necessarily.

Embryonic stem cells from “left-over” frozen embryos are just one example of pluripotent stem cells (pluripotent: the potential to develop into all body tissues). Embryonic stem cells have been important model systems for research, but they will have the same tissue compatibility problems as other transplanted organs.

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The most therapeutically useful stem cells will be pluripotent stem cells that contain the genes of the patient. At present, there are three ways to accomplish that, two of which require the assistance of an unfertilized human egg, one of which is new technology developed in 2007 by Japanese scientists:

(1) Genetic transplantation (“Somatic Cell Nuclear Transplants”)
Human eggs are huge cells with the capacity to “remodel” genetic information transplanted into them, just like they “remodel” sperm at fertilization. This powerful capacity is not fully understood. All cells contain all of a person’s genes, on the order of 25,000. Specific genes are turned “off” and others turned “on” to make the proteins needed by that particular cell’s function. Which genes are “on” and which “off” define the “gene program” for that cell.

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An egg has the capacity to change the gene program of an adult cell, such as a skin cell, and convert it back to the program expressed during early embryo development, a process termed “re-programming to pluripotency.” An egg can do this even after its own genes have been removed. Then, when activated artificially by chemicals or an electrical pulse, the egg uses the transplanted genes to develop into a line of stem cells genetically identical to the skin cell donor.

This technology has been developed well for many animal species, but not for human eggs; reports by a Korean research team in 2005 were found to be false. Moreover, because this same basic technology led to cloning Dolly the sheep in 1997, there is fear it could lead to cloning a human. Such fears could obviously be set aside by legislation to outlaw cloning a human, but allow gene transplantation technology to go forward.

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(2) Parthenogenesis
Another avenue for creating pluripotent human stem cells is artificial egg activation, termed “parthenogenesis.” It has been known for many years that human eggs spontaneously activate, sometimes inside the ovary, leading to dermoid cysts, and sometimes outside the ovary, leading to benign tumors called teratomas. Teratomas contain different types of cells, such as hair and teeth, and support the concept that activated, unfertilized human eggs could be a valuable source of pluripotent stem cells without destroying human embryos.

The first attempt to activate unfertilized human eggs appeared in 2001, but no stem cell lines were derived (see FAQs, this site). A parthenote cell line from an unfertilized monkey egg (Cyno-1), was developed, however, in 1994, and has demonstrated promise in monkey models of several human diseases. The first human parthenote stem cell lines were reported by a team of Russian scientists in 2007, working in a California-based company, International Stem Cell Corp.

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But does technology requiring human eggs exploit women? A woman is born with about one million eggs; by the time she is 55 years old, they are all gone. Thus, approximately 2000 eggs naturally die each month; only one or two are released during her monthly cycle. If the technology could be perfected, some of the eggs that would otherwise be wasted could be used for stem cells. Unfortunately, the U.S. congress included all forms of activated human eggs, including eggs not fertilized by sperm, in its moratorium on federal funding in 1996. President Bush extended the moratorium in 2001.

Therefore, the research can go on only in privately funded laboratories in the U.S, which has generated legitimate concerns about ethical oversight. Conducting the research in public charities with strong, active ethical oversight is an obvious answer. The Bedford Stem Cell Research Foundation, a Massachusetts public charity, conducted such research with unfertilized human eggs from 2000 to 2004 (see reference below). The eggs were donated by woman under rigorous guidelines developed specifically for stem cell research by an ethics advisory board originally chaired by Professor Ron Green, Dartmouth College, and now chaired by Professor Arthur Applbaum, Harvard University. The work will resume when funding becomes available.

Private funding is essential to continue the work in the U.S. The National Institutes of Health grants about 24 billion dollars a year to U.S. scientists. Without cutting funds to other meritorious programs, the NIH will not be able to dedicate substantial funds to pluripotent stem cell research for several years. Thus, in the short term, with or without government approval, the funds must come from the private sector.

(3) Induced pluripotent stem cells
New research has revealed promising techniques to remodel the gene program of a cell without needing eggs. A Japanese team, led by Dr. Shinya Yamanaka, Kyoto University, systematically compared the gene programs in human embryonic stem cells and adult skin cells. He discovered about two dozen genes whose proteins seemed important to maintaining the pluripotency and self-renewal characteristics of human embryonic stem cells. To get the proteins of interest to be expressed in adult cells, such as skin cells growing in the laboratory, he engineered viruses to carry extra copies of those genes into the cells, and then followed the change in the cells from skin cells, to pluripotent cells.