Current Status of Research Cloning
Several groups have shown that cloned embryonic stem cells can be derived from mouse cells and that these cells can be differentiated into several different kinds of somatic cells. However, they have found it a more difficult feat to derive cloned embryonic stem cells using cells that are human. Two accounts of human cloning for research and therapy were published by Woo Suk Hwang and his colleagues at Seoul National University in South Korea, one in 2004 and one in 2005. Commentators initially observed that these studies amounted to a great leap forward in the development of research cloning. However, these reports from the South Korean scientists proved false.
In 2006, they were retracted by the journal in which they were published. Right now, stem cell investigators Evan Snyder and Jeanne Loring observe, ‘‘we do not know whether the procedure (i.e., research cloning) works at all, though we still suspect that the hurdles are more technological than biologic.’’ Other centers have attempted to carry out research cloning in humans. A small biotech firm, Advanced Cell Technology, created a stir around the subject of human cloning when it announced in 2001 that it had cloned several human embryos for transplantation into humans. However, it is arguable that the resulting six-cell clusters, which died almost immediately, could not have been embryos because they did not lead to the development of a human being.
In 2005, researchers at Newcastle University in the United Kingdom, led by Alison Murdoch, announced that they had cloned a human embryo. That embryo, however, also ceased growing, although it lived for several days. Investigators are attempting to discern why this cessation of growth occurs when research cloning is attempted and how to remedy it. Rudolph Jaenisch and his colleagues at Massachusetts Institute of Technology have found that two crucial genes essential to embryonic development fail to function in cloned blastocysts. they suggest that this might explain the problem. If these genes were activated, this would enable the cloned blastocyst to continue to develop, they maintain. Stem cell investigators are pursuing this and other avenues in hopes of finding a reliable method of research cloning.
Scientific and Practical Concerns with Cloning Research
There has been some disagreement about whether research cloning is likely to provide a major new therapeutic route in stem cell research. Some contend that genetic irregularities found in mammalian embryos developed for reproductive cloning would also appear in human embryos cloned for research and therapy, rendering them unsuitable for use in patients. The President’s Council on Bioethics, for instance, observed that the reproductive cloning procedure ‘‘resulted in high rates of death, deformity, and disability in the animals that come to birth following SCNT (somatic cell nuclear transfer)’’ and that research cloning would do the same. In support of this observation, the council cited a study by Rudolf Jaenisch and colleagues indicating that about 4 percent of the genes in newborn mice that had been developed by means of reproductive cloning functioned abnormally.
However, later studies by these same investigators, Hochedlinger and Jaenisch, found that the cells of blastocysts that were developed through research cloning showed no signs of the epigenetic abnormalities (abnormalities that affect a cell and that may indirectly affect the expression of its genome) that appear in animals cloned for reproductive purposes. They explain the reason for this: The derivation of embryonic stem cells from cloned blastocysts may be the result of selection for a few successfully reprogrammed cells within a cloned embryo. In contrast, the development of a cloned embryo after implantation most likely does not allow for the in vivo selection of a few functional cells, thus causing developmental failure of the clone or phenotypic abnormalities.
In short, they indicate that research cloning is more efficient than reproductive cloning because it selects for working, rather than abnormal, cells. They therefore maintain that embryonic stem cell lines derived from cloned embryos have the same therapeutic potential as those derived from IVF fertilized embryos. They conclude that the concern that cloned embryonic stem cells would not be safe to use in patients because they would be peppered with genetic aberrations can be set aside. Another difficulty with research cloning that has been posed by some scientists is that there would not be sufficient time to treat patients who have an acute injury, such as a heart attack, with derivatives of cloned embryonic stem cells, for these patients would require immediate treatment and cloning is not a speedy process.
It would take days to obtain a somatic cell from these patients, as well as a human egg from a donor, and then to fuse them and grow stem cells from the resulting cloned embryos in order to differentiate them and transfer them to these patients. Patients with an acute coronary condition could not wait that long to be treated. To make research cloning feasible for therapeutic uses in the acute care situation, it would be necessary to have multiple fresh donated human eggs at hand. This is not likely to happen since women could not provide eggs for research cloning on short notice. It would not be possible to develop a bank of frozen human eggs to call on in carrying out this sort of cloning since safe techniques for egg freezing are not yet assured.
Alternatives to using human eggs in research cloning, such as reprogramming ordinary human body cells to function in ways akin to the cytoplasm of human eggs, are possible. However, a final difficulty is that no matter what materials are used, individualized treatments using research cloning would be very expensive and would be available only to a few who could afford them. For such reasons, the use of research cloning in therapeutic stem cell research is not likely to become widespread in the near future.