Suggested Alternative Sources Of Embryonic Stem Cells

In light of the moral quandaries surrounding embryonic stem cell research, some scientists are seeking alternative sources for stem cells -- options that wouldn't involve destroying a human embryo, and thus, may qualify for federal research funding.

However, embryonic stem cell research is itself in its infancy -- so most of the suggested alternatives are theoretical at this point. But that hasn't stopped ethicists from weighing in.

In May 2005, the President's Council on Bioethics released a white paper titled, "Alternative Sources of Human Pluripotent Stem Cells." The thoughtful report outlined several possible options for embryonic stem cell sources, including their scientific feasibility and whether they're ethically sound.

Here's an overview of some of the proposed alternatives:

Extract stem cells only from embryos that are considered organismically dead.

The concept of embryonic death is an alternative to embryonic stem cell research that would require changes in public perception instead of scientific advances.

The proposal, offered by Dr. Donald Landry and Dr. Howard Zucker of the Columbia University College of Physicians and Surgeons, defines embryonic death as the "irreversible end of cell division," according to Landry.

"A fully developed human being is considered organismically dead -- even as the cells of various organs remain alive -- if the function of the brain is irretrievably lost," Landry and Zucker wrote in their review article, published in the Nov. 1, 2004, issue of the Journal of Clinical Investigation.

Thus, they argue, the same framework that justifies harvesting organs from brain-dead patients could be extended to cover obtaining stem cells from dead human embryos. They point out that if stem cells are extracted from an embryo that's already dead, a major ethical hurdle will be avoided.

However, research has suggested that embryos determined to be organismically dead could still contain cells with normal developmental potential and could be viable for research.

But with the concept of embryonic death, there's still one outstanding question: Are stem cells from embryos that are organismically dead inferior to stem cells from healthy embryos? The jury is still out, according to the President's Council on Bioethics.

Avoid embryo destruction by extracting blastomeres.

In theory, stem cell lines could be derived from small numbers of cells -- or blastomeres -- removed from living human embryos without harming the embryos.

Embryos with one or two blastomeres extracted have gone on to develop into apparently healthy children. In fact, blastomere extraction has been performed on in-vitro fertilization embryos to conduct preimplantation genetic diagnosis, or PGD, which is a test for genetic and chromosomal abnormalities before an embryo is implanted into a woman's uterus.

A research letter outlining the process in mice was published in the journal Nature in October 2005.

However, the white paper says long-term studies are sorely needed on whether the blastomere extraction has a subtle or later-developing effect in children.

In addition, it might be quite a while -- if ever -- before human stem cell lines can successfully be derived from only a few blastomeres.

Alter therapeutic cloning procedure so an embryo is never actually created.

Several proposals have revolved around the idea of altering the somatic cell nuclear transfer -- or therapeutic cloning -- procedure in a way to avoid creating a cloned embryo.

In regular somatic cell nuclear transfer, the nucleus is removed from a somatic cell -- any cell in the body that isn't a sperm or egg cell. Separately, the nucleus of a female's egg is also removed. Then the nucleus of the somatic cell is inserted into the egg cell, thus fertilizing the egg.

William Hurlbut, Stanford University professor and a member of the President's Council on Bioethics, has advocated the idea of "altered nuclear transfer," in which the nucleus of the somatic cell would be altered before it's inserted into the egg cell in such a way that it lacks the essential attributes of a human embryo. Thus, the procedure creates a "biological artifact" instead of a fertilized egg.

In theory, Hurlbut argues, the stem cells from this "biological artifact" would be extracted, and then the genes that were originally removed from the somatic cell would be reinserted into the stem cells, and then "normal" pluripotent stem cells would be derived from them.

Hurlbut says that since no embryo would be created or destroyed in this process, it would sidestep the ethical problems with regular somatic cell nuclear transfer.

Researchers at the Whitehead Institute for Biomedical Research in Cambridge, Mass., announced in October 2005 in the journal Nature that the procedure is possible -- at least in mice. But even Hurlbut admits that it would be months or years before the process could be perfected using human tissues.

Another such proposal is that from Karl Swann and colleagues at the University of Wales College of Medicine. The team biochemically "tricked" a human oocyte into thinking it had been fertilized. Then the eggs divide until the blastocyst stage, at which point stem cells can presumably be extracted. But since the eggs have been altered so that they lack the potential for human life, Swann argues that they aren't really embryos.

Critics say these proposals seem to advocate creating doomed embryos -- rather than "biological artifacts" -- for the sole purpose of stem cell research, which poses an entirely new set of ethical questions.

And many scientists would likely be hesitant to perfect such complicated procedures that have no rational purpose other than to satisfy the ethical objections of others.

Reprogram somatic cells so they revert back to an embryonic state.

The idea of reverting a cell in the body so that it regains the same plutipotency that embryonic stem cells poses not an ethical dilemma, but a technical one. Essentially, the idea is to prompt a cell to move backwards developmentally from its current state to form its own precursor, less specialized cell.

This process, called "dedifferentiation," would require new scientific advances, the council's white paper said. But there are examples in nature of cells reverting into a form that can multiply into different types of tissue -- such as the regeneration of missing limbs in amphibians.

Research into the process is in preliminary stages, but in the past year, promising research has been reported from several institutions.

In the Aug. 26, 2005, issue of the journal Science, Harvard researchers reported their success with fusing adult skin cells with embryonic stem cells. The fused cells were "reprogrammed to their embryonic state," they said, and they differentiated into cells from each of the three main tissue types that form in a developing embryo.