Developments in Embryo Research

Anne Dickinson

In the last few years while New Zealanders have been debating cloning and assisted human reproduction and the government has been legislating to deal with these issues, human embryo research has moved in new directions in other countries.

Such research takes many forms. For example, in the USA scientists have created human embryos which were part male and part female, by implanting cells from male embryos into female embryos. The hybrid embryos developed normally in some cases, with intermixed male and female cells, and abnormally in others. The embryos were destroyed after six days of development.

The search for stem cells

Much of the current research involving human embryos focuses on finding sources of embryonic stem cells potentially for use in medical treatments. In May 2005 Korean scientists created 31 human embryos by cloning and extracted stem cells from 11 of them, creating 11 new stem cell lines. These cell lines are almost identical genetically to the patients who supplied the DNA from skin cells, so in theory they can be used to treat the patients' conditions with less chance of triggering a rejection response. The process used far fewer human eggs than previous attempts. The stem cells were grown on a human tissue medium rather than a mouse medium as used in the past, thus reducing the risk of contamination. These developments have overcome many of the technical difficulties involved in creating stem cells from cloned human embryos.

Dr Woo Suk Hwang, leader of the Korean team, rejects the idea that the cells he creates by somatic nuclear transfer (cloning) are cloned human embryos, and therefore sees no ethical problem with destroying them to obtain stem cells. Researchers in the UK have also created cloned human embryos, although they have not been as successful as the Koreans in taking stem cells from them.

In the USA Dr Leon Kass, chairman of the President's Council on Bioethics, said of these developments in embryo research and cloning: "Whatever its technical merit, this research is morally troubling: it creates human embryos solely for research, makes it much easier to produce cloned babies, and exploits women as egg donors not for their benefit."

In China cloning techniques have been used to create embryos which contain both human and rabbit DNA. Human skin cells were fused with rabbit eggs from New Zealand, resulting in a hybrid embryo. The vast majority of the DNA in each embryo was human, with a small amount of DNA (called mitochondrial DNA) being contributed by the rabbit egg. The researchers are hoping that the hybrid embryos will be a new source of stem cells. It is not known if these embryos would develop into viable fetuses, although indications from other research indicate they would not. Richard Doerflinger, of the U.S. Conference of Catholic Bishops, said he felt certain that the human-rabbit embryos were human enough to deserve protection. "I think because all the nuclear DNA is human," Doerflinger said, "we'd consider this an organism of the human species."

Sidestepping the ethical issues

The ban on federal funding of embryonic stem cell research in the US has led to a number of proposals to avoid the ethical issues associated with the destructive use of embryos.

Drs Donald Landry and Howard Zucker have proposed applying to embryos the principles which guide organ donation in adults. Up to 75% of frozen embryos may no longer be able to undergo cell division when thawed, as a result of biological accidents soon after fertilization. Researchers argue that because these embryos do not have the capacity for human life, they can be considered to be analogous to brain dead adults. Just as brain dead adults can have healthy functioning organs, so embryos which cannot develop any further may have some healthy normal cells. When removed from "dead" embryos, these cells still have the capacity to develop into stem cells.

In this proposal the time of the death of the embryo would be a crucial factor in the removal of stem cells. If the embryo dies in the first four days while each of its cells are totipotent, that is, i.e. capable of becoming an entire human being, then the stem cell removed is capable of developing into a human being and must be considered to be an embryo. If the embryo dies at a later point any stem cells removed would be pluripotent, that is could form all the tissues found in a human body but would not be able to organize into a human being.

In March 2005, at a conference at Regina Apostolorum University in Rome, the Landry-Zucker method of obtaining stem cells was the subject of considerable discussion. While the participants had some sympathy for what Landry and Zucker were trying to do, there were also concerns. The absence of cell division may not be a totally reliable indicator of death, and there is always the possibility that approving the use of dead embryos may encourage researchers to create embryos – or thaw them – simply to let them die so their stem cells can be removed.

Also in the USA, a proposal by Dr William Hurlbut to produce human embryonic stem cells without creating an embryo, called "altered nuclear transfer", is being debated. This method would involve turning off the genes in an adult skin cell which are crucial for the organizational processes in embryonic development. The DNA would then be removed from a human egg, and the altered skin cell would be placed in the egg and cell division stimulated. This process would normally result in a cloned human embryo. However, with the organizational genes turned off the cluster of dividing cells would not have the capacity to organize into a human fetus. It would produce a mass of cells, many of which would be stem cells. These cells could be extracted and their inactivated genes turned on again to make them normal stem cells.

Hurlbut argues that because the entity lacks the ability to organize itself it is not a human life. Some ethicists support him, but make clear that the gene concerned must alter development from the very beginning, not after a period of normal development. Some see the process as a means of passing directly from an adult cell to pluripotent stem cells without forming a cloned human embryo. Others ask whether the result of altered nuclear transfer is actually a disabled embryo, which would raise profound moral questions about the technique. There are also questions about whether it is right to manipulate the human genome to get around a theological or ethical problem, especially as the technique proposed takes scientists into new and murkier ethical areas. Altering the human genome in a way which is destructive rather than for healing is also considered by some to be a morally indefensible means of reaching a good end.

"Embryo biopsy" has also been proposed as a means of obtaining stem cells without destroying embryos. In this process a biopsy is performed on an embryo to remove a stem cell. It is assumed that the process will not harm the embryo, but it is by no means conclusive that this is the case. The timing of the biopsy is critical, because the stem cell must be pluripotent rather than totipotent if it is not to become another embryo when removed. Many ethicists reject this method of obtaining stem cells on the grounds that it is an invasive procedure which is not carried out for the benefit of the embryo from which the stem cell is taken. It would effectively expose the embryo to harm in order to benefit someone else.

Some scientists have also been experimenting with parthenogenesis as a means of obtaining stem cells without creating embryos. This involves stimulating an egg to begin dividing as an embryo would, without fertilization by sperm. After ovulation an egg contains half the human chromosome complement, so various techniques are used to acquire eggs which have the full chromosome complement. Eggs can be artificially stimulated to replicate their chromosomes so they have the full number found in body cells or in an embryo. Egg cells taken from a women's ovary before they mature can also be used, as they still contain the full human chromosome complement. These egg cells are biochemically tricked into beginning cell division as if they had been fertilized, and stem cells can be removed from them at the appropriate point. There is evidence that these eggs are not able to develop very far, so may not be able to develop into a fetus. There is no agreement about whether in fact these dividing eggs are embryos or not. There are also scientific questions about whether any stem cells will be too genetically flawed for use.

Re-programming body cells so as to restore to them to pluripotency is another route to stem cells, but without the ethical difficulties associated with embryos. There are significant technical difficulties to be overcome but as long as the cells are restored only to pluripotency, not totipotency (which would raise questions about whether they were embryos) this method represents the least ethically problematic method of obtaining pluripotent stem cells. At the same time, research into adult stem cells is advancing rapidly, offering processes which are ethically sound and increasingly, technically feasible.

Ethical Questions

There are some ethical questions which are generic to a number of these proposals. The most difficult issue is whether in fact the entities produced are simply masses of human tissue or whether researchers are actually creating disabled or defective human embryos. If the ability to organize itself is an essential distinguishing feature of an embryo, it is fair to ask whether the absence of this ability means that the entity is not an embryo.

Many of these methods of conducting research on embryos also rely upon a supply of eggs. Obtaining eggs from women is not without pain and risk, and the commodification of eggs is already a fact in some countries. The exploitation of women has to be seen as an ethical consideration in its own right. There are serious questions about whether we should treat eggs and sperm – "the seeds of the next generation" – in this way. Many people are uneasy about deliberately creating entities from our own gametes and cells that may be less than human.

The motivation for many of these types of research is to gain access to a plentiful supply of embryonic stem cells, or to find ways around ethical objections to the use of human embryos. The scientific community has been divided in its response to such research, with many challenges being issued to those proposing or conducting the research. These developments also pose significant challenges for Catholic theologians and thinkers.

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Anne Dickinson is Executive Officer of the New Zealand Catholic Bishops Conference.