What We Know About Embryonic Stem Cells

[The following excerpt is from an article “What We Know About Embryonic Stem Cells” originally published in First Things, January, 2007 (www.firstthings.com) and is reprinted with permission. This excellent article may be read in its entirety at http://www.firstthings.com/article.php3?id_article=5420 —Ed.]

[…] Experience from multiple laboratories over the past decade confirms that it is extremely difficult to clone any animal. Cloned embryos are generally quite abnormal, with those that are sufficiently normal to survive to live birth typically representing between 0.1 and 2 percent. The problems do not end with the technical difficulty of somatic-cell nuclear transfer itself. Extensive evidence indicates that even the cloned animals that make it to birth are not untarnished success stories.

Following Ian Wilmut’s production of Dolly the sheep, the world’s first cloned mammal, it was almost immediately evident that Dolly was not normal; she experienced a number of medical problems that resulted in her being euthanized, due to poor health, at the age of six years, about half the lifespan of a healthy sheep. Dolly was the only clone to survive to live birth out of the 277 cloned embryos Wilmut’s group generated, yet this success did not prove that cloning can produce a normal sheep. Dolly was merely normal enough to survive to birth.

In the past five years, a number of studies have carefully examined patterns of gene expression in mice and other cloned animals that survived to birth. Not one of these animals is genetically normal, and multiple genes are aberrantly expressed in multiple tissues. Both the severity and the extent of these genetic abnormalities came as a surprise to the cloning field, and yet, in retrospect, they are not surprising at all. The fact that most cloned embryos die at early stages of development is entirely consistent with the conclusion that somatic-cell nuclear transfer does not generate normal embryos, even in the rare cases where clones survive to birth. Thus, the optimistic contention that “therapeutic cloning” would fix the immune problem facing potential embryonic stem cell-based therapies for humans seems thus far entirely unsupported by the scientific evidence.

The dwindling numbers of therapeutic-cloning supporters defend this procedure by asserting that the genetic abnormalities are only a problem if you are attempting to produce a live birth. Thus, in a 2004 New York Times article, George Daley, a stem cell researcher at Children’s Hospital in Boston, acknowledged that cloned animals show multiple genetic abnormalities, yet optimistically asserted, “Cloned tissues are not likely to have the same problems.” In light of the mounting evidence that cloned animals experience severe genetic disregulation, such tentative reassurance is wearing thin, with even Daley admitting that his optimistic prediction that cloned tissues will prove normal enough for medical purposes has “yet to be proven.”

The question of how normal cloned tissue needs to be is not merely a detail that needs to be worked out. It is, in practice, a fundamentally unanswerable question. If cloned human embryos are to be used as a source of stem cells, we will be faced with this simple question for every single patient: How normal is this particular cloned embryo, the one we are going to use to generate stem cells to treat this particular patient? Without allowing that embryo to develop and observing precisely how abnormal it proves to be, it is simply impossible to know whether it is normal enough for medical use. Every patient will be an experiment with no quality control. Perhaps the particular cells will be normal enough to cure this particular patient, but then again perhaps they will be so grotesquely abnormal that they will create a condition worse than the one they were intended to treat.

The limitation in our ability to determine which cloned embryos are of sufficient normalcy to generate medically useful replacement tissue is one that no research can address unless scientists develop some kind of test to determine in advance which cloned embryos are normal enough. Developing such a test would almost certainly require the horrific scenario of growing human embryos to a sufficient state of maturity that the normalcy of their developing tissues could be empirically determined. This would mean implanting cloned embryos into surrogate wombs and then aborting them at specific times to examine the embryo’s development. Based on this information, it might be possible (although difficult) to identify features of very early embryos that predict whether they are capable of generating therapeutically useful tissue. Whether Americans are willing to accept the unknown (yet potentially large) risk of being treated with stem cells of undetermined (and essentially undeterminable) quality or whether we would prefer to accept the kind of experimentation on human embryos and fetuses that would be required to ensure embryonic stem cell safety are questions of profound social and moral importance.